STRINGSTRING
M6PR M6PR CFTR CFTR DVL2 DVL2 CD4 CD4 VAMP3 VAMP3 HBEGF HBEGF APOB APOB VAMP4 VAMP4 CLTA CLTA EREG EREG NEDD8 NEDD8 TOR1B TOR1B SYT1 SYT1 VAMP7 VAMP7 VAMP8 VAMP8 STAM2 STAM2 CBL CBL WNT5A WNT5A SCARB2 SCARB2 EGF EGF COPS3 COPS3 SH3GL1 SH3GL1 RPS27A RPS27A EGFR EGFR COPS2 COPS2 CD3D CD3D TACR1 TACR1 COPS6 COPS6 ADRB2 ADRB2 IL7R IL7R CLTB CLTB GRK2 GRK2 DAB2 DAB2 GRK3 GRK3 SH3GL3 SH3GL3 EPN2 EPN2 SYT9 SYT9 AP2A2 AP2A2 HGS HGS UBQLN2 UBQLN2 TOR1A TOR1A COPS8 COPS8 ITSN2 ITSN2 IGF2R IGF2R REPS2 REPS2 COPS5 COPS5 AP2A1 AP2A1 SYT2 SYT2 SYT11 SYT11 SGIP1 SGIP1 EPS15 EPS15 SLC2A8 SLC2A8 SLC18A3 SLC18A3 LDLRAP1 LDLRAP1 UBQLN1 UBQLN1 STAM STAM KIAA0319 KIAA0319 AVP AVP SH3GL2 SH3GL2 ITSN1 ITSN1 SYT8 SYT8 GPS1 GPS1 TFRC TFRC GRB2 GRB2 PICALM PICALM BTC BTC AREG AREG SH3KBP1 SH3KBP1 STON1 STON1 TF TF TGOLN2 TGOLN2 AAK1 AAK1 COPS7B COPS7B AGFG1 AGFG1 UBA52 UBA52 NECAP2 NECAP2 REPS1 REPS1 EPS15L1 EPS15L1 FCHO2 FCHO2 AGTR1 AGTR1 CHRM2 CHRM2 SNAP91 SNAP91 AP2M1 AP2M1 ARRB2 ARRB2 TGFA TGFA EPN1 EPN1 ARRB1 ARRB1 EPGN EPGN VAMP2 VAMP2 COPS4 COPS4 CD3G CD3G FZD4 FZD4 CLTCL1 CLTCL1 UBC UBC COPS7A COPS7A STON2 STON2 LDLR LDLR AP2S1 AP2S1 FCHO1 FCHO1 UBB UBB CLTC CLTC AP2B1 AP2B1 NECAP1 NECAP1 AVPR2 AVPR2 LRP2 LRP2
Nodes:
Network nodes represent proteins
splice isoforms or post-translational modifications are collapsed, i.e. each node represents all the proteins produced by a single, protein-coding gene locus.
Node Color
colored nodes:
query proteins and first shell of interactors
white nodes:
second shell of interactors
Node Content
empty nodes:
proteins of unknown 3D structure
filled nodes:
a 3D structure is known or predicted
Edges:
Edges represent protein-protein associations
associations are meant to be specific and meaningful, i.e. proteins jointly contribute to a shared function; this does not necessarily mean they are physically binding to each other.
