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Protein

Hepatocyte growth factor-regulated tyrosine kinase substrate

Gene

HGS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section specifies the position(s) and type(s) of zinc fingers within the protein.<p><a href='/help/zn_fing' target='_top'>More...</a></p>Zinc fingeri160 – 220FYVE-typePROSITE-ProRule annotationAdd BLAST61

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • protein domain specific binding Source: UniProtKB
  • ubiquitin-like protein ligase binding Source: UniProtKB

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Biological processProtein transport, Transport
LigandMetal-binding, Zinc

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-182971 EGFR downregulation
R-HSA-432720 Lysosome Vesicle Biogenesis
R-HSA-5689880 Ub-specific processing proteases
R-HSA-6807004 Negative regulation of MET activity
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828 Clathrin-mediated endocytosis
R-HSA-8875360 InlB-mediated entry of Listeria monocytogenes into host cell
R-HSA-917729 Endosomal Sorting Complex Required For Transport (ESCRT)

SignaLink: a signaling pathway resource with multi-layered regulatory networks

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SignaLinki
O14964

SIGNOR Signaling Network Open Resource

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SIGNORi
O14964

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Hepatocyte growth factor-regulated tyrosine kinase substrate
Alternative name(s):
Hrs1 Publication
Protein pp110
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:HGS
Synonyms:HRS
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 17

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000185359.12

Human Gene Nomenclature Database

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HGNCi
HGNC:4897 HGS

Online Mendelian Inheritance in Man (OMIM)

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MIMi
604375 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_O14964

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endosome, Membrane

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi266A → Q: Strongly reduced ubiquitin-binding. Reduced degradation of ubiquitinated EGFR. 1 Publication1
Mutagenesisi268A → Q: Strongly reduced ubiquitin-binding. Reduced degradation of ubiquitinated EGFR. 1 Publication1

Organism-specific databases

DisGeNET

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DisGeNETi
9146

Open Targets

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OpenTargetsi
ENSG00000185359

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA29271

Chemistry databases

Drug and drug target database

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DrugBanki
DB04272 Citric Acid

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
HGS

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000987081 – 777Hepatocyte growth factor-regulated tyrosine kinase substrateAdd BLAST777

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei207N6-acetyllysineCombined sources1
Modified residuei216PhosphotyrosineCombined sources1
Modified residuei308PhosphotyrosineBy similarity1
Modified residuei329PhosphotyrosineBy similarity1
Modified residuei334PhosphotyrosineBy similarity1
Modified residuei551N6-succinyllysineBy similarity1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

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.By similarity
Ubiquitinated (PubMed:25588945). Ubiquitinated by ITCH (PubMed:14602072, PubMed:24790097).3 Publications

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
O14964

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
O14964

MaxQB - The MaxQuant DataBase

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MaxQBi
O14964

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
O14964

PeptideAtlas

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PeptideAtlasi
O14964

PRoteomics IDEntifications database

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PRIDEi
O14964

ProteomicsDB human proteome resource

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ProteomicsDBi
48337
48338 [O14964-2]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
O14964

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
O14964

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Ubiquitous expression in adult and fetal tissues with higher expression in testis and peripheral blood leukocytes.2 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000185359 Expressed in 224 organ(s), highest expression level in left adrenal gland

CleanEx database of gene expression profiles

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CleanExi
HS_HGS

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
O14964 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
O14964 HS

Organism-specific databases

Human Protein Atlas

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HPAi
HPA004872
HPA007728

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

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 (PubMed:12551915). Interacts with STAM (PubMed:9407053). 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 (PubMed:23166352). Found in a complex with STAM and E3 ligase ITCH and DTX3L (PubMed:24790097). 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 (PubMed:24790097). Interacts with NF2; the interaction is direct (PubMed:10861283). Interacts with ubiquitin; the interaction is direct (By similarity). Interacts with VPS37C (PubMed:15509564). Interacts with SMAD1, SMAD2 and SMAD3 (By similarity). Interacts with TSG101; the interaction mediates the association with the ESCRT-I complex (PubMed:21070952). 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 (PubMed:18675823). Interacts with TRAK2 (By similarity). Component of the CART complex, at least composed of ACTN4, HGS/HRS, MYO5B and TRIM3 (PubMed:15772161). Interacts (via UIM domain) with UBQLN1 (via ubiquitin-like domain) (By similarity). Interacts with ARRDC3 (PubMed:23208550). Identified in a complex containing at least ARRDC4, AVPR2 and HGS (PubMed:23236378). Interacts with LAPTM4B; promotes HGS ubiquitination (PubMed:25588945).By similarity15 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

