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Q8TDQ0 (HAVR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:HAVCR2
Synonyms:TIM3, TIMD3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length301 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.8 Ref.9

Subcellular location

Membrane; Single-pass type I membrane protein Potential.

Tissue specificity

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

Post-translational modification

O-glycosylated with core 1 or possibly core 8 glycans. Ref.10

Sequence similarities

Belongs to the immunoglobulin superfamily. TIM family.

Contains 1 Ig-like V-type (immunoglobulin-like) domain.

Ontologies

Keywords
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainImmunoglobulin domain
Signal
Transmembrane
Transmembrane helix
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Cellular_componentintegral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8TDQ0-1)

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.
Isoform 2 (identifier: Q8TDQ0-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Chain22 – 301280Hepatitis A virus cellular receptor 2
PRO_0000042101

Regions

Topological domain22 – 202181Extracellular Potential
Transmembrane203 – 22321Helical; Potential
Topological domain224 – 30178Cytoplasmic Potential
Domain22 – 124103Ig-like V-type

Amino acid modifications

Glycosylation1451O-linked (GalNAc...) Ref.10
Glycosylation1721N-linked (GlcNAc...) Potential
Disulfide bond38 ↔ 110 By similarity
Disulfide bond52 ↔ 63 By similarity
Disulfide bond58 ↔ 109 By similarity

Natural variations

Alternative sequence132 – 14211AKVTPAPTRQR → GEWTFACHLYE in isoform 2.
VSP_017287
Alternative sequence143 – 301159Missing in isoform 2.
VSP_017288
Natural variant1401R → L. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Ref.7
Corresponds to variant rs1036199 [ dbSNP | Ensembl ].
VAR_025342

Experimental info

Sequence conflict1011T → I in AAM19100. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 2, 2010. Version 3.
Checksum: 519A5B0D512B6173

FASTA30133,394
        10         20         30         40         50         60 
MFSHLPFDCV LLLLLLLLTR SSEVEYRAEV GQNAYLPCFY TPAAPGNLVP VCWGKGACPV 

        70         80         90        100        110        120 
FECGNVVLRT DERDVNYWTS RYWLNGDFRK GDVSLTIENV TLADSGIYCC RIQIPGIMND 

       130        140        150        160        170        180 
EKFNLKLVIK PAKVTPAPTR QRDFTAAFPR MLTTRGHGPA ETQTLGSLPD INLTQISTLA 

       190        200        210        220        230        240 
NELRDSRLAN DLRDSGATIR IGIYIGAGIC AGLALALIFG ALIFKWYSHS KEKIQNLSLI 

       250        260        270        280        290        300 
SLANLPPSGL ANAVAEGIRS EENIYTIEEN VYEVEEPNEY YCYVSSRQQP SQPLGCRFAM 


P 

« Hide

Isoform 2 [UniParc].

Checksum: E2C82D8B5AABC23E
Show »

FASTA14216,149

References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_116171.3. NM_032782.4.
UniGeneHs.710500.

3D structure databases

ProteinModelPortalQ8TDQ0.
SMRQ8TDQ0. Positions 26-130.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid124313. 3 interactions.
STRING9606.ENSP00000312002.

PTM databases

PhosphoSiteQ8TDQ0.

Polymorphism databases

DMDM311033536.

Proteomic databases

PaxDbQ8TDQ0.
PRIDEQ8TDQ0.

Protocols and materials databases

DNASU84868.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000307851; ENSP00000312002; ENSG00000135077. [Q8TDQ0-1]
GeneID84868.
KEGGhsa:84868.
UCSCuc003lwk.2. human. [Q8TDQ0-1]
uc003lwl.3. human. [Q8TDQ0-2]

Organism-specific databases

CTD84868.
GeneCardsGC05M156512.
H-InvDBHIX0005353.
HGNCHGNC:18437. HAVCR2.
HPACAB026003.
HPA010505.
MIM606652. gene.
neXtProtNX_Q8TDQ0.
PharmGKBPA134883425.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG41841.
HOVERGENHBG098563.
InParanoidQ8TDQ0.
OMAPRMLTTR.
OrthoDBEOG74XS6M.
PhylomeDBQ8TDQ0.
TreeFamTF336163.

Gene expression databases

ArrayExpressQ8TDQ0.
BgeeQ8TDQ0.
CleanExHS_HAVCR2.
GenevestigatorQ8TDQ0.

Family and domain databases

Gene3D2.60.40.10. 1 hit.
InterProIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]
PfamPF07686. V-set. 1 hit.
[Graphical view]
SMARTSM00409. IG. 1 hit.
[Graphical view]
PROSITEPS50835. IG_LIKE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiHAVCR2.
GenomeRNAi84868.
NextBio75147.
PROQ8TDQ0.
SOURCESearch...

Entry information

Entry nameHAVR2_HUMAN
AccessionPrimary (citable) accession number: Q8TDQ0
Secondary accession number(s): B2RAY2, Q8WW60, Q96K94
Entry history
Integrated into UniProtKB/Swiss-Prot: September 27, 2005
Last sequence update: November 2, 2010
Last modified: April 16, 2014
This is version 93 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM