HAVR1_MOUSE
ID HAVR1_MOUSE Reviewed; 305 AA.
AC Q5QNS5; Q7TPU2; Q8VIM1; Q8VIM2;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2005, sequence version 2.
DT 25-MAY-2022, entry version 118.
DE RecName: Full=Hepatitis A virus cellular receptor 1 homolog;
DE Short=HAVcr-1;
DE AltName: Full=Kidney injury molecule 1;
DE Short=KIM-1;
DE AltName: Full=T cell immunoglobulin and mucin domain-containing protein 1;
DE Short=TIMD-1;
DE AltName: Full=T cell membrane protein 1;
DE AltName: Full=T-cell immunoglobulin mucin receptor 1;
DE Short=TIM-1;
DE AltName: CD_antigen=CD365;
DE Flags: Precursor;
GN Name=Havcr1; Synonyms=Kim1, Tim1, Timd1;
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] (ISOFORMS 1 AND 2), POLYMORPHISM, VARIANTS HBA,
RP AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ; 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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Blastocyst;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION.
RX PubMed=15793576; DOI=10.1038/ni1185;
RA Meyers J.H., Chakravarti S., Schlesinger D., Illes Z., Waldner H.,
RA Umetsu S.E., Kenny J., Zheng X.X., Umetsu D.T., DeKruyff R.H., Strom T.B.,
RA Kuchroo V.K.;
RT "TIM-4 is the ligand for TIM-1, and the TIM-1-TIM-4 interaction regulates T
RT cell proliferation.";
RL Nat. Immunol. 6:455-464(2005).
RN [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=21821911; DOI=10.1172/jci46274;
RA Ding Q., Yeung M., Camirand G., Zeng Q., Akiba H., Yagita H., Chalasani G.,
RA Sayegh M.H., Najafian N., Rothstein D.M.;
RT "Regulatory B cells are identified by expression of TIM-1 and can be
RT induced through TIM-1 ligation to promote tolerance in mice.";
RL J. Clin. Invest. 121:3645-3656(2011).
RN [6]
RP FUNCTION, AND INTERACTION WITH SELPLG.
RX PubMed=24703780; DOI=10.1016/j.immuni.2014.03.004;
RA Angiari S., Donnarumma T., Rossi B., Dusi S., Pietronigro E., Zenaro E.,
RA Della Bianca V., Toffali L., Piacentino G., Budui S., Rennert P., Xiao S.,
RA Laudanna C., Casasnovas J.M., Kuchroo V.K., Constantin G.;
RT "TIM-1 glycoprotein binds the adhesion receptor P-selectin and mediates T
RT cell trafficking during inflammation and autoimmunity.";
RL Immunity 40:542-553(2014).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25582854; DOI=10.4049/jimmunol.1402632;
RA Xiao S., Brooks C.R., Sobel R.A., Kuchroo V.K.;
RT "Tim-1 is essential for induction and maintenance of IL-10 in regulatory B
RT cells and their regulation of tissue inflammation.";
RL J. Immunol. 194:1602-1608(2015).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25645598; DOI=10.1111/ajt.13087;
RA Yeung M.Y., Ding Q., Brooks C.R., Xiao S., Workman C.J., Vignali D.A.,
RA Ueno T., Padera R.F., Kuchroo V.K., Najafian N., Rothstein D.M.;
RT "TIM-1 signaling is required for maintenance and induction of regulatory B
RT cells.";
RL Am. J. Transplant. 15:942-953(2015).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=32668241; DOI=10.1016/j.celrep.2020.107892;
RA Xiao S., Bod L., Pochet N., Kota S.B., Hu D., Madi A., Kilpatrick J.,
RA Shi J., Ho A., Zhang H., Sobel R., Weiner H.L., Strom T.B., Quintana F.J.,
RA Joller N., Kuchroo V.K.;
RT "Checkpoint Receptor TIGIT Expressed on Tim-1+ B Cells Regulates Tissue
RT Inflammation.";
RL Cell Rep. 32:107892-107892(2020).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 20-130, AND DISULFIDE BONDS.
RX PubMed=17363299; DOI=10.1016/j.immuni.2007.01.014;
RA Santiago C., Ballesteros A., Tami C., Martinez-Munoz L., Kaplan G.G.,
RA Casasnovas J.M.;
RT "Structures of T Cell immunoglobulin mucin receptors 1 and 2 reveal
RT mechanisms for regulation of immune responses by the TIM receptor family.";
RL Immunity 26:299-310(2007).
