STRINGSTRING
RB1CC1 RB1CC1 GADD45B GADD45B MAPK1 MAPK1 BIRC7 BIRC7 PAGE4 PAGE4 RIPK2 RIPK2 SFRP1 SFRP1 HGF HGF WNT16 WNT16 NOD1 NOD1 FKTN FKTN DUSP3 DUSP3 SPI1 SPI1 LTBR LTBR IL26 IL26 EIF2AK2 EIF2AK2 MMP8 MMP8 DUSP1 DUSP1 MAPK8IP1 MAPK8IP1 UNC5CL UNC5CL RAP2A RAP2A BMP4 BMP4 CCR7 CCR7 PYCARD PYCARD TRAF2 TRAF2 GADD45G GADD45G MAP3K10 MAP3K10 MDFIC MDFIC EDAR EDAR DAB2IP DAB2IP CCL21 CCL21 RIPK1 RIPK1 TRAF5 TRAF5 TAOK1 TAOK1 FLT4 FLT4 AXIN1 AXIN1 TRAF4 TRAF4 PHLPP1 PHLPP1 PRDX1 PRDX1 MAP2K2 MAP2K2 MAPK3 MAPK3 IL1A IL1A IL1B IL1B WNT5A WNT5A MECOM MECOM AMBP AMBP SEMA3A SEMA3A CD27 CD27 NCOR1 NCOR1 ARL6IP5 ARL6IP5 SFRP2 SFRP2 EGFR EGFR MFHAS1 MFHAS1 PDCD4 PDCD4 SERPINB3 SERPINB3 SH3RF1 SH3RF1 APP APP WNT7A WNT7A FZD7 FZD7 GDF6 GDF6 NCF1 NCF1 MAP4K2 MAP4K2 FGF19 FGF19 F2RL1 F2RL1 TLR3 TLR3 RELL2 RELL2 DUSP16 DUSP16 MARVELD3 MARVELD3 CRK CRK NOD2 NOD2 IGFBP6 IGFBP6 ULK4 ULK4 MAP2K1 MAP2K1 HDAC3 HDAC3 HIPK3 HIPK3 MAGI3 MAGI3 TPD52L1 TPD52L1 SEMA4C SEMA4C QARS1 QARS1 CCL19 CCL19 SH3RF3 SH3RF3 MAP3K11 MAP3K11 ZNF622 ZNF622 TAOK2 TAOK2 RASGRP1 RASGRP1 LEP LEP SPHK1 SPHK1 PER1 PER1 SERPINF2 SERPINF2 MTURN MTURN STK25 STK25 MAPK8IP2 MAPK8IP2 EMC10 EMC10 KLHDC10 KLHDC10 MEN1 MEN1 DACT1 DACT1 PLCB1 PLCB1 EZR EZR AIDA AIDA WNT7B WNT7B RNF13 RNF13 CAV3 CAV3 FOXM1 FOXM1 NBR1 NBR1 MAP4K4 MAP4K4 HMGB1 HMGB1 DLG1 DLG1 ANKRD6 ANKRD6 DUSP19 DUSP19 MINK1 MINK1 STK39 STK39 COPS5 COPS5 FCGR2B FCGR2B MAP3K5 MAP3K5 HAND2 HAND2 PTPN22 PTPN22 ZNF675 ZNF675 TLR9 TLR9 PJA2 PJA2 MAP3K3 MAP3K3 PRKN PRKN DUSP10 DUSP10 TGFB2 TGFB2 SASH1 SASH1 CCN2 CCN2 KLHL31 KLHL31 GADD45A GADD45A XIAP XIAP CARD9 CARD9 ZMPSTE24 ZMPSTE24 NOX1 NOX1 ZC3H12A ZC3H12A TREM2 TREM2 TRAF1 TRAF1 TLR4 TLR4 IGBP1 IGBP1 PINK1 PINK1 AGER AGER NPPA NPPA BMP2 BMP2 RASSF2 RASSF2 XDH XDH FOXO1 FOXO1 DNAJA1 DNAJA1 ZMYND11 ZMYND11 TNFRSF19 TNFRSF19 MAP3K4 MAP3K4 TAOK3 TAOK3 TIRAP TIRAP TRAF3 TRAF3 PDCD10 PDCD10 EDA2R EDA2R GPS2 GPS2 PAFAH1B1 PAFAH1B1 PTK2B PTK2B MAP2K7 MAP2K7 EPHB1 EPHB1 GSTP1 GSTP1 TNFSF11 TNFSF11 HIPK2 HIPK2 CYLD CYLD INAVA INAVA MAPKBP1 MAPKBP1 DIXDC1 DIXDC1 DUSP22 DUSP22 TNF TNF RELL1 RELL1 TNIK TNIK MBIP MBIP PRMT1 PRMT1 TRPV4 TRPV4 HRAS HRAS CRACR2A CRACR2A MAP2K4 MAP2K4 MID1 MID1 PPIA PPIA SH3RF2 SH3RF2 SDCBP SDCBP PBK PBK NAIP NAIP LYN LYN STK3 STK3 TRAF6 TRAF6 SLAMF1 SLAMF1 SCIMP SCIMP SIRPA SIRPA MYC MYC MAPK8IP3 MAPK8IP3 IGF1R IGF1R MYD88 MYD88 FAS FAS ITCH ITCH
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RB1CC1RB1-inducible coiled-coil protein 1; Involved in autophagy. Regulates early events but also late events of autophagosome formation through direct interaction with Atg16L1. Required for the formation of the autophagosome-like double-membrane structure that surrounds the Salmonella-containing vacuole (SCV) during S.typhimurium infection and subsequent xenophagy (By similarity). Involved in repair of DNA damage caused by ionizing radiation, which subsequently improves cell survival by decreasing apoptosis (By similarity). Inhibits PTK2/FAK1 and PTK2B/PYK2 kinase activity, affecting their [...] (1594 aa)
GADD45BGrowth arrest and DNA damage-inducible protein GADD45 beta; Involved in the regulation of growth and apoptosis. Mediates activation of stress-responsive MTK1/MEKK4 MAPKKK. (160 aa)
MAPK1Mitogen-activated protein kinase 1; Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays a [...] (360 aa)
BIRC7Baculoviral IAP repeat-containing protein 7 30kDa subunit; Apoptotic regulator capable of exerting proapoptotic and anti-apoptotic activities and plays crucial roles in apoptosis, cell proliferation, and cell cycle control. Its anti-apoptotic activity is mediated through the inhibition of CASP3, CASP7 and CASP9, as well as by its E3 ubiquitin-protein ligase activity. As it is a weak caspase inhibitor, its anti-apoptotic activity is thought to be due to its ability to ubiquitinate DIABLO/SMAC targeting it for degradation thereby promoting cell survival. May contribute to caspase inhibit [...] (298 aa)
PAGE4P antigen family member 4; Intrinsically disordered protein that potentiates the transcriptional activator activity of JUN. Protects cells from stress-induced apoptosis by inhibiting reactive oxygen species (ROS) production and via regulation of the MAPK signaling pathway. (102 aa)
RIPK2Receptor-interacting serine/threonine-protein kinase 2; Serine/threonine/tyrosine kinase that plays an essential role in modulation of innate and adaptive immune responses. Upon stimulation by bacterial peptidoglycans, NOD1 and NOD2 are activated, oligomerize and recruit RIPK2 through CARD-CARD domains. Contributes to the tyrosine phosphorylation of the guanine exchange factor ARHGEF2 through Src tyrosine kinase leading to NF-kappaB activation by NOD2. Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases XIAP, BIRC2 and BIRC3 [...] (540 aa)
SFRP1Secreted frizzled-related protein 1; Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types. SFRP1 decreases intracellular beta-catenin levels (By similarity). Has antiproliferative effects on vascular cells, in vitro and in vivo, and can induce, in vivo, an angiogenic response. In vascular cell cycle, delays the G1 phase and entry into the S phase (By similarity). In kidney development, inhibits tubule formation and bud growth in metane [...] (314 aa)
HGFHepatocyte growth factor alpha chain; Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types. Activating ligand for the receptor tyrosine kinase MET by binding to it and promoting its dimerization. Belongs to the peptidase S1 family. Plasminogen subfamily. (728 aa)
WNT16Protein Wnt-16; Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters (By similarity). (365 aa)
NOD1Nucleotide-binding oligomerization domain-containing protein 1; Enhances caspase-9-mediated apoptosis. Induces NF-kappa-B activity via RIPK2 and IKK-gamma. Confers responsiveness to intracellular bacterial lipopolysaccharides (LPS). Forms an intracellular sensing system along with ARHGEF2 for the detection of microbial effectors during cell invasion by pathogens. Required for RHOA and RIPK2 dependent NF-kappa-B signaling pathway activation upon S.flexneri cell invasion. Involved not only in sensing peptidoglycan (PGN)-derived muropeptides but also in the activation of NF-kappa-B by Shi [...] (953 aa)
FKTNFukutin; Catalyzes the transfer of CDP-ribitol to the distal N- acetylgalactosamine of the phosphorylated O-mannosyl trisaccharide (N- acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate- 6-)mannose), a carbohydrate structure present in alpha-dystroglycan (DAG1). This constitutes the first step in the formation of the ribitol 5-phosphate tandem repeat which links the phosphorylated O- mannosyl trisaccharide to the ligand binding moiety composed of repeats of 3-xylosyl-alpha-1,3-glucuronic acid-beta-1. Required for normal location of POMGNT1 in Golgi membranes, and for norm [...] (461 aa)
DUSP3Dual specificity protein phosphatase 3; Shows activity both for tyrosine-protein phosphate and serine-protein phosphate, but displays a strong preference toward phosphotyrosines. Specifically dephosphorylates and inactivates ERK1 and ERK2. (185 aa)
SPI1Transcription factor PU.1; Binds to the PU-box, a purine-rich DNA sequence (5'-GAGGAA- 3') that can act as a lymphoid-specific enhancer. This protein is a transcriptional activator that may be specifically involved in the differentiation or activation of macrophages or B-cells. Also binds RNA and may modulate pre-mRNA splicing (By similarity); Belongs to the ETS family. (271 aa)
LTBRTumor necrosis factor receptor superfamily member 3; Receptor for the heterotrimeric lymphotoxin containing LTA and LTB, and for TNFS14/LIGHT. Promotes apoptosis via TRAF3 and TRAF5. May play a role in the development of lymphoid organs. (435 aa)
IL26Interleukin-26; May play a role in local mechanisms of mucosal immunity and seems to have a proinflammatory function. May play a role in inflammatory bowel disease. Activates STAT1 and STAT3, MAPK1/3 (ERK1/2), JUN and AKT. Induces expression of SOCS3, TNF-alpha and IL-8, secretion of IL-8 and IL-10 and surface expression of ICAM1. Decreases proliferation of intestinal epithelial cells. Is inhibited by heparin. (171 aa)
EIF2AK2Interferon-induced, double-stranded RNA-activated protein kinase; IFN-induced dsRNA-dependent serine/threonine-protein kinase which plays a key role in the innate immune response to viral infection and is also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation. Exerts its antiviral activity on a wide range of DNA and RNA viruses including hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1). Inhibits viral replication via phosphorylation of the alpha subunit of eukaryotic initiation fac [...] (551 aa)
MMP8Neutrophil collagenase; Can degrade fibrillar type I, II, and III collagens; Belongs to the peptidase M10A family. (467 aa)
DUSP1Dual specificity protein phosphatase 1; Dual specificity phosphatase that dephosphorylates MAP kinase MAPK1/ERK2 on both 'Thr-183' and 'Tyr-185', regulating its activity during the meiotic cell cycle. (367 aa)
MAPK8IP1C-Jun-amino-terminal kinase-interacting protein 1; The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module. Required for JNK activation in response to excitotoxic stress. Cytoplasmic MAPK8IP1 causes inhibition of JNK-regulated activity by retaining JNK in the cytoplasm and inhibiting JNK phosphorylation of c-Jun. May also participate in ApoER2-specific reelin signaling. Directly, or indirectly, regulates GLUT2 gene expression and beta-cell function. A [...] (711 aa)
