HAVR2_MOUSE
ID HAVR2_MOUSE Reviewed; 281 AA.
AC Q8VIM0;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Hepatitis A virus cellular receptor 2 homolog;
DE Short=HAVcr-2;
DE AltName: Full=T-cell immunoglobulin and mucin domain-containing protein 3;
DE Short=TIMD-3;
DE AltName: Full=T-cell immunoglobulin mucin receptor 3;
DE Short=TIM-3;
DE AltName: Full=T-cell membrane protein 3;
DE AltName: CD_antigen=CD366;
DE Flags: Precursor;
GN Name=Havcr2; Synonyms=Tim3, Timd3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=DBA/2J; TISSUE=Spleen;
RX PubMed=11725301; DOI=10.1038/ni739;
RA McIntire J.J., Umetsu S.E., Akbari O., Potter M., Kuchroo V.K., Barsh G.S.,
RA Freeman G.J., Umetsu D.T., DeKruyff R.H.;
RT "Identification of Tapr (an airway hyperreactivity regulatory locus) and
RT the linked Tim gene family.";
RL Nat. Immunol. 2:1109-1116(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11823861; DOI=10.1038/415536a;
RA Monney L., Sabatos C.A., Gaglia J.L., Ryu A., Waldner H., Chernova T.,
RA Manning S., Greenfield E.A., Coyle A.J., Sobel R.A., Freeman G.J.,
RA Kuchroo V.K.;
RT "Th1-specific cell surface protein Tim-3 regulates macrophage activation
RT and severity of an autoimmune disease.";
RL Nature 415:536-541(2002).
RN [4]
RP ALTERNATIVE SPLICING, FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=14556006; DOI=10.1038/ni988;
RA Sabatos C.A., Chakravarti S., Cha E., Schubart A., Sanchez-Fueyo A.,
RA Zheng X.X., Coyle A.J., Strom T.B., Freeman G.J., Kuchroo V.K.;
RT "Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses
RT and induction of peripheral tolerance.";
RL Nat. Immunol. 4:1102-1110(2003).
RN [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17620455; DOI=10.1182/blood-2006-11-058800;
RA Nakae S., Iikura M., Suto H., Akiba H., Umetsu D.T., Dekruyff R.H.,
RA Saito H., Galli S.J.;
RT "TIM-1 and TIM-3 enhancement of Th2 cytokine production by mast cells.";
RL Blood 110:2565-2568(2007).
RN [6]
RP FUNCTION.
RX PubMed=18006747; DOI=10.1126/science.1148536;
RA Anderson A.C., Anderson D.E., Bregoli L., Hastings W.D., Kassam N., Lei C.,
RA Chandwaskar R., Karman J., Su E.W., Hirashima M., Bruce J.N., Kane L.P.,
RA Kuchroo V.K., Hafler D.A.;
RT "Promotion of tissue inflammation by the immune receptor Tim-3 expressed on
RT innate immune cells.";
RL Science 318:1141-1143(2007).
RN [7]
RP PHOSPHATIDYLSERINE-BINDING, TISSUE SPECIFICITY, FUNCTION, AND MUTAGENESIS
RP OF GLN-62; ARG-112 AND 120-ASN-ASP-121.
RX PubMed=19224762; DOI=10.1182/blood-2008-10-185884;
RA Nakayama M., Akiba H., Takeda K., Kojima Y., Hashiguchi M., Azuma M.,
RA Yagita H., Okumura K.;
RT "Tim-3 mediates phagocytosis of apoptotic cells and cross-presentation.";
RL Blood 113:3821-3830(2009).
RN [8]
RP FUNCTION.
RX PubMed=20937702; DOI=10.1084/jem.20100687;
RA Jayaraman P., Sada-Ovalle I., Beladi S., Anderson A.C., Dardalhon V.,
RA Hotta C., Kuchroo V.K., Behar S.M.;
RT "Tim3 binding to galectin-9 stimulates antimicrobial immunity.";
RL J. Exp. Med. 207:2343-2354(2010).