Known Interactions
from curated databases
experimentally determined
Predicted Interactions
gene neighborhood
gene fusions
gene co-occurrence
Others
textmining
co-expression
protein homology
Your Input:
M6PRCation-dependent mannose-6-phosphate receptor; Transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelyosomal compartment where the low pH mediates the dissociation of the complex. (277 aa)
CFTRCystic fibrosis transmembrane conductance regulator; Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis. Mediates the transport of chloride ions across the cell membrane. Channel activity is coupled to ATP hydrolysis. The ion channel is also permeable to HCO(3-); selectivity depends on the extracellular chloride concentration. Exerts its function also by modulating the activity of other ion channels and transporters. Plays an important role in airway fluid homeostasis. Contributes to the regulation of the pH [...] (1480 aa)
DVL2Segment polarity protein dishevelled homolog DVL-2; Plays a role in the signal transduction pathways mediated by multiple Wnt genes. Participates both in canonical and non-canonical Wnt signaling by binding to the cytoplasmic C-terminus of frizzled family members and transducing the Wnt signal to down-stream effectors. Promotes internalization and degradation of frizzled proteins upon Wnt signaling; Belongs to the DSH family. (736 aa)
CD4T-cell surface glycoprotein CD4; Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class II molecule:peptide complex. The antigens presented by class II peptides are derived from extracellular proteins while class I peptides are derived from cytosolic proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class II presented by antigen presenting cells (APCs). In turn, recruits the Src kina [...] (458 aa)
VAMP3Vesicle-associated membrane protein 3; SNARE involved in vesicular transport from the late endosomes to the trans-Golgi network. (100 aa)
HBEGFProheparin-binding EGF-like growth factor; Growth factor that mediates its effects via EGFR, ERBB2 and ERBB4. Required for normal cardiac valve formation and normal heart function. Promotes smooth muscle cell proliferation. May be involved in macrophage-mediated cellular proliferation. It is mitogenic for fibroblasts, but not endothelial cells. It is able to bind EGF receptor/EGFR with higher affinity than EGF itself and is a far more potent mitogen for smooth muscle cells than EGF. Also acts as a diphtheria toxin receptor. (208 aa)
APOBApolipoprotein B-100; Apolipoprotein B is a major protein constituent of chylomicrons (apo B-48), LDL (apo B-100) and VLDL (apo B-100). Apo B- 100 functions as a recognition signal for the cellular binding and internalization of LDL particles by the apoB/E receptor. (4563 aa)
VAMP4Vesicle-associated membrane protein 4; Involved in the pathway that functions to remove an inhibitor (probably synaptotagmin-4) of calcium-triggered exocytosis during the maturation of secretory granules. May be a marker for this sorting pathway that is critical for remodeling the secretory response of granule. (141 aa)
CLTAClathrin light chain A; Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Acts as component of the TACC3/ch- TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter- microtubule bridge. (248 aa)
EREGProepiregulin; Ligand of the EGF receptor/EGFR and ERBB4. Stimulates EGFR and ERBB4 tyrosine phosphorylation. Contributes to inflammation, wound healing, tissue repair, and oocyte maturation by regulating angiogenesis and vascular remodeling and by stimulating cell proliferation. (169 aa)
NEDD8NEDD8; Ubiquitin-like protein which plays an important role in cell cycle control and embryogenesis. Covalent attachment to its substrates requires prior activation by the E1 complex UBE1C-APPBP1 and linkage to the E2 enzyme UBE2M. Attachment of NEDD8 to cullins activates their associated E3 ubiquitin ligase activity, and thus promotes polyubiquitination and proteasomal degradation of cyclins and other regulatory proteins. (81 aa)
TOR1BTorsin-1B; May serve as a molecular chaperone assisting in the proper folding of secreted and/or membrane proteins. Plays a role in non- neural cells nuclear envelope and endoplasmic reticulum integrity. May have a redundant function with TOR1A in non-neural tissues. Belongs to the ClpA/ClpB family. Torsin subfamily. (336 aa)
