UniProt Accession

 HGS_RAT; Q9JJ50; P97847; Q5XIV8; Q76N76 

Genbank Protein ID

 U87863; AB002811; AF036344; BC083561 

Genbank Nucleotide ID

 AAB49681.1; BAD08342.1; AAF76251.1; AAH83561.1 

Protein Name

 Hepatocyte growth factor-regulated tyrosine kinase substrate 

Protein Synonyms/Alias

 SNAP-25-interacting protein Hrs-2 

Gene Name

 Hgs 

Gene Synonyms/Alias

 Hrs; Hrs2 

Created Date

 July 27, 2013 

Organism

 Rattus norvegicus (Rat) 

NCBI Taxa ID

 10116 

Lysine Modification

Position	Peptide	Type	References
126	FRNEPKYKVVQDTYQ	ubiquitination	[1]
207	IPKFGIEKEVRVCEP	ubiquitination	[1]
226	LNKKAEGKAASTTEL	ubiquitination	[1]

Reference

 [1] Synaptic protein ubiquitination in rat brain revealed by antibody-based ubiquitome analysis.
 Na CH, Jones DR, Yang Y, Wang X, Xu Y, Peng J.
 J Proteome Res. 2012 Sep 7;11(9):4722-32. [PMID: 22871113] 

Functional Description

 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. 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 (By similarity). May contribute to the efficient recruitment of SMADs to the activin receptor complex. 

Sequence Annotation

 DOMAIN 15 143 VHS.
 REPEAT 258 277 UIM.
 ZN_FING 160 220 FYVE-type.
 REGION 225 542 Interaction with SNX1.
 REGION 444 542 Interaction with SNAP25 and TRAK2.
 REGION 453 571 Interaction with STAM1 (By similarity).
 REGION 479 776 Interaction with NF2 (By similarity).
 MOD_RES 207 207 N6-acetyllysine (By similarity).
 MOD_RES 216 216 Phosphotyrosine (By similarity).
 MOD_RES 308 308 Phosphotyrosine (By similarity).
 MOD_RES 329 329 Phosphotyrosine (By similarity).
 MOD_RES 334 334 Phosphotyrosine (By similarity).  

Keyword

 Acetylation; Alternative splicing; Complete proteome; Cytoplasm; Endosome; Membrane; Metal-binding; Phosphoprotein; Protein transport; Reference proteome; Transport; Ubl conjugation; Zinc; Zinc-finger. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 776 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; IDA:RGD.
 GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
 GO:0016020; C:membrane; IDA:RGD.
 GO:0032585; C:multivesicular body membrane; IEA:UniProtKB-SubCell.
 GO:0030141; C:secretory granule; IDA:RGD.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0019904; F:protein domain specific binding; NAS:RGD.
 GO:0008333; P:endosome to lysosome transport; IMP:RGD.
 GO:0006886; P:intracellular protein transport; IEA:InterPro.
 GO:0046426; P:negative regulation of JAK-STAT cascade; IEA:Compara. 

Interpro

 IPR008942; ENTH_VHS.
 IPR027426; HGS.
 IPR024641; HRS_helical.
 IPR017073; Ubi-bd_Hrs_VPS27.
 IPR003903; Ubiquitin-int_motif.
 IPR002014; VHS.
 IPR018205; VHS_subgr.
 IPR000306; Znf_FYVE.
 IPR017455; Znf_FYVE-rel.
 IPR011011; Znf_FYVE_PHD.
 IPR013083; Znf_RING/FYVE/PHD. 

Pfam

 PF01363; FYVE
 PF12210; Hrs_helical
 PF00790; VHS 

SMART

 SM00064; FYVE
 SM00726; UIM
 SM00288; VHS 

PROSITE

 PS50330; UIM
 PS50179; VHS
 PS50178; ZF_FYVE 

PRINTS