RN [9]
RP FUNCTION, INTERACTION WITH PIK3R1; PIK3R2 AND FYN, MUTAGENESIS OF TYR-256
RP AND TYR-263, PHOSPHORYLATION, AND GLYCOSYLATION.
RX PubMed=21807895; DOI=10.1128/mcb.05297-11;
RA Lee J., Su E.W., Zhu C., Hainline S., Phuah J., Moroco J.A.,
RA Smithgall T.E., Kuchroo V.K., Kane L.P.;
RT "Phosphotyrosine-dependent coupling of Tim-3 to T-cell receptor signaling
RT pathways.";
RL Mol. Cell. Biol. 31:3963-3974(2011).
RN [10]
RP FUNCTION, INTERACTION WITH HMGB1, AND INVOLVEMENT IN CHEMOTHERAPY.
RX PubMed=22842346; DOI=10.1038/ni.2376;
RA Chiba S., Baghdadi M., Akiba H., Yoshiyama H., Kinoshita I.,
RA Dosaka-Akita H., Fujioka Y., Ohba Y., Gorman J.V., Colgan J.D.,
RA Hirashima M., Uede T., Takaoka A., Yagita H., Jinushi M.;
RT "Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune
RT responses through interactions between the receptor TIM-3 and the alarmin
RT HMGB1.";
RL Nat. Immunol. 13:832-842(2012).
RN [11]
RP FUNCTION, INTERACTION WITH BAG6, AND MUTAGENESIS OF TYR-256 AND TYR-263.
RX PubMed=22863785; DOI=10.1038/nm.2871;
RA Rangachari M., Zhu C., Sakuishi K., Xiao S., Karman J., Chen A., Angin M.,
RA Wakeham A., Greenfield E.A., Sobel R.A., Okada H., McKinnon P.J., Mak T.W.,
RA Addo M.M., Anderson A.C., Kuchroo V.K.;
RT "Bat3 promotes T cell responses and autoimmunity by repressing Tim-3-
RT mediated cell death and exhaustion.";
RL Nat. Med. 18:1394-1400(2012).
RN [12]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=24567532; DOI=10.4049/jimmunol.1302290;
RA Gorman J.V., Starbeck-Miller G., Pham N.L., Traver G.L., Rothman P.B.,
RA Harty J.T., Colgan J.D.;
RT "Tim-3 directly enhances CD8 T cell responses to acute Listeria
RT monocytogenes infection.";
RL J. Immunol. 192:3133-3142(2014).
RN [13]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=25337993; DOI=10.1371/journal.pone.0110585;
RA Hou H., Liu W., Wu S., Lu Y., Peng J., Zhu Y., Lu Y., Wang F., Sun Z.;
RT "Tim-3 negatively mediates natural killer cell function in LPS-induced
RT endotoxic shock.";
RL PLoS ONE 9:E110585-E110585(2014).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 29-233 IN COMPLEX WITH
RP PHOSPHATIDYLSERINE, DISULFIDE BOND, FUNCTION, DOMAIN, AND MUTAGENESIS OF
RP TRP-53; 60-TRP--GLN-62; 118-LEU-MET-119 AND 120-ASN-ASP-121.
RX PubMed=20083673; DOI=10.4049/jimmunol.0903059;
RA DeKruyff R.H., Bu X., Ballesteros A., Santpiago C., Chim Y.L., Lee H.H.,
RA Karisola P., Pichavant M., Kaplan G.G., Umetsu D.T., Freeman G.J.,
RA Casasnovas J.M.;
RT "T cell/transmembrane, Ig, and mucin-3 allelic variants differentially
RT recognize phosphatidylserine and mediate phagocytosis of apoptotic cells.";
RL J. Immunol. 184:1918-1930(2010).
CC -!- FUNCTION: Cell surface receptor implicated in modulating innate and
CC adaptive immune responses. Generally accepted to have an inhibiting
CC function. Reports on stimulating functions suggest that the activity
CC may be influenced by the cellular context and/or the respective ligand
CC (PubMed:18006747). Regulates macrophage activation (PubMed:11823861).
