ID CXCR3_HUMAN Reviewed; 368 AA. AC P49682; B2R982; O15185; Q7Z710; Q9P2T4; Q9P2T5; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 2. DT 27-MAR-2024, entry version 213. DE RecName: Full=C-X-C chemokine receptor type 3; DE Short=CXC-R3; DE Short=CXCR-3; DE AltName: Full=CKR-L2; DE AltName: Full=G protein-coupled receptor 9; DE AltName: Full=Interferon-inducible protein 10 receptor; DE Short=IP-10 receptor; DE AltName: CD_antigen=CD183; GN Name=CXCR3; Synonyms=GPR9; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Blood; RX PubMed=9064356; DOI=10.1084/jem.184.3.963; RA Loetscher M., Gerber B., Loetscher P., Jones S.A., Piali L., RA Clark-Lewis I., Baggiolini M., Moser B.; RT "Chemokine receptor specific for IP10 and mig: structure, function, and RT expression in activated T-lymphocytes."; RL J. Exp. Med. 184:963-969(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION (ISOFORMS 1 AND 2), RP SUBCELLULAR LOCATION (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY. RX PubMed=12782716; DOI=10.1084/jem.20021897; RA Lasagni L., Francalanci M., Annunziato F., Lazzeri E., Giannini S., RA Cosmi L., Sagrinati C., Mazzinghi B., Orlando C., Maggi E., Marra F., RA Romagnani S., Serio M., Romagnani P.; RT "An alternatively spliced variant of CXCR3 mediates the inhibition of RT endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as RT functional receptor for platelet factor 4."; RL J. Exp. Med. 197:1537-1549(2003). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND FUNCTION. RC TISSUE=Endothelial cell, and Thymus; RX PubMed=18291705; DOI=10.1016/j.biocel.2008.01.008; RA Petrai I., Rombouts K., Lasagni L., Annunziato F., Cosmi L., RA Romanelli R.G., Sagrinati C., Mazzinghi B., Pinzani M., Romagnani S., RA Romagnani P., Marra F.; RT "Activation of p38(MAPK) mediates the angiostatic effect of the chemokine RT receptor CXCR3-B."; RL Int. J. Biochem. Cell Biol. 40:1764-1774(2008). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2). RA Gutierrez J., Varona R., Zaballos A., Lind P., Marquez G.; RL Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Leukocyte; RA Warren C.N., Aronstam R.S., Sharma S.V.; RT "cDNA clones of human proteins involved in signal transduction sequenced by RT the Guthrie cDNA resource center (www.cdna.org)."; RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Colon; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain, Lung, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 5-368. RX PubMed=8666380; DOI=10.1006/geno.1995.9996; RA Marchese A., Heiber M., Nguyen T., Heng H.H.Q., Saldivia V.R., Cheng R., RA Murphy P.M., Tsui L.-C., Shi X., Gregor P., George S.R., O'Dowd B.F., RA Docherty J.M.; RT "Cloning and chromosomal mapping of three novel genes, GPR9, GPR10, and RT GPR14, encoding receptors related to interleukin 8, neuropeptide Y, and RT somatostatin receptors."; RL Genomics 29:335-344(1995). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 278-368, AND VARIANTS GLN-292 AND RP THR-363. RX PubMed=11196695; DOI=10.1038/sj.gene.6363682; RA Kato H., Tsuchiya N., Tokunaga K.; RT "Single nucleotide polymorphisms in the coding regions of human CXC- RT chemokine receptors CXCR1, CXCR2 and CXCR3."; RL Genes Immun. 