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UniProtKB - Q8TDQ0 (HAVR2_HUMAN)

Entry version 157 (23 Feb 2022)
Sequence version 3 (02 Nov 2010)
Previous versions | rss
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Protein

Hepatitis A virus cellular receptor 2

Gene

HAVCR2

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

Cell surface receptor implicated in modulating innate and adaptive immune responses. Generally accepted to have an inhibiting function. Reports on stimulating functions suggest that the activity may be influenced by the cellular context and/or the respective ligand (PubMed:24825777).

Regulates macrophage activation (PubMed:11823861).

Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune responses and promotes immunological tolerance (PubMed:14556005).

In CD8+ cells attenuates TCR-induced signaling, specifically by blocking NF-kappaB and NFAT promoter activities resulting in the loss of IL-2 secretion. The function may implicate its association with LCK proposed to impair phosphorylation of TCR subunits, and/or LGALS9-dependent recruitment of PTPRC to the immunological synapse (PubMed:24337741, PubMed:26492563).

In contrast, shown to activate TCR-induced signaling in T-cells probably implicating ZAP70, LCP2, LCK and FYN (By similarity).

Expressed on Treg cells can inhibit Th17 cell responses (PubMed:24838857).

Receptor for LGALS9 (PubMed:16286920, PubMed:24337741).

Binding to LGALS9 is believed to result in suppression of T-cell responses; the resulting apoptosis of antigen-specific cells may implicate HAVCR2 phosphorylation and disruption of its association with BAG6. Binding to LGALS9 is proposed to be involved in innate immune response to intracellular pathogens. Expressed on Th1 cells interacts with LGALS9 expressed on Mycobacterium tuberculosis-infected macrophages to stimulate antibactericidal activity including IL-1 beta secretion and to restrict intracellular bacterial growth (By similarity).

However, the function as receptor for LGALS9 has been challenged (PubMed:23555261).

Also reported to enhance CD8+ T-cell responses to an acute infection such as by Listeria monocytogenes (By similarity).

Receptor for phosphatidylserine (PtSer); PtSer-binding is calcium-dependent. May recognize PtSer on apoptotic cells leading to their phagocytosis. Mediates the engulfment of apoptotic cells by dendritic cells. Expressed on T-cells, promotes conjugation but not engulfment of apoptotic cells. Expressed on dendritic cells (DCs) positively regulates innate immune response and in synergy with Toll-like receptors promotes secretion of TNF-alpha. In tumor-imfiltrating DCs suppresses nucleic acid-mediated innate immune repsonse by interaction with HMGB1 and interfering with nucleic acid-sensing and trafficking of nucleid acids to endosomes (By similarity).

Expressed on natural killer (NK) cells acts as a coreceptor to enhance IFN-gamma production in response to LGALS9 (PubMed:22323453).

In contrast, shown to suppress NK cell-mediated cytotoxicity (PubMed:22383801).

Negatively regulates NK cell function in LPS-induced endotoxic shock (By similarity).

By similarity1 Publication8 Publications

Caution

Experimental results based on the injection of HAVCR2/TIM-3 antibodies or use of HAVCR2/TIM-3-Fc fusion proteins can reflect changes in the activity of several cell types and pathways as HAVCR2/TIM-3 is expressed by multiple immune cell types.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei111PhosphatidylserineBy similarity1
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the 'Description' field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi116Calcium; via carbonyl oxygenBy similarity1
Binding sitei118Phosphatidylserine; via amide nitrogenBy similarity1
Metal bindingi119CalciumBy similarity1

<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

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<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 processAdaptive immunity, Immunity, Inflammatory response, Innate immunity
LigandMetal-binding

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		Q8TDQ0

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-451927, Interleukin-2 family signaling

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

More...SignaLinki		Q8TDQ0

<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%5Fand%5Ftaxonomy%5Fsection">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:
Hepatitis A virus cellular receptor 2
Short name:
HAVcr-2
Alternative name(s):
T-cell immunoglobulin and mucin domain-containing protein 3
Short name:
TIMD-3
T-cell immunoglobulin mucin receptor 3
Short name:
TIM-3
T-cell membrane protein 3
CD_antigen: CD366
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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:HAVCR2
Synonyms:TIM3, TIMD3
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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%5Fand%5Ftaxonomy%5Fsection">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%5Fand%5Ftaxonomy%5Fsection">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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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%5Fmanual">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 5

