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| | PDK3 | [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrial; Inhibits pyruvate dehydrogenase activity by phosphorylation of the E1 subunit PDHA1, and thereby regulates glucose metabolism and aerobic respiration. Can also phosphorylate PDHA2. Decreases glucose utilization and increases fat metabolism in response to prolonged fasting, and as adaptation to a high-fat diet. Plays a role in glucose homeostasis and in maintaining normal blood glucose levels in function of nutrient levels and under starvation. Plays a role in the generation of reactive oxygen species. Belon [...] (415 aa) |
| | NR1H2 | Oxysterols receptor LXR-beta; Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity. Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8; DLDLR and LRP8. Interplays functionally with RORA for the regulation of genes involved in liver metabolism (By similarity). Plays an anti-inflammatory role during the hepatic acute phase response by acting as a corepressor: inhibits [...] (460 aa) |
| | ITCH | E3 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) |
| | HNF4G | Hepatocyte nuclear factor 4-gamma; Transcription factor. Has a lower transcription activation potential than HNF4-alpha; Belongs to the nuclear hormone receptor family. NR2 subfamily. (445 aa) |
| | UBR5 | E3 ubiquitin-protein ligase UBR5; E3 ubiquitin-protein ligase which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific N- terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation (By similarity). Involved in maturation and/or transcriptional regulation of mRNA by activating CDK9 by polyubiquitination. May play a role in control of cell cycle progression. May have tumor suppressor function. Regulates DNA topoisomerase II binding protein (TopBP1) in the DNA damage response. Pl [...] (2799 aa) |
| | TRAF6 | TNF 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) |
| | TRERF1 | Transcriptional-regulating factor 1; Binds DNA and activates transcription of CYP11A1. Interaction with CREBBP and EP300 results in a synergistic transcriptional activation of CYP11A1. (1220 aa) |
| | FAM120B | Constitutive coactivator of peroxisome proliferator-activated receptor gamma; Functions as a transactivator of PPARG and ESR1. Functions in adipogenesis through PPARG activation (By similarity); Belongs to the constitutive coactivator of PPAR-gamma family. (933 aa) |
| | NR4A1 | Nuclear receptor subfamily 4 group A member 1; Orphan nuclear receptor. May act concomitantly with NURR1 in regulating the expression of delayed-early genes during liver regeneration. Binds the NGFI-B response element (NBRE) 5'-AAAAGGTCA-3' (By similarity). May inhibit NF-kappa-B transactivation of IL2. Participates in energy homeostasis by sequestrating the kinase STK11 in the nucleus, thereby attenuating cytoplasmic AMPK activation. Plays a role in the vascular response to injury (By similarity). ECO:0000250|UniProtKB:P12813. (652 aa) |
| | PHB2 | Prohibitin-2; Acts as a mediator of transcriptional repression by nuclear hormone receptors via recruitment of histone deacetylases (By similarity). Functions as an estrogen receptor (ER)-selective coregulator that potentiates the inhibitory activities of antiestrogens and represses the activity of estrogens. Competes with NCOA1 for modulation of ER transcriptional activity. In mitochondria, regulates cytochrome-c oxidase assembly (COX) and mitochondrial respiration. Binding to sphingoid 1-phosphate (SPP) modulates its regulator activity. (299 aa) |
| | LSM14A | Protein LSM14 homolog A; Essential for formation of P-bodies, cytoplasmic structures that provide storage sites for non-translating mRNAs. (463 aa) |
| | NR1H4 | Bile acid receptor; Ligand-activated transcription factor. Receptor for bile acids (BAs) such as chenodeoxycholic acid (CDCA), lithocholic acid, deoxycholic acid (DCA) and allocholic acid (ACA). Plays a essential role in BA homeostasis through the regulation of genes involved in BA synthesis, conjugation and enterohepatic circulation. Also regulates lipid and glucose homeostasis and is involved innate immune response. The FXR-RXR heterodimer binds predominantly to farnesoid X receptor response elements (FXREs) containing two inverted repeats of the consensus sequence 5'-AGGTCA-3' in wh [...] (486 aa) |
| | CALCOCO1 | Calcium-binding and coiled-coil domain-containing protein 1; Functions as a coactivator for aryl hydrocarbon and nuclear receptors (NR). Recruited to promoters through its contact with the N- terminal basic helix-loop-helix-Per-Arnt-Sim (PAS) domain of transcription factors or coactivators, such as NCOA2. During ER- activation acts synergistically in combination with other NCOA2-binding proteins, such as EP300, CREBBP and CARM1. Involved in the transcriptional activation of target genes in the Wnt/CTNNB1 pathway. Functions as a secondary coactivator in LEF1-mediated transcriptional act [...] (691 aa) |
| | SNW1 | SNW domain-containing protein 1; Involved in pre-mRNA splicing as component of the spliceosome. Is required in the specific splicing of CDKN1A pre-mRNA; the function probably involves the recruitment of U2AF2 to the mRNA. Is proposed to recruit PPIL1 to the spliceosome. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. Involved in transcriptional regulation. Modulates TGF-beta-mediated transcription via association with SMAD proteins, MYOD1-mediated transcription via association with PABPN1, [...] (571 aa) |
| | NCOA4 | Nuclear receptor coactivator 4; Enhances the androgen receptor transcriptional activity in prostate cancer cells. Ligand-independent coactivator of the peroxisome proliferator-activated receptor (PPAR) gamma. (650 aa) |
| | ALDH1A2 | Retinal dehydrogenase 2; Converts retinaldehyde to retinoic acid. Recognizes as substrates free retinal and cellular retinol-binding protein-bound retinal. Can metabolize octanal and decanal, but has only very low activity with benzaldehyde, acetaldehyde and propanal. Displays complete lack of activity with citral (By similarity). Belongs to the aldehyde dehydrogenase family. (518 aa) |
| | SAFB | Scaffold attachment factor B1; Binds to scaffold/matrix attachment region (S/MAR) DNA and forms a molecular assembly point to allow the formation of a 'transcriptosomal' complex (consisting of SR proteins and RNA polymerase II) coupling transcription and RNA processing (By similarity). Can function as an estrogen receptor corepressor and can also bind to the HSP27 promoter and decrease its transcription. When associated with RBMX, binds to and stimulates transcription from the SREBF1 promoter (By similarity). Can inhibit cell proliferation. (917 aa) |
| | MAP2K6 | Dual specificity mitogen-activated protein kinase kinase 6; Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. With MAP3K3/MKK3, catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinases p38 MAPK11, MAPK12, MAPK13 and MAPK14 and plays an important role in the regulation of cellular responses to cytokines and all kinds of stresses. Especially, MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 and MAPK13 induced by environmental stress, whereas MAP2K6/MKK6 i [...] (334 aa) |
| | WBP2 | WW domain-binding protein 2; Acts as transcriptional coactivator of estrogen and progesterone receptors (ESR1 and PGR) upon hormone activation. In presence of estrogen, binds to ESR1-responsive promoters. Required for YAP1 coactivation function on PGR activity. Synergizes with WBP2 in enhancing PGR activity. Modulates expression of post-synaptic scaffolding proteins via regulation of ESR1, ESR2 and PGR (By similarity). (261 aa) |
| | EGLN2 | Egl nine homolog 2; Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF2A. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is [...] (407 aa) |
| | IRF3 | Interferon regulatory factor 3; Key transcriptional regulator of type I interferon (IFN)- dependent immune responses which plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Acts as a more potent activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA) gene and plays a critical role in both the early and late phases of the IFNA/B gene induction. Found in an inactive [...] (452 aa) |
| | NR1H3 | Oxysterols receptor LXR-alpha; Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity. Interaction with retinoic acid receptor (RXR) shifts RXR from its role as a silent DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by LXRES (By similarity). LXRES are DR4-type response elements characterized by direct repeats of two similar hexanuclotide half-sites spaced by four nucleotides (By similarity). Plays an important role in the regulation of cholesterol homeostasis, regulating cholesterol up [...] (453 aa) |
| | CRY2 | Cryptochrome-2; 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, cardiovascular, and renal [...] (614 aa) |
| | YAP1 | Transcriptional coactivator YAP1; Transcriptional regulator which can act both as a coactivator and a corepressor and is the critical downstream regulatory target in the Hippo signaling pathway that 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 regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncopro [...] (508 aa) |
| | PHB | Prohibitin; Prohibitin inhibits DNA synthesis. It has a role in regulating proliferation. As yet it is unclear if the protein or the mRNA exhibits this effect. May play a role in regulating mitochondrial respiration activity and in aging. (272 aa) |
| | TNFAIP3 | Tumor necrosis factor alpha-induced protein 3; Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities. Involved in immune and inflammatory responses signaled by cytokines, such as TNF-alpha and IL-1 beta, or pathogens via Toll-like receptors (TLRs) through terminating NF-kappa-B activity. Essential component of a ubiquitin-editing protein complex, comprising also RNF11, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways. In cooperation with TAX1BP1 promotes disassembly of E2-E3 ubiquitin protein ligase complexes in [...] (790 aa) |
| | NR4A3 | Nuclear receptor subfamily 4 group A member 3; Transcriptional activator that binds to regulatory elements in promoter regions in a cell- and response element (target)-specific manner. Induces gene expression by binding as monomers to the NR4A1 response element (NBRE) 5'-AAAAGGTCA-3' site and as homodimers to the Nur response element (NurRE) site in the promoter of their regulated target genes (By similarity). Plays a role in the regulation of proliferation, survival and differentiation of many different cell types and also in metabolism and inflammation. Mediates proliferation of vasc [...] (637 aa) |
| | PTGES3 | Prostaglandin E synthase 3; Cytosolic prostaglandin synthase that catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2). Molecular chaperone that localizes to genomic response elements in a hormone-dependent manner and disrupts receptor-mediated transcriptional activation, by promoting disassembly of transcriptional regulatory complexes. Facilitates HIF alpha proteins hydroxylation via interaction with EGLN1/PHD2, leading to recruit EGLN1/PHD2 to the HSP90 pathway. (164 aa) |
| | NR2E3 | Photoreceptor-specific nuclear receptor; Orphan nuclear receptor of retinal photoreceptor cells. Transcriptional factor that is an activator of rod development and repressor of cone development. Binds the promoter region of a number of rod- and cone-specific genes, including rhodopsin, M- and S-opsin and rod-specific phosphodiesterase beta subunit. Enhances rhodopsin expression. Represses M- and S-cone opsin expression. Belongs to the nuclear hormone receptor family. NR2 subfamily. (410 aa) |
| | NR2C2 | Nuclear receptor subfamily 2 group C member 2; Orphan nuclear receptor that can act as a repressor or activator of transcription. An important repressor of nuclear receptor signaling pathways such as retinoic acid receptor, retinoid X, vitamin D3 receptor, thyroid hormone receptor and estrogen receptor pathways. May regulate gene expression during the late phase of spermatogenesis. Together with NR2C1, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription including that of GATA1. Binds to hormone response element [...] (615 aa) |
| | ENSP00000490530 | Uncharacterized protein. (797 aa) |
| | TMF1 | TATA element modulatory factor; Potential coactivator of the androgen receptor. Mediates STAT3 degradation. May play critical roles in two RAB6-dependent retrograde transport processes: one from endosomes to the Golgi and the other from the Golgi to the ER. This protein binds the HIV-1 TATA element and inhibits transcriptional activation by the TATA-binding protein (TBP). (1096 aa) |
| | DHX58 | Probable ATP-dependent RNA helicase DHX58; Acts as a regulator of DDX58/RIG-I and IFIH1/MDA5 mediated antiviral signaling. Cannot initiate antiviral signaling as it lacks the CARD domain required for activating MAVS/IPS1-dependent signaling events. Can have both negative and positive regulatory functions related to DDX58/RIG-I and IFIH1/MDA5 signaling and this role in regulating signaling may be complex and could probably depend on characteristics of the infecting virus or target cells, or both. Its inhibitory action on DDX58/RIG-I signaling may involve the following mechanisms: compet [...] (678 aa) |
| | ACTN4 | Alpha-actinin-4; F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein (Probable). Probably involved in vesicular trafficking via its association with the CART complex. The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation. Involved in tight junction assembly in epithelial cells probably through interaction with MICALL2. Links MICALL2 to the actin cytoskeleton and recruits it to the tight junctions (By similarity). May also function as a transcriptional coacti [...] (911 aa) |
| | RARA | Retinoic acid receptor alpha; Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9- cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcr [...] (462 aa) |
