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Protein

C-X-C chemokine receptor type 3

Gene

CXCR3

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

Functioni

Isoform 1: Receptor for the C-X-C chemokine CXCL9, CXCL10 and CXCL11 and mediates the proliferation, survival and angiogenic activity of human mesangial cells (HMC) through a heterotrimeric G-protein signaling pathway (PubMed:12782716). Binds to CCL21. Probably promotes cell chemotaxis response.1 Publication
Isoform 2: Receptor for the C-X-C chemokine CXCL4 and also mediates the inhibitory activities of CXCL9, CXCL10 and CXCL11 on the proliferation, survival and angiogenic activity of human microvascular endothelial cells (HMVEC) through a cAMP-mediated signaling pathway (PubMed:12782716). Does not promote cell chemotaxis respons. Interaction with CXCL4 or CXCL10 leads to activation of the p38MAPK pathway and contributes to inhibition of angiogenesis. Overexpression in renal cancer cells down-regulates expression of the anti-apoptotic protein HMOX1 and promotes apoptosis.1 Publication
Isoform 3: Mediates the activity of CXCL11.

GO - Molecular functioni

  • chemokine binding Source: BHF-UCL
  • chemokine receptor activity Source: ProtInc
  • C-X-C chemokine binding Source: UniProtKB
  • C-X-C chemokine receptor activity Source: Ensembl
  • receptor activity Source: UniProtKB

GO - Biological processi

  • angiogenesis Source: UniProtKB-KW
  • apoptotic process Source: UniProtKB-KW
  • calcium-mediated signaling Source: Ensembl
  • cell adhesion Source: ProtInc
  • cell surface receptor signaling pathway Source: BHF-UCL
  • chemokine (C-C motif) ligand 11 production Source: UniProtKB
  • chemotaxis Source: ProtInc
  • G-protein coupled receptor signaling pathway Source: UniProtKB
  • inflammatory response Source: InterPro
  • movement of cell or subcellular component Source: ProtInc
  • negative regulation of angiogenesis Source: UniProtKB
  • negative regulation of endothelial cell proliferation Source: UniProtKB
  • negative regulation of execution phase of apoptosis Source: UniProtKB
  • positive regulation of angiogenesis Source: UniProtKB
  • positive regulation of cAMP-mediated signaling Source: UniProtKB
  • positive regulation of cAMP metabolic process Source: UniProtKB
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of chemotaxis Source: UniProtKB
  • positive regulation of cytosolic calcium ion concentration Source: ProtInc
  • positive regulation of execution phase of apoptosis Source: UniProtKB
  • positive regulation of release of sequestered calcium ion into cytosol Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • regulation of leukocyte migration Source: InterPro
  • T cell chemotaxis Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Angiogenesis, Apoptosis, Chemotaxis

Enzyme and pathway databases

BioCyciZFISH:G66-32883-MONOMER.
ReactomeiR-HSA-380108. Chemokine receptors bind chemokines.
R-HSA-418594. G alpha (i) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
C-X-C chemokine receptor type 3
Short name:
CXC-R3
Short name:
CXCR-3
Alternative name(s):
CKR-L2
G protein-coupled receptor 9
Interferon-inducible protein 10 receptor
Short name:
IP-10 receptor
CD_antigen: CD183
Gene namesi
Name:CXCR3
Synonyms:GPR9
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:4540. CXCR3.

Subcellular locationi

Isoform 1 :
Isoform 2 :

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 53ExtracellularSequence analysisAdd BLAST53
Transmembranei54 – 80Helical; Name=1Sequence analysisAdd BLAST27
Topological domaini81 – 89CytoplasmicSequence analysis9
Transmembranei90 – 110Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini111 – 125ExtracellularSequence analysisAdd BLAST15
Transmembranei126 – 147Helical; Name=3Sequence analysisAdd BLAST22
Topological domaini148 – 169CytoplasmicSequence analysisAdd BLAST22
Transmembranei170 – 189Helical; Name=4Sequence analysisAdd BLAST20
Topological domaini190 – 212ExtracellularSequence analysisAdd BLAST23
Transmembranei213 – 233Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini234 – 255CytoplasmicSequence analysisAdd BLAST22
Transmembranei256 – 277Helical; Name=6Sequence analysisAdd BLAST22
Topological domaini278 – 298ExtracellularSequence analysisAdd BLAST21
Transmembranei299 – 321Helical; Name=7Sequence analysisAdd BLAST23
Topological domaini322 – 368CytoplasmicSequence analysisAdd BLAST47

