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Protein

Hepatitis A virus cellular receptor 2 homolog

Gene

Havcr2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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:18006747). Regulates macrophage activation (PubMed:11823861). Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune responses and promotes immunological tolerance (PubMed:14556006, PubMed:18006747). 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 (By similarity). In contrast, shown to activate TCR-induced signaling in T cells probably implicating ZAP70, LCP2, LCK and FYN (PubMed:21807895). Expressed on Treg cells can inhibit Th17 cell responses (By similarity). Receptor for LGALS9. 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 (PubMed:22863785). 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 (PubMed:20937702). However, the function as receptor for LGALS9 has been challenged (By similarity). Also reported to enhance CD8+ T cell responses to an acute infection such as by Listeria monocytogenes (PubMed:24567532). Receptor for phosphatidylserine (PtSer); PtSer-binding is calcium-dependent (PubMed:20083673). May recognize PtSer on apoptotic cells leading to their phagocytosis. Mediates the engulfment of apoptotic cells by dendritic cells (PubMed:19224762). Expressed on T cells, promotes conjugation but not engulfment of apoptotic cells (PubMed:20083673). Expressed on dendritic cells (DCs) positively regulates innate immune response and in synergy with Toll-like receptors promotes secretion of TNF-alpha (PubMed:18006747). 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 (PubMed:22842346). Can enhance mast cell production of Th2 cytokines Il-4, IL-6 and IL-13 (PubMed:17620455). Expressed on natural killer (NK) cells acts as a coreceptor to enhance IFN-gamma production in response to LGALS9. In contrast, shown to suppress NK cell-mediated cytotoxicity (By similarity). Negatively regulates NK cell function in LPS-induced endotoxic shock (PubMed:25337993).By similarity1 Publication11 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei61 – 611PhosphatidylserineCombined sources1 Publication
Binding sitei62 – 621Phosphatidylserine; via amide nitrogenCombined sources1 Publication
Binding sitei112 – 1121PhosphatidylserineCombined sources1 Publication
Metal bindingi115 – 1151Calcium; via carbonyl oxygenCombined sources1 Publication
Metal bindingi117 – 1171Calcium; via carbonyl oxygenCombined sources1 Publication
Binding sitei119 – 1191Phosphatidylserine; via amide nitrogenCombined sources1 Publication
Metal bindingi120 – 1201CalciumCombined sources1 Publication

GO - Molecular functioni

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • cellular response to lipopolysaccharide Source: UniProtKB
  • defense response to Gram-positive bacterium Source: UniProtKB
  • inflammatory response Source: UniProtKB-KW
  • innate immune response Source: UniProtKB-KW
  • macrophage activation involved in immune response Source: UniProtKB
  • maternal process involved in female pregnancy Source: UniProtKB
  • natural killer cell tolerance induction Source: MGI
  • negative regulation of defense response to bacterium Source: UniProtKB
  • negative regulation of gene expression Source: MGI
  • negative regulation of granulocyte colony-stimulating factor production Source: MGI
  • negative regulation of immune response to tumor cell Source: UniProtKB
  • negative regulation of immunological synapse formation Source: UniProtKB
  • negative regulation of innate immune response Source: UniProtKB
  • negative regulation of interferon-alpha production Source: MGI
  • negative regulation of interferon-gamma production Source: UniProtKB
  • negative regulation of interleukin-2 production Source: UniProtKB
  • negative regulation of interleukin-3 production Source: MGI
  • negative regulation of interleukin-6 production Source: UniProtKB
  • negative regulation of myeloid dendritic cell activation Source: MGI
  • negative regulation of natural killer cell activation Source: UniProtKB
  • negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target Source: UniProtKB
  • negative regulation of NF-kappaB transcription factor activity Source: MGI
  • negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell Source: MGI
  • negative regulation of T cell proliferation Source: UniProtKB
  • negative regulation of T-helper 1 type immune response Source: UniProtKB
  • negative regulation of tumor necrosis factor production Source: MGI
  • negative regulation of type I interferon production Source: UniProtKB
  • positive regulation of chemokine production Source: UniProtKB
  • positive regulation of cytokine production Source: UniProtKB
  • positive regulation of defense response to bacterium Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • positive regulation of innate immune response Source: UniProtKB
  • positive regulation of interferon-gamma production Source: UniProtKB
  • positive regulation of interleukin-1 production Source: UniProtKB
  • positive regulation of interleukin-4 production Source: MGI
  • positive regulation of macrophage activation Source: UniProtKB
  • positive regulation of NIK/NF-kappaB signaling Source: UniProtKB
  • positive regulation of T cell proliferation Source: UniProtKB
  • positive regulation of tumor necrosis factor secretion Source: UniProtKB
  • regulation of tolerance induction dependent upon immune response Source: UniProtKB
  • toll-like receptor 3 signaling pathway Source: UniProtKB
  • toll-like receptor 7 signaling pathway Source: UniProtKB
  • toll-like receptor 9 signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Adaptive immunity, Immunity, Inflammatory response, Innate immunity

Keywords - Ligandi

Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Hepatitis A virus cellular receptor 2 homolog
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
Gene namesi
Name:Havcr2
Synonyms:Tim3, Timd3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:2159682. Havcr2.

Subcellular locationi

Isoform 1 :
  • Membrane Curated; Single-pass type I membrane protein Curated
  • Cell junction By similarity

  • Note: Localizes to the immunological synapse between CD8+ T cells and target cells.By similarity
Isoform 2 :

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini20 – 193174ExtracellularSequence analysisAdd
BLAST
Transmembranei194 – 21421HelicalSequence analysisAdd
BLAST
Topological domaini215 – 28167CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • cell junction Source: UniProtKB-SubCell
  • cell surface Source: UniProtKB
  • early endosome Source: UniProtKB
  • extracellular exosome Source: MGI
  • immunological synapse Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi53 – 531W → A: Greatly decreases phosphatidylserine binding. 1 Publication
Mutagenesisi60 – 623WSQ → VFE: Decreases phosphatidylserine binding. 1 Publication
Mutagenesisi62 – 621Q → A: No effect on phagocytic activity. 1 Publication
Mutagenesisi112 – 1121R → A: Abolishes phagocytic activity. 1 Publication
Mutagenesisi118 – 1192LM → AA: Decreases phosphatidylserine binding. 1 Publication
Mutagenesisi120 – 1212ND → AA: Decreases phosphatidylserine binding, abolishes phagocytic activity. 2 Publications
Mutagenesisi256 – 2561Y → F: Abolishes phosphorylation, disrupts interaction with PIK3R1 and PIK3R2, no LGALS9-mediated disruption of interaction with BAG6; when associated with F-263. 2 Publications
Mutagenesisi263 – 2631Y → F: Abolishes phosphorylation, disrupts interaction with PIK3R1 and PIK3R2, no LGALS9-mediated disruption of interaction with BAG6; when associated with F-256. 2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919Sequence analysisAdd
BLAST
Chaini20 – 281262Hepatitis A virus cellular receptor 2 homologPRO_0000042102Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi38 ↔ 111PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi52 ↔ 63PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi58 ↔ 110PROSITE-ProRule annotationCombined sources1 Publication
Glycosylationi74 – 741N-linked (GlcNAc...)Sequence analysis
Glycosylationi100 – 1001N-linked (GlcNAc...)Sequence analysis
Glycosylationi146 – 1461O-linked (GalNAc...)By similarity
Glycosylationi172 – 1721N-linked (GlcNAc...)Sequence analysis
Modified residuei256 – 2561Phosphotyrosine; by ITKBy similarity

Post-translational modificationi

Phosphorylated on tyrosine residues; modestly increased after TCR/CD28 stimulation. Can be phosphorylated in the cytoplasmatic domain by FYN (PubMed:21807895). Phosphorylation at Tyr-256 is increased by stimulation with ligand LGALS9 (By similarity).By similarity1 Publication
N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ8VIM0.
PaxDbiQ8VIM0.
PRIDEiQ8VIM0.

PTM databases

PhosphoSiteiQ8VIM0.

Expressioni

Tissue specificityi

Expressed in T-helper type 1 lymphocytes. Not expressed by naive T-cells but up-regulated as they differentiate into T-helper-1 cells. Also expressed by differentiated type 1 CD8+ cytotoxic T-cells. Expressed on peritoneal exudate macrophages, monocytes, and splenic dendritic cells (DCs). Expression on natural killer (NK) cells is inversely associated with IFN-gamma production during the initial 24 h of LPS-induced endotoxic shock. Expressed on mast cells.6 Publications

Gene expression databases

BgeeiQ8VIM0.
CleanExiMM_HAVCR2.
ExpressionAtlasiQ8VIM0. baseline and differential.
GenevisibleiQ8VIM0. MM.

Interactioni

Subunit structurei

Interacts with HMGB1; impairs HMGB1 binding to B-DNA and likely HMGB1-mediated innate immume response (PubMed:22842346). Interacts with BAG6 (PubMed:22863785). Interacts (phosphorylated) with PIK3R1 and PIK3R2. Interacts (not dependent on its phosphorylation status) with FYN (PubMed:21807895). 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 (By similarity).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Hmgb1P631584EBI-6665112,EBI-6665811
Lgals9O08573-24EBI-6665112,EBI-11316797

Protein-protein interaction databases

BioGridi228588. 1 interaction.
DIPiDIP-61460N.
IntActiQ8VIM0. 6 interactions.
STRINGi10090.ENSMUSP00000020668.

Structurei

Secondary structure

1
281
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi34 – 363Combined sources
Beta strandi51 – 577Combined sources
Beta strandi60 – 623Combined sources
Beta strandi66 – 705Combined sources
Beta strandi72 – 776Combined sources
Beta strandi81 – 855Combined sources
Helixi89 – 913Combined sources
Beta strandi96 – 1005Combined sources
Helixi103 – 1053Combined sources
Beta strandi107 – 1137Combined sources
Beta strandi116 – 1194Combined sources
Beta strandi125 – 1306Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3KAAX-ray3.00A/B29-133[»]
ProteinModelPortaliQ8VIM0.
SMRiQ8VIM0. Positions 25-131.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8VIM0.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini20 – 125106Ig-like V-typeAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni252 – 27019Interaction with BAG61 PublicationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi221 – 2244Poly-Lys

Domaini

The Ig-like V-type (immunoglobulin-like) domain mediates binding to PtSer involving a Ca2+ ion.1 Publication

Sequence similaritiesi

Belongs to the immunoglobulin superfamily. TIM family.Curated

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IJGA. Eukaryota.
ENOG410YSF7. LUCA.
GeneTreeiENSGT00440000039800.
HOVERGENiHBG098563.
InParanoidiQ8VIM0.
OMAiGCRFAMP.
OrthoDBiEOG74XS6M.
PhylomeDBiQ8VIM0.
TreeFamiTF336163.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF07686. V-set. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8VIM0-1) [UniParc]FASTAAdd to basket

Also known as: Tim-3L, flTim-3

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
MFSGLTLNCV LLLLQLLLAR SLENAYVFEV GKNAYLPCSY TLSTPGALVP
60 70 80 90 100
MCWGKGFCPW SQCTNELLRT DERNVTYQKS SRYQLKGDLN KGDVSLIIKN
110 120 130 140 150
VTLDDHGTYC CRIQFPGLMN DKKLELKLDI KAAKVTPAQT AHGDSTTASP
160 170 180 190 200
RTLTTERNGS ETQTLVTLHN NNGTKISTWA DEIKDSGETI RTAIHIGVGV
210 220 230 240 250
SAGLTLALII GVLILKWYSC KKKKLSSLSL ITLANLPPGG LANAGAVRIR
260 270 280
SEENIYTIEE NVYEVENSNE YYCYVNSQQP S
Length:281
Mass (Da):30,934
Last modified:March 1, 2002 - v1
Checksum:iC0349E4BD0E5761D
GO
Isoform 2 (identifier: Q8VIM0-2) [UniParc]FASTAAdd to basket

Also known as: sTim-3

The sequence of this isoform differs from the canonical sequence as follows:
     133-217: AKVTPAQTAH...LIIGVLILKW → G

Show »
Length:197
Mass (Da):22,087
Checksum:iAD3DEA16E03F3113
GO

Polymorphismi

Polymorphic differences between BALB/c and HBA alleles in the Ig-like V-type domain are the reason for distinct binding affinities for PtSer. The HBA2 allele binds PtSer approximately 50% less than BALB/c.1 Publication

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei133 – 21785AKVTP…LILKW → G in isoform 2. 1 PublicationVSP_058116Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF399831 mRNA. Translation: AAL35776.1.
AL669948 Genomic DNA. No translation available.
CCDSiCCDS36135.1. [Q8VIM0-1]
RefSeqiNP_599011.2. NM_134250.2. [Q8VIM0-1]
UniGeneiMm.72168.

Genome annotation databases

EnsembliENSMUST00000020668; ENSMUSP00000020668; ENSMUSG00000020399. [Q8VIM0-1]
GeneIDi171285.
KEGGimmu:171285.
UCSCiuc011xtp.1. mouse. [Q8VIM0-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Functional Glycomics Gateway - Glycan Binding

TIMD-3

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF399831 mRNA. Translation: AAL35776.1.
AL669948 Genomic DNA. No translation available.
CCDSiCCDS36135.1. [Q8VIM0-1]
RefSeqiNP_599011.2. NM_134250.2. [Q8VIM0-1]
UniGeneiMm.72168.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3KAAX-ray3.00A/B29-133[»]
ProteinModelPortaliQ8VIM0.
SMRiQ8VIM0. Positions 25-131.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi228588. 1 interaction.
DIPiDIP-61460N.
IntActiQ8VIM0. 6 interactions.
STRINGi10090.ENSMUSP00000020668.

PTM databases

PhosphoSiteiQ8VIM0.

Proteomic databases

MaxQBiQ8VIM0.
PaxDbiQ8VIM0.
PRIDEiQ8VIM0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000020668; ENSMUSP00000020668; ENSMUSG00000020399. [Q8VIM0-1]
GeneIDi171285.
KEGGimmu:171285.
UCSCiuc011xtp.1. mouse. [Q8VIM0-1]

Organism-specific databases

CTDi84868.
MGIiMGI:2159682. Havcr2.

Phylogenomic databases

eggNOGiENOG410IJGA. Eukaryota.
ENOG410YSF7. LUCA.
GeneTreeiENSGT00440000039800.
HOVERGENiHBG098563.
InParanoidiQ8VIM0.
OMAiGCRFAMP.
OrthoDBiEOG74XS6M.
PhylomeDBiQ8VIM0.
TreeFamiTF336163.

Miscellaneous databases

ChiTaRSiHavcr2. mouse.
EvolutionaryTraceiQ8VIM0.
NextBioi370963.
PROiQ8VIM0.
SOURCEiSearch...

