C-X-C chemokine receptor type 3 - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot P49682 (CXCR3_HUMAN)

Last modified June 16, 2009. Version 94. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    C-X-C chemokine receptor type 3
      Short name=CXC-R3
      Short name=CXCR-3
Alternative name(s):
    Interferon-inducible protein 10 receptor
      Short name=IP-10 receptor
    CKR-L2
    G protein-coupled receptor 9
    CD_antigen=CD183

Gene names

Name:	CXCR3
Synonyms:	GPR9

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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Protein attributes

Sequence length	368 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Receptor for CXCL9, CXCL10 and CXCL11 and mediates the proliferation of human mesangial cells (HMC). Isoform 2 is a receptor for CXCL4 and also mediates the inhibitory activities of CXCL9, CXCL10 and CXCL11 on the growth of human microvascular endothelial cells (HMVEC). Isoform 2 may play a role in angiogenesis. Isoform 3 mediates activity of CXCL11. Ref.2 Ref.8
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Isoform 1 and isoform 2 are mainly expressed in heart, kidney, liver and skeletal muscle. Isoform 1 is also expressed in placenta. Ref.2
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

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Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Gene Ontology (GO)
Biological process	G-protein coupled receptor protein signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW cell adhesion Traceable author statement. Source: ProtInc cell motion Traceable author statement. Source: ProtInc chemotaxis Traceable author statement. Source: ProtInc elevation of cytosolic calcium ion concentration Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Traceable author statement. Source: ProtInc integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	C-C chemokine receptor activity Inferred from electronic annotation. Source: InterPro C-X-C chemokine receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P49682-1) Also known as: CXCR3-A; 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: P49682-2) Also known as: CXCR3-B; The sequence of this isoform differs from the canonical sequence as follows: 1-4: MVLE → MELRKYGPGRLAGTVIGGAAQSKSQTKSDSITKEFLPGLYTAPSSPFPPSQ

Isoform 3 (identifier: P49682-3) Also known as: CXCR3-alt; The sequence of this isoform differs from the canonical sequence as follows: 210-368: VGRTALRVLQ...ETSEASYSGL → GSSSGSGCGC...AGIRAPLSPI
Note: Due to exon skipping.

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 368

368

C-X-C chemokine receptor type 3

PRO_0000069346

Regions

Topological domain

1 – 53

Extracellular Potential

Transmembrane

54 – 80

1 Potential

Topological domain

81 – 89

Cytoplasmic Potential

Transmembrane

90 – 110

2 Potential

Topological domain

111 – 125

Extracellular Potential

Transmembrane

126 – 147

3 Potential

Topological domain

148 – 169

Cytoplasmic Potential

Transmembrane

170 – 189

4 Potential

Topological domain

190 – 212

Extracellular Potential

Transmembrane

213 – 233

5 Potential

Topological domain

234 – 255

Cytoplasmic Potential

Transmembrane

256 – 277

6 Potential

Topological domain

278 – 298

Extracellular Potential

Transmembrane

299 – 321

7 Potential

Topological domain

322 – 368

Cytoplasmic Potential

Amino acid modifications

Glycosylation

N-linked (GlcNAc...) Potential

Glycosylation

N-linked (GlcNAc...) Potential

Disulfide bond

124 ↔ 203

By similarity

Natural variations

Alternative sequence

1 – 4

MVLE → MELRKYGPGRLAGTVIGGAA QSKSQTKSDSITKEFLPGLY TAPSSPFPPSQ in isoform 2.

VSP_015684

Alternative sequence

210 – 368

159

VGRTA…SYSGL → GSSSGSGCGCCSCAWAAPTR EGSRGSHRLPAGIHPGLRPQ RPPTRACEAGIRAPLSPI in isoform 3.

