hepatocyte growth factor-regulated tyrosine kinase substrate; protein pp110 (Hrs, HGS)

Function: - role in intracellular signal transduction mediated by cytokines & growth factors - wen associated with STAM, suppresses DNA signaling upon stimulation by IL-2 & GM-CSF - could be a direct effector of PI3-kinase in vesicular pathway via early endosomes - may regulate trafficking to early & late endosomes by recruiting clathrin - may concentrate ubiquitinated receptors within clathrin-coated regions - involved in down-regulation of receptor tyrosine kinase via multivesicular body when complexed with STAM (ESCRT-0 complex) - may contribute to the efficient recruitment of SMADs to the activin receptor comple - involved in receptor recycling via its association with the CART complex - phosphorylated on Tyr-334 - a minor site of phosphorylation on Tyr-329 is detected (putative) - phosphorylation occurs in response to EGF, IL-2, GM-CSF & HGF - ubiquitinated by ITCH - interacts with TRAK1 & TRAK2 - component of the ESCRT-0 complex - part of a complex at least composed of HSG, STAM2 (or probably STAM) & EPS15 - interacts with STAM & with STAM2 - interacts with EPS15; interaction is Ca⁺²-dependent & inhibited by SNAP25 - interacts with NF2 - interacts with ubiquitin - interacts with VPS37C - interacts with SMAD1, SMAD2 & SMAD3 - interacts with TSG101 - interaction mediates the association with the ESCRT-I complex interacts with SNAP25 - interaction decreases with increasing free Ca⁺² - interacts with SNX1 - component of a 550 kD membrane complex at least composed of HGS & SNX1 but excluding EGFR. component of the CART complex, at least composed of ACTN4, HGS/HRS, MYO5B & TRIM3 Structure: - has a double-sided UIM that can bind 2 ubiquitins, one on each side of the helix - the FYVE-type Zn⁺² finger domain mediates interactions with phosphatidylinositol 3-phosphate in membranes of early endosomes & penetrates bilayers - the FYVE domain insertion into Ptdins(3)P-enriched membranes is substantially increased in acidic conditions - contains 1 FYVE-type Zn⁺² finger - contains 1 UIM (ubiquitin-interacting motif) repeat - contains 1 VHS domain Compartment: - cytoplasm - membrane-associated, cytoplasmic side - multivesicular body membrane - localized to early endosomes, peripheral Expression: - ubiquitous expression in adult & fetal tissues - highest expression in testis & peripheral blood leukocytes

General

phosphoprotein zinc finger protein

Properties

SIZE: entity length = 777 aa MW = 86 kD COMPARTMENT: cytoplasm MOTIF: VHS domain {15-143} MOTIF: Tyr phosphorylation site {Y132} Zn finger Fyve-type SITE: 160-220 EFFECTOR-BOUND: Zn+2 MOTIF: Tyr phosphorylation site {Y216} SNX1 interaction {225-543} MOTIF: Ser phosphorylation site {S240} UIM {258-277} Tyr phosphorylation site {Y286} Tyr phosphorylation site {Y289} Tyr phosphorylation site {Y308} Tyr phosphorylation site {Y329} Tyr phosphorylation site {Y334} proline-rich region SITE: 346-394 MOTIF: proline residue (SEVERAL) SNAP25/TRAK2 interaction {445-543} STAM1 interaction {454-572} NF2 interaction {480-777} MOTIF: glutamine-rich region {505-772} MOTIF: glutamine residue (SEVERAL)

Database Correlations

OMIM 604375 UniProt O14964 PFAM correlations Entrez Gene 9146 Kegg hsa:9146

References

UniProt :accession O14964