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Protein

Hepatitis A virus cellular receptor 2

Gene

HAVCR2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Regulates macrophage activation. Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune responses and promotes immunological tolerance. May be also involved in T-cell homing. Receptor for LGALS9.2 Publications

Enzyme and pathway databases

ReactomeiREACT_27283. Interleukin-2 signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Hepatitis A virus cellular receptor 2
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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:18437. HAVCR2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini22 – 202181ExtracellularSequence AnalysisAdd
BLAST
Transmembranei203 – 22321HelicalSequence AnalysisAdd
BLAST
Topological domaini224 – 30178CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • cell surface Source: Ensembl
  • extracellular exosome Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134883425.

Polymorphism and mutation databases

BioMutaiHAVCR2.
DMDMi311033536.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence AnalysisAdd
BLAST
Chaini22 – 301280Hepatitis A virus cellular receptor 2PRO_0000042101Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi38 ↔ 110PROSITE-ProRule annotation
Disulfide bondi52 ↔ 63PROSITE-ProRule annotation
Disulfide bondi58 ↔ 109PROSITE-ProRule annotation
Glycosylationi145 – 1451O-linked (GalNAc...)1 Publication
Glycosylationi172 – 1721N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

O-glycosylated with core 1 or possibly core 8 glycans.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ8TDQ0.
PRIDEiQ8TDQ0.

PTM databases

PhosphoSiteiQ8TDQ0.

Expressioni

Tissue specificityi

T-helper type 1 lymphocyte (Th1)-specific.

Gene expression databases

BgeeiQ8TDQ0.
CleanExiHS_HAVCR2.
ExpressionAtlasiQ8TDQ0. baseline and differential.
GenevisibleiQ8TDQ0. HS.

Organism-specific databases

HPAiCAB026003.
HPA010505.
HPA047581.

Interactioni

Protein-protein interaction databases

BioGridi124313. 79 interactions.
STRINGi9606.ENSP00000312002.

Structurei

Secondary structure

1
301
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi49 – 579Combined sources
Beta strandi59 – 613Combined sources
Beta strandi64 – 729Combined sources
Turni73 – 764Combined sources
Beta strandi77 – 804Combined sources
Beta strandi86 – 905Combined sources
Beta strandi92 – 943Combined sources
Beta strandi96 – 1005Combined sources
Beta strandi107 – 1159Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4QYCX-ray3.40A/B22-126[»]
ProteinModelPortaliQ8TDQ0.
SMRiQ8TDQ0. Positions 30-126.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini22 – 124103Ig-like V-typeAdd
BLAST

Sequence similaritiesi

Belongs to the immunoglobulin superfamily. TIM family.Curated

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG41841.
GeneTreeiENSGT00440000039800.
HOVERGENiHBG098563.
InParanoidiQ8TDQ0.
OMAiGCRFAMP.
OrthoDBiEOG74XS6M.
PhylomeDBiQ8TDQ0.
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]
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: Q8TDQ0-1) [UniParc]FASTAAdd to basket

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
MFSHLPFDCV LLLLLLLLTR SSEVEYRAEV GQNAYLPCFY TPAAPGNLVP
60 70 80 90 100
VCWGKGACPV FECGNVVLRT DERDVNYWTS RYWLNGDFRK GDVSLTIENV
110 120 130 140 150
TLADSGIYCC RIQIPGIMND EKFNLKLVIK PAKVTPAPTR QRDFTAAFPR
160 170 180 190 200
MLTTRGHGPA ETQTLGSLPD INLTQISTLA NELRDSRLAN DLRDSGATIR
210 220 230 240 250
IGIYIGAGIC AGLALALIFG ALIFKWYSHS KEKIQNLSLI SLANLPPSGL
260 270 280 290 300
ANAVAEGIRS EENIYTIEEN VYEVEEPNEY YCYVSSRQQP SQPLGCRFAM

P
Length:301
Mass (Da):33,394
Last modified:November 2, 2010 - v3
Checksum:i519A5B0D512B6173
GO
Isoform 2 (identifier: Q8TDQ0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     132-142: AKVTPAPTRQR → GEWTFACHLYE
     143-301: Missing.

Show »
Length:142
Mass (Da):16,149
Checksum:iE2C82D8B5AABC23E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti101 – 1011T → I in AAM19100 (Ref. 2) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti140 – 1401R → L.6 Publications
Corresponds to variant rs1036199 [ dbSNP | Ensembl ].
VAR_025342

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei132 – 14211AKVTPAPTRQR → GEWTFACHLYE in isoform 2. 1 PublicationVSP_017287Add
BLAST
Alternative sequencei143 – 301159Missing in isoform 2. 1 PublicationVSP_017288Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF251707 mRNA. Translation: AAM19100.1.
AY069944 mRNA. Translation: AAL55401.1.
AK027334 mRNA. Translation: BAB55044.1.
AK314406 mRNA. Translation: BAG37029.1.
AC011377 Genomic DNA. No translation available.
CH471062 Genomic DNA. Translation: EAW61614.1.
BC020843 mRNA. Translation: AAH20843.1.
BC063431 mRNA. Translation: AAH63431.1.
CCDSiCCDS4333.1. [Q8TDQ0-1]
RefSeqiNP_116171.3. NM_032782.4. [Q8TDQ0-1]
UniGeneiHs.710500.

Genome annotation databases

EnsembliENST00000307851; ENSP00000312002; ENSG00000135077.
GeneIDi84868.
KEGGihsa:84868.
UCSCiuc003lwk.2. human. [Q8TDQ0-1]
uc003lwl.3. human. [Q8TDQ0-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF251707 mRNA. Translation: AAM19100.1.
AY069944 mRNA. Translation: AAL55401.1.
AK027334 mRNA. Translation: BAB55044.1.
AK314406 mRNA. Translation: BAG37029.1.
AC011377 Genomic DNA. No translation available.
CH471062 Genomic DNA. Translation: EAW61614.1.
BC020843 mRNA. Translation: AAH20843.1.
BC063431 mRNA. Translation: AAH63431.1.
CCDSiCCDS4333.1. [Q8TDQ0-1]
RefSeqiNP_116171.3. NM_032782.4. [Q8TDQ0-1]
UniGeneiHs.710500.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4QYCX-ray3.40A/B22-126[»]
ProteinModelPortaliQ8TDQ0.
SMRiQ8TDQ0. Positions 30-126.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124313. 79 interactions.
STRINGi9606.ENSP00000312002.

PTM databases

PhosphoSiteiQ8TDQ0.

Polymorphism and mutation databases

BioMutaiHAVCR2.
DMDMi311033536.

Proteomic databases

PaxDbiQ8TDQ0.
PRIDEiQ8TDQ0.

Protocols and materials databases

DNASUi84868.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000307851; ENSP00000312002; ENSG00000135077.
GeneIDi84868.
KEGGihsa:84868.
UCSCiuc003lwk.2. human. [Q8TDQ0-1]
uc003lwl.3. human. [Q8TDQ0-2]

Organism-specific databases

CTDi84868.
GeneCardsiGC05M156512.
H-InvDBHIX0005353.
HGNCiHGNC:18437. HAVCR2.
HPAiCAB026003.
HPA010505.
HPA047581.
MIMi606652. gene.
neXtProtiNX_Q8TDQ0.
PharmGKBiPA134883425.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG41841.
GeneTreeiENSGT00440000039800.
HOVERGENiHBG098563.
InParanoidiQ8TDQ0.
OMAiGCRFAMP.
OrthoDBiEOG74XS6M.
PhylomeDBiQ8TDQ0.
TreeFamiTF336163.

Enzyme and pathway databases

ReactomeiREACT_27283. Interleukin-2 signaling.

Miscellaneous databases

GeneWikiiHAVCR2.
GenomeRNAii84868.
NextBioi75147.
PROiQ8TDQ0.
SOURCEiSearch...

Gene expression databases

BgeeiQ8TDQ0.
CleanExiHS_HAVCR2.
ExpressionAtlasiQ8TDQ0. baseline and differential.
GenevisibleiQ8TDQ0. HS.

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]
PROSITEiPS50835. IG_LIKE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "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: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LEU-140.
  2. "Novel human hepatitis A virus cellular receptor."
    Zhang W., Wan T., Li N., Cao X.
    Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LEU-140.
  3. "A homolog to human kidney injury molecule-1 is expressed in hepatoma cells."
    Kuehn E.W., Ichimura T., Bonventre J.V.
    Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LEU-140.
    Tissue: Hepatoma.
  4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT LEU-140.
    Tissue: Embryo and Umbilical cord blood.
  5. "The DNA sequence and comparative analysis of human chromosome 5."
    Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.
    , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
    Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT LEU-140.
  7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT LEU-140.
    Tissue: Lung and Pancreas.
  8. "Tim-3 inhibits T helper type 1-mediated auto- and alloimmune responses and promotes immunological tolerance."
    Sanchez-Fueyo A., Tian J., Picarella D., Domenig C., Zheng X.X., Sabatos C.A., Manlongat N., Bender O., Kamradt T., Kuchroo V.K., Gutierrez-Ramos J.-C., Coyle A.J., Strom T.B.
    Nat. Immunol. 4:1093-1101(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity."
    Zhu C., Anderson A.C., Schubart A., Xiong H., Imitola J., Khoury S.J., Zheng X.X., Strom T.B., Kuchroo V.K.
    Nat. Immunol. 6:1245-1252(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS A RECEPTOR FOR LGALS9.
  10. "Human urinary glycoproteomics; attachment site specific analysis of N-and O-linked glycosylations by CID and ECD."
    Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.
    Mol. Cell. Proteomics 0:0-0(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION AT THR-145, STRUCTURE OF CARBOHYDRATES, IDENTIFICATION BY MASS SPECTROMETRY.

Entry informationi

Entry nameiHAVR2_HUMAN
AccessioniPrimary (citable) accession number: Q8TDQ0
Secondary accession number(s): B2RAY2, Q8WW60, Q96K94
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 27, 2005
Last sequence update: November 2, 2010
Last modified: July 22, 2015
This is version 107 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.