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Aliases for HAVCR2 Gene

Aliases for HAVCR2 Gene

  • Hepatitis A Virus Cellular Receptor 2 2 3 5
  • T-Cell Immunoglobulin And Mucin Domain-Containing Protein 3 3 4
  • T-Cell Immunoglobulin Mucin Family Member 3 2 3
  • T-Cell Immunoglobulin Mucin Receptor 3 3 4
  • T-Cell Membrane Protein 3 3 4
  • HAVcr-2 3 4
  • TIMD-3 3 4
  • Tim-3 3 4
  • TIMD3 3 4
  • TIM3 3 4
  • T Cell Immunoglobulin Mucin 3 3
  • T Cell Immunoglobulin Mucin-3 3
  • Kidney Injury Molecule-3 3
  • CD366 3
  • KIM-3 3

External Ids for HAVCR2 Gene

Previous GeneCards Identifiers for HAVCR2 Gene

  • GC05M156448
  • GC05M156493
  • GC05M156445
  • GC05M151601
  • GC05M156512

Summaries for HAVCR2 Gene

Entrez Gene Summary for HAVCR2 Gene

  • The protein encoded by this gene belongs to the immunoglobulin superfamily, and TIM family of proteins. CD4-positive T helper lymphocytes can be divided into types 1 (Th1) and 2 (Th2) on the basis of their cytokine secretion patterns. Th1 cells are involved in cell-mediated immunity to intracellular pathogens and delayed-type hypersensitivity reactions, whereas, Th2 cells are involved in the control of extracellular helminthic infections and the promotion of atopic and allergic diseases. This protein is a Th1-specific cell surface protein that regulates macrophage activation, and inhibits Th1-mediated auto- and alloimmune responses, and promotes immunological tolerance. [provided by RefSeq, Sep 2011]

GeneCards Summary for HAVCR2 Gene

HAVCR2 (Hepatitis A Virus Cellular Receptor 2) is a Protein Coding gene. Diseases associated with HAVCR2 include Hepatitis A and Hepatitis. Among its related pathways are NF-kappaB Signaling and Immune System. An important paralog of this gene is HAVCR1.

UniProtKB/Swiss-Prot for HAVCR2 Gene

  • 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).

Gene Wiki entry for HAVCR2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HAVCR2 Gene

Genomics for HAVCR2 Gene

Regulatory Elements for HAVCR2 Gene

Enhancers for HAVCR2 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around HAVCR2 on UCSC Golden Path with GeneCards custom track

Promoters for HAVCR2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around HAVCR2 on UCSC Golden Path with GeneCards custom track

Genomic Location for HAVCR2 Gene

Chromosome:
5
Start:
157,085,832 bp from pter
End:
157,142,869 bp from pter
Size:
57,038 bases
Orientation:
Minus strand

Genomic View for HAVCR2 Gene

Genes around HAVCR2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HAVCR2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HAVCR2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HAVCR2 Gene

Proteins for HAVCR2 Gene

  • Protein details for HAVCR2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8TDQ0-HAVR2_HUMAN
    Recommended name:
    Hepatitis A virus cellular receptor 2
    Protein Accession:
    Q8TDQ0
    Secondary Accessions:
    • B2RAY2
    • Q8WW60
    • Q96K94

    Protein attributes for HAVCR2 Gene

    Size:
    301 amino acids
    Molecular mass:
    33394 Da
    Quaternary structure:
    • Interacts with HMGB1; impairs HMGB1 binding to B-DNA and likely HMGB1-mediated innate immume 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).

    Three dimensional structures from OCA and Proteopedia for HAVCR2 Gene

    Alternative splice isoforms for HAVCR2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for HAVCR2 Gene

Proteomics data for HAVCR2 Gene at MOPED

Post-translational modifications for HAVCR2 Gene

  • O-glycosylated with core 1 or possibly core 8 glycans.
  • 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.
  • Glycosylation at Thr 145 and Asn 172
  • Modification sites at PhosphoSitePlus

Other Protein References for HAVCR2 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for HAVCR2 (TIM-3)

No data available for DME Specific Peptides for HAVCR2 Gene

Domains & Families for HAVCR2 Gene

Gene Families for HAVCR2 Gene

Protein Domains for HAVCR2 Gene

Suggested Antigen Peptide Sequences for HAVCR2 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q8TDQ0

UniProtKB/Swiss-Prot:

HAVR2_HUMAN :
  • Contains 1 Ig-like V-type (immunoglobulin-like) domain.
  • Belongs to the immunoglobulin superfamily. TIM family.
Domain:
  • Contains 1 Ig-like V-type (immunoglobulin-like) domain.
Family:
  • Belongs to the immunoglobulin superfamily. TIM family.
genes like me logo Genes that share domains with HAVCR2: view

Function for HAVCR2 Gene

Molecular function for HAVCR2 Gene

UniProtKB/Swiss-Prot Function:
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).
genes like me logo Genes that share phenotypes with HAVCR2: view

Animal Models for HAVCR2 Gene

MGI Knock Outs for HAVCR2:

Animal Model Products

  • Taconic Biosciences Mouse Models for HAVCR2

CRISPR Products

No data available for Enzyme Numbers (IUBMB) , Gene Ontology (GO) - Molecular Function , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for HAVCR2 Gene

Localization for HAVCR2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HAVCR2 Gene

Membrane; Single-pass type I membrane protein. Cell junction. Note=Localizes to the immunological synapse between CD8+ T cells and target cells. {ECO:0000269 PubMed:24337741}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for HAVCR2 Gene COMPARTMENTS Subcellular localization image for HAVCR2 gene
Compartment Confidence
extracellular 5
plasma membrane 4
cytoskeleton 2
nucleus 2
cytosol 1

No data available for Gene Ontology (GO) - Cellular Components for HAVCR2 Gene

Pathways & Interactions for HAVCR2 Gene

genes like me logo Genes that share pathways with HAVCR2: view

Pathways by source for HAVCR2 Gene

1 Cell Signaling Technology pathway for HAVCR2 Gene
1 R&D Systems pathway for HAVCR2 Gene

Interacting Proteins for HAVCR2 Gene

STRING Interaction Network Preview (showing 3 interactants - click image to see details)
http://string-db.org/version_10/api/image/networkList?limit=0&targetmode=proteins&caller_identity=gene_cards&network_flavor=evidence&identifiers=9606.ENSP00000312002%0d%0a9606.ENSP00000365131%0d%0a9606.ENSP00000337825%0d%0a9606.ENSP00000343040%0d%0a
Selected Interacting proteins: ENSP00000312002 for HAVCR2 Gene via STRING

Gene Ontology (GO) - Biological Process for HAVCR2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001819 positive regulation of cytokine production IEA --
GO:0002250 adaptive immune response IEA --
GO:0002281 macrophage activation involved in immune response IEA --
GO:0002519 natural killer cell tolerance induction IMP 25578313
GO:0002652 regulation of tolerance induction dependent upon immune response IEA --
genes like me logo Genes that share ontologies with HAVCR2: view

No data available for SIGNOR curated interactions for HAVCR2 Gene

Drugs & Compounds for HAVCR2 Gene

No Compound Related Data Available

Transcripts for HAVCR2 Gene

Unigene Clusters for HAVCR2 Gene

Hepatitis A virus cellular receptor 2:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for HAVCR2 Gene

ExUns: 1 ^ 2a · 2b ^ 3a · 3b ^ 4 ^ 5 ^ 6a · 6b ^ 7
SP1: - -
SP2: - - -
SP3:
SP4:

Relevant External Links for HAVCR2 Gene

GeneLoc Exon Structure for
HAVCR2
ECgene alternative splicing isoforms for
HAVCR2

Expression for HAVCR2 Gene

mRNA expression in normal human tissues for HAVCR2 Gene

mRNA differential expression in normal tissues according to GTEx for HAVCR2 Gene

This gene is overexpressed in Whole Blood (x8.4) and Kidney - Cortex (x4.0).

Protein differential expression in normal tissues from HIPED for HAVCR2 Gene

This gene is overexpressed in Urine (59.1) and Pancreas (9.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for HAVCR2 Gene



SOURCE GeneReport for Unigene cluster for HAVCR2 Gene Hs.710500

mRNA Expression by UniProt/SwissProt for HAVCR2 Gene

Q8TDQ0-HAVR2_HUMAN
Tissue specificity: 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.
genes like me logo Genes that share expression patterns with HAVCR2: view