1:330-337(2000). RN [10] RP ALTERNATIVE SPLICING (ISOFORM 3), AND FUNCTION. RX PubMed=15528361; DOI=10.4049/jimmunol.173.10.6234; RA Ehlert J.E., Addison C.A., Burdick M.D., Kunkel S.L., Strieter R.M.; RT "Identification and partial characterization of a variant of human CXCR3 RT generated by posttranscriptional exon skipping."; RL J. Immunol. 173:6234-6240(2004). RN [11] RP LIGAND-BINDING. RC TISSUE=Fetal astrocyte; RX PubMed=9625760; DOI=10.1084/jem.187.12.2009; RA Cole K.E., Strick C.A., Paradis T.J., Ogborne K.T., Loetscher M., RA Gladue R.P., Lin W., Boyd J.G., Moser B., Wood D.E., Sahagan B.G., RA Neote K.; RT "Interferon-inducible T cell alpha chemoattractant (I-TAC): a novel non-ELR RT CXC chemokine with potent activity on activated T cells through selective RT high affinity binding to CXCR3."; RL J. Exp. Med. 187:2009-2021(1998). RN [12] RP SULFATION AT TYR-27, AND MUTAGENESIS OF 1-MET--VAL-16; GLU-4; GLU-21; RP TYR-27; 27-TYR--TYR-29; TYR-29; ASP-112; ARG-197; ARG-212; ARG-216; RP ASP-278; ASP-282 AND GLU-293. RX PubMed=16847335; DOI=10.1128/mcb.00556-06; RA Colvin R.A., Campanella G.S., Manice L.A., Luster A.D.; RT "CXCR3 requires tyrosine sulfation for ligand binding and a second RT extracellular loop arginine residue for ligand-induced chemotaxis."; RL Mol. Cell. Biol. 26:5838-5849(2006). RN [13] RP SULFATION AT TYR-27 AND TYR-29, AND MUTAGENESIS OF TYR-27 AND TYR-29. RX PubMed=19151743; DOI=10.1038/aps.2008.24; RA Gao J.M., Xiang R.L., Jiang L., Li W.H., Feng Q.P., Guo Z.J., Sun Q., RA Zeng Z.P., Fang F.D.; RT "Sulfated tyrosines 27 and 29 in the N-terminus of human CXCR3 participate RT in binding native IP-10."; RL Acta Pharmacol. Sin. 30:193-201(2009). RN [14] RP FUNCTION. RX PubMed=20855888; DOI=10.1074/jbc.m110.170324; RA Datta D., Banerjee P., Gasser M., Waaga-Gasser A.M., Pal S.; RT "CXCR3-B can mediate growth-inhibitory signals in human renal cancer cells RT by down-regulating the expression of heme oxygenase-1."; RL J. Biol. Chem. 285:36842-36848(2010). RN [15] RP SUBUNIT, AND TISSUE SPECIFICITY. RX PubMed=23121557; DOI=10.1111/bph.12042; RA Vinet J., van Zwam M., Dijkstra I.M., Brouwer N., van Weering H.R., RA Watts A., Meijer M., Fokkens M.R., Kannan V., Verzijl D., Vischer H.F., RA Smit M.J., Leurs R., Biber K., Boddeke H.W.; RT "Inhibition of CXCR3-mediated chemotaxis by the human chemokine receptor- RT like protein CCX-CKR."; RL Br. J. Pharmacol. 168:1375-1387(2013). CC -!- FUNCTION: [Isoform 1]: Receptor for the C-X-C chemokine CXCL9, CXCL10 CC and CXCL11 and mediates the proliferation, survival and angiogenic CC activity of human mesangial cells (HMC) through a heterotrimeric G- CC protein signaling pathway (PubMed:12782716). Binds to CCL21. Probably CC promotes cell chemotaxis response. {ECO:0000269|PubMed:12782716}. CC -!- FUNCTION: [Isoform 2]: Receptor for the C-X-C chemokine CXCL4 and also CC mediates the inhibitory activities of CXCL9, CXCL10 and CXCL11 on the CC proliferation, survival and angiogenic activity of human microvascular CC endothelial cells (HMVEC) through a cAMP-mediated signaling pathway CC (PubMed:12782716). Does not promote cell chemotaxis respons. CC Interaction with CXCL4 or CXCL10 leads to activation of the p38MAPK CC pathway and contributes to inhibition of angiogenesis. Overexpression CC in renal cancer cells down-regulates expression of the anti-apoptotic CC protein HMOX1 and promotes apoptosis. {ECO:0000269|PubMed:12782716}. CC -!