SYT1Synaptotagmin-1; Calcium sensor that participates in triggering neurotransmitter release at the synapse (By similarity). May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse (By similarity). It binds acidic phospholipids with a specificity that requires the presence of both an acidic head group and a diacyl backbone. A Ca(2+)- dependent interaction between synaptotagmin and putative receptors for activated protein kinase C has also been reported. It can bind to at least three additional proteins in a Ca(2+)-in [...] (422 aa)
VAMP7Vesicle-associated membrane protein 7; Involved in the targeting and/or fusion of transport vesicles to their target membrane during transport of proteins from the early endosome to the lysosome. Required for heterotypic fusion of late endosomes with lysosomes and homotypic lysosomal fusion. Required for calcium regulated lysosomal exocytosis. Involved in the export of chylomicrons from the endoplasmic reticulum to the cis Golgi. Required for exocytosis of mediators during eosinophil and neutrophil degranulation, and target cell killing by natural killer cells. Required for focal exocy [...] (260 aa)
VAMP8Vesicle-associated membrane protein 8; SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. VAMP8 is a SNARE involved in autophagy through the direct control of autophagosome membrane fusion with the lysososome membrane via its interaction with the STX17-SNAP29 binary t- SNARE complex. Also required for dense-granule secretion in platelets. Plays als [...] (100 aa)
STAM2Signal transducing adapter molecule 2; Involved in intracellular signal transduction mediated by cytokines and growth factors. Upon IL-2 and GM-CSL stimulation, it plays a role in signaling leading to DNA synthesis and MYC induction. May also play a role in T-cell development. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with HGS (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking process [...] (525 aa)
CBLE3 ubiquitin-protein ligase CBL; Adapter protein that functions as a negative regulator of many signaling pathways that are triggered by activation of cell surface receptors. Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, EGFR, CSF1R, EPHA8 and KDR and terminates signaling. Recognizes membrane-bound HCK, SRC and other kinases of the SRC family [...] (906 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)
SCARB2Lysosome membrane protein 2; Acts as a lysosomal receptor for glucosylceramidase (GBA) targeting. (478 aa)
EGFPro-epidermal growth factor; EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. Magnesiotropic hormone that stimulates magnesium reabsorption in the renal distal convoluted tubule via engagement of EGFR and activation of the magnesium channel TRPM6. Can induce neurite outgrowth in motoneurons of the pond snail Lymnaea stagnalis in vitro. (1207 aa)
COPS3COP9 signalosome complex subunit 3; Component 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 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/ICSBP, possibly via its association with CK2 and PKD kinases. CSN- [...] (423 aa)
SH3GL1Endophilin-A2; Implicated in endocytosis. May recruit other proteins to membranes with high curvature (By similarity); Belongs to the endophilin family. (368 aa)
RPS27AUbiquitin-40S ribosomal protein S27a; [Ubiquitin]: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be i [...] (156 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)
COPS2COP9 signalosome complex subunit 2; Essential component 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 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/ICSBP, possibly via its association with CK2 and PKD kina [...] (450 aa)
CD3DT-cell surface glycoprotein CD3 delta chain; Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR- mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of [...] (171 aa)
TACR1Substance-P receptor; This is a receptor for the tachykinin neuropeptide substance P. It is probably associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: substance P > substance K > neuromedin-K; Belongs to the G-protein coupled receptor 1 family. (407 aa)
COPS6COP9 signalosome complex subunit 6; Component 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 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 kinases. CSN-depend [...] (327 aa)
ADRB2Beta-2 adrenergic receptor; Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30- fold greater affinity than it does norepinephrine. Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRB2 sub-subfamily. (413 aa)
IL7RInterleukin-7 receptor subunit alpha; Receptor for interleukin-7. Also acts as a receptor for thymic stromal lymphopoietin (TSLP); Belongs to the type I cytokine receptor family. Type 4 subfamily. (459 aa)