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:18437, HAVCR2

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		606652, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_Q8TDQ0

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000135077

<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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini22 – 202ExtracellularSequence analysisAdd BLAST181
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei203 – 223HelicalSequence analysisAdd BLAST21
Topological domaini224 – 301CytoplasmicSequence analysisAdd BLAST78

Keywords - Cellular componenti

Cell junction, Cell membrane, 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

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

May be involved in T-cell exhaustion associated with chronic viral infections such as with human immunodeficiency virus (HIV) and hepatitic C virus (HCV).2 Publications
T-cell lymphoma, subcutaneous panniculitis-like (SPTCL)3 Publications
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Disease descriptionAn uncommon form of T-cell non-Hodgkin lymphoma, in which cytotoxic CD8+ T-cells infiltrate subcutaneous adipose tissue, and rimming adipocytes in a lace-like pattern. Affected individuals typically present with multiple subcutaneous nodules, systemic B-cell symptoms, and, in a subset of cases, autoimmune disorders, most commonly systemic lupus erythematosus. A subset of patients develop hemophagocytic lymphohistiocytosis. SPTCL transmission pattern is consistent with autosomal recessive inheritance with incomplete penetrance.
Related information in OMIM
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_08221182Y → C in SPTCL; associated with disease susceptibility; results in dysregulated secretion of inflammatory cytokines by macrophages; affects protein folding; decreased localization at the cell membrane. 2 PublicationsCorresponds to variant dbSNP:rs184868814EnsemblClinVar.1
Natural variantiVAR_08221297I → M in SPTCL; associated with disease susceptibility; affects protein folding; decreased localization at the cell membrane. 1 PublicationCorresponds to variant dbSNP:rs35960726EnsemblClinVar.1
Natural variantiVAR_082213101T → I in SPTCL; may be associated with disease susceptibility. 2 PublicationsCorresponds to variant dbSNP:rs147827860EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'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>Mutagenesisi265Y → A: Abolishes TCR-induced NFAT activation; when associated with A-272. 1 Publication1
Mutagenesisi265Y → E: No effect on TCR-induced NFAT activation (phosphomimetic mutation); when associated with E-272. 1 Publication1
Mutagenesisi272Y → A: Abolishes TCR-induced NFAT activation; when associated with A-265. 1 Publication1
Mutagenesisi272Y → E: No effect on TCR-induced NFAT activation (phosphomimetic mutation); when associated with E-265. 1 Publication1

Keywords - Diseasei

Disease variant

Organism-specific databases

DisGeNET

More...DisGeNETi		84868

MalaCards human disease database

More...MalaCardsi		HAVCR2
MIMi618398, phenotype

Open Targets

More...OpenTargetsi		ENSG00000135077

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		86884, Subcutaneous panniculitis-like T-cell lymphoma

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA134883425

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		Q8TDQ0, Tbio

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL4630879

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		HAVCR2

Domain mapping of disease mutations (DMDM)

More...DMDMi		311033536

<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 denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 21Sequence analysisAdd BLAST21
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000004210122 – 301Hepatitis A virus cellular receptor 2Add BLAST280

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi38 ↔ 110PROSITE-ProRule annotationBy similarity
Disulfide bondi52 ↔ 63PROSITE-ProRule annotationBy similarity
Disulfide bondi58 ↔ 109PROSITE-ProRule annotationBy similarity
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi145O-linked (GalNAc...) threonine1 Publication1
Glycosylationi172N-linked (GlcNAc...) asparagineSequence analysis1
<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 residuei265Phosphotyrosine; by ITK1 Publication1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">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

O-glycosylated with core 1 or possibly core 8 glycans.1 Publication
Phosphorylated on tyrosine residues; modestly increased after TCR/CD28 stimulation. Can be phosphorylated in the cytoplasmatic domain by FYN (By similarity). Phosphorylation at Tyr-265 is increased by stimulation with ligand LGALS9.By similarity2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		Q8TDQ0