CC -!- FUNCTION: Phosphatidylserine receptor that plays an important
CC functional role in regulatory B-cells homeostasis including generation,
CC expansion and suppressor functions (PubMed:21821911, PubMed:25645598,
CC PubMed:32668241). As P-selectin/SELPLG ligand, plays a specialized role
CC in activated but not naive T-cell trafficking during inflammatory
CC responses (PubMed:24703780). Controls thereby T-cell accumulation in
CC the inflamed central nervous system (CNS) and the induction of
CC autoimmune disease (PubMed:24703780). Regulates also expression of
CC various anti-inflammatory cytokines and co-inhibitory ligands including
CC IL10 (PubMed:25582854, PubMed:25645598). Acts as regulator of T-cell
CC proliferation (PubMed:15793576). May play a role in kidney injury and
CC repair (By similarity). {ECO:0000250|UniProtKB:Q96D42,
CC ECO:0000269|PubMed:15793576, ECO:0000269|PubMed:21821911,
CC ECO:0000269|PubMed:24703780, ECO:0000269|PubMed:25582854,
CC ECO:0000269|PubMed:25645598, ECO:0000269|PubMed:32668241}.
CC -!- SUBUNIT: Interacts with STAM (By similarity). Interacts with SELPLG
CC (PubMed:24703780). {ECO:0000250|UniProtKB:Q96D42,
CC ECO:0000269|PubMed:24703780}.
CC -!- INTERACTION:
CC Q5QNS5; Q6U7R4: Timd4; NbExp=4; IntAct=EBI-20217708, EBI-16764486;
CC Q5QNS5-2; Q6U7R4: Timd4; NbExp=2; IntAct=EBI-20217763, EBI-16764486;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q96D42};
CC Single-pass type I membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5QNS5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5QNS5-2; Sequence=VSP_015224;
CC -!- TISSUE SPECIFICITY: Expressed by stimulated T-cells. Expressed during
CC primary antigen stimulation (PubMed:11725301). Expressed at higher
CC levels on B rather than T-cells, both constitutively and after
CC activation (PubMed:21821911). {ECO:0000269|PubMed:11725301,
CC ECO:0000269|PubMed:21821911}.
CC -!- DOMAIN: Possesses an immunoglobulin V-like domxain, a mucin domain, a
CC single transmembrane region, and a cytoplasmic tail containing a
CC tyrosine phosphorylation motif. {ECO:0000269|PubMed:25645598}.
CC -!- POLYMORPHISM: Highly polymorphic. Depending on the alleles, expression
CC is associated with an increase and early (BALB/c allele) or decrease
CC (HBA allele) of T-helper type 2 cytokine expression. Associated with
CC asthma susceptibility. {ECO:0000269|PubMed:11725301}.
CC -!- DISRUPTION PHENOTYPE: Mutant show progressive loss of IL10 production
CC in B-cells and with age develop severe multiorgan tissue inflammation
CC (PubMed:25582854). Mucin-domain deletion mice exhibit decreased
CC phosphatidylserine binding and are also unable to produce IL10 in
CC response to apoptotic cells (PubMed:25645598). Specific deletion on B-
CC cells results in spontaneous systemic autoimmunity (PubMed:32668241).
CC {ECO:0000269|PubMed:25582854, ECO:0000269|PubMed:25645598,
CC ECO:0000269|PubMed:32668241}.
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 -!- SIMILARITY: Belongs to the immunoglobulin superfamily. TIM family.
CC {ECO:0000305}.
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DR EMBL; AF399829; AAL35774.1; -; mRNA.
DR EMBL; AF399830; AAL35775.1; -; mRNA.
DR EMBL; AL669892; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC053400; AAH53400.1; -; mRNA.
DR CCDS; CCDS24583.1; -. [Q5QNS5-1]
DR CCDS; CCDS48778.1; -. [Q5QNS5-2]
DR RefSeq; NP_001160103.1; NM_001166631.1.
DR RefSeq; NP_001160104.1; NM_001166632.1.
DR RefSeq; NP_599009.2; NM_134248.2.
DR PDB; 2OR8; X-ray; 2.50 A; A/B=20-130.
DR PDBsum; 2OR8; -.
DR AlphaFoldDB; Q5QNS5; -.
DR SMR; Q5QNS5; -.
DR IntAct; Q5QNS5; 1.
DR STRING; 10090.ENSMUSP00000043827; -.
DR GlyGen; Q5QNS5; 1 site.