VSP_015685

Natural variant

292

R → Q Ref.7

VAR_016240

Natural variant

363

A → T Ref.7

VAR_016241

Experimental info

Sequence conflict

A → R in CAB02143. Ref.3

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Sequences

Sequence		Length	Mass (Da)
Isoform 1 (CXCR3-A) [UniParc]. Last modified November 1, 1997. Version 2. Checksum: F08A3B44B2BBAD04 Show »	FASTA	368	40,660
10 20 30 40 50 60 MVLEVSDHQV LNDAEVAALL ENFSSSYDYG ENESDSCCTS PPCPQDFSLN FDRAFLPALY 70 80 90 100 110 120 SLLFLLGLLG NGAVAAVLLS RRTALSSTDT FLLHLAVADT LLVLTLPLWA VDAAVQWVFG 130 140 150 160 170 180 SGLCKVAGAL FNINFYAGAL LLACISFDRY LNIVHATQLY RRGPPARVTL TCLAVWGLCL 190 200 210 220 230 240 LFALPDFIFL SAHHDERLNA THCQYNFPQV GRTALRVLQL VAGFLLPLLV MAYCYAHILA 250 260 270 280 290 300 VLLVSRGQRR LRAMRLVVVV VVAFALCWTP YHLVVLVDIL MDLGALARNC GRESRVDVAK 310 320 330 340 350 360 SVTSGLGYMH CCLNPLLYAF VGVKFRERMW MLLLRLGCPN QRGLQRQPSS SRRDSSWSET SEASYSGL « Hide
Isoform 2 (CXCR3-B). Checksum: 325C8A65982A43C4 Show »	FASTA	415	45,523
10 20 30 40 50 60 MELRKYGPGR LAGTVIGGAA QSKSQTKSDS ITKEFLPGLY TAPSSPFPPS QVSDHQVLND 70 80 90 100 110 120 AEVAALLENF SSSYDYGENE SDSCCTSPPC PQDFSLNFDR AFLPALYSLL FLLGLLGNGA 130 140 150 160 170 180 VAAVLLSRRT ALSSTDTFLL HLAVADTLLV LTLPLWAVDA AVQWVFGSGL CKVAGALFNI 190 200 210 220 230 240 NFYAGALLLA CISFDRYLNI VHATQLYRRG PPARVTLTCL AVWGLCLLFA LPDFIFLSAH 250 260 270 280 290 300 HDERLNATHC QYNFPQVGRT ALRVLQLVAG FLLPLLVMAY CYAHILAVLL VSRGQRRLRA 310 320 330 340 350 360 MRLVVVVVVA FALCWTPYHL VVLVDILMDL GALARNCGRE SRVDVAKSVT SGLGYMHCCL 370 380 390 400 410 NPLLYAFVGV KFRERMWMLL LRLGCPNQRG LQRQPSSSRR DSSWSETSEA SYSGL « Hide
Isoform 3 (CXCR3-alt). Checksum: 8E5C6052A5A3E518 Show »	FASTA	267	28,715
10 20 30 40 50 60 MVLEVSDHQV LNDAEVAALL ENFSSSYDYG ENESDSCCTS PPCPQDFSLN FDRAFLPALY 70 80 90 100 110 120 SLLFLLGLLG NGAVAAVLLS RRTALSSTDT FLLHLAVADT LLVLTLPLWA VDAAVQWVFG 130 140 150 160 170 180 SGLCKVAGAL FNINFYAGAL LLACISFDRY LNIVHATQLY RRGPPARVTL TCLAVWGLCL 190 200 210 220 230 240 LFALPDFIFL SAHHDERLNA THCQYNFPQG SSSGSGCGCC SCAWAAPTRE GSRGSHRLPA 250 260 GIHPGLRPQR PPTRACEAGI RAPLSPI « Hide

