HGS

The protein encoded by this gene regulates endosomal sorting and plays a critical role in the recycling and degradation of membrane receptors. The encoded protein sorts monoubiquitinated membrane proteins into the multivesicular body, targeting these proteins for lysosome-dependent degradation.

hepatocyte 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 (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. Involved in receptor recycling via its association with the CART complex, a multiprotein complex required for efficient transferrin receptor recycling but not for EGFR degradation.

Endosomal transport Source: UniProtKB
Macroautophagy Source: ParkinsonsUK-UCL
Membrane invagination Source: UniProtKB
Multivesicular body assembly Source: ParkinsonsUK-UCL
Negative regulation of angiogenesis Source: BHF-UCL
Negative regulation of cell population proliferation Source: ProtInc
Negative regulation of platelet-derived growth factor receptor signaling pathway Source: BHF-UCL
Negative regulation of receptor signaling pathway via JAK-STAT Source: HGNC-UCL
Negative regulation of vascular endothelial growth factor receptor signaling pathway Source: BHF-UCL
Positive regulation of exosomal secretion Source: UniProtKB
Positive regulation of gene expression Source: UniProtKB
Protein localization to membrane Source: UniProtKB
Protein targeting to lysosome Source: UniProtKB
Regulation of MAP kinase activity Source: UniProtKB
Regulation of protein catabolic process Source: HGNC-UCL
Signal transduction Source: ProtInc

Early endosome membrane; Multivesicular body membrane; Cytoplasm. Colocalizes with UBQLN1 in ubiquitin-rich cytoplasmic aggregates that are not endocytic compartments.

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.
Ubiquitinated (PubMed:25588945). Ubiquitinated by ITCH (PubMed:14602072, PubMed:24790097).