DR iPTMnet; Q5QNS5; -.
DR PhosphoSitePlus; Q5QNS5; -.
DR PaxDb; Q5QNS5; -.
DR PRIDE; Q5QNS5; -.
DR ABCD; Q5QNS5; 22 sequenced antibodies.
DR DNASU; 171283; -.
DR GeneID; 171283; -.
DR KEGG; mmu:171283; -.
DR CTD; 26762; -.
DR MGI; MGI:2159680; Havcr1.
DR eggNOG; ENOG502S454; Eukaryota.
DR InParanoid; Q5QNS5; -.
DR OrthoDB; 1147868at2759; -.
DR PhylomeDB; Q5QNS5; -.
DR TreeFam; TF336163; -.
DR BioGRID-ORCS; 171283; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Havcr1; mouse.
DR EvolutionaryTrace; Q5QNS5; -.
DR PRO; PR:Q5QNS5; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q5QNS5; protein.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0005903; C:brush border; IDA:MGI.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031514; C:motile cilium; ISO:MGI.
DR GO; GO:0045335; C:phagocytic vesicle; ISO:MGI.
DR GO; GO:0001786; F:phosphatidylserine binding; IDA:MGI.
DR GO; GO:0001618; F:virus receptor activity; ISO:MGI.
DR GO; GO:0006911; P:phagocytosis, engulfment; ISO:MGI.
DR GO; GO:0033005; P:positive regulation of mast cell activation; IDA:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; IDA:MGI.
DR GO; GO:0009611; P:response to wounding; IMP:MGI.
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; Alternative splicing; Cell membrane; Disulfide bond;
KW Glycoprotein; Immunoglobulin domain; Membrane; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..305
FT /note="Hepatitis A virus cellular receptor 1 homolog"
FT /id="PRO_0000014982"
FT TOPO_DOM 22..237
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 238..258
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 259..305
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 22..122
FT /note="Ig-like V-type"
FT REGION 129..185
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 140..182
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 208
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 37..108
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:17363299, ECO:0007744|PDB:2OR8"
FT DISULFID 49..60
FT /evidence="ECO:0000269|PubMed:17363299,
FT ECO:0007744|PDB:2OR8"
FT DISULFID 55..107
FT /evidence="ECO:0000269|PubMed:17363299,
FT ECO:0007744|PDB:2OR8"
FT VAR_SEQ 183..205
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11725301,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_015224"
FT VARIANT 18
FT /note="A -> T (in strain: HBA)"
FT VARIANT 137
FT /note="T -> R (in strain: HBA)"
FT VARIANT 164
FT /note="I -> T (in strain: HBA)"
FT VARIANT 190..204
FT /note="Missing (in strain: HBA)"
FT CONFLICT 152
FT /note="T -> A (in Ref. 3; AAH53400)"
FT /evidence="ECO:0000305"
FT STRAND 23..28
FT /evidence="ECO:0007829|PDB:2OR8"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:2OR8"
FT STRAND 48..53
FT /evidence="ECO:0007829|PDB:2OR8"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:2OR8"
FT STRAND 63..67
FT /evidence="ECO:0007829|PDB:2OR8"
FT STRAND 69..77
FT /evidence="ECO:0007829|PDB:2OR8"
FT HELIX 86..88
FT /evidence="ECO:0007829|PDB:2OR8"
FT STRAND 93..97
FT /evidence="ECO:0007829|PDB:2OR8"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:2OR8"
FT STRAND 104..110
FT /evidence="ECO:0007829|PDB:2OR8"
FT STRAND 119..128
FT /evidence="ECO:0007829|PDB:2OR8"
SQ SEQUENCE 305 AA; 33361 MW; F995C93A9125E4FE CRC64;
MNQIQVFISG LILLLPGAVD SYVEVKGVVG HPVTLPCTYS TYRGITTTCW GRGQCPSSAC
QNTLIWTNGH RVTYQKSSRY NLKGHISEGD VSLTIENSVE SDSGLYCCRV EIPGWFNDQK
VTFSLQVKPE IPTRPPTRPT TTRPTATGRP TTISTRSTHV PTSIRVSTST PPTSTHTWTH
KPEPTTFCPH ETTAEVTGIP SHTPTDWNGT VTSSGDTWSN HTEAIPPGKP QKNPTKGFYV
GICIAALLLL LLVSTVAITR YILMKRKSAS LSVVAFRVSK IEALQNAAVV HSRAEDNIYI
VEDRP