GO - Cellular componenti

  • cytoplasm Source: ProtInc
  • external side of plasma membrane Source: Ensembl
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1 – 16Missing : Reduces binding to CXCL10 and CXCL11, and reduces CXCL10- and CXCL11-induced chemotaxis and activation. Does not affect CXCL9-induced chemotaxis and activation. 1 PublicationAdd BLAST16
Mutagenesisi4E → K: Does not affect binding to CXCL9, CXCL10 and CXCL11 or activation. 1 Publication1
Mutagenesisi21E → K: Reduces slightly CXCL9-, CXCL10- and CXCL11-induced chemotaxis. 1 Publication1
Mutagenesisi27 – 29YDY → ADA: Abolishes binding to CXCL10 and CXCL11 and CXCL9-, CXCL10- and CXCL11-induced chemotaxis. 1 Publication3
Mutagenesisi27Y → F: Reduces sulfation and CXCL9-, CXCL10- and CXCL11-induced chemotaxis. Abolishes binding to CXCL10. Abolishes sulfation, binding to CXCL11, ligand-induced receptor internalization and CXCL9-, CXCL10- and CXCL11-induced chemotaxis; when associated with F-29. 2 Publications1
Mutagenesisi29Y → F: Reduces sulfation, binding to CXCL10 and CXCL9-, CXCL10- and CXCL11-induced chemotaxis. Abolishes sulfation, binding to CXCL10 and CXCL11 and CXCL9-, CXCL10- and CXCL11-induced chemotaxis; when associated with F-27. 2 Publications1
Mutagenesisi112D → A: Abolishes binding to CXCL10 and CXCL11. Reduces CXCL9-, CXCL10- and CXCL11-induced chemotaxis. 1 Publication1
Mutagenesisi112D → K: Abolishes binding to CXCL10 and CXCL11 and CXCL10- and CXCL11-induced chemotaxis. Reduces CXCL9-induced chemotaxis. 1 Publication1
Mutagenesisi197R → A: Abolishes binding to CXCL10 and CXCL11 and CXCL9-, CXCL10- and CXCL11-induced chemotaxis. Reduces ligand-induced receptor internalization. 1 Publication1
Mutagenesisi212R → A: Abolishes CXCL10-induced chemotaxis. Reduces CXCL9- and CXCL11-induced chemotaxis. Does not affect binding to CXCL10 and CXCL11. 1 Publication1
Mutagenesisi216R → A: Reduces CXCL9-, CXCL10- and CXCL11-induced chemotaxis. Does not affect binding to CXCL10 and CXCL11 or receptor internalization. 1 Publication1
Mutagenesisi278D → A: Abolishes binding to CXCL10 and CXCL11 and CXCL11-induced chemotaxis. Reduces CXCL9 and CXCL10-induced chemotaxis. 1 Publication1
Mutagenesisi278D → K: Abolishes binding to CXCL10 and CXCL11 and CXCL9-, CXCL10- and CXCL11-induced chemotaxis. 1 Publication1
Mutagenesisi282D → A: Reduces binding to CXCL10 and CXCL9-, CXCL10- and CXCL11-induced chemotaxis. Abolishes binding to CXCL11. 1 Publication1
Mutagenesisi282D → K: Reduces binding to CXCL10 and CXCL11 and CXCL9-, CXCL10- and CXCL11-induced chemotaxis. 1 Publication1
Mutagenesisi293E → A: Reduces binding to CXCL10 and CXCL9- and CXCL11-induced chemotaxis. Abolishes binding to CXCL11 and CXCL10-induced chemotaxis. 1 Publication1
Mutagenesisi293E → K: Abolishes binding to CXCL10 and CXCL11 and CXCL9-, CXCL10- and CXCL11-induced chemotaxis. 1 Publication1

Organism-specific databases

DisGeNETi2833.
OpenTargetsiENSG00000186810.
PharmGKBiPA35049.

Chemistry databases

ChEMBLiCHEMBL4441.
GuidetoPHARMACOLOGYi70.

Polymorphism and mutation databases

BioMutaiCXCR3.
DMDMi2829400.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000693461 – 368C-X-C chemokine receptor type 3Add BLAST368

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi22N-linked (GlcNAc...)Sequence analysis1
Modified residuei27Sulfotyrosine2 Publications1
Modified residuei29Sulfotyrosine1 Publication1
Glycosylationi32N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi124 ↔ 203PROSITE-ProRule annotation

Post-translational modificationi

Sulfation on Tyr-27 and Tyr-29 is essential for CXCL10 binding and subsequent signal transduction induction.2 Publications
N-glycosylated.