UNC5CLUNC5C-like protein; Inhibits NF-kappa-B-dependent transcription by impairing NF- kappa-B binding to its targets; Belongs to the unc-5 family. (518 aa)
RAP2ARas-related protein Rap-2a; Small GTP-binding protein which cycles between a GDP-bound inactive and a GTP-bound active form. In its active form interacts with and regulates several effectors including MAP4K4, MINK1 and TNIK. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it is part of several signaling cascades and may regulate cytoskeletal rearrangements, cell migration, cell adhesion and cell spreading. Belongs to the small GTPase superfamily. Ras family. (183 aa)
BMP4Bone morphogenetic protein 4; Induces cartilage and bone formation. Also acts in mesoderm induction, tooth development, limb formation and fracture repair. Acts in concert with PTHLH/PTHRP to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction (By similarity). (408 aa)
CCR7C-C chemokine receptor type 7; Receptor for the MIP-3-beta chemokine. Probable mediator of EBV effects on B-lymphocytes or of normal lymphocyte functions; Belongs to the G-protein coupled receptor 1 family. (378 aa)
PYCARDApoptosis-associated speck-like protein containing a CARD; Functions as key mediator in apoptosis and inflammation. Promotes caspase-mediated apoptosis involving predominantly caspase-8 and also caspase-9 in a probable cell type-specific manner. Involved in activation of the mitochondrial apoptotic pathway, promotes caspase-8- dependent proteolytic maturation of BID independently of FADD in certain cell types and also mediates mitochondrial translocation of BAX and activates BAX-dependent apoptosis coupled to activation of caspase- 9, -2 and -3. Involved in macrophage pyroptosis, a cas [...] (195 aa)
TRAF2TNF receptor-associated factor 2; Regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis. Required for normal antibody isotype switching from IgM to IgG. Has E3 ubiquitin-protein ligase activity and promotes 'Lys-63'-linked ubiquitination of target proteins, such as BIRC3, RIPK1 and TICAM1. Is an essential constituent of several E3 ubiquitin-protein ligase complexes, where it promotes the ubiquitination of target proteins by bringing them into contact with other E3 ubiquitin ligases. Regulates BIRC2 and BIRC3 protein levels [...] (501 aa)
GADD45GGrowth arrest and DNA damage-inducible protein GADD45 gamma; Involved in the regulation of growth and apoptosis. Mediates activation of stress-responsive MTK1/MEKK4 MAPKKK; Belongs to the GADD45 family. (159 aa)
MAP3K10Mitogen-activated protein kinase kinase kinase 10; Activates the JUN N-terminal pathway; Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily. (954 aa)
MDFICMyoD family inhibitor domain-containing protein; Acts as a transcriptional activator or repressor. Inhibits the transcriptional activation of Zic family proteins ZIC1, ZIC2 and ZIC3. Retains nuclear Zic proteins ZIC1, ZIC2 and ZIC3 in the cytoplasm. Modulates the expression from both cellular and viral promoters. Down-regulates Tat-dependent transcription of the human immunodeficiency virus type 1 (HIV-1) LTR by interacting with HIV-1 Tat and Rev and impairing their nuclear import, probably by rendering the NLS domains inaccessible to importin-beta. Also stimulates activation of human [...] (355 aa)
EDARTumor necrosis factor receptor superfamily member EDAR; Receptor for EDA isoform A1, but not for EDA isoform A2. Mediates the activation of NF-kappa-B and JNK. May promote caspase- independent cell death. (448 aa)
DAB2IPDisabled homolog 2-interacting protein; Functions as a scaffold protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Involved in several processes such as innate immune response, inflammation and cell growth inhibition, apoptosis, cell survival, angiogenesis, cell migration and maturation. Plays also a role in cell cycle checkpoint control; reduces G1 phase cyclin levels resulting in G0/G1 cell cycle arrest. Mediates signal transduction by receptor- mediated inflammatory signals, such as the tumor necrosis factor (TNF), interferon [...] (1132 aa)
CCL21C-C motif chemokine 21; Inhibits hemopoiesis and stimulates chemotaxis. Chemotactic in vitro for thymocytes and activated T-cells, but not for B-cells, macrophages, or neutrophils. Shows preferential activity towards naive T-cells. May play a role in mediating homing of lymphocytes to secondary lymphoid organs. Binds to atypical chemokine receptor ACKR4 and mediates the recruitment of beta-arrestin (ARRB1/2) to ACKR4. (134 aa)
RIPK1Receptor-interacting serine/threonine-protein kinase 1; Serine-threonine kinase which is a key regulator of both cell death and cell survival. Exhibits kinase activity- dependent functions that trigger cell death and kinase-independent scaffold functions regulating inflammatory signaling and cell survival. Initiates ripoptocide which describes cell death that is dependent on RIPK1, be it apoptosis or necroptosis. Upon binding of TNF to TNFR1, RIPK1 is recruited to the TNF-R1 signaling complex (TNF-RSC also known as complex I) where it acts as a scaffold protein promoting cell survival, [...] (671 aa)
TRAF5TNF receptor-associated factor 5; Adapter protein and signal transducer that links members of the tumor necrosis factor receptor family to different signaling pathways by association with the receptor cytoplasmic domain and kinases. Mediates activation of NF-kappa-B and probably JNK. Seems to be involved in apoptosis. Plays a role in mediating activation of NF- kappa-B by EIF2AK2/PKR. (557 aa)
TAOK1Serine/threonine-protein kinase TAO1; Serine/threonine-protein kinase involved in various processes such as p38/MAPK14 stress-activated MAPK cascade, DNA damage response and regulation of cytoskeleton stability. Phosphorylates MAP2K3, MAP2K6 and MARK2. Acts as an activator of the p38/MAPK14 stress-activated MAPK cascade by mediating phosphorylation and subsequent activation of the upstream MAP2K3 and MAP2K6 kinases. Involved in G-protein coupled receptor signaling to p38/MAPK14. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK1 [...] (1001 aa)
FLT4Vascular endothelial growth factor receptor 3; Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced production of VEGFC, and to a lesser degree VEGFA, thereby creating a positive feedback loop that enhances FLT4 signaling. Modulates KDR signaling by [...] (1363 aa)
AXIN1Axin-1; Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling. Controls dorsoventral patterning via two opposing effects; down-regulates CTNNB1 to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt- independent JNK signaling pathway. In Wnt signaling, probably facilitates the phosphorylation of CTNNB1 and APC by GSK3B. Likely to function as a tumor suppressor. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin l [...] (862 aa)
TRAF4TNF receptor-associated factor 4; Adapter protein and signal transducer that links members of the tumor necrosis factor receptor (TNFR) family to different signaling pathways. Plays a role in the activation of NF-kappa-B and JNK, and in the regulation of cell survival and apoptosis. Regulates activation of NF-kappa-B in response to signaling through Toll-like receptors. Required for normal skeleton development, and for normal development of the respiratory tract (By similarity). Required for activation of RPS6KB1 in response to TNF signaling. Modulates TRAF6 functions. (470 aa)
PHLPP1PH domain leucine-rich repeat-containing protein phosphatase 1; Protein phosphatase involved in regulation of Akt and PKC signaling. Mediates dephosphorylation in the C-terminal domain hydrophobic motif of members of the AGC Ser/Thr protein kinase family; specifically acts on 'Ser-473' of AKT2 and AKT3, 'Ser-660' of PRKCB and 'Ser-657' of PRKCA. Isoform 2 seems to have a major role in regulating Akt signaling in hippocampal neurons (By similarity). Akt regulates the balance between cell survival and apoptosis through a cascade that primarily alters the function of transcription factors [...] (1717 aa)
PRDX1Peroxiredoxin-1; Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides and as sensor of hydrogen peroxide-mediated signaling events. Might participate in the signaling cascades of growth factors and tumor necrosis factor-alpha by regulating the intracellular concentrations of H(2)O(2). Reduces an intramolecular disulfide bond in GDPD5 that gates the ability to GDPD5 to drive postmitotic motor neuron differentiation (By s [...] (199 aa)
MAP2K2Dual specificity mitogen-activated protein kinase kinase 2; Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation. (400 aa)
MAPK3Mitogen-activated protein kinase 3; Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays a [...] (379 aa)
IL1AInterleukin-1 alpha; Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells. (271 aa)
IL1BInterleukin-1 beta; Potent proinflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B- cell activation and antibody production, and fibroblast proliferation and collagen production. Promotes Th17 differentiation of T-cells. Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T- helper 1 (Th1) cells. (269 aa)