WithEntry#Exp.IntActNotes
ABI2Q9NYB93EBI-740220,EBI-743598
AESQ08117-25EBI-740220,EBI-11741437
ARFIP2P533653EBI-740220,EBI-638194
BCAS2O759343EBI-740220,EBI-1050106
C1orf94Q6P1W53EBI-740220,EBI-946029
CCDC103Q8IW403EBI-740220,EBI-10261970
CCDC114Q96M638EBI-740220,EBI-10173858
CDR2Q018505EBI-740220,EBI-1181367
CEP55Q53EZ44EBI-740220,EBI-747776
CEP57L1Q8IYX8-23EBI-740220,EBI-10181988
CEP63Q96MT8-35EBI-740220,EBI-11522539
COG8Q96MW53EBI-740220,EBI-720875
CRXO431865EBI-740220,EBI-748171
CSTF2P332405EBI-740220,EBI-711360
CSTF2TQ9H0L43EBI-740220,EBI-747012
CTTNBP2NLQ9P2B43EBI-740220,EBI-1774273
DAZAP2Q150386EBI-740220,EBI-724310
EXOC5O004713EBI-740220,EBI-949824
EXOC7Q9UPT54EBI-740220,EBI-720048
FAM168AQ92567-25EBI-740220,EBI-11978259
FANCGA0A0S2Z4A73EBI-740220,EBI-16433879
FCHSD2O94868-33EBI-740220,EBI-11958845
GOLGA2Q083793EBI-740220,EBI-618309
HSFY2Q96LI63EBI-740220,EBI-3957665
ING5Q8WYH85EBI-740220,EBI-488533
INTS4Q96HW73EBI-740220,EBI-5663129
INTS4Q96HW7-23EBI-740220,EBI-16438029
JAKMIP2Q96AA83EBI-740220,EBI-752007
KRT13P136465EBI-740220,EBI-1223876
KRT15P190125EBI-740220,EBI-739566
KRT18P057836EBI-740220,EBI-297888
KRT19P087273EBI-740220,EBI-742756
KRT31Q153235EBI-740220,EBI-948001
KRT33BQ145255EBI-740220,EBI-1049638
KRT38O760155EBI-740220,EBI-1047263
KRT40Q6A1626EBI-740220,EBI-10171697
KRT6AP025386EBI-740220,EBI-702198
KRTAP26-1Q6PEX33EBI-740220,EBI-3957672
LDOC1O957519EBI-740220,EBI-740738
LITAFQ997327EBI-740220,EBI-725647
LURAP1Q96LR23EBI-740220,EBI-741355
MAGEB4O154813EBI-740220,EBI-751857
MAGED1Q9Y5V35EBI-740220,EBI-716006
MAPK1IP1LQ8NDC06EBI-740220,EBI-741424
MED7O435134EBI-740220,EBI-394632
MIF4GDA9UHW64EBI-740220,EBI-373498
MIF4GDA9UHW6-25EBI-740220,EBI-9118295
MRFAP1L1Q96HT85EBI-740220,EBI-748896
NDC80O147775EBI-740220,EBI-715849
NEFLI6L9F63EBI-740220,EBI-10178578
NMIQ132879EBI-740220,EBI-372942
NUP54Q7Z3B45EBI-740220,EBI-741048
P4HA3Q7Z4N85EBI-740220,EBI-10181968
PEF1Q9UBV83EBI-740220,EBI-724639
POGZQ7Z3K35EBI-740220,EBI-1389308
PPP1R32Q7Z5V6-24EBI-740220,EBI-12000762
RFX6Q8HWS33EBI-740220,EBI-746118
sh3rf1Q6NRD33EBI-740220,EBI-7734031From Xenopus laevis.
SNX7Q9UNH63EBI-740220,EBI-751422
SS18L1O75177-53EBI-740220,EBI-12035119
STAMQ927832EBI-740220,EBI-752333
STAMQ92783-15EBI-740220,EBI-15763634
STX11O755583EBI-740220,EBI-714135
SUMO1P631653EBI-740220,EBI-80140
TADA2AO754783EBI-740220,EBI-742268
TADA2AO75478-23EBI-740220,EBI-16433586
taxP034104EBI-740220,EBI-9676218From Human T-cell leukemia virus 2.
taxP140794EBI-740220,EBI-9675698From Human T-cell leukemia virus 1 (isolate Caribbea HS-35 subtype A).
TEKT1Q969V45EBI-740220,EBI-10180409
TRAF4Q9BUZ45EBI-740220,EBI-3650647
TRIM17Q9Y5775EBI-740220,EBI-743894
TRIM69Q86WT6-27EBI-740220,EBI-11525489
TSG101Q998164EBI-740220,EBI-346882
TSG101Q99816-12EBI-740220,EBI-15891993
UBBP0CG537EBI-740220,EBI-5333021From Bos taurus.
UBCP629902EBI-740220,EBI-413053From a different organism.
UBQLN2Q9UHD94EBI-740220,EBI-947187
USHBP1Q8N6Y04EBI-740220,EBI-739895
VPS37BQ9H9H45EBI-740220,EBI-4400866
VPS37CA5D8V63EBI-740220,EBI-2559305
VPS52Q8N1B43EBI-740220,EBI-2799833
WHAMMP3Q1A5X74EBI-740220,EBI-11956783