Protein tissue co-expression partners for HAVCR2 Gene

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery for HAVCR2 Gene

Orthologs for HAVCR2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for HAVCR2 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia HAVCR2 35
  • 79.26 (n)
  • 68.35 (a)
dog
(Canis familiaris)
Mammalia HAVCR2 35
  • 81.83 (n)
  • 71.48 (a)
HAVCR2 36
  • 65 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Havcr2 35
  • 74.64 (n)
  • 66.79 (a)
Havcr2 16
Havcr2 36
  • 63 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia HAVCR2 35
  • 98.45 (n)
  • 97.01 (a)
HAVCR2 36
  • 97 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Havcr2 35
  • 76.43 (n)
  • 67.86 (a)
oppossum
(Monodelphis domestica)
Mammalia HAVCR2 36
  • 34 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 25 (a)
OneToMany
-- 36
  • 33 (a)
OneToMany
chicken
(Gallus gallus)
Aves HAVCR1 36
  • 25 (a)
OneToMany
lizard
(Anolis carolinensis)
Reptilia -- 36
  • 2 (a)
ManyToMany
zebrafish
(Danio rerio)
Actinopterygii timd4 36
  • 25 (a)
OneToMany
Species with no ortholog for HAVCR2:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for HAVCR2 Gene

ENSEMBL:
Gene Tree for HAVCR2 (if available)
TreeFam:
Gene Tree for HAVCR2 (if available)

Paralogs for HAVCR2 Gene

Paralogs for HAVCR2 Gene

(1) SIMAP similar genes for HAVCR2 Gene using alignment to 3 proteins:

genes like me logo Genes that share paralogs with HAVCR2: view

Variants for HAVCR2 Gene

Sequence variations from dbSNP and Humsavar for HAVCR2 Gene

SNP ID Clin Chr 05 pos Sequence Context AA Info Type
rs1036199 - 157,104,725(+) TCTGC(A/C)GAGTC reference, missense
rs919744 -- 157,104,243(+) GGAAG(C/G)TGATG intron-variant
rs919745 -- 157,104,268(+) TAGAA(A/G)GCATC intron-variant
rs919746 -- 157,104,305(+) AGTTC(C/T)CAAAC intron-variant
rs919747 -- 157,104,319(+) GACTG(A/G)CACCA intron-variant

Variation tolerance for HAVCR2 Gene

Residual Variation Intolerance Score: 85.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.01; 37.09% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for HAVCR2 Gene

Human Gene Mutation Database (HGMD)
HAVCR2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for HAVCR2 Gene

Disorders for HAVCR2 Gene

MalaCards: The human disease database

(7) MalaCards diseases for HAVCR2 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
hepatitis a
  • viral hepatitis a
hepatitis
  • hepatitis a
far eastern spotted fever
  • rickettsia heilongjiangensis spotted fever
histiocytic sarcoma
adenoiditis
  • chronic adenoiditis
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

HAVR2_HUMAN
  • Note=May be involved in T cell exhaustion associated with chronic viral infections such as with human immunodeficiency virus (HIV) and hepatitic C virus (HCV). {ECO:0000269 PubMed:19001139, ECO:0000269 PubMed:19587053}.

Relevant External Links for HAVCR2

Genetic Association Database (GAD)
HAVCR2
Human Genome Epidemiology (HuGE) Navigator
HAVCR2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
HAVCR2
genes like me logo Genes that share disorders with HAVCR2: view

No data available for Genatlas for HAVCR2 Gene

Publications for HAVCR2 Gene

  1. Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. (PMID: 11823861) Monney L. … Kuchroo V.K. (Nature 2002) 2 3 4 23 67
  2. TIM-3 as a new therapeutic target in systemic lupus erythematosus. (PMID: 19768575) Pan H.F. … Ye D.Q. (Mol. Biol. Rep. 2010) 3 23
  3. T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) mediates natural killer cell suppression in chronic hepatitis B. (PMID: 20133006) Ju Y. … Ma C. (J. Hepatol. 2010) 3 23
  4. The role of T-cell immunoglobulin- and mucin-domain-containing molecule-3 polymorphisms in idiopathic thrombocytopenic purpura. (PMID: 19332093) Du W.T. … Yang R.C. (Hum. Immunol. 2009) 3 23
  5. Altered expression of T cell immunoglobulin-mucin (TIM) molecules in bronchoalveolar lavage CD4+ T cells in sarcoidosis. (PMID: 19480659) Idali F. … Grunewald J. (Respir. Res. 2009) 3 23

Products for HAVCR2 Gene

Sources for HAVCR2 Gene

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