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Q9JJ50 (HGS_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Hepatocyte growth factor-regulated tyrosine kinase substrate
Alternative name(s):
SNAP-25-interacting protein Hrs-2
Gene names
Name:Hgs
Synonyms:Hrs, Hrs2
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length776 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

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. Interacts with EPS15; the interaction is direct, calcium-dependent and inhibited by SNAP25. Interacts with NF2; the interaction is direct. Interacts with ubiquitin; the interaction is direct. Interacts with VPS37C. Interacts with SMAD1, SMAD2 and SMAD3. Interacts with TSG101; the interaction mediates the association with the ESCRT-I complex. Component of the CART complex, at least composed of ACTN4, HGS/HRS, MYO5B and TRIM3 By similarity. Interacts with SNAP25; the interaction is direct and decreases with addition of increasing concentrations of free calcium. Interacts with SNX1; the interaction is direct. Component of a 550 kDa membrane complex at least composed of HGS and SNX1 but excluding EGFR. Interacts with TRAK2. Interacts with TRAK1 By similarity. Ref.1 Ref.3 Ref.5 Ref.6 Ref.7

Subcellular location

Cytoplasm. Early endosome membrane; Peripheral membrane protein; Cytoplasmic side. Endosome › multivesicular body membrane; Peripheral membrane protein Ref.3.

Tissue specificity

Ubiquitously expressed. Ref.1 Ref.2 Ref.3

Domain

Has a double-sided UIM that can bind 2 ubiquitin molecules, one on each side of the helix By similarity. Ref.3 Ref.6

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 PtdIns3P-enriched membranes is substantially increased in acidic conditions By similarity. Ref.3 Ref.6

Post-translational modification

Phosphorylated on Tyr-334. This phosphorylation occurs in response to EGF. A minor site of phosphorylation on Tyr-329 is detected. Protein phosphorylation may also be triggered in response to IL-2, GM-CSF and HGF By similarity.

Ubiquitinated by ITCH By similarity.

Sequence similarities

Contains 1 FYVE-type zinc finger.

Contains 1 UIM (ubiquitin-interacting motif) repeat.

Contains 1 VHS domain.

Sequence caution

The sequence AAB49681.1 differs from that shown. Reason: Frameshift at positions 256, 270, 480, 487, 503, 573, 597, 614, 640, 646, 649, 653, 658, 733, 748 and 754.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9JJ50-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9JJ50-2)

The sequence of this isoform differs from the canonical sequence as follows:
     671-675: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 776776Hepatocyte growth factor-regulated tyrosine kinase substrate
PRO_0000098710

Regions

Domain15 – 143129VHS
Repeat258 – 27720UIM
Zinc finger160 – 22061FYVE-type
Region225 – 542318Interaction with SNX1
Region444 – 54299Interaction with SNAP25 and TRAK2
Region453 – 571119Interaction with STAM1 By similarity
Region479 – 776298Interaction with NF2 By similarity
Compositional bias504 – 55956Gln-rich
Compositional bias560 – 764205Pro-rich

Amino acid modifications

Modified residue2071N6-acetyllysine By similarity
Modified residue2161Phosphotyrosine By similarity
Modified residue3081Phosphotyrosine By similarity
Modified residue3291Phosphotyrosine By similarity
Modified residue3341Phosphotyrosine By similarity

Natural variations

Alternative sequence671 – 6755Missing in isoform 2.
VSP_014852

Experimental info

Sequence conflict3941Missing in AAB49681. Ref.1
Sequence conflict3981G → A in AAH83561. Ref.4
Sequence conflict5611A → V in AAH83561. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: FD61BEC121F37E67

FASTA77686,246
        10         20         30         40         50         60 
MGRGSGTFER LLDKATSQLL LETDWESILQ ICDLIRQGDT QAKYAVNSIK KKVNDKNPHV 

        70         80         90        100        110        120 
ALYALEVMES VVKNCGQTVH DEVANKQTME ELKELLKRQV EVNVRNKILY LIQAWAHAFR 

       130        140        150        160        170        180 
NEPKYKVVQD TYQIMKVEGH VFPEFKESDA MFAAERAPDW VDAEECHRCR VQFGVVTRKH 

       190        200        210        220        230        240 
HCRACGQIFC GKCSSKYSTI PKFGIEKEVR VCEPCYEQLN KKAEGKAAST TELPPEYLTS 

       250        260        270        280        290        300 
PLSQQSQLPP KRDETALQEE EELQLALALS QSEAEEKERM RQKSTYTAHP KSEPAPLASS 

       310        320        330        340        350        360 
APPAGSLYSS PVNSSAPLAE DIDPELARYL NRNYWEKKQE EARKSPTPSA PVPLTEPAAQ 

       370        380        390        400        410        420 
PGEGHTAPNS MVEAPLPETD SQPITSCSGP FSEQYQNGES EESHEQFLKA LQNAVSTFVN 

       430        440        450        460        470        480 
RMKSNHMRGR SITNDSAVLS LFQSINSTHP QLLELLNRLD ERRLYYEGLQ DKLAQIRDAR 