CLTBClathrin light chain B; Clathrin is the major protein of the polyhedral coat of coated pits and vesicles; Belongs to the clathrin light chain family. (229 aa)
GRK2Beta-adrenergic receptor kinase 1; Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them. Key regulator of LPAR1 signaling. Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor. Desensitizes LPAR1 and LPAR2 in a phosphorylation- independent manner. Positively regulates ciliary smoothened (SMO)-dependent Hedgehog (Hh) signaling pathway by facilitating the trafficking of SMO into the cilium and the stimulation of SMO activity (By similarity). Belong [...] (689 aa)
DAB2Disabled homolog 2; Adapter protein that functions as clathrin-associated sorting protein (CLASP) required for clathrin-mediated endocytosis of selected cargo proteins. Can bind and assemble clathrin, and binds simultaneously to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and cargos containing non-phosphorylated NPXY internalization motifs, such as the LDL receptor, to recruit them to clathrin-coated pits. Can function in clathrin-mediated endocytosis independently of the AP-2 complex. Involved in endocytosis of integrin beta-1; this function seems to redundant with the AP-2 [...] (770 aa)
GRK3Beta-adrenergic receptor kinase 2; Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors; Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily. (688 aa)
SH3GL3Endophilin-A3; Implicated in endocytosis. May recruit other proteins to membranes with high curvature (By similarity). (355 aa)
EPN2Epsin-2; Plays a role in the formation of clathrin-coated invaginations and endocytosis; Belongs to the epsin family. (641 aa)
SYT9Synaptotagmin-9; May be involved in Ca(2+)-dependent exocytosis of secretory vesicles through Ca(2+) and phospholipid binding to the C2 domain or may serve as Ca(2+) sensors in the process of vesicular trafficking and exocytosis. (491 aa)
AP2A2AP-2 complex subunit alpha-2; Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold [...] (940 aa)
HGSHepatocyte growth factor-regulated tyrosine kinase substrate; Involved in intracellular signal transduction mediated by cytokines and growth factors. When associated with STAM, it suppresses DNA signaling upon stimulation by IL-2 and GM-CSF. Could be a direct effector of PI3-kinase in vesicular pathway via early endosomes and may regulate trafficking to early and late endosomes by recruiting clathrin. May concentrate ubiquitinated receptors within clathrin- coated regions. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with STAM (E [...] (777 aa)
UBQLN2Ubiquilin-2; Plays an important role in the regulation of different protein degradation mechanisms and pathways including ubiquitin- proteasome system (UPS), autophagy and the endoplasmic reticulum- associated protein degradation (ERAD) pathway. Mediates the proteasomal targeting of misfolded or accumulated proteins for degradation by binding (via UBA domain) to their polyubiquitin chains and by interacting (via ubiquitin-like domain) with the subunits of the proteasome. Plays a role in the ERAD pathway via its interaction with ER-localized proteins FAF2/UBXD8 and HERPUD1 and may form [...] (624 aa)
TOR1ATorsin-1A; Protein with chaperone functions important for the control of protein folding, processing, stability and localization as well as for the reduction of misfolded protein aggregates. Involved in the regulation of synaptic vesicle recycling, controls STON2 protein stability in collaboration with the COP9 signalosome complex (CSN). In the nucleus, may link the cytoskeleton with the nuclear envelope, this mechanism seems to be crucial for the control of nuclear polarity, cell movement and, specifically in neurons, nuclear envelope integrity. Participates in the cellular traffickin [...] (332 aa)
COPS8COP9 signalosome complex subunit 8; Component 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 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/ICSBP, possibly via its association with CK2 and PKD kinases. CSN- [...] (209 aa)
ITSN2Intersectin-2; Adapter protein that may provide indirect link between the endocytic membrane traffic and the actin assembly machinery. May regulate the formation of clathrin-coated vesicles (CCPs). Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR). Plays a role in dendrite formation by melanocytes. (1697 aa)
IGF2RCation-independent mannose-6-phosphate receptor; Transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelyosomal compartment where the low pH mediates the dissociation of the complex. This receptor also binds IGF2. Acts as a positive regulator of T-cell coactivation, by binding DPP4. (2491 aa)