Keywords - PTMi

Disulfide bond, Glycoprotein, Sulfation

Proteomic databases

PaxDbiP49682.
PeptideAtlasiP49682.
PRIDEiP49682.

PTM databases

iPTMnetiP49682.
PhosphoSitePlusiP49682.

Expressioni

Tissue specificityi

Isoform 1 and isoform 2 are mainly expressed in heart, kidney, liver and skeletal muscle. Isoform 1 is also expressed in placenta. Isoform 2 is expressed in endothelial cells. Expressed in T-cells (at protein level).2 Publications

Gene expression databases

BgeeiENSG00000186810.
CleanExiHS_CXCR3.
GenevisibleiP49682. HS.

Organism-specific databases

HPAiHPA045942.

Interactioni

Subunit structurei

Homomer. Forms heteromers with ACKR4.1 Publication

GO - Molecular functioni

  • chemokine binding Source: BHF-UCL
  • C-X-C chemokine binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109094. 5 interactors.
DIPiDIP-5891N.
MINTiMINT-91399.
STRINGi9606.ENSP00000362795.

Chemistry databases

BindingDBiP49682.

Structurei

3D structure databases

ProteinModelPortaliP49682.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IE41. Eukaryota.
ENOG410YWPA. LUCA.
GeneTreeiENSGT00760000118785.
HOGENOMiHOG000234122.
HOVERGENiHBG106917.
InParanoidiP49682.
KOiK04188.
OMAiAYCYARI.
OrthoDBiEOG091G0EDT.
PhylomeDBiP49682.
TreeFamiTF330966.

Family and domain databases

InterProiIPR004070. Chemokine_CXCR3.
IPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00657. CCCHEMOKINER.
PR01532. CXCCHMKINER3.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P49682-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MVLEVSDHQV LNDAEVAALL ENFSSSYDYG ENESDSCCTS PPCPQDFSLN
60 70 80 90 100
FDRAFLPALY SLLFLLGLLG NGAVAAVLLS RRTALSSTDT FLLHLAVADT
110 120 130 140 150
LLVLTLPLWA VDAAVQWVFG SGLCKVAGAL FNINFYAGAL LLACISFDRY
160 170 180 190 200
LNIVHATQLY RRGPPARVTL TCLAVWGLCL LFALPDFIFL SAHHDERLNA
210 220 230 240 250
THCQYNFPQV GRTALRVLQL VAGFLLPLLV MAYCYAHILA VLLVSRGQRR
260 270 280 290 300
LRAMRLVVVV VVAFALCWTP YHLVVLVDIL MDLGALARNC GRESRVDVAK
310 320 330 340 350
SVTSGLGYMH CCLNPLLYAF VGVKFRERMW MLLLRLGCPN QRGLQRQPSS
360
SRRDSSWSET SEASYSGL
Length:368
Mass (Da):40,660
Last modified:November 1, 1997 - v2
Checksum:iF08A3B44B2BBAD04
GO
Isoform 2 (identifier: P49682-2) [UniParc]FASTAAdd to basket
Also known as: CXCR3-B

The sequence of this isoform differs from the canonical sequence as follows:
     1-4: MVLE → MELRKYGPGRLAGTVIGGAAQSKSQTKSDSITKEFLPGLYTAPSSPFPPSQ

Show »
Length:415
Mass (Da):45,523
Checksum:i325C8A65982A43C4
GO
Isoform 3 (identifier: P49682-3) [UniParc]FASTAAdd to basket
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.
Show »
Length:267
Mass (Da):28,715
Checksum:i8E5C6052A5A3E518
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti75A → R in CAB02143 (Ref. 4) Curated1
Sequence conflicti157T → I in BAG36429 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_016240292R → Q.1 PublicationCorresponds to variant rs139226823dbSNPEnsembl.1
Natural variantiVAR_016241363A → T.1 PublicationCorresponds to variant rs766348940dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0156841 – 4MVLE → MELRKYGPGRLAGTVIGGAA QSKSQTKSDSITKEFLPGLY TAPSSPFPPSQ in isoform 2. 2 Publications4
Alternative sequenceiVSP_015685210 – 368VGRTA…SYSGL → GSSSGSGCGCCSCAWAAPTR EGSRGSHRLPAGIHPGLRPQ RPPTRACEAGIRAPLSPI in isoform 3. CuratedAdd BLAST159