       490        500        510        520        530        540 
GALSALREEH REKLRRAAEE AERQRQIQLA QKLEIMRQKK QEYLEVQRQL AIQRLQEQEK 

       550        560        570        580        590        600 
ERQMRLEQQK QTVQMRAQMP AFPLPYAQLQ AMPTAGGVLY QPSGPTSFPG TFSPAGSVEG 

       610        620        630        640        650        660 
SPMHGVYMSQ PAPATGPYPS MPGTTADPSM VSAYMYPAGA PGAQAAPQAQ AGPTTNPAYS 

       670        680        690        700        710        720 
SYQPTPTPGY QNVASQAPQS LPAISQPPQT SNIGYMGSQP MSMGYQPYNM QNLMTTLPGQ 

       730        740        750        760        770 
DASLPAQQPY ITGQQPMYQQ MAPSTGPPQQ QPPVAQPPPT QGPPAQGNET QLISFD

« Hide

Isoform 2 [UniParc].

Checksum: 626D111BE89783CB
Show »

FASTA77185,747

References

« Hide 'large scale' references
[1]"Hrs-2 is an ATPase implicated in calcium-regulated secretion."
Bean A.J., Seifert R., Chen Y.A., Sacks R., Scheller R.H.
Nature 385:826-829(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INTERACTION WITH SNAP25.
[2]"Molecular cloning of a rat brain cDNA, with homology to a tyrosine kinase substrate, that induces galactosylceramide expression in COS-7 cells."
Ogura K., Kohno K., Tai T.
J. Neurochem. 71:1827-1836(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
Strain: Wistar.
Tissue: Brain.
[3]"Hrs interacts with SNAP-25 and regulates Ca2+-dependent exocytosis."
Kwong J., Roudabush F.L., Moore P.H., Montague M., Oldham W., Li Y., Chin L.-S., Li L.
J. Cell Sci. 113:2273-2284(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, SUBCELLULAR LOCATION, DOMAIN, INTERACTION WITH SNAP25.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Testis.
[5]"Hrs-2 regulates receptor-mediated endocytosis via interactions with Eps15."
Bean A.J., Davanger S., Chou M.F., Gerhardt B., Tsujimoto S., Chang Y.
J. Biol. Chem. 275:15271-15278(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EPS15.
[6]"Hrs interacts with sorting nexin 1 and regulates degradation of epidermal growth factor receptor."
Chin L.-S., Raynor M.C., Wei X., Chen H.-Q., Li L.
J. Biol. Chem. 276:7069-7078(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SNX1, DOMAIN.
[7]"GRIF1 binds Hrs and is a new regulator of endosomal trafficking."
Kirk E., Chin L.S., Li L.
J. Cell Sci. 119:4689-4701(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TRAK2.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		U87863 mRNA. Translation: AAB49681.1. Frameshift.
AB002811 mRNA. Translation: BAD08342.1.
AF036344 mRNA. Translation: AAF76251.1.
BC083561 mRNA. Translation: AAH83561.1.
IPIIPI00201027.
IPI00208700.
RefSeqNP_062260.2. NM_019387.2.
UniGeneRn.21.

3D structure databases

ProteinModelPortalQ9JJ50.
SMRQ9JJ50. Positions 6-221.
ModBaseSearch...

Protein-protein interaction databases

MINTMINT-107197.

PTM databases

PhosphoSiteQ9JJ50.

Proteomic databases

PRIDEQ9JJ50.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000054966; ENSRNOP00000051849; ENSRNOG00000036696.
GeneID56084.
KEGGrno:56084.

Organism-specific databases

CTD9146.
RGD69225. Hgs.

Phylogenomic databases

eggNOGNOG257212.
GeneTreeENSGT00670000098022.
HOVERGENHBG062917.
KOK12182.
OrthoDBEOG4H463C.

Gene expression databases

ArrayExpressQ9JJ50.
GenevestigatorQ9JJ50.

Family and domain databases

Gene3D1.25.40.90. 1 hit.
3.30.40.10. 1 hit.
InterProIPR008942. ENTH_VHS.
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.
[Graphical view]
PfamPF01363. FYVE. 1 hit.
PF12210. Hrs_helical. 1 hit.
PF00790. VHS. 1 hit.
[Graphical view]
PIRSFPIRSF036956. Hrs_Vps27. 1 hit.
SMARTSM00064. FYVE. 1 hit.
SM00726. UIM. 1 hit.
SM00288. VHS. 1 hit.
[Graphical view]
SUPFAMSSF48464. ENTH_VHS. 1 hit.
SSF57903. FYVE_PHD_ZnF. 1 hit.
PROSITEPS50330. UIM. 1 hit.
PS50179. VHS. 1 hit.
PS50178. ZF_FYVE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio611106.

Entry information

Entry nameHGS_RAT
AccessionPrimary (citable) accession number: Q9JJ50
Secondary accession number(s): P97847, Q5XIV8, Q76N76
Entry history
Integrated into UniProtKB/Swiss-Prot: July 19, 2005
Last sequence update: October 1, 2000
Last modified: April 3, 2013
This is version 93 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents