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Symbol HAVCR2 contributors: mct - updated : 02-02-2016
HGNC name hepatitis A virus cellular receptor 2
HGNC id 18437
Location 5q33.3      Physical location : 156.512.842 - 156.536.138
Genatlas name T cell immunoglobulin and mucin domain containing molecule
Synonym name
  • T cell immunoglobulin mucin 3
  • kidney injury molecule-3
  • Synonym symbol(s) TIM3, KIM-3, TIMD3, Tim-3, FLJ14428, CD366
    TYPE functioning gene
    STRUCTURE 23.40 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    FLJ11526 5q33.2 hypothetical protein FLJ11526 HAND1 5q32 heart and neural crest derivatives expressed 1 LOC389339 5 LOC389339 LARP 5q33.2 likely ortholog of mouse la related protein C5orf4 5q31-q32 chromosome 5 open reading frame 4 CNOT8 5q31-q33 CCR4-NOT transcription complex, subunit 8 GEMIN5 5q33.3 gem (nuclear organelle) associated protein 5 MRPL22 5q33.1-q33.3 mitochondrial ribosomal protein L22 LOC285643 5q33.2 similar to Chromosome-associated kinesin KIF4A (Chromokinesin) LOC391842 5 similar to 60S ribosomal protein L6 (TAX-responsive enhancer element binding protein 107) (TAXREB107) (Neoplasm-related protein C140) LOC389340 5 LOC389340 SGCD 5q33 sarcoglycan, delta (35kDa dystrophin-associated glycoprotein) LOC153743 5q33.3 similar to protein phosphatase 1, regulatory (inhibitor) subunit 2 LOC91937 5q33.3 hypothetical protein BC008988 HAVCR1 5q33.2 hepatitis A virus cellular receptor 1 HAVCR2 5q34 hepatitis A virus cellular receptor 2 CRSP9 5q33.2 cofactor required for Sp1 transcriptional activation, subunit 9, 33kDa MGC26988 5q33.3 hypothetical protein MGC26988 ITK 5q33.1 IL2-inducible T-cell kinase CYFIP2 5q34 cytoplasmic FMR1 interacting protein 2 LOC348938 5q33.3 hypothetical protein LOC348938 ADAM19 5q32-q33 a disintegrin and metalloproteinase domain 19 (meltrin beta) SOX30 5q33 a disintegrin and metalloproteinase domain 19 (meltrin beta) LOC389341 5 similar to RIKEN cDNA 4921536K21 FLJ20546 5q33.3 hypothetical protein FLJ20546 LSM11 5q33.3 U7 snRNA-associated Sm-like protein ENTH 5q23.1-q33.3 U7 snRNA-associated Sm-like protein LOC391843 5 similar to 60S acidic ribosomal protein P2 LOC345471 5q33.3 similar to Hsp90 co-chaperone Cdc37 (Hsp90 chaperone protein kinase-targeting subunit) (p50Cdc37) LOC285721 5q33.3 hypothetical LOC285721 EBF 5q34 early B-cell factor FLJ31951 5q33.3 hypothetical protein FLJ31951 MGC10067 5q33.3 hypothetical protein MGC10067 IL12B 5q31.1-q33.1 interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40)
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 2448 - 301 - 2013 24121505
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivepharynx   highly
    Lymphoid/Immunespleen   highly
     thymus   highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    SystemCellPubmedSpeciesStageRna symbol
    Nervousglia Homo sapiens
    Skeletonosteoclast Homo sapiens
    cell lineage
    cell lines
    at STAGE
  • immunoglobulin V-type domain-mucin-like domain
  • cytoplasmic domain with a tyrosine phosphorylation motif
    FAMILY T cell immunoglobulin and mucin domain (Tim) family of proteins
    CATEGORY immunity/defense
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • role in the induction of allergies and autoimmune diseases by regulating macrophage activation and/or functions
  • negatively regulates IFN-gamma secretion and influences the ability to induce T cell tolerance
  • is strikingly up-regulated in peripheral blood of pregnant women, most by monocytes but not by T or B cells
  • is a negative regulator of human T cells and regulates Th1 and Th17 cytokine secretion
  • has a role as a regulator of pro- and anti-inflammatory innate immune responses
  • marks human natural killer cell maturation and suppresses cell-mediated cytotoxicity
  • transmembrane protein that is involved in the regulation of T-helper 1 cell-mediated immunity
  • is a novel target for ADAM-mediated ectodomain shedding and suggest a role of HAVCR2 shedding in TLR-mediated immune responses of CD14(+) monocytes
  • can stimulate T cells under conditions involving acute stimulation, suggesting that the role of HAVCR2 may vary depending on context
  • negative regulatory molecule that plays a critical role in controlling inflammation
  • activation-induced inhibitory molecule involved in tolerance and shown to induce T-cell exhaustion in chronic viral infection and cancers
  • plays critical roles in both the adaptive and the innate immune system
  • modulates microglia activity and regulates the interaction of microglia-neural cells
  • important regulatory factor in both adaptive and innate immunity
  • schistosome-induced expression of HAVCR2 on critical immune cell populations, which may be involved in the Th2-biased immune response and alternative activation of macrophages during infection
    PHYSIOLOGICAL PROCESS immunity/defense
  • HAVCR2- pathway plays an inhibitory role in NK cell function, which might be a potential target in modulating the excessive inflammatory response of LPS-induced endotoxic shock
  • a component
  • is co-expressed and forms a heterodimer with carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1)
    small molecule
  • its expression is regulated by the Th1-specific transcription factor TBX21
  • LGALS9 is a ligand for HAVCR2, a type I glycoprotein induced on T cells during chronic inflammation
  • BAG6 acts as an inhibitor of HAVCR2–dependent exhaustion and cell death
  • HAVCR2 serves as a functional receptor in structural cells of the airways and via the ligand LGALS9 can modulate the inflammatory response
  • possible involvement of the HAVCR2/LGALS9 system in the modulation of inflammatory bone destruction
  • CEACAM1 serves as a heterophilic ligand for HAVCR2 that is required for its ability to mediate T-cell inhibition, and this interaction has a crucial role in regulating autoimmunity and anti-tumour immunity
  • IL27/NFIL3 signalling axis is a key regulator of effector T-cell responses via induction of HAVCR2, IL10 and T-cell dysfunction
  • HAVCR2-signaling inhibited phosphorylation of IRF3, a TLR4 downstream transcriptional factor regulating macrophage polarization
  • cell & other
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --other  
    dysregulated T cell expression in multiple sclerosis
    tumoral     --over  
    in human acute myeloid leukaemia cell
    constitutional     --other  
    expression in renal tissue from the patients with systemic lupus erythematosus (SLE), but rarely expression in cases without SLE
    constitutional     --other  
    altered expression might play an important role in the pathogenesis of intracerebral hemorrhage
  • to ankylosing spondylitis (AS)
  • to pancreatic cancer
  • Variant & Polymorphism other
  • HAVCR2 -574T allele revealed a positive association with AS
  • prevalence of +4259TG genotype and +4259G allele were significantly increased in the pancreatic cancer cases
  • Candidate gene
  • might be a novel candidate molecule for prognosis evaluation of intracerebral hemorrhage patients
  • Marker
    Therapy target
    could be used as a potential therapeutic target for immune therapy and drug delivery in human acute myeloid leukaemia cells
    respiratoryCF (mucoviscidosis) 
    manipulation of the TIM-3 signaling pathway may be of therapeutic value in CF, preferably in conjunction with antiprotease treatment