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X95876 mRNA. Translation: CAA65126.1.
AF469635 mRNA. Translation: AAP55851.1.
Z79783 Genomic DNA. Translation: CAB02143.1.
AY242128 mRNA. Translation: AAO92295.1.
AK313679 mRNA. Translation: BAG36429.1.
BC034403 mRNA. Translation: AAH34403.1.
U32674 Genomic DNA. Translation: AAC50505.1.
AB032735 Genomic DNA. Translation: BAA92297.1.
AB032736 Genomic DNA. Translation: BAA92298.1.
CCDSiCCDS14416.1. [P49682-1]
CCDS48135.1. [P49682-2]
RefSeqiNP_001136269.1. NM_001142797.1. [P49682-2]
NP_001495.1. NM_001504.1. [P49682-1]
XP_016884924.1. XM_017029435.1. [P49682-2]
UniGeneiHs.198252.

Genome annotation databases

EnsembliENST00000373691; ENSP00000362795; ENSG00000186810. [P49682-2]
ENST00000373693; ENSP00000362797; ENSG00000186810. [P49682-1]
GeneIDi2833.
KEGGihsa:2833.
UCSCiuc004eaf.3. human. [P49682-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
Wikipedia

CXC chemokine receptors entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X95876 mRNA. Translation: CAA65126.1.
AF469635 mRNA. Translation: AAP55851.1.
Z79783 Genomic DNA. Translation: CAB02143.1.
AY242128 mRNA. Translation: AAO92295.1.
AK313679 mRNA. Translation: BAG36429.1.
BC034403 mRNA. Translation: AAH34403.1.
U32674 Genomic DNA. Translation: AAC50505.1.
AB032735 Genomic DNA. Translation: BAA92297.1.
AB032736 Genomic DNA. Translation: BAA92298.1.
CCDSiCCDS14416.1. [P49682-1]
CCDS48135.1. [P49682-2]
RefSeqiNP_001136269.1. NM_001142797.1. [P49682-2]
NP_001495.1. NM_001504.1. [P49682-1]
XP_016884924.1. XM_017029435.1. [P49682-2]
UniGeneiHs.198252.

3D structure databases

ProteinModelPortaliP49682.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109094. 5 interactors.
DIPiDIP-5891N.
MINTiMINT-91399.
STRINGi9606.ENSP00000362795.

Chemistry databases

BindingDBiP49682.
ChEMBLiCHEMBL4441.
GuidetoPHARMACOLOGYi70.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP49682.
PhosphoSitePlusiP49682.

Polymorphism and mutation databases

BioMutaiCXCR3.
DMDMi2829400.

Proteomic databases

PaxDbiP49682.
PeptideAtlasiP49682.
PRIDEiP49682.

Protocols and materials databases

DNASUi2833.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000373691; ENSP00000362795; ENSG00000186810. [P49682-2]
ENST00000373693; ENSP00000362797; ENSG00000186810. [P49682-1]
GeneIDi2833.
KEGGihsa:2833.
UCSCiuc004eaf.3. human. [P49682-1]

Organism-specific databases

CTDi2833.
DisGeNETi2833.
GeneCardsiCXCR3.
HGNCiHGNC:4540. CXCR3.
HPAiHPA045942.
MIMi300574. gene.
neXtProtiNX_P49682.
OpenTargetsiENSG00000186810.
PharmGKBiPA35049.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IE41. Eukaryota.
ENOG410YWPA. LUCA.
GeneTreeiENSGT00760000118785.
HOGENOMiHOG000234122.
HOVERGENiHBG106917.
InParanoidiP49682.
KOiK04188.
OMAiAYCYARI.
OrthoDBiEOG091G0EDT.
PhylomeDBiP49682.
TreeFamiTF330966.

Enzyme and pathway databases

BioCyciZFISH:G66-32883-MONOMER.
ReactomeiR-HSA-380108. Chemokine receptors bind chemokines.
R-HSA-418594. G alpha (i) signalling events.

Miscellaneous databases

GeneWikiiCXCR3.
GenomeRNAii2833.
PROiP49682.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000186810.
CleanExiHS_CXCR3.
GenevisibleiP49682. HS.

Family and domain databases

InterProiIPR004070. Chemokine_CXCR3.
IPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00657. CCCHEMOKINER.
PR01532. CXCCHMKINER3.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCXCR3_HUMAN
AccessioniPrimary (citable) accession number: P49682
Secondary accession number(s): B2R982
, O15185, Q7Z710, Q9P2T4, Q9P2T5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: November 1, 1997
Last modified: November 2, 2016
This is version 167 of the entry and version 2 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

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  3. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  4. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  7. SIMILARITY comments
    Index of protein domains and families

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 one 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.