| | RORA | Nuclear receptor ROR-alpha; Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of embryonic development, cellular differentiation, immunity, circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25-hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcriptional activity [...] (556 aa) |
| | TRIP4 | Activating signal cointegrator 1; Transcription coactivator which associates with nuclear receptors, transcriptional coactivators including EP300, CREBBP and NCOA1, and basal transcription factors like TBP and TFIIA to facilitate nuclear receptors-mediated transcription. May thereby play an important role in establishing distinct coactivator complexes under different cellular conditions. Plays a role in thyroid hormone receptor and estrogen receptor transactivation. Also involved in androgen receptor transactivation (By similarity). Plays a pivotal role in the transactivation of NF-kap [...] (581 aa) |
| | THRA | Thyroid hormone receptor alpha; [Isoform Alpha-1]: Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine. Belongs to the nuclear hormone receptor family. NR1 subfamily. (490 aa) |
| | STAT3 | Signal transducer and activator of transcription 3; Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the interleukin-6 (IL-6)-responsive elements identified in the promoters of various acute-phase protein genes. Activated by IL31 through IL31RA. Acts as a regulator of inflammatory response by regulating differenti [...] (770 aa) |
| | PLPP1 | Phospholipid phosphatase 1; Magnesium-independent phospholipid phosphatase of the plasma membrane that catalyzes the dephosphorylation of a variety of glycerolipid and sphingolipid phosphate esters including phosphatidate/PA, lysophosphatidate/LPA, diacylglycerol pyrophosphate/DGPP, sphingosine 1-phosphate/S1P and ceramide 1- phosphate/C1P. Also acts on N-oleoyl ethanolamine phosphate/N-(9Z-octadecenoyl)-ethanolamine phosphate, a potential physiological compound. Through its extracellular phosphatase activity allows both the hydrolysis and the cellular uptake of these bioactive lipid m [...] (285 aa) |
| | DAXX | Death domain-associated protein 6; Transcription corepressor known to repress transcriptional potential of several sumoylated transcription factors. Down-regulates basal and activated transcription. Its transcription repressor activity is modulated by recruiting it to subnuclear compartments like the nucleolus or PML/POD/ND10 nuclear bodies through interactions with MCSR1 and PML, respectively. Seems to regulate transcription in PML/POD/ND10 nuclear bodies together with PML and may influence TNFRSF6-dependent apoptosis thereby. Inhibits transcriptional activation of PAX3 and ETS1 throu [...] (740 aa) |
| | PML | Protein PML; Functions via its association with PML-nuclear bodies (PML- NBs) in a wide range of important cellular processes, including tumor suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. Acts as the scaffold of PML-NBs allowing other proteins to shuttle in and out, a process which is regulated by SUMO-mediated modifications and interactions. Isoform PML-4 has a multifaceted role in the regulation of apoptosis and growth suppression: activates RB1 and inhibits AKT1 via interactions with PP1 and PP2A phosphatases resp [...] (882 aa) |
| | POU4F2 | POU domain, class 4, transcription factor 2; Tissue-specific DNA-binding transcription factor involved in the development and differentiation of target cells. Functions either as activator or repressor modulating the rate of target gene transcription through RNA polymerase II enzyme in a promoter-dependent manner. Binds to the consensus octamer motif 5'-AT[A/T]A[T/A]T[A/T]A-3' of promoter of target genes. Plays a fundamental role in the gene regulatory network essential for retinal ganglion cell (RGC) differentiation. Binds to an octamer site to form a ternary complex with ISL1; cooper [...] (409 aa) |
| | OTULIN | Ubiquitin thioesterase otulin; Deubiquitinase that specifically removes linear ('Met-1'- linked) polyubiquitin chains to substrates and acts as a regulator of angiogenesis and innate immune response. Required during angiogenesis, craniofacial and neuronal development by regulating the canonical Wnt signaling together with the LUBAC complex. Acts as a negative regulator of NF-kappa-B by regulating the activity of the LUBAC complex. OTULIN function is mainly restricted to homeostasis of the LUBAC complex: acts by removing 'Met- 1'-linked autoubiquitination of the LUBAC complex, thereby p [...] (352 aa) |
| | PPARG | Peroxisome proliferator-activated receptor gamma; Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut ho [...] (505 aa) |
| | NR2F6 | Nuclear receptor subfamily 2 group F member 6; Transcription factor predominantly involved in transcriptional repression. Binds to promoter/enhancer response elements that contain the imperfect 5'-AGGTCA-3' direct or inverted repeats with various spacings which are also recognized by other nuclear hormone receptors. Involved in modulation of hormonal responses. Represses transcriptional activity of the lutropin- choriogonadotropic hormone receptor/LHCGR gene, the renin/REN gene and the oxytocin-neurophysin/OXT gene. Represses the triiodothyronine- dependent and -independent transcripti [...] (404 aa) |
| | CLPB | Caseinolytic peptidase B protein homolog; May function as a regulatory ATPase and be related to secretion/protein trafficking process. (707 aa) |
| | NOD2 | Nucleotide-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) |
| | MED1 | Mediator of RNA polymerase II transcription subunit 1; Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene- specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Acts as a coactivator for [...] (1581 aa) |
| | TADA3 | Transcriptional adapter 3; Functions as a component of the PCAF complex. The PCAF complex is capable of efficiently acetylating histones in a nucleosomal context. The PCAF complex could be considered as the human version of the yeast SAGA complex. Also known as a coactivator for p53/TP53- dependent transcriptional activation. Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4. Belongs to the NGG1 family. (432 aa) |
| | NR1D2 | Nuclear receptor subfamily 1 group D member 2; Transcriptional repressor which coordinates circadian rhythm and metabolic pathways in a heme-dependent manner. Integral component of the complex transcription machinery that governs circadian rhythmicity and forms a critical negative limb of the circadian clock by directly repressing the expression of core clock components ARNTL/BMAL1 and CLOCK. Also regulates genes involved in metabolic functions, including lipid metabolism and the inflammatory response. Acts as a receptor for heme which stimulates its interaction with the NCOR1/HDAC3 co [...] (579 aa) |
