Q8TDQ0 (HAVR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 membrane protein 3
TIM-3

Gene names

Name:	HAVCR2
Synonyms:	TIM3, TIMD3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	301 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.
Sequence similarities	Belongs to the immunoglobulin superfamily. TIM family. Contains 1 Ig-like V-type (immunoglobulin-like) domain.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Immunoglobulin domain Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular component	integral to 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Chain	22 – 301	280	Hepatitis A virus cellular receptor 2		PRO_0000042101
Regions
	Topological domain	22 – 202	181	Extracellular Potential
	Transmembrane	203 – 223	21	Helical; Potential
	Topological domain	224 – 301	78	Cytoplasmic Potential
	Domain	22 – 124	103	Ig-like V-type
Amino acid modifications
	Glycosylation	172	1	N-linked (GlcNAc...) Potential
	Disulfide bond	38 ↔ 110		By similarity
	Disulfide bond	52 ↔ 63		By similarity
	Disulfide bond	58 ↔ 109		By similarity
Natural variations
	Alternative sequence	132 – 142	11	AKVTPAPTRQR → GEWTFACHLYE in isoform 2.		VSP_017287
	Alternative sequence	143 – 301	159	Missing in isoform 2.		VSP_017288
	Natural variant	140	1	R → L. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Ref.7 Corresponds to variant rs1036199 [ dbSNP | Ensembl ].		VAR_025342
Experimental info
	Sequence conflict	101	1	T → I in AAM19100. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 2, 2010. Version 3. Checksum: 519A5B0D512B6173	FASTA	301	33,394
	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
	Isoform 2 [UniParc]. Checksum: E2C82D8B5AABC23E	FASTA	142	16,149
	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 EKFNLKLVIK PGEWTFACHL YE

References

	« Hide 'large scale' referencesShow '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: 11823861] [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: 14702039] [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: 15372022] [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. , 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: 15489334] [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: 14556005] [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: 16286920] [Abstract] Cited for: FUNCTION AS A RECEPTOR FOR LGALS9.
+	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.
IPI	IPI00383032. IPI00651768.
RefSeq	NP_116171.3. NM_032782.4.
UniGene	Hs.710500.
3D structure databases
ProteinModelPortal	Q8TDQ0.
SMR	Q8TDQ0. Positions 26-130.
ModBase	Search...
Protein-protein interaction databases
STRING	Q8TDQ0.
PTM databases
PhosphoSite	Q8TDQ0.
Polymorphism databases
DMDM	311033536.
Proteomic databases
PRIDE	Q8TDQ0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000307851; ENSP00000312002; ENSG00000135077.
GeneID	84868.
KEGG	hsa:84868.
UCSC	uc003lwl.2. human.
Organism-specific databases
CTD	84868.
GeneCards	GC05M156445.
H-InvDB	HIX0005351.
HGNC	HGNC:18437. HAVCR2.
HPA	CAB026003. HPA010505.
MIM	606652. gene.
neXtProt	NX_Q8TDQ0.
PharmGKB	PA134883425.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG18155.
GeneTree	ENSGT00440000039800.
HOGENOM	HBG125079.
HOVERGEN	HBG098563.
InParanoid	Q8TDQ0.
OMA	QNALLPC.
OrthoDB	EOG4MGS86.
PhylomeDB	Q8TDQ0.
Gene expression databases
ArrayExpress	Q8TDQ0.
Bgee	Q8TDQ0.
CleanEx	HS_HAVCR2.
Genevestigator	Q8TDQ0.
GermOnline	ENSG00000135077. Homo sapiens.
Family and domain databases
InterPro	IPR007110. Ig-like. IPR013783. Ig-like_fold. IPR003599. Ig_sub. IPR013106. Ig_V-set. [Graphical view]
Gene3D	G3DSA:2.60.40.10. Ig-like_fold. 1 hit.
Pfam	PF07686. V-set. 1 hit. [Graphical view]
SMART	SM00409. IG. 1 hit. [Graphical view]
PROSITE	PS50835. IG_LIKE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	75147.
SOURCE	Search...

Entry information

Entry name

HAVR2_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 72 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.