WNT5AProtein Wnt-5a; Ligand for members of the frizzled family of seven transmembrane receptors. Can activate or inhibit canonical Wnt signaling, depending on receptor context. In the presence of FZD4, activates beta-catenin signaling. In the presence of ROR2, inhibits the canonical Wnt pathway by promoting beta-catenin degradation through a GSK3-independent pathway which involves down-regulation of beta- catenin-induced reporter gene expression (By similarity). Suppression of the canonical pathway allows chondrogenesis to occur and inhibits tumor formation. Stimulates cell migration. Decre [...] (380 aa)
MECOMHistone-lysine N-methyltransferase MECOM; [Isoform 1]: Functions as a transcriptional regulator binding to DNA sequences in the promoter region of target genes and regulating positively or negatively their expression. Oncogene which plays a role in development, cell proliferation and differentiation. May also play a role in apoptosis through regulation of the JNK and TGF-beta signaling. Involved in hematopoiesis. (1116 aa)
AMBPInter-alpha-trypsin inhibitor light chain; Inter-alpha-trypsin inhibitor inhibits trypsin, plasmin, and lysosomal granulocytic elastase. Inhibits calcium oxalate crystallization; In the N-terminal section; belongs to the calycin superfamily. Lipocalin family. (352 aa)
SEMA3ASemaphorin-3A; Involved in the development of the olfactory system and in neuronal control of puberty. Induces the collapse and paralysis of neuronal growth cones. Could serve as a ligand that guides specific growth cones by a motility-inhibiting mechanism. Binds to the complex neuropilin-1/plexin-1; Belongs to the semaphorin family. (771 aa)
CD27CD27 antigen; Receptor for CD70/CD27L. May play a role in survival of activated T-cells. May play a role in apoptosis through association with SIVA1. (260 aa)
NCOR1Nuclear receptor corepressor 1; Mediates transcriptional repression by certain nuclear receptors. Part of a complex which promotes histone deacetylation and the formation of repressive chromatin structures which may impede the access of basal transcription factors. Participates in the transcriptional repressor activity produced by BCL6. Recruited by ZBTB7A to the androgen response elements/ARE on target genes, negatively regulates androgen receptor signaling and androgen-induced cell proliferation. Mediates the NR1D1-dependent repression and circadian regulation of TSHB expression (By [...] (2440 aa)
ARL6IP5PRA1 family protein 3; Regulates intracellular concentrations of taurine and glutamate. Negatively modulates SLC1A1/EAAC1 glutamate transport activity by decreasing its affinity for glutamate in a PKC activity- dependent manner. May be involved in membrane traffic. (188 aa)
SFRP2Secreted frizzled-related protein 2; Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types. SFRP2 may be important for eye retinal development and for myogenesis. (295 aa)
EGFREpidermal growth factor receptor; Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin- binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at leas [...] (1210 aa)
MFHAS1Malignant fibrous histiocytoma-amplified sequence 1; Probable GTP-binding protein. Functions in innate immunity and more specifically the inflammatory response as a regulator of the Toll-like receptor TLR2 and TLR4 signaling pathways. Negatively regulates the part of the TLR4 signaling pathway that leads to the activation of the transcription factor AP-1. By retaining the phosphatase complex PP2A into the cytoplasm, prevents the dephosphorylation of the AP-1 subunit JUN which is required for proper activation of the transcription factor. Both inhibits and activates the TLR2-dependent s [...] (1052 aa)
PDCD4Programmed cell death protein 4; Inhibits translation initiation and cap-dependent translation. May excert its function by hindering the interaction between EIF4A1 and EIF4G. Inhibits the helicase activity of EIF4A. Modulates the activation of JUN kinase. Down-regulates the expression of MAP4K1, thus inhibiting events important in driving invasion, namely, MAPK85 activation and consequent JUN-dependent transcription. May play a role in apoptosis. Tumor suppressor. Inhibits tumor promoter-induced neoplastic transformation. Binds RNA (By similarity). Belongs to the PDCD4 family. (469 aa)
SERPINB3Serpin B3; May act as a papain-like cysteine protease inhibitor to modulate the host immune response against tumor cells. Also functions as an inhibitor of UV-induced apoptosis via suppression of the activity of c-Jun NH(2)-terminal kinase (JNK1). (390 aa)
SH3RF1E3 ubiquitin-protein ligase SH3RF1; Has E3 ubiquitin-protein ligase activity. In the absence of an external substrate, it can catalyze self-ubiquitination. Stimulates ubiquitination of potassium channel KCNJ1, enhancing it's dynamin-dependent and clathrin- independent endocytosis. Acts as a scaffold protein that coordinates with MAPK8IP1/JIP1 in organizing different components of the JNK pathway, including RAC1 or RAC2, MAP3K11/MLK3 or MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and/or MAPK9/JNK2 into a functional multiprotein complex to ensure the effective activation of the JNK signaling pa [...] (888 aa)
APPGamma-secretase C-terminal fragment 50; Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on neighboring cells promotes synaptogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis- inducing pathways such as those mediated by G(O) and JIP. Inhibits [...] (770 aa)
WNT7AProtein Wnt-7a; Ligand for members of the frizzled family of seven transmembrane receptors that functions in the canonical Wnt/beta- catenin signaling pathway (By similarity). Plays an important role in embryonic development, including dorsal versus ventral patterning during limb development, skeleton development and urogenital tract development. Required for central nervous system (CNS) angiogenesis and blood-brain barrier regulation. Required for normal, sexually dimorphic development of the Mullerian ducts, and for normal fertility in both sexes (By similarity). Required for normal [...] (349 aa)
FZD7Frizzled-7; Receptor for Wnt proteins. Most frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to invo [...] (574 aa)
GDF6Growth/differentiation factor 6; Growth factor that controls proliferation and cellular differentiation in the retina and bone formation. Plays a key role in regulating apoptosis during retinal development. Establishes dorsal- ventral positional information in the retina and controls the formation of the retinotectal map. Required for normal formation of bones and joints in the limbs, skull, digits and axial skeleton. Plays a key role in establishing boundaries between skeletal elements during development. Regulation of GDF6 expression seems to be a mechanism for evolving species-speci [...] (455 aa)
NCF1Neutrophil cytosol factor 1; NCF2, NCF1, and a membrane bound cytochrome b558 are required for activation of the latent NADPH oxidase (necessary for superoxide production). (390 aa)
MAP4K2Mitogen-activated protein kinase kinase kinase kinase 2; Serine/threonine-protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Acts as a MAPK kinase kinase kinase (MAP4K) and is an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway and to a lesser extent of the p38 MAPKs signaling pathway. Required for the efficient activation of JNKs by TRAF6- dependent stimuli, including pathogen-associated molecular patterns (PAMPs) such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides [...] (820 aa)
FGF19Fibroblast growth factor 19; Involved in the suppression of bile acid biosynthesis through down-regulation of CYP7A1 expression, following positive regulation of the JNK and ERK1/2 cascades. Stimulates glucose uptake in adipocytes. Activity requires the presence of KLB and FGFR4. Belongs to the heparin-binding growth factors family. (216 aa)
F2RL1Proteinase-activated receptor 2, alternate cleaved 1; Receptor for trypsin and trypsin-like enzymes coupled to G proteins. Its function is mediated through the activation of several signaling pathways including phospholipase C (PLC), intracellular calcium, mitogen-activated protein kinase (MAPK), I-kappaB kinase/NF-kappaB and Rho. Can also be transactivated by cleaved F2R/PAR1. Involved in modulation of inflammatory responses and regulation of innate and adaptive immunity, and acts as a sensor for proteolytic enzymes generated during infection. Generally is promoting inflammation. Can [...] (397 aa)
TLR3Toll-like receptor 3; Key component of innate and adaptive immunity. TLRs (Toll- like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR3 is a nucleotide-sensing TLR which is activated by double-stranded RNA, a sign of viral infection. Acts via the adapter TRIF/TICAM1, leading to NF-kappa-B activation, IRF3 nuclear translocation, cytokine secretion and the inflammatory response. (904 aa)
RELL2RELT-like protein 2; Induces activation of MAPK14/p38 cascade, when overexpressed. Induces apoptosis, when overexpressed ; Belongs to the RELT family. (303 aa)
DUSP16Dual specificity protein phosphatase 16; Dual specificity protein phosphatase involved in the inactivation of MAP kinases. Dephosphorylates MAPK10 bound to ARRB2. (665 aa)
MARVELD3MARVEL domain containing 3. (410 aa)
CRKAdapter molecule crk; [Isoform Crk-II]: Regulates cell adhesion, spreading and migration. Mediates attachment-induced MAPK8 activation, membrane ruffling and cell motility in a Rac-dependent manner. Involved in phagocytosis of apoptotic cells and cell motility via its interaction with DOCK1 and DOCK4. May regulate the EFNA5-EPHA3 signaling. (304 aa)