- FUNCTION: [Isoform 3]: Mediates the activity of CXCL11. CC -!- SUBUNIT: Homomer. Forms heteromers with ACKR4. CC {ECO:0000269|PubMed:23121557}. CC -!- INTERACTION: CC P49682; O14523: C2CD2L; NbExp=3; IntAct=EBI-12836456, EBI-12822627; CC P49682; Q8N6F1-2: CLDN19; NbExp=3; IntAct=EBI-12836456, EBI-12256978; CC P49682; P61073: CXCR4; NbExp=5; IntAct=EBI-12836456, EBI-489411; CC P49682; Q9Y6G1: TMEM14A; NbExp=3; IntAct=EBI-12836456, EBI-2800360; CC P49682-3; Q969F0: FATE1; NbExp=3; IntAct=EBI-16432539, EBI-743099; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane CC {ECO:0000269|PubMed:12782716}; Multi-pass membrane protein CC {ECO:0000269|PubMed:12782716}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane CC {ECO:0000269|PubMed:12782716}; Multi-pass membrane protein CC {ECO:0000269|PubMed:12782716}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=CXCR3-A; CC IsoId=P49682-1; Sequence=Displayed; CC Name=2; Synonyms=CXCR3-B; CC IsoId=P49682-2; Sequence=VSP_015684; CC Name=3; Synonyms=CXCR3-alt; CC IsoId=P49682-3; Sequence=VSP_015685; CC -!- TISSUE SPECIFICITY: Isoform 1 and isoform 2 are mainly expressed in CC heart, kidney, liver and skeletal muscle. Isoform 1 is also expressed CC in placenta. Isoform 2 is expressed in endothelial cells. Expressed in CC T-cells (at protein level). {ECO:0000269|PubMed:12782716, CC ECO:0000269|PubMed:23121557}. CC -!- PTM: Sulfation on Tyr-27 and Tyr-29 is essential for CXCL10 binding and CC subsequent signal transduction induction. {ECO:0000269|PubMed:16847335, CC ECO:0000269|PubMed:19151743}. CC -!- PTM: N-glycosylated. CC -!- MISCELLANEOUS: [Isoform 3]: Due to exon skipping. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. CC {ECO:0000255|PROSITE-ProRule:PRU00521}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/40224/CXCR3"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=CXC chemokine receptors entry; CC URL="https://en.wikipedia.org/wiki/CXC_chemokine_receptors"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X95876; CAA65126.1; -; mRNA. DR EMBL; AF469635; AAP55851.1; -; mRNA. DR EMBL; Z79783; CAB02143.1; -; Genomic_DNA. DR EMBL; AY242128; AAO92295.1; -; mRNA. DR EMBL; AK313679; BAG36429.1; -; mRNA. DR EMBL; BC034403; AAH34403.1; -; mRNA. DR EMBL; U32674; AAC50505.1; -; Genomic_DNA. DR EMBL; AB032735; BAA92297.1; -; Genomic_DNA. DR EMBL; AB032736; BAA92298.1; -; Genomic_DNA. DR CCDS; CCDS14416.1; -. [P49682-1] DR CCDS; CCDS48135.1; -. [P49682-2] DR RefSeq; NP_001136269.1; NM_001142797.1. [P49682-2] DR RefSeq; NP_001495.1; NM_001504.1. [P49682-1] DR RefSeq; XP_016884924.1; XM_017029435.1. [P49682-2] DR PDB; 8HNK; EM; 3.01 A; R=1-361. DR PDB; 8HNL; EM; 2.98 A; R=1-361. DR PDB; 8HNM; EM; 2.94 A; R=1-361. DR PDB; 8HNN; EM; 3.60 A; R=1-240, R=258-361. DR PDB; 8K2W; EM; 3.00 A; R=1-240, R=258-361. DR PDB; 8K2X; EM; 3.20 A; R=1-361. DR PDBsum; 8HNK; -. DR PDBsum; 8HNL; -. DR PDBsum; 8HNM; -. DR PDBsum; 8HNN; -. DR PDBsum; 8K2W; -. DR PDBsum; 8K2X; -. DR AlphaFoldDB; P49682; -. DR EMDB; EMD-34917; -. DR EMDB; EMD-36841; -. DR SMR; P49682; -. DR BioGRID; 109094; 498. DR DIP; DIP-5891N; -. DR IntAct; P49682; 9. DR STRING; 9606.ENSP00000362795; -. DR