CC Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune
CC responses and promotes immunological tolerance (PubMed:14556006,
CC PubMed:18006747). In CD8+ cells attenuates TCR-induced signaling,
CC specifically by blocking NF-kappaB and NFAT promoter activities
CC resulting in the loss of IL-2 secretion. The function may implicate its
CC association with LCK proposed to impair phosphorylation of TCR subunits
CC (By similarity). In contrast, shown to activate TCR-induced signaling
CC in T-cells probably implicating ZAP70, LCP2, LCK and FYN
CC (PubMed:21807895). Expressed on Treg cells can inhibit Th17 cell
CC responses (By similarity). Receptor for LGALS9. Binding to LGALS9 is
CC believed to result in suppression of T-cell responses; the resulting
CC apoptosis of antigen-specific cells may implicate HAVCR2
CC phosphorylation and disruption of its association with BAG6
CC (PubMed:22863785). Binding to LGALS9 is proposed to be involved in
CC innate immune response to intracellular pathogens. Expressed on Th1
CC cells interacts with LGALS9 expressed on Mycobacterium tuberculosis-
CC infected macrophages to stimulate antibactericidal activity including
CC IL-1 beta secretion and to restrict intracellular bacterial growth
CC (PubMed:20937702). However, the function as receptor for LGALS9 has
CC been challenged (By similarity). Also reported to enhance CD8+ T-cell
CC responses to an acute infection such as by Listeria monocytogenes
CC (PubMed:24567532). Receptor for phosphatidylserine (PtSer); PtSer-
CC binding is calcium-dependent (PubMed:20083673). May recognize PtSer on
CC apoptotic cells leading to their phagocytosis. Mediates the engulfment
CC of apoptotic cells by dendritic cells (PubMed:19224762). Expressed on
CC T-cells, promotes conjugation but not engulfment of apoptotic cells
CC (PubMed:20083673). Expressed on dendritic cells (DCs) positively
CC regulates innate immune response and in synergy with Toll-like
CC receptors promotes secretion of TNF-alpha (PubMed:18006747). In tumor-
CC imfiltrating DCs suppresses nucleic acid-mediated innate immune
CC repsonse by interaction with HMGB1 and interfering with nucleic acid-
CC sensing and trafficking of nucleid acids to endosomes
CC (PubMed:22842346). Can enhance mast cell production of Th2 cytokines
CC Il-4, IL-6 and IL-13 (PubMed:17620455). Expressed on natural killer
CC (NK) cells acts as a coreceptor to enhance IFN-gamma production in
CC response to LGALS9. In contrast, shown to suppress NK cell-mediated
CC cytotoxicity (By similarity). Negatively regulates NK cell function in
CC LPS-induced endotoxic shock (PubMed:25337993).
CC {ECO:0000250|UniProtKB:Q8TDQ0, ECO:0000269|PubMed:11823861,
CC ECO:0000269|PubMed:14556006, ECO:0000269|PubMed:17620455,
CC ECO:0000269|PubMed:18006747, ECO:0000269|PubMed:19224762,
CC ECO:0000269|PubMed:20083673, ECO:0000269|PubMed:20937702,
CC ECO:0000269|PubMed:21807895, ECO:0000269|PubMed:22842346,
CC ECO:0000269|PubMed:24567532, ECO:0000269|PubMed:25337993,
CC ECO:0000305|PubMed:22863785}.
CC -!- SUBUNIT: Interacts with HMGB1; impairs HMGB1 binding to B-DNA and
CC likely HMGB1-mediated innate immune response (PubMed:22842346).
CC Interacts with BAG6 (PubMed:22863785). Interacts (phosphorylated) with
CC PIK3R1 and PIK3R2. Interacts (not dependent on its phosphorylation
CC status) with FYN (PubMed:21807895). Interacts (in basal state T-cells)
CC with VAV1; AKT1/2, LCP2, ZAP70, SYK, PIK3R1, FYN, SH3BP2 and SH2D2A.
CC Interacts (in activated T-cells) with LCK and PLCG (By similarity).