NOD2Nucleotide-binding oligomerization domain-containing protein 2; Involved in gastrointestinal immunity. Upon stimulation by muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, binds the proximal adapter receptor-interacting RIPK2, which recruits ubiquitin ligases as XIAP, BIRC2, BIRC3, INAVA and the LUBAC complex, triggering activation of MAP kinases and activation of NF-kappa-B signaling. This in turn leads to the transcriptional activation of hundreds of genes involved in immune response. Required for MDP-induced NLRP1-dependent CASP1 activation and IL1B release in macroph [...] (1040 aa)
IGFBP6Insulin-like growth factor-binding protein 6; IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors. (240 aa)
ULK4Serine/threonine-protein kinase ULK4; May be involved in the remodeling of cytoskeletal components, such as alpha-tubulin, and in this way regulates neurite branching and elongation, as well as cell motility. (1275 aa)
MAP2K1Dual specificity mitogen-activated protein kinase kinase 1; Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine resid [...] (393 aa)
HDAC3Histone deacetylase 3; Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates. Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Participates in the BCL6 transcriptional repressor activity by deacetylating the H3 'Lys-27' (H3K27) on enhancer elements, antagonizing EP300 acetyltransferase activi [...] (428 aa)
HIPK3Homeodomain-interacting protein kinase 3; Serine/threonine-protein kinase involved in transcription regulation, apoptosis and steroidogenic gene expression. Phosphorylates JUN and RUNX2. Seems to negatively regulate apoptosis by promoting FADD phosphorylation. Enhances androgen receptor-mediated transcription. May act as a transcriptional corepressor for NK homeodomain transcription factors. The phosphorylation of NR5A1 activates SF1 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. In osteoblasts, supports transcription activation: phosphoryla [...] (1215 aa)
MAGI3Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 3; Acts as a scaffolding protein at cell-cell junctions, thereby regulating various cellular and signaling processes. Cooperates with PTEN to modulate the kinase activity of AKT1. Its interaction with PTPRB and tyrosine phosphorylated proteins suggests that it may link receptor tyrosine phosphatase with its substrates at the plasma membrane. In polarized epithelial cells, involved in efficient trafficking of TGFA to the cell surface. Regulates the ability of LPAR2 to activate ERK and RhoA pathways. Regulates the [...] (1481 aa)
TPD52L1Tumor protein D53; TPD52 like 1. (209 aa)
SEMA4CSemaphorin-4C; Cell surface receptor for PLXNB2 that plays an important role in cell-cell signaling. PLXNB2 binding promotes downstream activation of RHOA and phosphorylation of ERBB2 at 'Tyr-1248'. Required for normal brain development, axon guidance and cell migration (By similarity). Probable signaling receptor which may play a role in myogenic differentiation through activation of the stress-activated MAPK cascade; Belongs to the semaphorin family. (833 aa)
QARS1Glutamine--tRNA ligase; Glutamine--tRNA ligase. Plays a critical role in brain development. Belongs to the class-I aminoacyl-tRNA synthetase family. (775 aa)
CCL19C-C motif chemokine 19; May play a role not only in inflammatory and immunological responses but also in normal lymphocyte recirculation and homing. May play an important role in trafficking of T-cells in thymus, and T-cell and B-cell migration to secondary lymphoid organs. Binds to chemokine receptor CCR7. Recombinant CCL19 shows potent chemotactic activity for T-cells and B-cells but not for granulocytes and monocytes. Binds to atypical chemokine receptor ACKR4 and mediates the recruitment of beta- arrestin (ARRB1/2) to ACKR4; Belongs to the intercrine beta (chemokine CC) family. (98 aa)
SH3RF3E3 ubiquitin-protein ligase SH3RF3; Has E3 ubiquitin-protein ligase activity. (882 aa)
MAP3K11Mitogen-activated protein kinase kinase kinase 11; Activates the JUN N-terminal pathway. Required for serum- stimulated cell proliferation and for mitogen and cytokine activation of MAPK14 (p38), MAPK3 (ERK) and MAPK8 (JNK1) through phosphorylation and activation of MAP2K4/MKK4 and MAP2K7/MKK7. Plays a role in mitogen- stimulated phosphorylation and activation of BRAF, but does not phosphorylate BRAF directly. Influences microtubule organization during the cell cycle. (847 aa)
ZNF622Zinc finger protein 622; May behave as an activator of the bound transcription factor, MYBL2, and be involved in embryonic development. (477 aa)
TAOK2Serine/threonine-protein kinase TAO2; Serine/threonine-protein kinase involved in different processes such as membrane blebbing and apoptotic bodies formation DNA damage response and MAPK14/p38 MAPK stress-activated MAPK cascade. Phosphorylates itself, MBP, activated MAPK8, MAP2K3, MAP2K6 and tubulins. Activates the MAPK14/p38 MAPK signaling pathway through the specific activation and phosphorylation of the upstream MAP2K3 and MAP2K6 kinases. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress- activated MAPK cascade, pro [...] (1235 aa)
RASGRP1RAS guanyl-releasing protein 1; Functions as a calcium- and diacylglycerol (DAG)-regulated nucleotide exchange factor specifically activating Ras through the exchange of bound GDP for GTP. Activates the Erk/MAP kinase cascade. Regulates T- cell/B-cell development, homeostasis and differentiation by coupling T- lymphocyte/B-lymphocyte antigen receptors to Ras. Regulates NK cell cytotoxicity and ITAM-dependent cytokine production by activation of Ras-mediated ERK and JNK pathways. Functions in mast cell degranulation and cytokine secretion, regulating FcERI-evoked allergic responses (By [...] (797 aa)
LEPLeptin; Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in the activation of several major signaling pathways. In the hypothalamus, acts as an appetite-regulating factor that induces a decrease in food intake and an increase in energy consumption by inducing anorexinogenic factors and suppressing orexigenic neuropeptides, also regulates bone mass and secretion of hypothalamo- pituitary-adrenal hormones. In the periphery, increases basal me [...] (167 aa)
SPHK1Sphingosine kinase 1; Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. Also acts on D-erythro-sphingosine and to a lesser extent sphinganine, but not other lipids, such as D,L-threo- dihydrosphingosine, N,N-dimethylsphingosine, diacylglycerol, ceramide, or phosphatidylinositol. In contrast to proapoptotic SPHK2, has a negative effect on intracellular ceramide levels, enhances cell growth and inhibits apoptosis. Involved in the regulation of inflammatory response and neuroinflammation. Via [...] (470 aa)
PER1Period circadian protein homolog 1; Transcriptional repressor which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardi [...] (1290 aa)
SERPINF2Alpha-2-antiplasmin; Serine protease inhibitor. The major targets of this inhibitor are plasmin and trypsin, but it also inactivates matriptase- 3/TMPRSS7 and chymotrypsin. (491 aa)
MTURNMaturin; Promotes megakaryocyte differentiation by enhancing ERK and JNK signaling as well as up-regulating RUNX1 and FLI1 expression. Represses NF-kappa-B transcriptional activity by inhibiting phosphorylation of RELA at 'Ser-536'. May be involved in early neuronal development (By similarity). Belongs to the MTURN family. (131 aa)
STK25Serine/threonine-protein kinase 25; Oxidant stress-activated serine/threonine kinase that may play a role in the response to environmental stress. Targets to the Golgi apparatus where it appears to regulate protein transport events, cell adhesion, and polarity complexes important for cell migration. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily. (426 aa)
MAPK8IP2C-Jun-amino-terminal kinase-interacting protein 2; The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module. JIP2 inhibits IL1 beta-induced apoptosis in insulin-secreting cells. May function as a regulator of vesicle transport, through interactions with the JNK-signaling components and motor proteins (By similarity). (824 aa)
EMC10ER membrane protein complex subunit 10; Promotes angiogenesis and tissue repair in the heart after myocardial infarction. Stimulates cardiac endothelial cell migration and outgrowth via the activation of p38 MAPK, PAK and MAPK2 signaling pathways. (262 aa)
KLHDC10Kelch domain-containing protein 10; Participates in the oxidative stress-induced cell death through MAP3K5 activation. Inhibits PPP5C phosphatase activity on MAP3K5. (442 aa)
MEN1Menin; Essential component of a MLL/SET1 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3 (H3K4). Functions as a transcriptional regulator. Binds to the TERT promoter and represses telomerase expression. Plays a role in TGFB1-mediated inhibition of cell-proliferation, possibly regulating SMAD3 transcriptional activity. Represses JUND-mediated transcriptional activation on AP1 sites, as well as that mediated by NFKB subunit RELA. Positively regulates HOXC8 and HOXC6 gene expression. May be involved in normal hematopoiesis through the [...] (615 aa)
