HGS

Hepatocyte growth factor-regulated tyrosine kinase substrate ;
Hrs ;
Protein pp110 ;

domain:Has a double-sided UIM that can bind 2 ubiquitin molecules , one on each side of the helix. ,function: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 (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. May contribute to the efficient recruitment of SMADs to the activin receptor complex. ,PTM:Phosphorylated on Tyr-334. A minor site of phosphorylation on Tyr-329 is detected (By similarity) . Phosphorylation occurs in response to EGF , IL-2 , GM-CSF and HGF. ,similarity:Contains 1 FYVE-type zinc finger. ,similarity:Contains 1 UIM (ubiquitin-interacting motif) repeat. ,similarity:Contains 1 VHS domain. ,subunit:Component of the ESCRT-0 complex composed of STAM or STAM2 and HGS. Part of a complex at least composed of HSG , STAM2 (or probably STAM) and EPS15. Interacts with STAM. Interacts with STAM2. Interacts with EPS15; the interaction is direct , calcium-dependent and inhibited by SNAP25. Interacts with NF2; the interaction is direct. Interacts with ubiquitin; the interaction is direct. Interacts with VPS37C. Interacts with SMAD1 , SMAD2 and SMAD3. Interacts with TSG101; the interaction mediates the association with the ESCRT-I complex. Interacts with SNAP25; the interaction is direct and decreases with addition of increasing concentrations of free calcium. Interacts with SNX1; the interaction is direct. Component of a 550 kDa membrane complex at least composed of HGS and SNX1 but excluding EGFR. ,tissue specificity:Ubiquitous expression in adult and fetal tissues with higher expression in testis and peripheral blood leukocytes. ,

intracellular protein transport , protein localization , negative regulation of cell proliferation , regulation of catabolic process , negative regulation of signal transduction , regulation of protein kinase cascade , negative regulation of cell communication , negative regulation of protein kinase cascade , protein transport , vesicle-mediated transport ,endosome transport , cellular protein localization , regulation of cell proliferation , regulation of protein catabolic process , establishment of protein localization , regulation of JAK-STAT cascade , negative regulation of JAK-STAT cascade , intracellular transport , cellular macromolecule localization ,

Cytoplasm . Early endosome membrane ; Peripheral membrane protein ; Cytoplasmic side . Endosome , multivesicular body membrane ; Peripheral membrane protein . Colocalizes with UBQLN1 in ubiquitin-rich cytoplasmic aggregates that are not endocytic compartments. .