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Chemokine receptor specific for IP10 and mig: structure, function, and expression in activated T-lymphocytes." Loetscher M., Gerber B., Loetscher P., Jones S.A., Piali L., Clark-Lewis I., Baggiolini M., Moser B. J. Exp. Med. 184:963-969(1996) [PubMed: 9064356] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Blood.
[2]	"An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4." Lasagni L., Francalanci M., Annunziato F., Lazzeri E., Giannini S., Cosmi L., Sagrinati C., Mazzinghi B., Orlando C., Maggi E., Marra F., Romagnani S., Serio M., Romagnani P. J. Exp. Med. 197:1537-1549(2003) [PubMed: 12782716] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY.
[3]	Gutierrez J., Varona R., Zaballos A., Lind P., Marquez G. Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[4]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." Warren C.N., Aronstam R.S., Sharma S.V. Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Leukocyte.
[5]	"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] (ISOFORM 1). Tissue: Brain, Lung and Testis.
[6]	"Cloning and chromosomal mapping of three novel genes, GPR9, GPR10, and GPR14, encoding receptors related to interleukin 8, neuropeptide Y, and somatostatin receptors." Marchese A., Heiber M., Nguyen T., Heng H.H.Q., Saldivia V.R., Cheng R., Murphy P.M., Tsui L.-C., Shi X., Gregor P., George S.R., O'Dowd B.F., Docherty J.M. Genomics 29:335-344(1995) [PubMed: 8666380] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 5-368.
[7]	"Single nucleotide polymorphisms in the coding regions of human CXC-chemokine receptors CXCR1, CXCR2 and CXCR3." Kato H., Tsuchiya N., Tokunaga K. Genes Immun. 1:330-337(2000) [PubMed: 11196695] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 278-368, VARIANTS GLN-292 AND THR-363.
[8]	"Identification and partial characterization of a variant of human CXCR3 generated by posttranscriptional exon skipping." Ehlert J.E., Addison C.A., Burdick M.D., Kunkel S.L., Strieter R.M. J. Immunol. 173:6234-6240(2004) [PubMed: 15528361] [Abstract] Cited for: ALTERNATIVE SPLICING (ISOFORM 3), FUNCTION.
[9]	"Interferon-inducible T cell alpha chemoattractant (I-TAC): a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3." Cole K.E., Strick C.A., Paradis T.J., Ogborne K.T., Loetscher M., Gladue R.P., Lin W., Boyd J.G., Moser B., Wood D.E., Sahagan B.G., Neote K. J. Exp. Med. 187:2009-2021(1998) [PubMed: 9625760] [Abstract] Cited for: LIGAND-BINDING. Tissue: Fetal astrocyte.
+	Additional computationally mapped references.

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Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Wikipedia

CXC chemokine receptors entry

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Cross-references

Sequence databases
	X95876 mRNA. Translation: CAA65126.1. AF469635 mRNA. Translation: AAP55851.1. Z79783 Genomic DNA. Translation: CAB02143.1. Different initiation. AY242128 mRNA. Translation: AAO92295.1. BC034403 mRNA. Translation: AAH34403.1. U32674 Genomic DNA. Translation: AAC50505.1. AB032735 Genomic DNA. Translation: BAA92297.1. AB032736 Genomic DNA. Translation: BAA92298.1.
IPI	IPI00027754. IPI00640020. IPI00651732.
RefSeq	NP_001136269.1. NP_001495.1.
UniGene	Hs.198252
3D structure databases
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:5891N.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	P49682.
Proteomic databases
PRIDE	P49682.
Genome annotation databases
Ensembl	ENSG00000186810. Homo sapiens. [Contig view]
GeneID	2833.
KEGG	hsa:2833.
Organism-specific databases
GeneCards	GC0XM070752.
H-InvDB	HIX0016864.
HGNC	HGNC:4540. CXCR3.
HPA	CAB017820.
MIM	300574. gene.
PharmGKB	PA35049.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P49682.
OMA	P49682. STDTFLL.
Enzyme and pathway databases
Reactome	REACT_14797. Signaling by GPCR.
Gene expression databases
ArrayExpress	P49682.
Bgee	P49682.
CleanEx	HS_CXCR3.
GermOnline	ENSG00000186810. Homo sapiens.
Family and domain databases
InterPro	IPR000276. 7TM_GPCR_Rhodpsn. IPR000355. Chmkine_rcpt. IPR004070. CXC_3_rcpt. IPR017452. GPCR_Rhodpsn_supfam. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00657. CCCHEMOKINER. PR01532. CXCCHMKINER3. PR00237. GPCRRHODOPSN.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	11181.
SOURCE	Search...

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Entry information

Entry name

CXCR3_HUMAN

Accession

Primary (citable) accession number: P49682
Secondary accession number(s): O15185

Q9P2T5

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	November 1, 1997
Last modified:	June 16, 2009
This is version 94 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries

Human chromosome X

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents