Phospho-HGS (Tyr216) Antibody - #AF3861

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.

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. Ubiquitinated by ITCH.

Cytoplasm. Early endosome membrane>Peripheral membrane protein>Cytoplasmic side. Endosome>Multivesicular body membrane>Peripheral membrane protein.
Note: Colocalizes with UBQLN1 in ubiquitin-rich cytoplasmic aggregates that are not endocytic compartments.

Ubiquitous expression in adult and fetal tissues with higher expression in testis and peripheral blood leukocytes.

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 (By similarity). Interacts with EPS15; the interaction is direct, calcium-dependent and inhibited by SNAP25 (By similarity). Identified in a complex with STAM and LITAF. Found in a complex with STAM and E3 ligase ITCH and DTX3L. Interacts with E3 ligase DTX3L; the interaction brings together STAM and HSG, promotes their recruitment to early endosomes and decreases STAM and HGS ubiquitination by ITCH. Interacts with NF2; the interaction is direct. Interacts with ubiquitin; the interaction is direct (By similarity). Interacts with VPS37C. Interacts with SMAD1, SMAD2 and SMAD3 (By similarity). 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 (By similarity). Interacts with SNX1; the interaction is direct (By similarity). Component of a 550 kDa membrane complex at least composed of HGS and SNX1 but excluding EGFR (By similarity). Interacts with TRAK1. Interacts with TRAK2 (By similarity). Component of the CART complex, at least composed of ACTN4, HGS/HRS, MYO5B and TRIM3. Interacts (via UIM domain) with UBQLN1 (via ubiquitin-like domain) (By similarity). Interacts with ARRDC3. Identified in a complex containing at least ARRDC4, AVPR2 and HGS. Interacts with LAPTM4B; promotes HGS ubiquitination.

Has a double-sided UIM that can bind 2 ubiquitin molecules, one on each side of the helix.

The FYVE-type zinc finger domain mediates interactions with phosphatidylinositol 3-phosphate in membranes of early endosomes and penetrates bilayers. The FYVE domain insertion into PtdIns(3)P-enriched membranes is substantially increased in acidic conditions.