BindingDB; P49682; -. DR ChEMBL; CHEMBL4441; -. DR GuidetoPHARMACOLOGY; 70; -. DR GlyCosmos; P49682; 2 sites, No reported glycans. DR GlyGen; P49682; 2 sites. DR iPTMnet; P49682; -. DR PhosphoSitePlus; P49682; -. DR BioMuta; CXCR3; -. DR DMDM; 2829400; -. DR jPOST; P49682; -. DR MassIVE; P49682; -. DR PaxDb; 9606-ENSP00000362795; -. DR PeptideAtlas; P49682; -. DR ProteomicsDB; 56047; -. [P49682-1] DR ProteomicsDB; 56048; -. [P49682-2] DR Antibodypedia; 566; 1310 antibodies from 46 providers. DR DNASU; 2833; -. DR Ensembl; ENST00000373691.4; ENSP00000362795.4; ENSG00000186810.8. [P49682-2] DR Ensembl; ENST00000373693.4; ENSP00000362797.3; ENSG00000186810.8. [P49682-1] DR GeneID; 2833; -. DR KEGG; hsa:2833; -. DR MANE-Select; ENST00000373693.4; ENSP00000362797.3; NM_001504.2; NP_001495.1. DR UCSC; uc004eaf.3; human. [P49682-1] DR AGR; HGNC:4540; -. DR CTD; 2833; -. DR DisGeNET; 2833; -. DR GeneCards; CXCR3; -. DR HGNC; HGNC:4540; CXCR3. DR HPA; ENSG00000186810; Tissue enhanced (bone marrow, intestine, lymphoid tissue). DR MIM; 300574; gene. DR neXtProt; NX_P49682; -. DR OpenTargets; ENSG00000186810; -. DR PharmGKB; PA35049; -. DR VEuPathDB; HostDB:ENSG00000186810; -. DR eggNOG; KOG3656; Eukaryota. DR GeneTree; ENSGT01050000244848; -. DR HOGENOM; CLU_009579_8_3_1; -. DR InParanoid; P49682; -. DR OMA; SARHDER; -. DR OrthoDB; 5356683at2759; -. DR PhylomeDB; P49682; -. DR TreeFam; TF330966; -. DR PathwayCommons; P49682; -. DR Reactome; R-HSA-380108; Chemokine receptors bind chemokines. DR Reactome; R-HSA-418594; G alpha (i) signalling events. DR SignaLink; P49682; -. DR SIGNOR; P49682; -. DR BioGRID-ORCS; 2833; 16 hits in 765 CRISPR screens. DR GeneWiki; CXCR3; -. DR GenomeRNAi; 2833; -. DR Pharos; P49682; Tchem. DR PRO; PR:P49682; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; P49682; Protein. DR Bgee; ENSG00000186810; Expressed in granulocyte and 109 other cell types or tissues. DR GO; GO:0009986; C:cell surface; IDA:UniProt. DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc. DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0019957; F:C-C chemokine binding; IBA:GO_Central. DR GO; GO:0016493; F:C-C chemokine receptor activity; IBA:GO_Central. DR GO; GO:0019958; F:C-X-C chemokine binding; IDA:UniProtKB. DR GO; GO:0016494; F:C-X-C chemokine receptor activity; IEA:InterPro. DR GO; GO:0019956; F:chemokine binding; IPI:BHF-UCL. DR GO; GO:0004950; F:chemokine receptor activity; TAS:ProtInc. DR GO; GO:0038023; F:signaling receptor activity; IDA:UniProtKB. DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0019722; P:calcium-mediated signaling; IBA:GO_Central. DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc. DR GO; GO:0060326; P:cell chemotaxis; IBA:GO_Central. DR GO; GO:0007166; P:cell surface receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0006955; P:immune response; IBA:GO_Central. DR GO; GO:0006954; P:inflammatory response; IEA:InterPro. DR GO; GO:0016525; P:negative regulation of angiogenesis; IDA:UniProtKB. DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IDA:UniProtKB. DR GO; GO:1900118; P:negative regulation of execution phase of apoptosis; IDA:UniProtKB. DR GO; GO:0045766; P:positive regulation of angiogenesis; IDA:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB. DR GO; GO:0050921; P:positive regulation of chemotaxis; IDA:UniProtKB. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IBA:GO_Central. DR GO; GO:1900119; P:positive regulation of execution phase of apoptosis; IDA:UniProtKB. DR GO; GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0030155; P:regulation of cell adhesion; IDA:UniProtKB. DR GO; GO:0002685; P:regulation of leukocyte migration; IEA:InterPro. DR CDD; cd15180; 7tmA_CXCR3; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR004070; Chemokine_CXCR3. DR InterPro; IPR000355; Chemokine_rcpt. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR PANTHER; PTHR10489:SF671; C-X-C CHEMOKINE RECEPTOR TYPE 3; 1. DR PANTHER; PTHR10489; CELL ADHESION MOLECULE; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR00657; CCCHEMOKINER. DR PRINTS; PR01532; CXCCHMKINER3. DR PRINTS; PR00237; GPCRRHODOPSN. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. DR Genevisible; P49682; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Angiogenesis; Apoptosis; Cell membrane; KW Chemotaxis; Disulfide bond; G-protein coupled receptor; Glycoprotein; KW Membrane; Receptor; Reference proteome; Sulfation; Transducer; KW Transmembrane; Transmembrane helix. FT CHAIN 1..368 FT /note="C-X-C chemokine receptor type 3" FT /id="PRO_0000069346" FT TOPO_DOM 1..53 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 54..80 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 81..89 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 90..110 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 111..125 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 126..147 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 148..169 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 170..189 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 190..212 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 213..233 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 234..255 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 256..277 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 278..298 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 299..321 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 322..368 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 342..368 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 27 FT /note="Sulfotyrosine" FT /evidence="ECO:0000269|PubMed:16847335, FT ECO:0000269|PubMed:19151743" FT MOD_RES 29 FT /note="Sulfotyrosine" FT /evidence="ECO:0000269|PubMed:19151743" FT CARBOHYD 22 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 32 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 124..203 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521" FT VAR_SEQ 1..4 FT /note="MVLE -> MELRKYGPGRLAGTVIGGAAQSKSQTKSDSITKEFLPGLYTAPS FT SPFPPSQ (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12782716, FT ECO:0000303|PubMed:18291705" FT /id="VSP_015684" FT VAR_SEQ 210..368 FT /note="VGRTALRVLQLVAGFLLPLLVMAYCYAHILAVLLVSRGQRRLRAMRLVVVVV FT VAFALCWTPYHLVVLVDILMDLGALARNCGRESRVDVAKSVTSGLGYMHCCLNPLLYAF FT VGVKFRERMWMLLLRLGCPNQRGLQRQPSSSRRDSSWSETSEASYSGL -> GSSSGSG FT CGCCSCAWAAPTREGSRGSHRLPAGIHPGLRPQRPPTRACEAGIRAPLSPI (in FT isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_015685" FT VARIANT 292 FT /note="R -> Q (in