CC Interacts with ILF3; this interaction promotes ILF3 ubiquitination and
CC degradation (By similarity). {ECO:0000250|UniProtKB:Q8TDQ0,
CC ECO:0000269|PubMed:21807895, ECO:0000269|PubMed:22842346,
CC ECO:0000269|PubMed:22863785}.
CC -!- INTERACTION:
CC Q8VIM0; P63158: Hmgb1; NbExp=4; IntAct=EBI-6665112, EBI-6665811;
CC Q8VIM0; O08573-2: Lgals9; NbExp=4; IntAct=EBI-6665112, EBI-11316797;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Membrane {ECO:0000305}; Single-pass
CC type I membrane protein {ECO:0000305}. Cell junction
CC {ECO:0000250|UniProtKB:Q8TDQ0}. Note=Localizes to the immunological
CC synapse between CD8+ T-cells and target cells.
CC {ECO:0000250|UniProtKB:Q8TDQ0}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted
CC {ECO:0000269|PubMed:14556006}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Tim-3L, flTim-3;
CC IsoId=Q8VIM0-1; Sequence=Displayed;
CC Name=2; Synonyms=sTim-3;
CC IsoId=Q8VIM0-2; Sequence=VSP_058116;
CC -!- TISSUE SPECIFICITY: Expressed in T-helper type 1 lymphocytes. Not
CC expressed by naive T-cells but up-regulated as they differentiate into
CC T-helper-1 cells. Also expressed by differentiated type 1 CD8+
CC cytotoxic T-cells. Expressed on peritoneal exudate macrophages,
CC monocytes, and splenic dendritic cells (DCs). Expression on natural
CC killer (NK) cells is inversely associated with IFN-gamma production
CC during the initial 24 h of LPS-induced endotoxic shock. Expressed on
CC mast cells. {ECO:0000269|PubMed:11823861, ECO:0000269|PubMed:14556006,
CC ECO:0000269|PubMed:17620455, ECO:0000269|PubMed:19224762,
CC ECO:0000269|PubMed:24567532, ECO:0000269|PubMed:25337993}.
CC -!- DOMAIN: The Ig-like V-type (immunoglobulin-like) domain mediates
CC binding to PtSer involving a Ca(2+) ion. {ECO:0000269|PubMed:20083673}.
CC -!- PTM: Phosphorylated on tyrosine residues; modestly increased after
CC TCR/CD28 stimulation. Can be phosphorylated in the cytoplasmatic domain
CC by FYN (PubMed:21807895). Phosphorylation at Tyr-256 is increased by
CC stimulation with ligand LGALS9 (By similarity).
CC {ECO:0000250|UniProtKB:Q8TDQ0, ECO:0000269|PubMed:21807895}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:21807895}.
CC -!- POLYMORPHISM: Polymorphic differences between BALB/c and HBA alleles in
CC the Ig-like V-type domain are the reason for distinct binding
CC affinities for PtSer. The HBA2 allele binds PtSer approximately 50%
CC less than BALB/c. {ECO:0000269|PubMed:20083673}.
CC -!- MISCELLANEOUS: Belongs to the T-cell and airway phenotype regulator
CC (Tapr) locus, a single chromosomal region that confers reduced T-helper
CC type 2 responsiveness and protects against airway hyperactivity (AHR),
CC the hallmark of human asthma.
CC -!- MISCELLANEOUS: In vivo administration of antibody to HAVCR2 enhances
CC the clinical and pathological severity of experimental autoimmune
CC encephalomyelitis (EAE), a Th1-dependent autoimmune disease and
CC increases the number and activation level of macrophages.
CC -!- MISCELLANEOUS: Endogenous expression on dendritic cells is proposed to
CC act as a negative regulator of chemotherapy-induced antitumor
CC responses. {ECO:0000269|PubMed:22842346}.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. TIM family.
CC {ECO:0000305}.
CC -!- CAUTION: Experimental results based on the injection of HAVCR2/TIM-3
CC antibodies or use of HAVCR2/TIM-3-Fc fusion proteins can reflect
CC changes in the activity of several cell types and pathways as
CC HAVCR2/TIM-3 is expressed by multiple immune cell types. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding;
CC Note=TIMD-3;
CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_mou_other_382";
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DR EMBL; AF399831; AAL35776.1; -; mRNA.
DR EMBL; AL669948; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS36135.1; -. [Q8VIM0-1]
DR RefSeq; NP_599011.2; NM_134250.2. [Q8VIM0-1]
DR PDB; 3KAA; X-ray; 3.00 A; A/B=29-133.
DR PDBsum; 3KAA; -.
DR AlphaFoldDB; Q8VIM0; -.
DR SMR; Q8VIM0; -.
DR BioGRID; 228588; 1.
DR DIP; DIP-61460N; -.
DR IntAct; Q8VIM0; 8.
DR STRING; 10090.ENSMUSP00000020668; -.
DR GlyGen; Q8VIM0; 4 sites.
DR iPTMnet; Q8VIM0; -.
DR PhosphoSitePlus; Q8VIM0; -.
DR PaxDb; Q8VIM0; -.
DR PRIDE; Q8VIM0; -.
DR ProteomicsDB; 269812; -. [Q8VIM0-1]
DR ProteomicsDB; 269813; -. [Q8VIM0-2]
DR ABCD; Q8VIM0; 21 sequenced antibodies.
DR Antibodypedia; 2450; 1295 antibodies from 46 providers.
DR DNASU; 171285; -.
DR Ensembl; ENSMUST00000020668; ENSMUSP00000020668; ENSMUSG00000020399. [Q8VIM0-1]
DR GeneID; 171285; -.
DR KEGG; mmu:171285; -.
DR UCSC; uc011xtp.1; mouse. [Q8VIM0-1]
DR CTD; 84868; -.
DR MGI; MGI:2159682; Havcr2.
DR VEuPathDB; HostDB:ENSMUSG00000020399; -.
DR eggNOG; ENOG502S454; Eukaryota.
DR GeneTree; ENSGT00940000154444; -.
DR InParanoid; Q8VIM0; -.
DR OMA; EHGPAET; -.
DR OrthoDB; 1147868at2759; -.
DR PhylomeDB; Q8VIM0; -.
DR TreeFam; TF336163; -.
DR BioGRID-ORCS; 171285; 1 hit in 76 CRISPR screens.
DR ChiTaRS; Havcr2; mouse.
DR EvolutionaryTrace; Q8VIM0; -.
DR PRO; PR:Q8VIM0; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q8VIM0; protein.
DR Bgee; ENSMUSG00000020399; Expressed in gastrula and 44 other tissues.
DR ExpressionAtlas; Q8VIM0; baseline and differential.
DR Genevisible; Q8VIM0; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0001772; C:immunological synapse; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0002281; P:macrophage activation involved in immune response; IMP:UniProtKB.
DR GO; GO:0060135; P:maternal process involved in female pregnancy; IDA:UniProtKB.
DR GO; GO:0002519; P:natural killer cell tolerance induction; ISO:MGI.
DR GO; GO:1900425; P:negative regulation of defense response to bacterium; IMP:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0071656; P:negative regulation of granulocyte colony-stimulating factor production; ISO:MGI.
DR GO; GO:0002838; P:negative regulation of immune response to tumor cell; IMP:UniProtKB.
DR GO; GO:2000521; P:negative regulation of immunological synapse formation; IMP:UniProtKB.
DR GO; GO:0045824; P:negative regulation of innate immune response; IMP:UniProtKB.
DR GO; GO:0032687; P:negative regulation of interferon-alpha production; ISO:MGI.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; IMP:UniProtKB.
DR GO; GO:0032703; P:negative regulation of interleukin-2 production; IMP:UniProtKB.
DR GO; GO:0032712; P:negative regulation of interleukin-3 production; ISO:MGI.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IMP:UniProtKB.
DR GO; GO:0030886; P:negative regulation of myeloid dendritic cell activation; ISO:MGI.