REPS2RalBP1-associated Eps domain-containing protein 2; Involved in growth factor signaling through its influence on the Ral signaling pathway. (660 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)
AP2A1AP-2 complex subunit alpha-1; Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold [...] (977 aa)
SYT2Synaptotagmin-2; Exhibits calcium-dependent phospholipid and inositol polyphosphate binding properties (By similarity). May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse (By similarity). Plays a role in dendrite formation by melanocytes. Belongs to the synaptotagmin family. (419 aa)
SYT11Synaptotagmin-11; Synaptotagmin family member involved in vesicular and membrane trafficking which does not bind Ca(2+). Inhibits clathrin- mediated and bulk endocytosis, functions to ensure precision in vesicle retrieval. Plays an important role in dopamine transmission by regulating endocytosis and the vesicle-recycling process. Essential component of a neuronal vesicular trafficking pathway that differs from the synaptic vesicle trafficking pathway but is crucial for development and synaptic plasticity. In macrophages and microglia, inhibits the conventional cytokine secretion, of a [...] (431 aa)
SGIP1SH3-containing GRB2-like protein 3-interacting protein 1; May function in clathrin-mediated endocytosis. Has both a membrane binding/tubulating activity and the ability to recruit proteins essential to the formation of functional clathrin-coated pits. Has a preference for membranes enriched in phosphatidylserine and phosphoinositides and is required for the endocytosis of the transferrin receptor. May also bind tubulin. May play a role in the regulation of energy homeostasis. (828 aa)
EPS15Epidermal growth factor receptor substrate 15; Involved in cell growth regulation. May be involved in the regulation of mitogenic signals and control of cell proliferation. Involved in the internalization of ligand-inducible receptors of the receptor tyrosine kinase (RTK) type, in particular EGFR. Plays a role in the assembly of clathrin-coated pits (CCPs). Acts as a clathrin adapter required for post-Golgi trafficking. Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internaliz [...] (896 aa)
SLC2A8Solute carrier family 2, facilitated glucose transporter member 8; Insulin-regulated facilitative hexose transporter that mediates the transport of glucose and fructose. Also able to mediate the transport of dehydroascorbate. (477 aa)
SLC18A3Vesicular acetylcholine transporter; Involved in acetylcholine transport into synaptic vesicles. (532 aa)
LDLRAP1Low density lipoprotein receptor adapter protein 1; Adapter protein (clathrin-associated sorting protein (CLASP)) required for efficient endocytosis of the LDL receptor (LDLR) in polarized cells such as hepatocytes and lymphocytes, but not in non- polarized cells (fibroblasts). May be required for LDL binding and internalization but not for receptor clustering in coated pits. May facilitate the endocytocis of LDLR and LDLR-LDL complexes from coated pits by stabilizing the interaction between the receptor and the structural components of the pits. May also be involved in the internaliza [...] (308 aa)
UBQLN1Ubiquilin-1; Plays an important role in the regulation of different protein degradation mechanisms and pathways including ubiquitin- proteasome system (UPS), autophagy and endoplasmic reticulum-associated protein degradation (ERAD) pathway. Mediates the proteasomal targeting of misfolded or accumulated proteins for degradation by binding (via UBA domain) to their polyubiquitin chains and by interacting (via ubiquitin-like domain) with the subunits of the proteasome. Plays a role in the ERAD pathway via its interaction with ER-localized proteins UBXN4, VCP and HERPUD1 and may form a lin [...] (589 aa)
STAMSignal transducing adapter molecule 1; Involved in intracellular signal transduction mediated by cytokines and growth factors. Upon IL-2 and GM-CSL stimulation, it plays a role in signaling leading to DNA synthesis and MYC induction. May also play a role in T-cell development. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with HGS (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes. (540 aa)
KIAA0319Dyslexia-associated protein KIAA0319; Involved in neuronal migration during development of the cerebral neocortex. May function in a cell autonomous and a non-cell autonomous manner and play a role in appropriate adhesion between migrating neurons and radial glial fibers. May also regulate growth and differentiation of dendrites. (1072 aa)
AVPVasopressin-neurophysin 2-copeptin; Neurophysin 2 specifically binds vasopressin. (164 aa)
SH3GL2Endophilin-A1; Implicated in synaptic vesicle endocytosis. May recruit other proteins to membranes with high curvature. Required for BDNF-dependent dendrite outgrowth. Cooperates with SH3GL2 to mediate BDNF-NTRK2 early endocytic trafficking and signaling from early endosomes. (352 aa)
ITSN1Intersectin-1; Adapter protein that provides a link between the endocytic membrane traffic and the actin assembly machinery. Acts as guanine nucleotide exchange factor (GEF) for CDC42, and thereby stimulates actin nucleation mediated by WASL and the ARP2/3 complex. Plays a role in the assembly and maturation of clathrin-coated vesicles (By similarity). Recruits FCHSD2 to clathrin-coated pits. Involved in endocytosis of activated EGFR, and probably also other growth factor receptors (By similarity). Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); inter [...] (1721 aa)
SYT8Synaptotagmin-8; Isoform 4 may play a role in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues. Mediates Ca(2+)- regulation of exocytosis acrosomal reaction in sperm. May mediate Ca(2+)-regulation of exocytosis in insulin secreted cells (By similarity); Belongs to the synaptotagmin family. (401 aa)
GPS1COP9 signalosome complex subunit 1; Essential component 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 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/ICSBP, possibly via its association with CK2 and PKD kina [...] (527 aa)
TFRCTransferrin receptor protein 1, serum form; Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes. Endosomal acidification leads to iron release. The apotransferrin-receptor complex is then recycled to the cell surface with a return to neutral pH and the concomitant loss of affinity of apotransferrin for its receptor. Transferrin receptor is necessary for development of erythrocytes and the nervous system (By similarity). A second ligand, the heditary hemochromatosis protein HFE, competes for binding with tra [...] (760 aa)
GRB2Growth factor receptor-bound protein 2; Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway; Belongs to the GRB2/sem-5/DRK family. (217 aa)
PICALMPhosphatidylinositol-binding clathrin assembly protein; Cytoplasmic adapter protein that plays a critical role in clathrin-mediated endocytosis which is important in processes such as internalization of cell receptors, synaptic transmission or removal of apoptotic cells. Recruits AP-2 and attaches clathrin triskelions to the cytoplasmic side of plasma membrane leading to clathrin-coated vesicles (CCVs) assembly. Furthermore, regulates clathrin-coated vesicle size and maturation by directly sensing and driving membrane curvature. In addition to binding to clathrin, mediates the endocyto [...] (652 aa)
BTCProbetacellulin; Growth factor that binds to EGFR, ERBB4 and other EGF receptor family members. Potent mitogen for retinal pigment epithelial cells and vascular smooth muscle cells. (178 aa)
AREGAmphiregulin; Ligand of the EGF receptor/EGFR. Autocrine growth factor as well as a mitogen for a broad range of target cells including astrocytes, Schwann cells and fibroblasts; Belongs to the amphiregulin family. (252 aa)
SH3KBP1SH3 domain-containing kinase-binding protein 1; Adapter protein involved in regulating diverse signal transduction pathways. Involved in the regulation of endocytosis and lysosomal degradation of ligand-induced receptor tyrosine kinases, including EGFR and MET/hepatocyte growth factor receptor, through an association with CBL and endophilins. The association with CBL, and thus the receptor internalization, may be inhibited by an interaction with PDCD6IP and/or SPRY2. Involved in regulation of ligand-dependent endocytosis of the IgE receptor. Attenuates phosphatidylinositol 3- kinase ac [...] (665 aa)
STON1Stonin-1; May be involved in the endocytic machinery. (735 aa)
TFSerotransferrin; Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites of absorption and heme degradation to those of storage and utilization. Serum transferrin may also have a further role in stimulating cell proliferation. (698 aa)
TGOLN2Trans-Golgi network integral membrane protein 2; May be involved in regulating membrane traffic to and from trans-Golgi network. (453 aa)
AAK1AP2-associated protein kinase 1; Regulates clathrin-mediated endocytosis by phosphorylating the AP2M1/mu2 subunit of the adaptor protein complex 2 (AP-2) which ensures high affinity binding of AP-2 to cargo membrane proteins during the initial stages of endocytosis. Isoform 1 and isoform 2 display similar levels of kinase activity towards AP2M1. Regulates phosphorylation of other AP-2 subunits as well as AP-2 localization and AP-2-mediated internalization of ligand complexes. Phosphorylates NUMB and regulates its cellular localization, promoting NUMB localization to endosomes. Binds to [...] (961 aa)
COPS7BCOP9 signalosome complex subunit 7b; Component 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 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, JUN, I-kappa-B-alpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases. CSN-de [...] (278 aa)
AGFG1Arf-GAP domain and FG repeat-containing protein 1; Required for vesicle docking or fusion during acrosome biogenesis (By similarity). May play a role in RNA trafficking or localization. In case of infection by HIV-1, acts as a cofactor for viral Rev and promotes movement of Rev-responsive element-containing RNAs from the nuclear periphery to the cytoplasm. This step is essential for HIV-1 replication. (584 aa)
UBA52Ubiquitin-60S ribosomal protein L40; [Ubiquitin]: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be in [...] (128 aa)
NECAP2Adaptin ear-binding coat-associated protein 2; Involved in endocytosis. (273 aa)
REPS1RalBP1-associated Eps domain-containing protein 1; May coordinate the cellular actions of activated EGF receptors and Ral-GTPases. (796 aa)
EPS15L1Epidermal growth factor receptor substrate 15-like 1; Seems to be a constitutive component of clathrin-coated pits that is required for receptor-mediated endocytosis. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2. (910 aa)
FCHO2F-BAR domain only protein 2; Functions in an early step of clathrin-mediated endocytosis. Has both a membrane binding/bending activity and the ability to recruit proteins essential to the formation of functional clathrin-coated pits. Has a lipid-binding activity with a preference for membranes enriched in phosphatidylserine and phosphoinositides (Pi(4,5) biphosphate) like the plasma membrane. Its membrane-bending activity might be important for the subsequent action of clathrin and adaptors in the formation of clathrin-coated vesicles. Involved in adaptor protein complex AP-2- dependen [...] (810 aa)
AGTR1Type-1 angiotensin II receptor; Receptor for angiotensin II. Mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. (394 aa)
CHRM2Muscarinic acetylcholine receptor M2; The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol. (466 aa)
SNAP91Clathrin coat assembly protein AP180; Adaptins are components of the adapter complexes which link clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration. Binding of AP180 to clathrin triskelia induces their assembly into 60- 70 nm coats (By similarity); Belongs to the PICALM/SNAP91 family. (907 aa)
AP2M1AP-2 complex subunit mu; Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but i [...] (460 aa)
ARRB2Beta-arrestin-2; Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes. During homologous desensitization, beta- arrestins bind to the GPRK-phosphorylated receptor and sterically preclude its coupling to the cognate G-protein; the binding appears to require additional receptor determinants exposed only in the active receptor conformation. The beta-arrestins target many receptors for internalization by acting as endocytic adapters (CLASPs, clathrin- associated sorting proteins) and re [...] (430 aa)
TGFAProtransforming growth factor alpha; TGF alpha is a mitogenic polypeptide that is able to bind to the EGF receptor/EGFR and to act synergistically with TGF beta to promote anchorage-independent cell proliferation in soft agar. (166 aa)
EPN1Epsin-1; Binds to membranes enriched in phosphatidylinositol 4,5- bisphosphate (PtdIns(4,5)P2). Modifies membrane curvature and facilitates the formation of clathrin-coated invaginations (By similarity). Regulates receptor-mediated endocytosis. (662 aa)
ARRB1Beta-arrestin-1; Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes. During homologous desensitization, beta- arrestins bind to the GPRK-phosphorylated receptor and sterically preclude its coupling to the cognate G-protein; the binding appears to require additional receptor determinants exposed only in the active receptor conformation. The beta-arrestins target many receptors for internalization by acting as endocytic adapters (CLASPs, clathrin- associated sorting proteins) and re [...] (418 aa)
EPGNEpigen; Promotes the growth of epithelial cells. May stimulate the phosphorylation of EGFR and mitogen-activated protein kinases. (154 aa)
VAMP2Vesicle-associated membrane protein 2; Involved in the targeting and/or fusion of transport vesicles to their target membrane. Modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1. Belongs to the synaptobrevin family. (118 aa)
COPS4COP9 signalosome complex subunit 4; Component 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 SCF- type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. Also involved in the deneddylation of non-cullin subunits such as STON2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1, I [...] (420 aa)
CD3GT-cell surface glycoprotein CD3 gamma chain; Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR- mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of [...] (182 aa)
FZD4Frizzled-4; Receptor for Wnt proteins. Most frizzled receptors are coupled to the beta-catenin (CTNNB1) canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin (CTNNB1) and activation of Wnt target genes. Plays a critical role in retinal vascularization by acting as a receptor for Wnt proteins and norrin (NDP) (By similarity). In retina, it can be activated by Wnt protein-binding and also by Wnt-independent signaling via binding of norrin (NDP), promoting in both cases beta-catenin (CTNNB1) accu [...] (537 aa)
CLTCL1Clathrin heavy chain 2; Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Two different adapter protein complexes link the clathrin lattice either to the plasma membrane or to the trans- Golgi network (By similarity). (1640 aa)
UBCPolyubiquitin-C; [Ubiquitin]: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair [...] (685 aa)
COPS7ACOP9 signalosome complex subunit 7a; Component 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 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, JUN, I-kappa-B-alpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases. CSN-de [...] (275 aa)
STON2Stonin-2; Adapter protein involved in endocytic machinery. Involved in the synaptic vesicle recycling. May facilitate clathrin-coated vesicle uncoating; Belongs to the Stoned B family. (920 aa)
LDLRLow-density lipoprotein receptor; Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. (Microbial infection) Acts as a receptor for Vesicular stomatitis virus; Belongs to the LDLR family. (860 aa)
AP2S1AP-2 complex subunit sigma; Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein Transport via Transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold bu [...] (158 aa)
FCHO1F-BAR domain only protein 1; Functions in an early step of clathrin-mediated endocytosis. Has both a membrane binding/bending activity and the ability to recruit proteins essential to the formation of functional clathrin-coated pits. May regulate Bmp signaling by regulating clathrin-mediated endocytosis of Bmp receptors. (891 aa)
UBBPolyubiquitin-B; [Ubiquitin]: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair [...] (229 aa)
CLTCClathrin heavy chain 1; Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Two different adapter protein complexes link the clathrin lattice either to the plasma membrane or to the trans- Golgi network. Acts as component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge. The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension. Plays a role in early autophagosome formation. (1679 aa)
AP2B1AP-2 complex subunit beta; Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but [...] (951 aa)
NECAP1Adaptin ear-binding coat-associated protein 1; Involved in endocytosis. (275 aa)
AVPR2Vasopressin V2 receptor; Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Involved in renal water reabsorption; Belongs to the G-protein coupled receptor 1 family. Vasopressin/oxytocin receptor subfamily. (371 aa)
LRP2Low-density lipoprotein receptor-related protein 2; Multiligand endocytic receptor (By similarity). Acts together with CUBN to mediate endocytosis of high-density lipoproteins (By similarity). Mediates receptor-mediated uptake of polybasic drugs such as aprotinin, aminoglycosides and polymyxin B (By similarity). In the kidney, mediates the tubular uptake and clearance of leptin (By similarity). Also mediates transport of leptin across the blood-brain barrier through endocytosis at the choroid plexus epithelium (By similarity). Endocytosis of leptin in neuronal cells is required for hyp [...] (4655 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, human, man
Server load: low (22%) [HD]