| | CYP7B1 | Cytochrome P450 7B1; A cytochrome P450 monooxygenase involved in the metabolism of endogenous oxysterols and steroid hormones, including neurosteroids. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase). Catalyzes the hydroxylation of carbon hydrogen bonds of steroids with a preference for 7-alpha position. Usually metabolizes steroids carrying a hydroxy group at position 3, functioning as a 3- hydroxy [...] (506 aa) |
| | PPARD | Peroxisome proliferator-activated receptor delta; Ligand-activated transcription factor. Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma- linoleic acid and eicosapentanoic acid. Once activated by a ligand, the receptor binds to promoter elements of target genes. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the acyl-CoA oxidase gene. Decreases expression of NPC1L1 once activated by a ligand. Belongs to the nuclear hormone [...] (441 aa) |
| | PPARGC1B | Peroxisome proliferator-activated receptor gamma coactivator 1-beta; Plays a role of stimulator of transcription factors and nuclear receptors activities. Activates transcriptional activity of estrogen receptor alpha, nuclear respiratory factor 1 (NRF1) and glucocorticoid receptor in the presence of glucocorticoids. May play a role in constitutive non-adrenergic-mediated mitochondrial biogenesis as suggested by increased basal oxygen consumption and mitochondrial number when overexpressed. May be involved in fat oxidation and non- oxidative glucose metabolism and in the regulation of e [...] (1023 aa) |
| | TAF7 | Transcription initiation factor TFIID subunit 7; Functions as a component of the DNA-binding general transcription factor complex TFIID, a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. Present in both of the previously described TFIID species which either lack or contain TAFII30 (TFIID alpha and TFIID beta respectively); Belongs to the TAF7 family. (349 aa) |
| | HNF4A | Hepatocyte nuclear factor 4-alpha; Transcriptional regulator which controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitating the recruitment of RNA pol II to the promoters of target genes. Activates the transcription of CYP2C38 (By similarity). Represses the CLOCK- ARNTL/BMAL1 transcriptional activity and is essential for circadian rhythm maintenance and period regulation in the liver and colon cells. (474 aa) |
| | ALOXE3 | Hydroperoxide isomerase ALOXE3; Non-heme iron-containing lipoxygenase which is atypical in that it displays a prominent hydroperoxide isomerase activity and a reduced dioxygenase activity compared to other lipoxygenases. The hydroperoxide isomerase activity catalyzes the isomerization of hydroperoxides, derived from arachidonic and linoleic acid by ALOX12B, into hepoxilin-type epoxyalcohols. The dioxygenase activity requires a step of activation of the enzyme by molecular oxygen. In presence of oxygen, oxygenates polyunsaturated fatty acids, including arachidonic acid, to produce fatty [...] (843 aa) |
| | ARID1A | AT-rich interactive domain-containing protein 1A; Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Binds DNA non-specifically. Belongs to the neural progenitors- specific chromatin remodeling complex (npBAF complex) and the neuron- specific chromatin remodeling complex (nBAF complex). During neural dev [...] (2285 aa) |
| | CALR | Calreticulin; Calcium-binding chaperone that promotes folding, oligomeric assembly and quality control in the endoplasmic reticulum (ER) via the calreticulin/calnexin cycle. This lectin interacts transiently with almost all of the monoglucosylated glycoproteins that are synthesized in the ER. Interacts with the DNA-binding domain of NR3C1 and mediates its nuclear export. Involved in maternal gene expression regulation. May participate in oocyte maturation via the regulation of calcium homeostasis (By similarity); Belongs to the calreticulin family. (417 aa) |
| | DCBLD2 | Discoidin, CUB and LCCL domain containing 2. (775 aa) |
| | AHRR | Aryl hydrocarbon receptor repressor; Mediates dioxin toxicity and is involved in regulation of cell growth and differentiation. Represses the transcription activity of AHR by competing with this transcription factor for heterodimer formation with the ARNT and subsequently binding to the xenobiotic response element (XRE) sequence present in the promoter regulatory region of variety of genes. Represses CYP1A1 by binding the XRE sequence and recruiting ANKRA2, HDAC4 and/or HDAC5. Autoregulates its expression by associating with its own XRE site. (719 aa) |
| | DDX54 | ATP-dependent RNA helicase DDX54; Has RNA-dependent ATPase activity. Represses the transcriptional activity of nuclear receptors. (882 aa) |
| | RNF14 | E3 ubiquitin-protein ligase RNF14; Might act as an E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes and then transfers it to substrates, which could be nuclear proteins. Could play a role as a coactivator for androgen- and, to a lesser extent, progesterone-dependent transcription; Belongs to the RBR family. RNF14 subfamily. (474 aa) |
| | PGR | Progesterone receptor; The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Depending on the isoform, progesterone receptor functions as transcriptional activator or repressor. [Isoform B]: Transcriptional activator of several progesteron-dependent promoters in a variety of cell types. Involved in activation of SRC-dependent MAPK signaling on hormone stimulation. (933 aa) |
| | NR2F1 | COUP transcription factor 1; Coup (chicken ovalbumin upstream promoter) transcription factor binds to the ovalbumin promoter and, in conjunction with another protein (S300-II) stimulates initiation of transcription. Binds to both direct repeats and palindromes of the 5'-AGGTCA-3' motif. Represses transcriptional activity of LHCG. (423 aa) |
| | RORC | Nuclear receptor ROR-gamma; Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of cellular differentiation, immunity, peripheral circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25- hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcriptional activity, respectiv [...] (518 aa) |
| | RNF135 | E3 ubiquitin-protein ligase RNF135; E2-dependent E3 ubiquitin-protein ligase that functions as a RIG-I/DDX58 coreceptor in the sensing of viral RNAs in cell cytoplasm and the activation of the antiviral innate immune response. Together with the UBE2D3, UBE2N and UB2V1 E2 ligases, catalyzes the 'Lys-63'-linked polyubiquitination of RIG-I/DDX58 oligomerized on viral RNAs, an essential step in the activation of the RIG-I signaling pathway. Through a ubiquitin-independent parallel mechanism, which consists in bridging RIG-I/DDX58 filaments forming on longer viral RNAs, further activates th [...] (432 aa) |
| | DEFA3 | Neutrophil defensin 2; Defensin 2 and defensin 3 have antibiotic, fungicide and antiviral activities. Has antimicrobial activity against Gram-negative and Gram-positive bacteria. Defensins are thought to kill microbes by permeabilizing their plasma membrane. (94 aa) |
| | TBX1 | T-box transcription factor TBX1; Probable transcriptional regulator involved in developmental processes. Is required for normal development of the pharyngeal arch arteries (By similarity). (495 aa) |