DR GO; GO:0032815; P:negative regulation of natural killer cell activation; IMP:UniProtKB.
DR GO; GO:0002859; P:negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target; IMP:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:2001189; P:negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell; ISO:MGI.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; IMP:UniProtKB.
DR GO; GO:0002826; P:negative regulation of T-helper 1 type immune response; IMP:UniProtKB.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; ISO:MGI.
DR GO; GO:0032480; P:negative regulation of type I interferon production; IMP:UniProtKB.
DR GO; GO:0032722; P:positive regulation of chemokine production; IMP:UniProtKB.
DR GO; GO:0001819; P:positive regulation of cytokine production; IMP:UniProtKB.
DR GO; GO:1900426; P:positive regulation of defense response to bacterium; IMP:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR GO; GO:0045089; P:positive regulation of innate immune response; IMP:UniProtKB.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IMP:UniProtKB.
DR GO; GO:0032732; P:positive regulation of interleukin-1 production; IMP:UniProtKB.
DR GO; GO:0032753; P:positive regulation of interleukin-4 production; ISO:MGI.
DR GO; GO:0043032; P:positive regulation of macrophage activation; IMP:UniProtKB.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IMP:UniProtKB.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:UniProtKB.
DR GO; GO:0002652; P:regulation of tolerance induction dependent upon immune response; IMP:UniProtKB.
DR GO; GO:0034138; P:toll-like receptor 3 signaling pathway; IMP:UniProtKB.
DR GO; GO:0034154; P:toll-like receptor 7 signaling pathway; IMP:UniProtKB.
DR GO; GO:0034162; P:toll-like receptor 9 signaling pathway; IMP:UniProtKB.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR013106; Ig_V-set.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; Cell junction;
KW Disulfide bond; Glycoprotein; Immunity; Immunoglobulin domain;
KW Inflammatory response; Innate immunity; Membrane; Metal-binding;
KW Phosphoprotein; Reference proteome; Secreted; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..281
FT /note="Hepatitis A virus cellular receptor 2 homolog"
FT /id="PRO_0000042102"
FT TOPO_DOM 20..193
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 194..214
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 215..281
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 20..125
FT /note="Ig-like V-type"
FT REGION 139..160
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 252..270
FT /note="Interaction with BAG6"
FT /evidence="ECO:0000269|PubMed:22863785"
FT BINDING 61
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-L-serine"
FT /ligand_id="ChEBI:CHEBI:57262"
FT /evidence="ECO:0000269|PubMed:20083673,
FT ECO:0007744|PDB:3KAA"
FT BINDING 62
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-L-serine"
FT /ligand_id="ChEBI:CHEBI:57262"
FT /evidence="ECO:0000269|PubMed:20083673,
FT ECO:0007744|PDB:3KAA"
FT BINDING 112
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-L-serine"
FT /ligand_id="ChEBI:CHEBI:57262"
FT /evidence="ECO:0000269|PubMed:20083673,
FT ECO:0007744|PDB:3KAA"
FT BINDING 115
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:20083673,
FT ECO:0007744|PDB:3KAA"
FT BINDING 117
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:20083673,
FT ECO:0007744|PDB:3KAA"
FT BINDING 119
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-L-serine"
FT /ligand_id="ChEBI:CHEBI:57262"
FT /evidence="ECO:0000269|PubMed:20083673,
FT ECO:0007744|PDB:3KAA"
FT BINDING 120
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:20083673,
FT ECO:0007744|PDB:3KAA"
FT MOD_RES 256
FT /note="Phosphotyrosine; by ITK"
FT /evidence="ECO:0000250|UniProtKB:Q8TDQ0"
FT CARBOHYD 74
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 146
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q8TDQ0"
FT CARBOHYD 172
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 38..111
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:20083673, ECO:0007744|PDB:3KAA"
FT DISULFID 52..63
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:20083673, ECO:0007744|PDB:3KAA"
FT DISULFID 58..110
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:20083673, ECO:0007744|PDB:3KAA"
FT VAR_SEQ 133..217
FT /note="AKVTPAQTAHGDSTTASPRTLTTERNGSETQTLVTLHNNNGTKISTWADEIK
FT DSGETIRTAIHIGVGVSAGLTLALIIGVLILKW -> G (in isoform 2)"
FT /evidence="ECO:0000269|PubMed:14556006"
FT /id="VSP_058116"
FT MUTAGEN 53
FT /note="W->A: Greatly decreases phosphatidylserine binding."