Gene expression databases

BgeeiQ8VIM0.
CleanExiMM_HAVCR2.
ExpressionAtlasiQ8VIM0. baseline and differential.
GenevisibleiQ8VIM0. MM.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF07686. V-set. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Identification of Tapr (an airway hyperreactivity regulatory locus) and the linked Tim gene family."
    McIntire J.J., Umetsu S.E., Akbari O., Potter M., Kuchroo V.K., Barsh G.S., Freeman G.J., Umetsu D.T., DeKruyff R.H.
    Nat. Immunol. 2:1109-1116(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: DBA/2J.
    Tissue: Spleen.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. "Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease."
    Monney L., Sabatos C.A., Gaglia J.L., Ryu A., Waldner H., Chernova T., Manning S., Greenfield E.A., Coyle A.J., Sobel R.A., Freeman G.J., Kuchroo V.K.
    Nature 415:536-541(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.
  4. "Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance."
    Sabatos C.A., Chakravarti S., Cha E., Schubart A., Sanchez-Fueyo A., Zheng X.X., Coyle A.J., Strom T.B., Freeman G.J., Kuchroo V.K.
    Nat. Immunol. 4:1102-1110(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: ALTERNATIVE SPLICING, FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
  5. "TIM-1 and TIM-3 enhancement of Th2 cytokine production by mast cells."
    Nakae S., Iikura M., Suto H., Akiba H., Umetsu D.T., Dekruyff R.H., Saito H., Galli S.J.
    Blood 110:2565-2568(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.
  6. Cited for: FUNCTION.
  7. "Tim-3 mediates phagocytosis of apoptotic cells and cross-presentation."
    Nakayama M., Akiba H., Takeda K., Kojima Y., Hashiguchi M., Azuma M., Yagita H., Okumura K.
    Blood 113:3821-3830(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHATIDYLSERINE-BINDING, TISSUE SPECIFICITY, FUNCTION, MUTAGENESIS OF GLN-62; ARG-112 AND 120-ASN-ASP-121.
  8. Cited for: FUNCTION.
  9. "Phosphotyrosine-dependent coupling of Tim-3 to T-cell receptor signaling pathways."
    Lee J., Su E.W., Zhu C., Hainline S., Phuah J., Moroco J.A., Smithgall T.E., Kuchroo V.K., Kane L.P.
    Mol. Cell. Biol. 31:3963-3974(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH PIK3R1; PIK3R2 AND FYN, MUTAGENESIS OF TYR-256 AND TYR-263, PHOSPHORYLATION, GLYCOSYLATION.
  10. "Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1."
    Chiba S., Baghdadi M., Akiba H., Yoshiyama H., Kinoshita I., Dosaka-Akita H., Fujioka Y., Ohba Y., Gorman J.V., Colgan J.D., Hirashima M., Uede T., Takaoka A., Yagita H., Jinushi M.
    Nat. Immunol. 13:832-842(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH HMGB1, INVOLVEMENT IN CHEMOTHERAPY.
  11. "Bat3 promotes T cell responses and autoimmunity by repressing Tim-3-mediated cell death and exhaustion."
    Rangachari M., Zhu C., Sakuishi K., Xiao S., Karman J., Chen A., Angin M., Wakeham A., Greenfield E.A., Sobel R.A., Okada H., McKinnon P.J., Mak T.W., Addo M.M., Anderson A.C., Kuchroo V.K.
    Nat. Med. 18:1394-1400(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH BAG6, MUTAGENESIS OF TYR-256 AND TYR-263.
  12. "Tim-3 directly enhances CD8 T cell responses to acute Listeria monocytogenes infection."
    Gorman J.V., Starbeck-Miller G., Pham N.L., Traver G.L., Rothman P.B., Harty J.T., Colgan J.D.
    J. Immunol. 192:3133-3142(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.
  13. "Tim-3 negatively mediates natural killer cell function in LPS-induced endotoxic shock."
    Hou H., Liu W., Wu S., Lu Y., Peng J., Zhu Y., Lu Y., Wang F., Sun Z.
    PLoS ONE 9:E110585-E110585(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.
  14. "T cell/transmembrane, Ig, and mucin-3 allelic variants differentially recognize phosphatidylserine and mediate phagocytosis of apoptotic cells."
    DeKruyff R.H., Bu X., Ballesteros A., Santpiago C., Chim Y.L., Lee H.H., Karisola P., Pichavant M., Kaplan G.G., Umetsu D.T., Freeman G.J., Casasnovas J.M.
    J. Immunol. 184:1918-1930(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 29-233 IN COMPLEX WITH PHOSPHATIDYLSERINE, DISULFIDE BOND, FUNCTION, DOMAIN, MUTAGENESIS OF TRP-53; 60-TRP--GLN-62; 118-LEU-MET-119 AND 120-ASN-ASP-121.

Entry informationi

Entry nameiHAVR2_MOUSE
AccessioniPrimary (citable) accession number: Q8VIM0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 27, 2005
Last sequence update: March 1, 2002
Last modified: April 13, 2016
This is version 111 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Belongs to the T-cell and airway phenotype regulator (Tapr) locus, a single chromosomal region that confers reduced T-helper type 2 responsiveness and protects against airway hyperactivity (AHR), the hallmark of human asthma.
In vivo administration of antibody to HAVCR2 enhances the clinical and pathological severity of experimental autoimmune encephalomyelitis (EAE), a Th1-dependent autoimmune disease and increases the number and activation level of macrophages.
Endogenous expression on dendritic cells is proposed to act as a negative regulator of chemotherapy-induced antitumor responses.1 Publication

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.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.