DACT1Dapper homolog 1; Involved in regulation of intracellular signaling pathways during development. Specifically thought to play a role in canonical and/or non-canonical Wnt signaling pathways through interaction with DSH (Dishevelled) family proteins. The activation/inhibition of Wnt signaling may depend on the phosphorylation status. Proposed to regulate the degradation of CTNNB1/beta-catenin, thereby modulating the transcriptional activation of target genes of the Wnt signaling pathway. Its function in stabilizing CTNNB1 may involve inhibition of GSK3B activity. Promotes the membrane l [...] (836 aa)
PLCB11-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1; The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. (1216 aa)
EZREzrin; Probably involved in connections of major cytoskeletal structures to the plasma membrane. In epithelial cells, required for the formation of microvilli and membrane ruffles on the apical pole. Along with PLEKHG6, required for normal macropinocytosis. (586 aa)
AIDAAxin interactor, dorsalization-associated protein; Acts as a ventralizing factor during embryogenesis. Inhibits axin-mediated JNK activation by binding axin and disrupting axin homodimerization. This in turn antagonizes a Wnt/beta-catenin- independent dorsalization pathway activated by AXIN/JNK-signaling (By similarity). (306 aa)
WNT7BProtein Wnt-7b; Ligand for members of the frizzled family of seven transmembrane receptors that functions in the canonical Wnt/beta- catenin signaling pathway. Required for normal fusion of the chorion and the allantois during placenta development (By similarity). Required for central nervous system (CNS) angiogenesis and blood-brain barrier regulation. (349 aa)
RNF13E3 ubiquitin-protein ligase RNF13; E3 ubiquitin-protein ligase that may play a role in controlling cell proliferation. Involved in apoptosis regulation. Mediates ER stress-induced activation of JNK signaling pathway and apoptosis by promoting ERN1 activation and splicing of XBP1 mRNA. (381 aa)
CAV3Caveolin-3; May act as a scaffolding protein within caveolar membranes. Interacts directly with G-protein alpha subunits and can functionally regulate their activity. May also regulate voltage-gated potassium channels. Plays a role in the sarcolemma repair mechanism of both skeletal muscle and cardiomyocytes that permits rapid resealing of membranes disrupted by mechanical stress (By similarity). Mediates the recruitment of CAVIN2 and CAVIN3 proteins to the caveolae ; Belongs to the caveolin family. (151 aa)
FOXM1Forkhead box protein M1; Transcriptional factor regulating the expression of cell cycle genes essential for DNA replication and mitosis. Plays a role in the control of cell proliferation. Plays also a role in DNA breaks repair participating in the DNA damage checkpoint response. (801 aa)
NBR1Next to BRCA1 gene 1 protein; Acts probably as a receptor for selective autophagosomal degradation of ubiquitinated targets. (966 aa)
MAP4K4Mitogen-activated protein kinase kinase kinase kinase 4; Serine/threonine kinase that may play a role in the response to environmental stress and cytokines such as TNF-alpha. Appears to act upstream of the JUN N-terminal pathway. Phosphorylates SMAD1 on Thr- 322. (1273 aa)
HMGB1High mobility group protein B1; Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone involved in replication, transcription, chromatin remodeling, V(D)J recombination, DNA repair and genome stability. Proposed to be an universal biosensor for nucleic acids. Promotes host inflammatory response to sterile and infectious signals and is involved in the coordination and integration of innate and adaptive immune responses. In the cytoplasm functio [...] (215 aa)
DLG1Disks large homolog 1; Essential multidomain scaffolding protein required for normal development (By similarity). Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. May play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. Regulates the excitability of cardiac myocytes by modulating the functional expression of Kv4 channels. Functional regulator of Kv1.5 channel. During long-term depression in hippocampal neurons, it recruits ADAM10 to the plasma membrane. B [...] (926 aa)
ANKRD6Ankyrin repeat domain-containing protein 6; Recruits CKI-epsilon to the beta-catenin degradation complex that consists of AXN1 or AXN2 and GSK3-beta and allows efficient phosphorylation of beta-catenin, thereby inhibiting beta-catenin/Tcf signals. (727 aa)
DUSP19Dual specificity protein phosphatase 19; Has a dual specificity toward Ser/Thr and Tyr-containing proteins. (217 aa)
MINK1Misshapen-like kinase 1; Serine/threonine kinase which acts as a negative regulator of Ras-related Rap2-mediated signal transduction to control neuronal structure and AMPA receptor trafficking. Required for normal synaptic density, dendrite complexity, as well as surface AMPA receptor expression in hippocampal neurons. Can activate the JNK and MAPK14/p38 pathways and mediates stimulation of the stress-activated protein kinase MAPK14/p38 MAPK downstream of the Raf/ERK pathway. Phosphorylates: TANC1 upon stimulation by RAP2A, MBP and SMAD1. Has an essential function in negative selection [...] (1332 aa)
STK39STE20/SPS1-related proline-alanine-rich protein kinase; May act as a mediator of stress-activated signals. Mediates the inhibition of SLC4A4, SLC26A6 as well as CFTR activities by the WNK scaffolds, probably through phosphorylation. Phosphorylates RELT. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily. (545 aa)
COPS5COP9 signalosome complex subunit 5; Probable protease subunit of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of the SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8, possibly via its association with CK2 and PKD [...] (334 aa)
FCGR2BLow affinity immunoglobulin gamma Fc region receptor II-b; Receptor for the Fc region of complexed or aggregated immunoglobulins gamma. Low affinity receptor. Involved in a variety of effector and regulatory functions such as phagocytosis of immune complexes and modulation of antibody production by B-cells. Binding to this receptor results in down-modulation of previous state of cell activation triggered via antigen receptors on B-cells (BCR), T-cells (TCR) or via another Fc receptor. Isoform IIB1 fails to mediate endocytosis or phagocytosis. Isoform IIB2 does not trigger phagocytosis. (310 aa)
MAP3K5Mitogen-activated protein kinase kinase kinase 5; Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is required for the innate immune response, which is essential for host defense against a wide range of pathogens. Me [...] (1374 aa)
HAND2Heart- and neural crest derivatives-expressed protein 2; Essential for cardiac morphogenesis, particularly for the formation of the right ventricle and of the aortic arch arteries. Required for vascular development and regulation of angiogenesis, possibly through a VEGF signaling pathway. Plays also an important role in limb development, particularly in the establishment of anterior- posterior polarization, acting as an upstream regulator of sonic hedgehog (SHH) induction in the limb bud. Is involved in the development of branchial arches, which give rise to unique structures in the he [...] (217 aa)
PTPN22Tyrosine-protein phosphatase non-receptor type 22; Acts as negative regulator of T-cell receptor (TCR) signaling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signaling molecules. Associates with and probably dephosphorylates CBL. Dephosphorylates LCK at its activating 'Tyr-394' residue. Dephosphorylates ZAP70 at its activating 'Tyr-493' residue. Dephosphorylates the immune system activator SKAP2. Positively regulates toll-like receptor (TLR)-induced type 1 interferon production. Promotes host [...] (807 aa)
ZNF675Zinc finger protein 675; May be involved in transcriptional regulation. May play a role during osteoclast differentiation by modulating TRAF6 signaling activity. (568 aa)
TLR9Toll-like receptor 9; Key component of innate and adaptive immunity. TLRs (Toll- like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR9 is a nucleotide-sensing TLR which is activated by unmethylated cytidine- phosphate-guanosine (CpG) dinucleotides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Controls lymphocyte response to Helicobacter infection (By similarity). Upon CpG stimulation, induces B-cell proliferation, activation, survival and [...] (1032 aa)
PJA2E3 ubiquitin-protein ligase Praja-2; Has E2-dependent E3 ubiquitin-protein ligase activity. Responsible for ubiquitination of cAMP-dependent protein kinase type I and type II-alpha/beta regulatory subunits and for targeting them for proteasomal degradation. Essential for PKA-mediated long-term memory processes. Through the ubiquitination of MFHAS1, positively regulates the TLR2 signaling pathway that leads to the activation of the downstream p38 and JNK MAP kinases and promotes the polarization of macrophages toward the pro-inflammatory M1 phenotype. (708 aa)
MAP3K3Mitogen-activated protein kinase kinase kinase 3; Component of a protein kinase signal transduction cascade. Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional regulators. (657 aa)
PRKNE3 ubiquitin-protein ligase parkin; Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, TOMM20, USP30, ZNF746 and AIMP2. Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'- linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context. Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of m [...] (465 aa)
DUSP10Dual specificity protein phosphatase 10; Protein phosphatase involved in the inactivation of MAP kinases. Has a specificity for the MAPK11/MAPK12/MAPK13/MAPK14 subfamily. It preferably dephosphorylates p38. (482 aa)