FT /evidence="ECO:0000269|PubMed:20083673"
FT MUTAGEN 60..62
FT /note="WSQ->VFE: Decreases phosphatidylserine binding."
FT /evidence="ECO:0000269|PubMed:20083673"
FT MUTAGEN 62
FT /note="Q->A: No effect on phagocytic activity."
FT /evidence="ECO:0000269|PubMed:19224762"
FT MUTAGEN 112
FT /note="R->A: Abolishes phagocytic activity."
FT /evidence="ECO:0000269|PubMed:19224762"
FT MUTAGEN 118..119
FT /note="LM->AA: Decreases phosphatidylserine binding."
FT /evidence="ECO:0000269|PubMed:20083673"
FT MUTAGEN 120..121
FT /note="ND->AA: Decreases phosphatidylserine binding,
FT abolishes phagocytic activity."
FT /evidence="ECO:0000269|PubMed:19224762,
FT ECO:0000269|PubMed:20083673"
FT MUTAGEN 256
FT /note="Y->F: Abolishes phosphorylation, disrupts
FT interaction with PIK3R1 and PIK3R2, no LGALS9-mediated
FT disruption of interaction with BAG6; when associated with
FT F-263."
FT /evidence="ECO:0000269|PubMed:21807895,
FT ECO:0000269|PubMed:22863785"
FT MUTAGEN 263
FT /note="Y->F: Abolishes phosphorylation, disrupts
FT interaction with PIK3R1 and PIK3R2, no LGALS9-mediated
FT disruption of interaction with BAG6; when associated with
FT F-256."
FT /evidence="ECO:0000269|PubMed:21807895,
FT ECO:0000269|PubMed:22863785"
FT STRAND 26..28
FT /evidence="ECO:0007829|PDB:3KAA"
FT STRAND 34..36
FT /evidence="ECO:0007829|PDB:3KAA"
FT STRAND 51..57
FT /evidence="ECO:0007829|PDB:3KAA"
FT STRAND 60..62
FT /evidence="ECO:0007829|PDB:3KAA"
FT STRAND 66..70
FT /evidence="ECO:0007829|PDB:3KAA"
FT STRAND 72..77
FT /evidence="ECO:0007829|PDB:3KAA"
FT STRAND 81..85
FT /evidence="ECO:0007829|PDB:3KAA"
FT HELIX 89..91
FT /evidence="ECO:0007829|PDB:3KAA"
FT STRAND 96..100
FT /evidence="ECO:0007829|PDB:3KAA"
FT HELIX 103..105
FT /evidence="ECO:0007829|PDB:3KAA"
FT STRAND 107..113
FT /evidence="ECO:0007829|PDB:3KAA"
FT STRAND 116..119
FT /evidence="ECO:0007829|PDB:3KAA"
FT STRAND 125..130
FT /evidence="ECO:0007829|PDB:3KAA"
SQ SEQUENCE 281 AA; 30934 MW; C0349E4BD0E5761D CRC64;
MFSGLTLNCV LLLLQLLLAR SLENAYVFEV GKNAYLPCSY TLSTPGALVP MCWGKGFCPW
SQCTNELLRT DERNVTYQKS SRYQLKGDLN KGDVSLIIKN VTLDDHGTYC CRIQFPGLMN
DKKLELKLDI KAAKVTPAQT AHGDSTTASP RTLTTERNGS ETQTLVTLHN NNGTKISTWA
DEIKDSGETI RTAIHIGVGV SAGLTLALII GVLILKWYSC KKKKLSSLSL ITLANLPPGG
LANAGAVRIR SEENIYTIEE NVYEVENSNE YYCYVNSQQP S