| | RARB | Retinoic acid receptor beta; Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence or presence of hormone ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. The RXRA/RARB heterodimer can act as a repressor on the DR1 element [...] (448 aa) |
| | NR2C1 | Nuclear receptor subfamily 2 group C member 1; Orphan nuclear receptor. Binds the IR7 element in the promoter of its own gene in an autoregulatory negative feedback mechanism. Primarily repressor of a broad range of genes. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences. Together with NR2C2, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription. Also activator of OCT4 gene expression. May be involved in stem cell proliferation and differentiatio [...] (603 aa) |
| | ZMIZ1 | Zinc finger MIZ domain-containing protein 1; Acts as transcriptional coactivator. Increases ligand- dependent transcriptional activity of AR and promotes AR sumoylation. The stimulation of AR activity is dependent upon sumoylation. Also functions as a transcriptional coactivator in the TGF-beta signaling pathway by increasing the activity of the SMAD3/SMAD4 transcriptional complex. Involved in transcriptional activation of a subset of NOTCH1 target genes including MYC. Involved in thymocyte and T cell development (By similarity). (1067 aa) |
| | NR1I2 | Nuclear receptor subfamily 1 group I member 2; Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds [...] (473 aa) |
| | SP100 | Nuclear autoantigen Sp-100; Together with PML, this tumor suppressor is a major constituent of the PML bodies, a subnuclear organelle involved in a large number of physiological processes including cell growth, differentiation and apoptosis. Functions as a transcriptional coactivator of ETS1 and ETS2 according to. Under certain conditions, it may also act as a corepressor of ETS1 preventing its binding to DNA according to. Through the regulation of ETS1 it may play a role in angiogenesis, controlling endothelial cell motility and invasion. Through interaction with the MRN complex it ma [...] (885 aa) |
| | ESR2 | Estrogen receptor beta; Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature [...] (530 aa) |
| | NR4A2 | Nuclear receptor subfamily 4 group A member 2; Transcriptional regulator which is important for the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons during development. It is crucial for expression of a set of genes such as SLC6A3, SLC18A2, TH and DRD2 which are essential for development of mdDA neurons (By similarity); Belongs to the nuclear hormone receptor family. NR4 subfamily. (598 aa) |
| | PMEPA1 | Protein TMEPAI; Functions as a negative regulator of TGF-beta signaling and thereby probably plays a role in cell proliferation, differentiation, apoptosis, motility, extracellular matrix production and immunosuppression. In the canonical TGF-beta pathway, ZFYVE9/SARA recruits the intracellular signal transducer and transcriptional modulators SMAD2 and SMAD3 to the TGF-beta receptor. Phosphorylated by the receptor, SMAD2 and SMAD3 then form a heteromeric complex with SMAD4 that translocates to the nucleus to regulate transcription. Through interaction with SMAD2 and SMAD3, LDLRAD4 may [...] (287 aa) |
| | CRKL | Crk-like protein; May mediate the transduction of intracellular signals. (303 aa) |
| | SREBF1 | Processed sterol regulatory element-binding protein 1; Transcriptional activator required for lipid homeostasis. Regulates transcription of the LDL receptor gene as well as the fatty acid and to a lesser degree the cholesterol synthesis pathway (By similarity). Binds to the sterol regulatory element 1 (SRE-1) (5'- ATCACCCCAC-3'). Has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3'). (1177 aa) |
| | NR3C2 | Mineralocorticoid receptor; Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels; Belongs to the nuclear hormone receptor family. NR3 subfamily. (984 aa) |
| | ARNT | Aryl hydrocarbon receptor nuclear translocator; Required for activity of the Ah (dioxin) receptor. This protein is required for the ligand-binding subunit to translocate from the cytosol to the nucleus after ligand binding. The complex then initiates transcription of genes involved in the activation of PAH procarcinogens. The heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters and functions as a transcriptional regulator of the adaptive response to hypoxia (By similarity). The heterodimer ARNT:AHR binds to core DNA sequ [...] (789 aa) |
| | RXRG | Retinoic acid receptor RXR-gamma; Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid (By similarity). (463 aa) |
| | TIFA | TRAF-interacting protein with FHA domain-containing protein A; Adapter molecule that plays a key role in the activation of proinflammatory NF-kappa-B signaling following detection of bacterial pathogen-associated molecular pattern metabolites (PAMPs). Promotes activation of an innate immune response by inducing the oligomerization and polyubiquitination of TRAF6, which leads to the activation of TAK1 and IKK through a proteasome-independent mechanism. TIFA-dependent innate immune response is triggered by ADP-D-glycero- beta-D-manno-heptose (ADP-Heptose), a potent PAMP present in all Gr [...] (184 aa) |
| | ESRRG | Estrogen-related receptor gamma; Orphan receptor that acts as transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements (By similarity). Induces the expression of PERM1 in the skeletal muscle. (470 aa) |
| | NR5A2 | Nuclear receptor subfamily 5 group A member 2; Nuclear receptor that acts as a key metabolic sensor by regulating the expression of genes involved in bile acid synthesis, cholesterol homeostasis and triglyceride synthesis. Together with the oxysterol receptors NR1H3/LXR-alpha and NR1H2/LXR-beta, acts as an essential transcriptional regulator of lipid metabolism. Plays an anti- inflammatory role during the hepatic acute phase response by acting as a corepressor: inhibits the hepatic acute phase response by preventing dissociation of the N-Cor corepressor complex. Binds to the sequence e [...] (541 aa) |
| | NR1I3 | Nuclear receptor subfamily 1 group I member 3; Binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes. Transactivates both the phenobarbital responsive element module of the human CYP2B6 gene and the CYP3A4 xenobiotic response element; Belongs to the nuclear hormone receptor family. NR1 subfamily. (357 aa) |
| | NR2E1 | Nuclear receptor subfamily 2 group E member 1; Orphan receptor that binds DNA as a monomer to hormone response elements (HRE) containing an extended core motif half-site sequence 5'-AAGGTCA-3' in which the 5' flanking nucleotides participate in determining receptor specificity (By similarity). May be required to pattern anterior brain differentiation. Involved in the regulation of retinal development and essential for vision. During retinogenesis, regulates PTEN-Cyclin D expression via binding to the promoter region of PTEN and suppressing its activity (By similarity). May be involved [...] (422 aa) |