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		Q8TDQ0

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

More...PaxDbi		Q8TDQ0

PeptideAtlas

More...PeptideAtlasi		Q8TDQ0

PRoteomics IDEntifications database

More...PRIDEi		Q8TDQ0

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		74319 [Q8TDQ0-1]
74320 [Q8TDQ0-2]

PTM databases

GlyConnect protein glycosylation platform

More...GlyConnecti		712, 5 O-Linked glycans (1 site)

GlyGen: Computational and Informatics Resources for Glycoscience

More...GlyGeni		Q8TDQ0, 4 sites, 6 O-linked glycans (3 sites)

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		Q8TDQ0

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

More...PhosphoSitePlusi		Q8TDQ0

<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

Expressed in T-helper type 1 (Th1) lymphocytes. Expressed on regulatory T (Treg) cells after TCR stimulation. Expressed in dendritic cells and natural killer (NK) cells. Expressed in epithelial tissues. Expression is increased on CD4+ and CD8+ T-cells in chronic hepatitis C virus (HCV) infection. In progressive HIV-1 infection, expression is up-regulated on HIV-1-specific CD8 T-cells.8 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000135077, Expressed in layer of synovial tissue and 176 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		Q8TDQ0, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		Q8TDQ0, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000135077, Tissue enhanced (lymphoid)

<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%5Fsection">'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%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Interacts with HMGB1; impairs HMGB1 binding to B-DNA and likely HMGB1-mediated innate immune response (By similarity).

Interacts with BAG6 (By similarity).

Interacts (phosphorylated) with PIK3R1 and PIK3R2.

Interacts (not dependent on its phosphorylation status) with FYN (By similarity).

Interacts (in basal state T-cells) with VAV1; AKT1/2, LCP2, ZAP70, SYK, PIK3R1, FYN, SH3BP2 and SH2D2A.

Interacts (in activated T-cells) with LCK and PLCG (PubMed:26492563, PubMed:24337741).

Interacts with ILF3; this interaction promotes ILF3 ubiquitination and degradation (PubMed:34110282).

By similarity3 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">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="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		124313, 82 interactors

Database of interacting proteins

More...DIPi		DIP-61459N

Protein interaction database and analysis system

More...IntActi		Q8TDQ0, 79 interactors

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000312002

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		Q8TDQ0, protein

<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

1301
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

More...SMRi		Q8TDQ0

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

<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%5Fand%5Fdomains%5Fsection">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>Domaini22 – 124Ig-like V-typeAdd BLAST103

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the immunoglobulin superfamily. TIM family.Curated

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		ENOG502S454, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00940000154444

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		Q8TDQ0

Identification of Orthologs from Complete Genome Data

More...OMAi		EHGPAET

Database of Orthologous Groups

More...OrthoDBi		1147868at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		Q8TDQ0

TreeFam database of animal gene trees

More...TreeFami		TF336163

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		2.60.40.10, 1 hit

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR007110, Ig-like_dom
IPR036179, Ig-like_dom_sf
IPR013783, Ig-like_fold
IPR003599, Ig_sub
IPR013106, Ig_V-set

Pfam protein domain database

More...Pfami		View protein in Pfam
PF07686, V-set, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00409, IG, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF48726, SSF48726, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS50835, IG_LIKE, 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%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<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%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">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.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

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 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q8TDQ0-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <p><strong>What is the canonical sequence?</strong><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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
MFSHLPFDCV LLLLLLLLTR SSEVEYRAEV GQNAYLPCFY TPAAPGNLVP 
        60         70         80         90        100
VCWGKGACPV FECGNVVLRT DERDVNYWTS RYWLNGDFRK GDVSLTIENV 
       110        120        130        140        150
TLADSGIYCC RIQIPGIMND EKFNLKLVIK PAKVTPAPTR QRDFTAAFPR 
       160        170        180        190        200
MLTTRGHGPA ETQTLGSLPD INLTQISTLA NELRDSRLAN DLRDSGATIR 
       210        220        230        240        250
IGIYIGAGIC AGLALALIFG ALIFKWYSHS KEKIQNLSLI SLANLPPSGL 
       260        270        280        290        300
ANAVAEGIRS EENIYTIEEN VYEVEEPNEY YCYVSSRQQP SQPLGCRFAM 

P
Length:301
Mass (Da):33,394
Last modified:November 2, 2010 - v3
<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:i519A5B0D512B6173
GO
Isoform 2 (identifier: Q8TDQ0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     132-142: AKVTPAPTRQR → GEWTFACHLYE
     143-301: Missing.

