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

More general terms

• phosphoprotein
• zinc finger protein

Component of

• ESCRT-0 complex; STAM1/STAM2-HGS complex

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=9146
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:9146
• OMIM: https://mirror.omim.org/entry/604375
• UniProt: http://www.uniprot.org/uniprot/O14964.html