| | MAP3K7 | Mitogen-activated protein kinase kinase kinase 7; 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 signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR). Ceramides are also able to activate MAP3K7/TAK1. Once activated, acts as a [...] (606 aa) |
| | PIM1 | Serine/threonine-protein kinase pim-1; Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain pa [...] (313 aa) |
| | SRC | Proto-oncogene tyrosine-protein kinase Src; Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy bet [...] (536 aa) |
| | NR5A1 | Steroidogenic factor 1; Transcriptional activator. Essential for sexual differentiation and formation of the primary steroidogenic tissues. Binds to the Ad4 site found in the promoter region of steroidogenic P450 genes such as CYP11A, CYP11B and CYP21B. Also regulates the AMH/Muellerian inhibiting substance gene as well as the AHCH and STAR genes. 5'-YCAAGGYC-3' and 5'-RRAGGTCA-3' are the consensus sequences for the recognition by NR5A1. The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional activity. Binds phosphatidylcholine (By [...] (461 aa) |
| | TLR4 | Toll-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) |
| | RXRB | Retinoic acid receptor RXR-beta; Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE); Belongs to the nuclear hormone receptor family. NR2 subfamily. (537 aa) |
| | AR | Androgen receptor; Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins like ZBTB7A that recruits NCOR1 and NCOR2 to the androgen response elements/ARE on target genes, negatively regulating androgen receptor signaling and androgen-induced cell proliferation. Transcription activation is also down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DA [...] (920 aa) |
| | PADI2 | Protein-arginine deiminase type-2; Catalyzes the deimination of arginine residues of proteins. (665 aa) |
| | PTF1A | Pancreas transcription factor 1 subunit alpha; Transcription factor implicated in the cell fate determination in various organs. Binds to the E-box consensus sequence 5'-CANNTG-3'. Plays a role in early and late pancreas development and differentiation. Important for determining whether cells allocated to the pancreatic buds continue towards pancreatic organogenesis or revert back to duodenal fates. May be involved in the maintenance of exocrine pancreas-specific gene expression including ELA1 and amylase. Required for the formation of pancreatic acinar and ductal cells. Plays an impor [...] (328 aa) |
| | RORB | Nuclear receptor ROR-beta; Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Considered to have intrinsic transcriptional activity, have some natural ligands such as all-trans retinoic acid (ATRA) and other retinoids which act as inverse agonists repressing the transcriptional activity. Required for normal postnatal development of rod and cone photoreceptor cells. Modulates rod photoreceptors differentiation at least by inducing the transcription factor NRL-mediated p [...] (459 aa) |
| | CST11 | Cystatin-11; Has antibacterial activity against the Gram-negative bacteria E.coli. May play a role in sperm maturation and fertilization. Belongs to the cystatin family. (138 aa) |
| | DNAJA1 | DnaJ 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) |
| | DDX58 | Antiviral innate immune response receptor RIG-I; Innate immune receptor that senses cytoplasmic viral nucleic acids and activates a downstream signaling cascade leading to the production of type I interferons and proinflammatory cytokines. Forms a ribonucleoprotein complex with viral RNAs on which it homooligomerizes to form filaments. The homooligomerization allows the recruitment of RNF135 an E3 ubiquitin-protein ligase that activates and amplifies the RIG-I-mediated antiviral signaling in an RNA length-dependent manner through ubiquitination-dependent and -independent mechanisms. Up [...] (925 aa) |
| | NKX3-1 | Homeobox protein Nkx-3.1; Transcription factor, which binds preferentially the consensus sequence 5'-TAAGT[AG]-3' and can behave as a transcriptional repressor. Plays an important role in normal prostate development, regulating proliferation of glandular epithelium and in the formation of ducts in prostate. Acts as a tumor suppressor controlling prostate carcinogenesis, as shown by the ability to inhibit proliferation and invasion activities of PC-3 prostate cancer cells. Belongs to the NK-3 homeobox family. (234 aa) |
| | ESRRB | Steroid hormone receptor ERR2; [Isoform 3]: Transcription factor that binds a canonical ESRRB recognition (ERRE) sequence 5'TCAAGGTCA-3' localized on promoter and enhancer of targets genes regulating their expression or their transcription activity. Plays a role, in a LIF-independent manner, in maintainance of self-renewal and pluripotency of embryonic and trophoblast stem cells through different signaling pathways including FGF signaling pathway and Wnt signaling pathways. Upon FGF signaling pathway activation, interacts with KDM1A by directly binding to enhancer site of ELF5 and EOME [...] (508 aa) |
| | JAK2 | Tyrosine-protein kinase JAK2; Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin (THPO); or type II receptors including IFN-alpha, IFN- beta, IFN-gamma and multiple interleukins. Following ligand-binding to cell surface receptors [...] (1132 aa) |
| | DEFA1B | Neutrophil defensin 1; Defensin 1 and defensin 2 have antibacterial, fungicide and antiviral activities. Has antimicrobial activity against Gram-negative and Gram-positive bacteria. Defensins are thought to kill microbes by permeabilizing their plasma membrane. (94 aa) |
| | DEFA1 | Defensin alpha 1. (94 aa) |
| | RNF34 | E3 ubiquitin-protein ligase RNF34; E3 ubiquitin-protein ligase that regulates several biological processes through the ubiquitin-mediated proteasomal degradation of various target proteins. Ubiquitinates the caspases CASP8 and CASP10, promoting their proteasomal degradation, to negatively regulate cell death downstream of death domain receptors in the extrinsic pathway of apoptosis. May mediate 'Lys-48'-linked polyubiquitination of RIPK1 and its subsequent proteasomal degradation thereby indirectly regulating the tumor necrosis factor-mediated signaling pathway. Negatively regulates p5 [...] (373 aa) |
| | NR2F2 | COUP transcription factor 2; Ligand-activated transcription factor. Activated by high concentrations of 9-cis-retinoic acid and all-trans-retinoic acid, but not by dexamethasone, cortisol or progesterone (in vitro). Regulation of the apolipoprotein A-I gene transcription. Binds to DNA site A. (414 aa) |
| | THRB | Thyroid hormone receptor beta; Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine. (461 aa) |
| | DDX17 | Probable ATP-dependent RNA helicase DDX17; As an RNA helicase, unwinds RNA and alters RNA structures through ATP binding and hydrolysis. Involved in multiple cellular processes, including pre-mRNA splicing, alternative splicing, ribosomal RNA processing and miRNA processing, as well as transcription regulation. Regulates the alternative splicing of exons exhibiting specific features. For instance, promotes the inclusion of AC-rich alternative exons in CD44 transcripts. This function requires the RNA helicase activity. Affects NFAT5 and histone macro- H2A.1/MACROH2A1 alternative splicin [...] (731 aa) |
| | GPER1 | G-protein coupled estrogen receptor 1; G-protein coupled estrogen receptor that binds to 17-beta- estradiol (E2) with high affinity, leading to rapid and transient activation of numerous intracellular signaling pathways. Stimulates cAMP production, calcium mobilization and tyrosine kinase Src inducing the release of heparin-bound epidermal growth factor (HB-EGF) and subsequent transactivation of the epidermal growth factor receptor (EGFR), activating downstream signaling pathways such as PI3K/Akt and ERK/MAPK. Mediates pleiotropic functions among others in the cardiovascular, endocrine [...] (375 aa) |
| | IRF7 | Interferon regulatory factor 7; Key transcriptional regulator of type I interferon (IFN)- dependent immune responses and plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN- stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction via both the virus-activated, MyD88-independent pathway and the TLR-activated, MyD88-dependen [...] (516 aa) |
| | RELA | Transcription factor p65; NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain- containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The heterodimeric RELA-NFKB1 complex appears to be most abundant one. The dimers bind at kap [...] (551 aa) |
| | ESRRA | Steroid hormone receptor ERR1; Binds to an ERR-alpha response element (ERRE) containing a single consensus half-site, 5'-TNAAGGTCA-3'. Can bind to the medium- chain acyl coenzyme A dehydrogenase (MCAD) response element NRRE-1 and may act as an important regulator of MCAD promoter. Binds to the C1 region of the lactoferrin gene promoter. Requires dimerization and the coactivator, PGC-1A, for full activity. The ERRalpha/PGC1alpha complex is a regulator of energy metabolism. Induces the expression of PERM1 in the skeletal muscle. (423 aa) |
| | NCOA1 | Nuclear receptor coactivator 1; Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone- dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating m [...] (1441 aa) |
| | PPARA | Peroxisome proliferator-activated receptor alpha; Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn- glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and [...] (468 aa) |
| | KDM3A | Lysine-specific demethylase 3A; Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code. Preferentially demethylates mono- and dimethylated H3 'Lys-9' residue, with a preference for dimethylated residue, while it has weak or no activity on trimethylated H3 'Lys-9'. Demethylation of Lys residue generates formaldehyde and succinate. Involved in hormone-dependent transcriptional activation, by participating in recruitment to androgen-receptor target genes, resulting in H3 'Lys-9' demethylation and transcriptional activation. [...] (1321 aa) |
| | RARG | Retinoic acid receptor gamma; Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. Required for limb bud development. In concert with RARA or RARB, required for skeletal [...] (454 aa) |
| | LACC1 | Laccase domain-containing protein 1; Central regulator of the metabolic function and bioenergetic state of macrophages. In macrophages, promotes flux through de novo lipogenesis to concomitantly drive high levels of both fatty-acid oxidation and glycolysis. (430 aa) |
| | CYLD | Ubiquitin 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) |
| | INAVA | Innate 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) |
| | NCOA2 | Nuclear receptor coactivator 2; Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues. Critical regulator of glucose metabolism regulation, acts as RORA coactivator to specifically modulate G6PC expression. Involved in the positive regulation of the transcriptional activity of the glucocorticoid receptor NR3C1 by sumoylation enhancer RWDD3. Positively regulates the circadian clock by [...] (1464 aa) |
| | RHOA | Transforming protein RhoA; Small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. Mainly associated with cytoskeleton organization, in active state binds to a variety of effector proteins to regulate cellular responses such cytoskeletal dynamics, cell migration and cell cycle. Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Involved in a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Plays an essent [...] (193 aa) |
| | ESR1 | Estrogen receptor; Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE- independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial a [...] (595 aa) |
| | RBFOX2 | RNA binding protein fox-1 homolog 2; RNA-binding protein that regulates alternative splicing events by binding to 5'-UGCAUGU-3' elements. Prevents binding of U2AF2 to the 3'-splice site. Regulates alternative splicing of tissue- specific exons and of differentially spliced exons during erythropoiesis (By similarity). RNA-binding protein that seems to act as a coregulatory factor of ER-alpha. (451 aa) |
| | RXRA | Retinoic acid receptor RXR-alpha; Receptor for retinoic acid that acts as a transcription factor. Forms homo- or heterodimers with retinoic acid receptors (RARs) and binds to target response elements in response to their ligands, all-trans or 9-cis retinoic acid, to regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 to regulate transcription. The high affinity ligand for retinoid X receptors (RXRs) is 9-cis retinoic acid. In the absence of ligand, th [...] (462 aa) |
| | NR6A1 | Nuclear receptor subfamily 6 group A member 1; Orphan nuclear receptor. Binds to a response element containing the sequence 5'-TCAAGGTCA-3'. May be involved in the regulation of gene expression in germ cell development during gametogenesis (By similarity). (480 aa) |
| | RWDD1 | RWD domain-containing protein 1; Protects DRG2 from proteolytic degradation; Belongs to the RWDD1/GIR2 family. (243 aa) |
| | NEDD4 | E3 ubiquitin-protein ligase NEDD4; 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. Specifically ubiquitinates 'Lys-63' in target proteins. Involved in the pathway leading to the degradation of VEGFR-2/KDFR, independently of its ubiquitin-ligase activity. Monoubiquitinates IGF1R at multiple sites, thus leading to receptor internalization and degradation in lysosomes. Ubiquitinates FGFR1, leading to receptor internalization and degradation in lysosomes. [...] (1319 aa) |
| | AHRR-2 | Aryl-hydrocarbon receptor repressor. (557 aa) |
| | IRGM | Immunity-related GTPase family M protein; Putative GTPase which is required for clearance of acute protozoan and bacterial infections. Functions in innate immune response probably through regulation of autophagy. May regulate proinflammatory cytokine production and prevent endotoxemia upon infection. May also play a role in macrophages adhesion and motility (By similarity). Belongs to the TRAFAC class dynamin-like GTPase superfamily. IRG family. (181 aa) |
| | FKBP4 | Peptidyl-prolyl cis-trans isomerase FKBP4, N-terminally processed; Immunophilin protein with PPIase and co-chaperone activities. Component of steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). May play a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors between cytoplasm and nuclear compartments. The isomerase activity controls neuronal growth cones via regulation of TRPC1 channel opening. Acts also as a regulator of microtubule dynamics by inhibiting MAPT/TAU ability to promote microtubule assembly. May [...] (459 aa) |
| | CYP26B1 | Cytochrome P450 26B1; Involved in the metabolism of retinoic acid (RA), rendering this classical morphogen inactive through oxidation. Involved in the specific inactivation of all-trans-retinoic acid (all-trans-RA), with a preference for the following substrates: all-trans-RA > 9-cis-RA > 13- cis-RA. Generates several hydroxylated forms of RA, including 4-OH-RA, 4-oxo-RA, and 18-OH-RA. Catalyzes the hydroxylation of carbon hydrogen bonds of atRA primarily at C-4. Essential for postnatal survival. Plays a central role in germ cell development: acts by degrading RA in the developing test [...] (512 aa) |
| | CRY1 | Cryptochrome-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, cardiovascular, and renal [...] (586 aa) |
| | NFKBIA | NF-kappa-B inhibitor alpha; Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL dimers in the cytoplasm through masking of their nuclear localization signals. On cellular stimulation by immune and proinflammatory responses, becomes phosphorylated promoting ubiquitination and degradation, enabling the dimeric RELA to translocate to the nucleus and activate transcription. (317 aa) |
| | CYP24A1 | 1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial; A cytochrome P450 monooxygenase with a key role in vitamin D catabolism and calcium homeostasis. Via C24- and C23-oxidation pathways, catalyzes the inactivation of both the vitamin D precursor calcidiol (25-hydroxyvitamin D(3)) and the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)). With initial hydroxylation at C-24 (via C24-oxidation pathway), performs a sequential 6-step oxidation of calcitriol leading to the formation of the biliary metabolite calcitroic acid. With initial hydroxylation at C-23 (via C23-oxidati [...] (514 aa) |
| | RHOXF1 | Rhox homeobox family member 1; Transcription factor maybe involved in reproductive processes. Modulates expression of target genes encoding proteins involved in processes relevant to spermatogenesis. (184 aa) |
| | RIPK2 | Receptor-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) |
| | DDX5 | Probable ATP-dependent RNA helicase DDX5; Involved in the alternative regulation of pre-mRNA splicing; its RNA helicase activity is necessary for increasing tau exon 10 inclusion and occurs in a RBM4-dependent manner. Binds to the tau pre- mRNA in the stem-loop region downstream of exon 10. The rate of ATP hydrolysis is highly stimulated by single-stranded RNA. Involved in transcriptional regulation; the function is independent of the RNA helicase activity. Transcriptional coactivator for androgen receptor AR but probably not ESR1. Synergizes with DDX17 and SRA1 RNA to activate MYOD1 t [...] (614 aa) |
| | SCGB2A2 | Mammaglobin-A; Secretoglobin family 2A member 2; Belongs to the secretoglobin family. Lipophilin subfamily. (93 aa) |
| | OAS3 | 2'-5'-oligoadenylate synthase 3; Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response. In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation. Synthesizes preferentially dimers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNase L) leading to its dimerization and subsequent activation. Activation of RNase L leads to degradation of cellular as well as viral RNA, resulting in the inhibi [...] (1087 aa) |
| | NR3C1 | Glucocorticoid receptor; Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling. Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand- dependent manner which recruits the RNA helicase UPF1 and the mRNA- decapping enzyme D [...] (778 aa) |
| | AHR | Aryl hydrocarbon receptor; Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing [...] (848 aa) |
| | SCGB2A1 | Mammaglobin-B; May bind androgens and other steroids, may also bind estramustine, a chemotherapeutic agent used for prostate cancer. May be under transcriptional regulation of steroid hormones. (95 aa) |
| | NR1D1 | Nuclear receptor subfamily 1 group D member 1; Transcriptional repressor which coordinates circadian rhythm and metabolic pathways in a heme-dependent manner. Integral component of the complex transcription machinery that governs circadian rhythmicity and forms a critical negative limb of the circadian clock by directly repressing the expression of core clock components ARTNL/BMAL1, CLOCK and CRY1. Also regulates genes involved in metabolic functions, including lipid and bile acid metabolism, adipogenesis, gluconeogenesis and the macrophage inflammatory response. Acts as a receptor for [...] (614 aa) |
| | YWHAH | 14-3-3 protein eta; Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negatively regulates the kinase activity of PDPK1. (246 aa) |
| | IFIH1 | Interferon-induced helicase C domain-containing protein 1; Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and proinflammatory cytokines. Its ligands include mRNA lacking 2'-O-methylation at their 5' cap and long- dsRNA (>1 kb in length). Upon ligand binding it associates with mitochondria antiviral signaling protein (MAVS/IPS1) which activates the IKK-related kinases: TBK1 and IKBKE which phosphorylat [...] (1025 aa) |
| | UBE3A | Ubiquitin-protein ligase E3A; E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and transfers it to its substrates. Several substrates have been identified including the ARNTL/BMAL1, ARC, RAD23A and RAD23B, MCM7 (which is involved in DNA replication), annexin A1, the PML tumor suppressor, and the cell cycle regulator CDKN1B. Additionally, may function as a cellular quality control ubiquitin ligase by helping the degradation of the cytoplasmic misfolded proteins. Finally, UBE3A also promotes its own degradation in vivo [...] (875 aa) |
| | ALPK1 | Alpha-protein kinase 1; Serine/threonine-protein kinase that detects bacterial pathogen-associated molecular pattern metabolites (PAMPs) and initiates an innate immune response, a critical step for pathogen elimination and engagement of adaptive immunity. Specifically recognizes and binds ADP-D-glycero-beta- D-manno-heptose (ADP-Heptose), a potent PAMP present in all Gram- negative and some Gram-positive bacteria. ADP- Heptose-binding stimulates its kinase activity to phosphorylate and activate TIFA, triggering proinflammatory NF-kappa-B signaling. May be involved in monosodium urate m [...] (1244 aa) |