Show »
Length:142
Mass (Da):16,149
Checksum:iE2C82D8B5AABC23E
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 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E5RHN3E5RHN3_HUMAN
Hepatitis A virus cellular receptor...
HAVCR2
273Annotation 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>
E5RFR4E5RFR4_HUMAN
Hepatitis A virus cellular receptor...
HAVCR2
74Annotation 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>

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_08221182Y → C in SPTCL; associated with disease susceptibility; results in dysregulated secretion of inflammatory cytokines by macrophages; affects protein folding; decreased localization at the cell membrane. 2 PublicationsCorresponds to variant dbSNP:rs184868814EnsemblClinVar.1
Natural variantiVAR_08221297I → M in SPTCL; associated with disease susceptibility; affects protein folding; decreased localization at the cell membrane. 1 PublicationCorresponds to variant dbSNP:rs35960726EnsemblClinVar.1
Natural variantiVAR_082213101T → I in SPTCL; may be associated with disease susceptibility. 2 PublicationsCorresponds to variant dbSNP:rs147827860EnsemblClinVar.1
Natural variantiVAR_025342140R → L6 PublicationsCorresponds to variant dbSNP:rs1036199Ensembl.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.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_017287132 – 142AKVTPAPTRQR → GEWTFACHLYE in isoform 2. 1 PublicationAdd BLAST11
Alternative sequenceiVSP_017288143 – 301Missing in isoform 2. 1 PublicationAdd BLAST159

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
AF251707 mRNA Translation: AAM19100.1
AY069944 mRNA Translation: AAL55401.1
AK027334 mRNA Translation: BAB55044.1
AK314406 mRNA Translation: BAG37029.1
AC011377 Genomic DNA No translation available.
CH471062 Genomic DNA Translation: EAW61614.1
BC020843 mRNA Translation: AAH20843.1
BC063431 mRNA Translation: AAH63431.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS4333.1 [Q8TDQ0-1]

NCBI Reference Sequences

More...RefSeqi		NP_116171.3, NM_032782.4 [Q8TDQ0-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000307851; ENSP00000312002; ENSG00000135077

Database of genes from NCBI RefSeq genomes

More...GeneIDi		84868

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:84868

Matched Annotation from NCBI and EMBL-EBI (MANE) - Phase one

More...MANE-Selecti		ENST00000307851.9; ENSP00000312002.4; NM_032782.5; NP_116171.3

UCSC genome browser

More...UCSCi		uc003lwk.3, human [Q8TDQ0-1]

Keywords - Coding sequence diversityi

Alternative splicing

<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
AF251707 mRNA Translation: AAM19100.1
AY069944 mRNA Translation: AAL55401.1
AK027334 mRNA Translation: BAB55044.1
AK314406 mRNA Translation: BAG37029.1
AC011377 Genomic DNA No translation available.
CH471062 Genomic DNA Translation: EAW61614.1
BC020843 mRNA Translation: AAH20843.1
BC063431 mRNA Translation: AAH63431.1
CCDSiCCDS4333.1 [Q8TDQ0-1]
RefSeqiNP_116171.3, NM_032782.4 [Q8TDQ0-1]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5DZLX-ray3.40A/B22-126[»]
5F71X-ray2.40A/B22-130[»]
6DHBX-ray1.70A24-130[»]
6TXZX-ray3.06A/B/C/D22-130[»]
7M3YX-ray1.69B22-130[»]
7M3ZX-ray1.40A22-130[»]
7M41X-ray1.79A/B22-130[»]
SMRiQ8TDQ0
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi124313, 82 interactors
DIPiDIP-61459N
IntActiQ8TDQ0, 79 interactors
STRINGi9606.ENSP00000312002