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
114593, 215 interactors

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
O14964

Database of interacting proteins

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DIPi
DIP-29050N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

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ELMi
O14964

Protein interaction database and analysis system

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IntActi
O14964, 275 interactors

Molecular INTeraction database

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MINTi
O14964

STRING: functional protein association networks

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STRINGi
9606.ENSP00000331201

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1777
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2D3GX-ray1.70P257-277[»]
3F1IX-ray2.30H404-501[»]
3OBQX-ray1.40B346-354[»]
3ZYQX-ray1.48A1-225[»]
4AVXX-ray1.68A1-225[»]

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
O14964

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
O14964

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
O14964

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini15 – 143VHSPROSITE-ProRule annotationAdd BLAST129
Domaini258 – 277UIMPROSITE-ProRule annotationAdd BLAST20

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni225 – 543Interaction with SNX1By similarityAdd BLAST319
Regioni445 – 543Interaction with SNAP25 and TRAK2By similarityAdd BLAST99
Regioni454 – 572Interaction with STAMBy similarityAdd BLAST119
Regioni480 – 777Interaction with NF21 PublicationAdd BLAST298

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi346 – 394Pro-richAdd BLAST49
Compositional biasi505 – 772Gln-richAdd BLAST268

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

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 PtdIns3P-enriched membranes is substantially increased in acidic conditions.

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri160 – 220FYVE-typePROSITE-ProRule annotationAdd BLAST61

Keywords - Domaini

Zinc-finger

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG1818 Eukaryota
ENOG410XNRF LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000158297

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000044175

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG062917

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
O14964

KEGG Orthology (KO)

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KOi
K12182

Identification of Orthologs from Complete Genome Data

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OMAi
ERMRQKS

Database of Orthologous Groups

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OrthoDBi
828765at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
O14964

TreeFam database of animal gene trees

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TreeFami
TF314470

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
1.25.40.90, 1 hit
3.30.40.10, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR008942 ENTH_VHS
IPR024641 HRS_helical
IPR017073 Ubi-bd_Hrs_VPS27
IPR003903 UIM_dom
IPR002014 VHS_dom
IPR000306 Znf_FYVE
IPR017455 Znf_FYVE-rel
IPR011011 Znf_FYVE_PHD
IPR013083 Znf_RING/FYVE/PHD

Pfam protein domain database

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Pfami
View protein in Pfam
PF01363 FYVE, 1 hit
PF12210 Hrs_helical, 1 hit
PF00790 VHS, 1 hit

PIRSF; a whole-protein classification database

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PIRSFi
PIRSF036956 Hrs_Vps27, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00064 FYVE, 1 hit
SM00288 VHS, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF48464 SSF48464, 1 hit
SSF57903 SSF57903, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS50330 UIM, 1 hit
PS50179 VHS, 1 hit
PS50178 ZF_FYVE, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 2 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O14964-1) [UniParc]FASTAAdd to basket
Also known as: HRSi1

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.