TGFB2Transforming growth factor beta-2 proprotein; Transforming growth factor beta-2 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-2 (TGF-beta-2) chains, which constitute the regulatory and active subunit of TGF-beta-2, respectively. Transforming growth factor beta-2: Multifunctional protein that regulates various processes such as angiogenesis and heart development. Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi apparatus, Latency-associated peptide (LAP) and Transforming growth fact [...] (442 aa)
SASH1SAM and SH3 domain-containing protein 1; Is a positive regulator of NF-kappa-B signaling downstream of TLR4 activation. It acts as a scaffold molecule to assemble a molecular complex that includes TRAF6, MAP3K7, CHUK and IKBKB, thereby facilitating NF-kappa-B signaling activation. Regulates TRAF6 and MAP3K7 ubiquitination. Involved in the regulation of cell mobility. Regulates lipolysaccharide (LPS)-induced endothelial cell migration. Is involved in the regulation of skin pigmentation through the control of melanocyte migration in the epidermis. (1247 aa)
CCN2CCN family member 2; Major connective tissue mitoattractant secreted by vascular endothelial cells. Promotes proliferation and differentiation of chondrocytes. Mediates heparin- and divalent cation-dependent cell adhesion in many cell types including fibroblasts, myofibroblasts, endothelial and epithelial cells. Enhances fibroblast growth factor- induced DNA synthesis; Belongs to the CCN family. (349 aa)
KLHL31Kelch-like protein 31; Transcriptional repressor in MAPK/JNK signaling pathway to regulate cellular functions. Overexpression inhibits the transcriptional activities of both the TPA-response element (TRE) and serum response element (SRE). (634 aa)
GADD45AGrowth arrest and DNA damage-inducible protein GADD45 alpha; In T-cells, functions as a regulator of p38 MAPKs by inhibiting p88 phosphorylation and activity (By similarity). Might affect PCNA interaction with some CDK (cell division protein kinase) complexes; stimulates DNA excision repair in vitro and inhibits entry of cells into S phase; Belongs to the GADD45 family. (165 aa)
XIAPE3 ubiquitin-protein ligase XIAP; Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as well as cell invasion and metastasis. Acts as a direct caspase inhibitor. Directly bind to the active site pocket of CASP3 and CASP7 and obstructs substrate entry. Inactivates CASP9 by keeping it in a monomeric, inactive state. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and the target proteins for its E3 ubiquitin-protein ligas [...] (497 aa)
CARD9Caspase recruitment domain-containing protein 9; Adapter protein that plays a key role in innate immune response to a number of intracellular pathogens, such as C.albicans and L.monocytogenes. Is at the crossroads of ITAM-tyrosine kinase and the Toll-like receptors (TLR) and NOD2 signaling pathways. Probably controls various innate immune response pathways depending on the intracellular pathogen. In response to L.monocytogenes infection, acts by connecting NOD2 recognition of peptidoglycan to downstream activation of MAP kinases (MAPK) without activating NF-kappa-B. Also involved in ac [...] (536 aa)
ZMPSTE24CAAX prenyl protease 1 homolog; Proteolytically removes the C-terminal three residues of farnesylated proteins. Acts on lamin A/C. (475 aa)
NOX1NADPH oxidase 1; NOH-1S is a voltage-gated proton channel that mediates the H(+) currents of resting phagocytes and other tissues. It participates in the regulation of cellular pH and is blocked by zinc. NOH-1L is a pyridine nucleotide-dependent oxidoreductase that generates superoxide and might conduct H(+) ions as part of its electron transport mechanism, whereas NOH-1S does not contain an electron transport chain. (564 aa)
ZC3H12AEndoribonuclease ZC3H12A; Endoribonuclease involved in various biological functions such as cellular inflammatory response and immune homeostasis, glial differentiation of neuroprogenitor cells, cell death of cardiomyocytes, adipogenesis and angiogenesis. Functions as an endoribonuclease involved in mRNA decay. Modulates the inflammatory response by promoting the degradation of a set of translationally active cytokine-induced inflammation-related mRNAs, such as IL6 and IL12B, during the early phase of inflammation. Prevents aberrant T-cell-mediated immune reaction by degradation of mul [...] (599 aa)
TREM2Triggering receptor expressed on myeloid cells 2; Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding. Acts as a receptor for amyloid-beta protein 42, a cleavage product of the amyloid-beta precursor protein APP, and mediates its uptake and degradation by microglia. Binding to amyloid-beta 42 mediates microglial activation, proliferation, migration, apoptosis and expression of pro- inflammatory cytokines, such as IL6R and CCL3, and the anti- inflammatory cytokine ARG1 (By similarity). Acts as a receptor for lipoprotein pa [...] (230 aa)
TRAF1TNF receptor-associated factor 1; Adapter molecule that regulates the activation of NF-kappa-B and JNK. Plays a role in the regulation of cell survival and apoptosis. The heterotrimer formed by TRAF1 and TRAF2 is part of a E3 ubiquitin- protein ligase complex that promotes ubiquitination of target proteins, such as MAP3K14. The TRAF1/TRAF2 complex recruits the antiapoptotic E3 protein-ubiquitin ligases BIRC2 and BIRC3 to TNFRSF1B/TNFR2. (416 aa)
TLR4Toll-like receptor 4; Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS). Acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni(2+). Responses triggered by Ni(2+) require non- conserved histidines and are, therefore, species-specific. Both M.tuberculosis HSP70 (dnaK) and HSP65 (groEL-2) act via this protein to stimulate NF-kappa-B expression. In complex with [...] (839 aa)
IGBP1Immunoglobulin-binding protein 1; Associated to surface IgM-receptor; may be involved in signal transduction. Involved in regulation of the catalytic activity of the phosphatases PP2A, PP4 and PP6 by protecting their partially folded catalytic subunits from degradative polyubiquitination until they associate with regulatory subunits. (339 aa)
PINK1Serine/threonine-protein kinase PINK1, mitochondrial; Protects against mitochondrial dysfunction during cellular stress by phosphorylating mitochondrial proteins. Involved in the clearance of damaged mitochondria via selective autophagy (mitophagy) by mediating activation and translocation of PRKN. Targets PRKN to dysfunctional depolarized mitochondria through the phosphorylation of MFN2. Activates PRKN in 2 steps: (1) by mediating phosphorylation at 'Ser-65' of PRKN and (2) mediating phosphorylation of ubiquitin, converting PRKN to its fully-active form. Required for ubiquinone reduct [...] (581 aa)
AGERAdvanced glycosylation end product-specific receptor; Mediates interactions of advanced glycosylation end products (AGE). These are nonenzymatically glycosylated proteins which accumulate in vascular tissue in aging and at an accelerated rate in diabetes. Acts as a mediator of both acute and chronic vascular inflammation in conditions such as atherosclerosis and in particular as a complication of diabetes. AGE/RAGE signaling plays an important role in regulating the production/expression of TNF-alpha, oxidative stress, and endothelial dysfunction in type 2 diabetes. Interaction with S1 [...] (420 aa)
NPPAAtrial natriuretic factor; Hormone playing a key role in cardiovascular homeostasis through regulation of natriuresis, diuresis, and vasodilation. Also plays a role in female pregnancy by promoting trophoblast invasion and spiral artery remodeling in uterus. Specifically binds and stimulates the cGMP production of the NPR1 receptor. Binds the clearance receptor NPR3. (151 aa)
BMP2Bone morphogenetic protein 2; Induces cartilage and bone formation. Stimulates the differentiation of myoblasts into osteoblasts via the EIF2AK3-EIF2A- ATF4 pathway. BMP2 activation of EIF2AK3 stimulates phosphorylation of EIF2A which leads to increased expression of ATF4 which plays a central role in osteoblast differentiation. In addition stimulates TMEM119, which upregulates the expression of ATF4 ; Belongs to the TGF-beta family. (396 aa)
RASSF2Ras association domain-containing protein 2; Potential tumor suppressor. Acts as a KRAS-specific effector protein. May promote apoptosis and cell cycle arrest. Stabilizes STK3/MST2 by protecting it from proteasomal degradation. (326 aa)
XDHXanthine dehydrogenase/oxidase; Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro). (1333 aa)
FOXO1Forkhead box protein O1; Transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress. Binds to the insulin response element (IRE) with consensus sequence 5'-TT[G/A]TTTTG-3' and the related Daf-16 family binding element (DBE) with consensus sequence 5'-TT[G/A]TTTAC-3'. Activity suppressed by insulin. Main regulator of redox balance and osteoblast numbers and controls bone mass. Orchestrates the endocrine function of the skeleton in regulating glucose metabolism. Acts synergistically with ATF4 to suppress osteocalc [...] (655 aa)
DNAJA1DnaJ homolog subfamily A member 1; Co-chaperone for HSPA8/Hsc70. Stimulates ATP hydrolysis, but not the folding of unfolded proteins mediated by HSPA1A (in vitro). Plays a role in protein transport into mitochondria via its role as co-chaperone. Functions as co- chaperone for HSPA1B and negatively regulates the translocation of BAX from the cytosol to mitochondria in response to cellular stress, thereby protecting cells against apoptosis. Promotes apoptosis in response to cellular stress mediated by exposure to anisomycin or UV. (397 aa)