Chemistry databases

ChEMBLiCHEMBL4630879

PTM databases

GlyConnecti712, 5 O-Linked glycans (1 site)
GlyGeniQ8TDQ0, 4 sites, 6 O-linked glycans (3 sites)
iPTMnetiQ8TDQ0
PhosphoSitePlusiQ8TDQ0

Genetic variation databases

BioMutaiHAVCR2
DMDMi311033536

Proteomic databases

jPOSTiQ8TDQ0
MassIVEiQ8TDQ0
PaxDbiQ8TDQ0
PeptideAtlasiQ8TDQ0
PRIDEiQ8TDQ0
ProteomicsDBi74319 [Q8TDQ0-1]
74320 [Q8TDQ0-2]

Protocols and materials databases

ABCD curated depository of sequenced antibodies

More...ABCDi		Q8TDQ0, 1 sequenced antibody

Antibodypedia a portal for validated antibodies

More...Antibodypediai		2450, 1324 antibodies from 44 providers

The CPTC Antibody Portal

More...CPTCi		Q8TDQ0, 1 antibody

The DNASU plasmid repository

More...DNASUi		84868

Genome annotation databases

EnsembliENST00000307851; ENSP00000312002; ENSG00000135077
GeneIDi84868
KEGGihsa:84868
MANE-SelectiENST00000307851.9; ENSP00000312002.4; NM_032782.5; NP_116171.3
UCSCiuc003lwk.3, human [Q8TDQ0-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		84868
DisGeNETi84868

GeneCards: human genes, protein and diseases

More...GeneCardsi		HAVCR2
HGNCiHGNC:18437, HAVCR2
HPAiENSG00000135077, Tissue enhanced (lymphoid)
MalaCardsiHAVCR2
MIMi606652, gene
618398, phenotype
neXtProtiNX_Q8TDQ0
OpenTargetsiENSG00000135077
Orphaneti86884, Subcutaneous panniculitis-like T-cell lymphoma
PharmGKBiPA134883425
VEuPathDBiHostDB:ENSG00000135077

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiENOG502S454, Eukaryota
GeneTreeiENSGT00940000154444
InParanoidiQ8TDQ0
OMAiEHGPAET
OrthoDBi1147868at2759
PhylomeDBiQ8TDQ0
TreeFamiTF336163

Enzyme and pathway databases

PathwayCommonsiQ8TDQ0
ReactomeiR-HSA-451927, Interleukin-2 family signaling
SignaLinkiQ8TDQ0

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		84868, 5 hits in 1041 CRISPR screens

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

More...ChiTaRSi		HAVCR2, human

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		HAVCR2

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

More...GenomeRNAii		84868
PharosiQ8TDQ0, Tbio

Protein Ontology

More...PROi		PR:Q8TDQ0
RNActiQ8TDQ0, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000135077, Expressed in layer of synovial tissue and 176 other tissues
ExpressionAtlasiQ8TDQ0, baseline and differential
GenevisibleiQ8TDQ0, HS

Family and domain databases

Gene3Di2.60.40.10, 1 hit
InterProiView protein in InterPro
IPR007110, Ig-like_dom
IPR036179, Ig-like_dom_sf
IPR013783, Ig-like_fold
IPR003599, Ig_sub
IPR013106, Ig_V-set
PfamiView protein in Pfam
PF07686, V-set, 1 hit
SMARTiView protein in SMART
SM00409, IG, 1 hit
SUPFAMiSSF48726, SSF48726, 1 hit
PROSITEiView protein in PROSITE
PS50835, IG_LIKE, 1 hit

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		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 nameiHAVR2_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: Q8TDQ0
Secondary accession number(s): B2RAY2, Q8WW60, Q96K94
<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%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 27, 2005
Last sequence update: November 2, 2010
Last modified: February 23, 2022
This is version 157 of the entry and version 3 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, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  3. Human entries with genetic variants
    List of human entries with genetic variants
  4. Human variants curated from literature reports
    Index of human variants curated from literature reports
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families
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