« Hide
        10         20         30         40         50
MGRGSGTFER LLDKATSQLL LETDWESILQ ICDLIRQGDT QAKYAVNSIK
60 70 80 90 100
KKVNDKNPHV ALYALEVMES VVKNCGQTVH DEVANKQTME ELKDLLKRQV
110 120 130 140 150
EVNVRNKILY LIQAWAHAFR NEPKYKVVQD TYQIMKVEGH VFPEFKESDA
160 170 180 190 200
MFAAERAPDW VDAEECHRCR VQFGVMTRKH HCRACGQIFC GKCSSKYSTI
210 220 230 240 250
PKFGIEKEVR VCEPCYEQLN RKAEGKATST TELPPEYLTS PLSQQSQLPP
260 270 280 290 300
KRDETALQEE EELQLALALS QSEAEEKERL RQKSTYTSYP KAEPMPSASS
310 320 330 340 350
APPASSLYSS PVNSSAPLAE DIDPELARYL NRNYWEKKQE EARKSPTPSA
360 370 380 390 400
PVPLTEPAAQ PGEGHAAPTN VVENPLPETD SQPIPPSGGP FSEPQFHNGE
410 420 430 440 450
SEESHEQFLK ALQNAVTTFV NRMKSNHMRG RSITNDSAVL SLFQSINGMH
460 470 480 490 500
PQLLELLNQL DERRLYYEGL QDKLAQIRDA RGALSALREE HREKLRRAAE
510 520 530 540 550
EAERQRQIQL AQKLEIMRQK KQEYLEVQRQ LAIQRLQEQE KERQMRLEQQ
560 570 580 590 600
KQTVQMRAQM PAFPLPYAQL QAMPAAGGVL YQPSGPASFP STFSPAGSVE
610 620 630 640 650
GSPMHGVYMS QPAPAAGPYP SMPSTAADPS MVSAYMYPAG ATGAQAAPQA
660 670 680 690 700
QAGPTASPAY SSYQPTPTAG YQNVASQAPQ SLPAISQPPQ SSTMGYMGSQ
710 720 730 740 750
SVSMGYQPYN MQNLMTTLPS QDASLPPQQP YIAGQQPMYQ QMAPSGGPPQ
760 770
QQPPVAQQPQ AQGPPAQGSE AQLISFD
Length:777
Mass (Da):86,192
Last modified:January 1, 1998 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iDD64167A19DCF030
GO
Isoform 2 (identifier: O14964-2) [UniParc]FASTAAdd to basket
Also known as: HRSi2

The sequence of this isoform differs from the canonical sequence as follows:
     518-604: Missing.

Note: Dubious isoform produced through aberrant splice sites.
Show »
Length:690
Mass (Da):76,376
Checksum:i9266F872DB03A3E6
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
I3L1P5I3L1P5_HUMAN
Hepatocyte growth factor-regulated ...
HGS
263Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
I3L2H4I3L2H4_HUMAN
Hepatocyte growth factor-regulated ...
HGS
59Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
I3L165I3L165_HUMAN
Hepatocyte growth factor-regulated ...
HGS
71Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
I3L1E3I3L1E3_HUMAN
Hepatocyte growth factor-regulated ...
HGS
292Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
I3L326I3L326_HUMAN
Hepatocyte growth factor-regulated ...
HGS
110Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
I3L1F1I3L1F1_HUMAN
Hepatocyte growth factor-regulated ...
HGS
63Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
I3L346I3L346_HUMAN
Hepatocyte growth factor-regulated ...
HGS
38Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti236E → D in AAF82361 (PubMed:10861283).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_0541547T → S1 PublicationCorresponds to variant dbSNP:rs753682847Ensembl.1
Natural variantiVAR_052981400E → D. Corresponds to variant dbSNP:rs34868130Ensembl.1
Natural variantiVAR_061991733A → S. Corresponds to variant dbSNP:rs56058441Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_036172518 – 604Missing in isoform 2. 1 PublicationAdd BLAST87

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

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DDBJi
Links Updated
U43895 mRNA Translation: AAC51929.1
D84064 mRNA Translation: BAA23366.1
AF260566 mRNA Translation: AAF82361.1
BT009754 mRNA Translation: AAP88756.1
BC003565 mRNA Translation: AAH03565.1

The Consensus CDS (CCDS) project

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CCDSi
CCDS11784.1 [O14964-1]

NCBI Reference Sequences

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RefSeqi
NP_004703.1, NM_004712.4 [O14964-1]

UniGene gene-oriented nucleotide sequence clusters

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UniGenei
Hs.661056

Genome annotation databases

Ensembl eukaryotic genome annotation project

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Ensembli
ENST00000329138; ENSP00000331201; ENSG00000185359 [O14964-1]

Database of genes from NCBI RefSeq genomes

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GeneIDi
9146

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
hsa:9146

UCSC genome browser

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UCSCi
uc002kbg.4 human [O14964-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43895 mRNA Translation: AAC51929.1
D84064 mRNA Translation: BAA23366.1
AF260566 mRNA Translation: AAF82361.1
BT009754 mRNA Translation: AAP88756.1
BC003565 mRNA Translation: AAH03565.1
CCDSiCCDS11784.1 [O14964-1]
RefSeqiNP_004703.1, NM_004712.4 [O14964-1]
UniGeneiHs.661056

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2D3GX-ray1.70P257-277[»]
3F1IX-ray2.30H404-501[»]
3OBQX-ray1.40B346-354[»]
3ZYQX-ray1.48A1-225[»]
4AVXX-ray1.68A1-225[»]
ProteinModelPortaliO14964
SMRiO14964
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114593, 215 interactors
CORUMiO14964
DIPiDIP-29050N
ELMiO14964
IntActiO14964, 275 interactors
MINTiO14964
STRINGi9606.ENSP00000331201

Chemistry databases

DrugBankiDB04272 Citric Acid

PTM databases

iPTMnetiO14964
PhosphoSitePlusiO14964

Polymorphism and mutation databases

BioMutaiHGS

Proteomic databases

EPDiO14964
jPOSTiO14964
MaxQBiO14964
PaxDbiO14964
PeptideAtlasiO14964
PRIDEiO14964
ProteomicsDBi48337
48338 [O14964-2]

Protocols and materials databases

The DNASU plasmid repository

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DNASUi
9146
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000329138; ENSP00000331201; ENSG00000185359 [O14964-1]
GeneIDi9146
KEGGihsa:9146
UCSCiuc002kbg.4 human [O14964-1]

Organism-specific databases

Comparative Toxicogenomics Database

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CTDi
9146
DisGeNETi9146
EuPathDBiHostDB:ENSG00000185359.12

GeneCards: human genes, protein and diseases

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GeneCardsi
HGS
HGNCiHGNC:4897 HGS
HPAiHPA004872
HPA007728
MIMi604375 gene
neXtProtiNX_O14964
OpenTargetsiENSG00000185359
PharmGKBiPA29271

GenAtlas: human gene database

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GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG1818 Eukaryota
ENOG410XNRF LUCA
GeneTreeiENSGT00940000158297
HOGENOMiHOG000044175
HOVERGENiHBG062917
InParanoidiO14964
KOiK12182
OMAiERMRQKS
OrthoDBi828765at2759
PhylomeDBiO14964
TreeFamiTF314470

Enzyme and pathway databases

ReactomeiR-HSA-182971 EGFR downregulation
R-HSA-432720 Lysosome Vesicle Biogenesis
R-HSA-5689880 Ub-specific processing proteases
R-HSA-6807004 Negative regulation of MET activity
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828 Clathrin-mediated endocytosis
R-HSA-8875360 InlB-mediated entry of Listeria monocytogenes into host cell
R-HSA-917729 Endosomal Sorting Complex Required For Transport (ESCRT)
SignaLinkiO14964
SIGNORiO14964

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

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ChiTaRSi
HGS human
EvolutionaryTraceiO14964

The Gene Wiki collection of pages on human genes and proteins

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GeneWikii
HGS_(gene)

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

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GenomeRNAii
9146

Protein Ontology

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PROi
PR:O14964

The Stanford Online Universal Resource for Clones and ESTs

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SOURCEi
Search...

Gene expression databases

BgeeiENSG00000185359 Expressed in 224 organ(s), highest expression level in left adrenal gland
CleanExiHS_HGS
ExpressionAtlasiO14964 baseline and differential
GenevisibleiO14964 HS

Family and domain databases

Gene3Di1.25.40.90, 1 hit
3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR008942 ENTH_VHS
IPR024641 HRS_helical
IPR017073 Ubi-bd_Hrs_VPS27
IPR003903 UIM_dom
IPR002014 VHS_dom
IPR000306 Znf_FYVE
IPR017455 Znf_FYVE-rel
IPR011011 Znf_FYVE_PHD
IPR013083 Znf_RING/FYVE/PHD
PfamiView protein in Pfam
PF01363 FYVE, 1 hit
PF12210 Hrs_helical, 1 hit
PF00790 VHS, 1 hit
PIRSFiPIRSF036956 Hrs_Vps27, 1 hit
SMARTiView protein in SMART
SM00064 FYVE, 1 hit
SM00288 VHS, 1 hit
SUPFAMiSSF48464 SSF48464, 1 hit
SSF57903 SSF57903, 1 hit
PROSITEiView protein in PROSITE
PS50330 UIM, 1 hit
PS50179 VHS, 1 hit
PS50178 ZF_FYVE, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

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ProtoNeti
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiHGS_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: O14964
Secondary accession number(s): Q9NR36
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2005
Last sequence update: January 1, 1998
Last modified: January 16, 2019
This is version 178 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
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