ZMYND11Zinc finger MYND domain-containing protein 11; Chromatin reader that specifically recognizes and binds histone H3.3 trimethylated at 'Lys-36' (H3.3K36me3) and regulates RNA polymerase II elongation. Does not bind other histone H3 subtypes (H3.1 or H3.2) (By similarity). Colocalizes with highly expressed genes and functions as a transcription corepressor by modulating RNA polymerase II at the elongation stage. Binds non-specifically to dsDNA. Acts as a tumor-suppressor by repressing a transcriptional program essential for tumor cell growth. (602 aa)
TNFRSF19Tumor necrosis factor receptor superfamily member 19; Can mediate activation of JNK and NF-kappa-B. May promote caspase-independent cell death. (423 aa)
MAP3K4Mitogen-activated protein kinase kinase kinase 4; Component of a protein kinase signal transduction cascade. Activates the CSBP2, P38 and JNK MAPK pathways, but not the ERK pathway. Specifically phosphorylates and activates MAP2K4 and MAP2K6. (1608 aa)
TAOK3Serine/threonine-protein kinase TAO3; Serine/threonine-protein kinase that acts as a regulator of the p38/MAPK14 stress-activated MAPK cascade and of the MAPK8/JNK cascade. Acts as an activator of the p38/MAPK14 stress-activated MAPK cascade. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of upstream MAP2K3 and MAP2K6 kinases. Inhibits basal activity of MAPK8/JNK cascade and diminishes its activation in response epidermal growth factor (EGF). Belongs to th [...] (898 aa)
TIRAPToll/interleukin-1 receptor domain-containing adapter protein; Adapter involved in TLR2 and TLR4 signaling pathways in the innate immune response. Acts via IRAK2 and TRAF-6, leading to the activation of NF-kappa-B, MAPK1, MAPK3 and JNK, and resulting in cytokine secretion and the inflammatory response. Positively regulates the production of TNF-alpha and interleukin-6. (235 aa)
TRAF3TNF receptor-associated factor 3; Regulates pathways leading to the activation of NF-kappa-B and MAP kinases, and plays a central role in the regulation of B-cell survival. Part of signaling pathways leading to the production of cytokines and interferon. Required for normal antibody isotype switching from IgM to IgG. Plays a role T-cell dependent immune responses. Plays a role in the regulation of antiviral responses. Is an essential constituent of several E3 ubiquitin-protein ligase complexes. May have E3 ubiquitin-protein ligase activity and promote 'Lys-63'- linked ubiquitination of [...] (568 aa)
PDCD10Programmed cell death protein 10; Promotes cell proliferation. Modulates apoptotic pathways. Increases mitogen-activated protein kinase activity and STK26 activity. Important for cell migration, and for normal structure and assembly of the Golgi complex. Important for KDR/VEGFR2 signaling. Increases the stability of KDR/VEGFR2 and prevents its breakdown. Required for normal cardiovascular development. Required for normal angiogenesis, vasculogenesis and hematopoiesis during embryonic development (By similarity). Belongs to the PDCD10 family. (212 aa)
EDA2RTumor necrosis factor receptor superfamily member 27; Receptor for EDA isoform A2, but not for EDA isoform A1. Mediates the activation of the NF-kappa-B and JNK pathways. Activation seems to be mediated by binding to TRAF3 and TRAF6. (318 aa)
GPS2G protein pathway suppressor 2; Key regulator of inflammation, lipid metabolism and mitochondrion homeostasis that acts by inhibiting the activity of the ubiquitin-conjugating enzyme UBE2N/Ubc13, thereby inhibiting 'Lys-63'- linked ubiquitination (By similarity). In the nucleus, can both acts as a corepressor and coactivator of transcription, depending on the context. Acts as a transcription coactivator in adipocytes by promoting the recruitment of PPARG to promoters: acts by inhibiting the activity of the ubiquitin-conjugating enzyme UBE2N/Ubc13, leading to stabilization of KDM4A and [...] (327 aa)
PAFAH1B1Platelet-activating factor acetylhydrolase IB subunit alpha; Required for proper activation of Rho GTPases and actin polymerization at the leading edge of locomoting cerebellar neurons and postmigratory hippocampal neurons in response to calcium influx triggered via NMDA receptors. Non-catalytic subunit of an acetylhydrolase complex which inactivates platelet-activating factor (PAF) by removing the acetyl group at the SN-2 position (By similarity). Positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule slidi [...] (410 aa)
PTK2BProtein-tyrosine kinase 2-beta; Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T-cells, and contributes to the regulation of T-cell responses. Promot [...] (1009 aa)
MAP2K7Dual specificity mitogen-activated protein kinase kinase 7; Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylati [...] (435 aa)
EPHB1Ephrin type-B receptor 1; Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Cognate/functional ephrin ligands for this receptor include EFNB1, EFNB2 and EFNB3. During nervous system development, regulates retinal axon guidance redirecting ipsilaterally ventrotempora [...] (984 aa)
GSTP1Glutathione S-transferase P; Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration. (210 aa)
TNFSF11Tumor necrosis factor ligand superfamily member 11, membrane form; Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy. Induces osteoclastogenesis by activating multiple signaling pathways in o [...] (317 aa)
HIPK2Homeodomain-interacting protein kinase 2; Serine/threonine-protein kinase involved in transcription regulation, p53/TP53-mediated cellular apoptosis and regulation of the cell cycle. Acts as a corepressor of several transcription factors, including SMAD1 and POU4F1/Brn3a and probably NK homeodomain transcription factors. Phosphorylates PDX1, ATF1, PML, p53/TP53, CREB1, CTBP1, CBX4, RUNX1, EP300, CTNNB1, HMGA1 and ZBTB4. Inhibits cell growth and promotes apoptosis through the activation of p53/TP53 both at the transcription level and at the protein level (by phosphorylation and indirect [...] (1198 aa)
CYLDUbiquitin carboxyl-terminal hydrolase CYLD; Deubiquitinase that specifically cleaves 'Lys-63'- and linear 'Met-1'-linked polyubiquitin chains and is involved in NF-kappa-B activation and TNF-alpha-induced necroptosis. Plays an important role in the regulation of pathways leading to NF-kappa-B activation. Contributes to the regulation of cell survival, proliferation and differentiation via its effects on NF- kappa-B activation. Negative regulator of Wnt signaling. Inhibits HDAC6 and thereby promotes acetylation of alpha-tubulin and stabilization of microtubules. Plays a role in the regu [...] (956 aa)
INAVAInnate immunity activator protein; Expressed in peripheral macrophages and intestinal myeloid- derived cells, is required for optimal PRR (pattern recognition receptor)-induced signaling, cytokine secretion, and bacterial clearance. Upon stimulation of a broad range of PRRs (pattern recognition receptor) such as NOD2 or TLR2, TLR3, TLR4, TLR5, TLR7 and TLR9, associates with YWHAQ/14-3-3T, which in turn leads to the recruitment and activation of MAP kinases and NF-kappa-B signaling complexes that amplifies PRR-induced downstream signals and cytokine secretion. In the intestine, regulate [...] (578 aa)
MAPKBP1Mitogen-activated protein kinase-binding protein 1; Negative regulator of NOD2 function. It down-regulates NOD2- induced processes such as activation of NF-kappa-B signaling, IL8 secretion and antibacterial response. Involved in JNK signaling pathway (By similarity). (1514 aa)
DIXDC1Dixin; Positive effector of the Wnt signaling pathway; activates WNT3A signaling via DVL2. Regulates JNK activation by AXIN1 and DVL2. (683 aa)
DUSP22Dual specificity protein phosphatase 22; Activates the Jnk signaling pathway. Dephosphorylates and deactivates p38 and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) (By similarity). (205 aa)
TNFTumor necrosis factor, membrane form; Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T- cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Upregulates the expression of protein phosphatase 1 [...] (233 aa)
RELL1RELT-like protein 1; Induces activation of MAPK14/p38 cascade, when overexpressed. Induces apoptosis, when overexpressed. (271 aa)
TNIKTRAF2 and NCK-interacting protein kinase; Serine/threonine kinase that acts as an essential activator of the Wnt signaling pathway. Recruited to promoters of Wnt target genes and required to activate their expression. May act by phosphorylating TCF4/TCF7L2. Appears to act upstream of the JUN N- terminal pathway. May play a role in the response to environmental stress. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it may play a role in cytoskeletal rearrangements and regulate [...] (1360 aa)
MBIPMAP3K12-binding inhibitory protein 1; Inhibits the MAP3K12 activity to induce the activation of the JNK/SAPK pathway. Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4. (344 aa)
PRMT1Protein arginine N-methyltransferase 1; Arginine methyltransferase that methylates (mono and asymmetric dimethylation) the guanidino nitrogens of arginyl residues present in proteins such as ESR1, histone H2, H3 and H4, ILF3, HNRNPA1, HNRNPD, NFATC2IP, SUPT5H, TAF15, EWS, HABP4 and SERBP1. Constitutes the main enzyme that mediates monomethylation and asymmetric dimethylation of histone H4 'Arg-4' (H4R3me1 and H4R3me2a, respectively), a specific tag for epigenetic transcriptional activation. May be involved in the regulation of TAF15 transcriptional activity, act as an activator of estr [...] (371 aa)
TRPV4Transient receptor potential cation channel subfamily V member 4; Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity. Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification. Also activated by heat, low pH, citrate and phorbol esters. Increase of intracellular Ca(2+) potentiates currents. Channel activity seems to be regulated by a calmodulin- dependent mechanism with a negative feedback mechanism. Promotes cell-cell junction formation in skin keratinocytes and plays an important role in t [...] (871 aa)
HRASGTPase HRas, N-terminally processed; Involved in the activation of Ras protein signal transduction. Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. (189 aa)
CRACR2AEF-hand calcium-binding domain-containing protein 4B; Ca(2+)-binding protein that plays a key role in store- operated Ca(2+) entry (SOCE) in T-cells by regulating CRAC channel activation. Acts as a cytoplasmic calcium-sensor that facilitates the clustering of ORAI1 and STIM1 at the junctional regions between the plasma membrane and the endoplasmic reticulum upon low Ca(2+) concentration. It thereby regulates CRAC channel activation, including translocation and clustering of ORAI1 and STIM1. Upon increase of cytoplasmic Ca(2+) resulting from opening of CRAC channels, dissociates from OR [...] (731 aa)
MAP2K4Dual specificity mitogen-activated protein kinase kinase 4; Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylati [...] (410 aa)
MID1E3 ubiquitin-protein ligase Midline-1; Has E3 ubiquitin ligase activity towards IGBP1, promoting its monoubiquitination, which results in deprotection of the catalytic subunit of protein phosphatase PP2A, and its subsequent degradation by polyubiquitination; Belongs to the TRIM/RBCC family. (667 aa)
PPIAPeptidyl-prolyl cis-trans isomerase A, N-terminally processed; PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. (165 aa)
SH3RF2E3 ubiquitin-protein ligase SH3RF2; Has E3 ubiquitin-protein ligase activity. Acts as an anti-apoptotic regulator of the JNK pathway by ubiquitinating and promoting the degradation of SH3RF1, a scaffold protein that is required for pro-apoptotic JNK activation. Facilitates TNF-alpha-mediated recruitment of adapter proteins TRADD and RIPK1 to TNFRSF1A and regulates PAK4 protein stability via inhibition of its ubiquitin-mediated proteasomal degradation. Inhibits PPP1CA phosphatase activity. (729 aa)
SDCBPSyntenin-1; Multifunctional adapter protein involved in diverse array of functions including trafficking of transmembrane proteins, neuro and immunomodulation, exosome biogenesis, and tumorigenesis. Positively regulates TGFB1-mediated SMAD2/3 activation and TGFB1-induced epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types. May increase TGFB1 signaling by enhancing cell-surface expression of TGFR1 by preventing the interaction between TGFR1 and CAV1 and subsequent CAV1-dependent internalization and degradation of TGFR1. In concert with SDC1/4 and PDCD6IP, [...] (318 aa)
PBKLymphokine-activated killer T-cell-originated protein kinase; Phosphorylates MAP kinase p38. Seems to be active only in mitosis. May also play a role in the activation of lymphoid cells. When phosphorylated, forms a complex with TP53, leading to TP53 destabilization and attenuation of G2/M checkpoint during doxorubicin- induced DNA damage; Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily. (333 aa)
NAIPBaculoviral IAP repeat-containing protein 1; Anti-apoptotic protein which acts by inhibiting the activities of CASP3, CASP7 and CASP9. Can inhibit the autocleavage of pro-CASP9 and cleavage of pro-CASP3 by CASP9. Capable of inhibiting CASP9 autoproteolysis at 'Asp-315' and decreasing the rate of auto proteolysis at 'Asp-330'. Acts as a mediator of neuronal survival in pathological conditions. Prevents motor-neuron apoptosis induced by a variety of signals. Possible role in the prevention of spinal muscular atrophy that seems to be caused by inappropriate persistence of motor- neuron ap [...] (1403 aa)
LYNTyrosine-protein kinase Lyn; Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, responses to growth factors and cytokines, integrin signaling, but also responses to DNA damage and genotoxic agents. Functions primarily as negative regulator, but can also function as activator, depending on the context. Required for the initiation of the B-cell response, but also for its down-regulation and termination. Plays an important role in the regulation of B-c [...] (512 aa)
STK3Serine/threonine-protein kinase 3 20kDa subunit; Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regul [...] (519 aa)
TRAF6TNF receptor-associated factor 6; E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, IRAK1, AKT1 and AKT2. Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation. Leads to the activation of NF-kappa-B and JUN. May be essential for the formation of functional osteoclasts. Seems to also play a role in dendritic cells (DCs) maturation and/or activation. Represses c-Myb-mediated transactivation, in B-lymphocytes. Adapter protein that seem [...] (522 aa)
SLAMF1Signaling lymphocytic activation molecule; Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. SLAMF1-induced signal-transduction events in T-lymphocytes are different from those [...] (357 aa)
SCIMPSLP adapter and CSK-interacting membrane protein; Lipid tetraspanin-associated transmembrane adapter/mediator that acts as a scaffold for Src-family kinases and other signaling proteins in immune cells. It is involved in major histocompatibility complex class II (MHC-II) signaling transduction in B cells, where it is required in generating the calcium response and enhancing ERK activity upon MHC-II stimulation. In dendritic cells, it is involved in sustaining CLEC7A/DECTIN1 signaling after CLEC7A activation by fungal beta-glucans (By similarity). It also acts as an agonist-inducible si [...] (145 aa)
SIRPATyrosine-protein phosphatase non-receptor type substrate 1; Immunoglobulin-like cell surface receptor for CD47. Acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. Supports adhesion of cerebellar neurons, neurite outgrowth and glial cell attachment. May play a key role in intracellular signaling during synaptogenesis and in synaptic function (By similarity). Involved in the negative regulation of receptor tyrosine kinase-coupled cellular responses induced by cell adhesion, growth factors or insulin. Medi [...] (508 aa)
MYCMyc proto-oncogene protein; Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Activates the transcription of growth-related genes. Binds to the VEGFA promoter, promoting VEGFA production and subsequent sprouting angiogenesis. Regulator of somatic reprogramming, controls self-renewal of embryonic stem cells. Functions with TAF6L to activate target gene expression through RNA polymerase II pause release (By similarity). (454 aa)
MAPK8IP3C-Jun-amino-terminal kinase-interacting protein 3; The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module. May function as a regulator of vesicle transport, through interactions with the JNK-signaling components and motor proteins (By similarity). Promotes neuronal axon elongation in a kinesin- and JNK-dependent manner. Activates cofilin at axon tips via local activation of JNK, thereby regulating filopodial dynamics and enhancing axon elongation. It [...] (1337 aa)
IGF1RInsulin-like growth factor 1 receptor alpha chain; Receptor tyrosine kinase which mediates actions of insulin- like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates ( [...] (1367 aa)
MYD88Myeloid differentiation primary response protein MyD88; Adapter protein involved in the Toll-like receptor and IL-1 receptor signaling pathway in the innate immune response. Acts via IRAK1, IRAK2, IRF7 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Increases IL-8 transcription. Involved in IL-18-mediated signaling pathway. Activates IRF1 resulting in its rapid migration into the nucleus to mediate an efficient induction of IFN-beta, NOS2/INOS, and IL12A genes. MyD88-mediated signaling in intestinal epithelial cells is crucial for maintena [...] (317 aa)
FASTumor necrosis factor receptor superfamily member 6; Receptor for TNFSF6/FASLG. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. FAS-mediated apoptosis may have a role in the induction of peripheral tolerance, in the antigen- stimulated suicide of mature T-cells, or both. The secreted isoforms 2 to 6 block apoptosis (in vitro). (335 aa)
ITCHE3 ubiquitin-protein ligase Itchy homolog; Acts as an E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Catalyzes 'Lys-29'-, 'Lys-48'- and 'Lys-63'-linked ubiquitin conjugation. Involved in the control of inflammatory signaling pathways. Essential component of a ubiquitin-editing protein complex, comprising also TNFAIP3, TAX1BP1 and RNF11, that ensures the transient nature of inflammatory signaling pathways. Promotes the association of the complex after [...] (903 aa)
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Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, human, man
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