dbSNP:rs139226823)" FT /evidence="ECO:0000269|PubMed:11196695" FT /id="VAR_016240" FT VARIANT 363 FT /note="A -> T (in dbSNP:rs766348940)" FT /evidence="ECO:0000269|PubMed:11196695" FT /id="VAR_016241" FT MUTAGEN 1..16 FT /note="Missing: Reduces binding to CXCL10 and CXCL11, and FT reduces CXCL10- and CXCL11-induced chemotaxis and FT activation. Does not affect CXCL9-induced chemotaxis and FT activation." FT /evidence="ECO:0000269|PubMed:16847335" FT MUTAGEN 4 FT /note="E->K: Does not affect binding to CXCL9, CXCL10 and FT CXCL11 or activation." FT /evidence="ECO:0000269|PubMed:16847335" FT MUTAGEN 21 FT /note="E->K: Reduces slightly CXCL9-, CXCL10- and FT CXCL11-induced chemotaxis." FT /evidence="ECO:0000269|PubMed:16847335" FT MUTAGEN 27..29 FT /note="YDY->ADA: Abolishes binding to CXCL10 and CXCL11 and FT CXCL9-, CXCL10- and CXCL11-induced chemotaxis." FT /evidence="ECO:0000269|PubMed:16847335" FT MUTAGEN 27 FT /note="Y->F: Reduces sulfation and CXCL9-, CXCL10- and FT CXCL11-induced chemotaxis. Abolishes binding to CXCL10. FT Abolishes sulfation, binding to CXCL11, ligand-induced FT receptor internalization and CXCL9-, CXCL10- and FT CXCL11-induced chemotaxis; when associated with F-29." FT /evidence="ECO:0000269|PubMed:16847335, FT ECO:0000269|PubMed:19151743" FT MUTAGEN 29 FT /note="Y->F: Reduces sulfation, binding to CXCL10 and FT CXCL9-, CXCL10- and CXCL11-induced chemotaxis. Abolishes FT sulfation, binding to CXCL10 and CXCL11 and CXCL9-, FT CXCL10- and CXCL11-induced chemotaxis; when associated with FT F-27." FT /evidence="ECO:0000269|PubMed:16847335, FT ECO:0000269|PubMed:19151743" FT MUTAGEN 112 FT /note="D->A: Abolishes binding to CXCL10 and CXCL11. FT Reduces CXCL9-, CXCL10- and CXCL11-induced chemotaxis." FT /evidence="ECO:0000269|PubMed:16847335" FT MUTAGEN 112 FT /note="D->K: Abolishes binding to CXCL10 and CXCL11 and FT CXCL10- and CXCL11-induced chemotaxis. Reduces FT CXCL9-induced chemotaxis." FT /evidence="ECO:0000269|PubMed:16847335" FT MUTAGEN 197 FT /note="R->A: Abolishes binding to CXCL10 and CXCL11 and FT CXCL9-, CXCL10- and CXCL11-induced chemotaxis. Reduces FT ligand-induced receptor internalization." FT /evidence="ECO:0000269|PubMed:16847335" FT MUTAGEN 212 FT /note="R->A: Abolishes CXCL10-induced chemotaxis. Reduces FT CXCL9- and CXCL11-induced chemotaxis. Does not affect FT binding to CXCL10 and CXCL11." FT /evidence="ECO:0000269|PubMed:16847335" FT MUTAGEN 216 FT /note="R->A: Reduces CXCL9-, CXCL10- and CXCL11-induced FT chemotaxis. Does not affect binding to CXCL10 and CXCL11 or FT receptor internalization." FT /evidence="ECO:0000269|PubMed:16847335" FT MUTAGEN 278 FT /note="D->A: Abolishes binding to CXCL10 and CXCL11 and FT CXCL11-induced chemotaxis. Reduces CXCL9 and CXCL10-induced FT chemotaxis." FT /evidence="ECO:0000269|PubMed:16847335" FT MUTAGEN 278 FT /note="D->K: Abolishes binding to CXCL10 and CXCL11 and FT CXCL9-, CXCL10- and CXCL11-induced chemotaxis." FT /evidence="ECO:0000269|PubMed:16847335" FT MUTAGEN 282 FT /note="D->A: Reduces binding to CXCL10 and CXCL9-, FT CXCL10- and CXCL11-induced chemotaxis. Abolishes binding to FT CXCL11." FT /evidence="ECO:0000269|PubMed:16847335" FT MUTAGEN 282 FT /note="D->K: Reduces binding to CXCL10 and CXCL11 and FT CXCL9-, CXCL10- and CXCL11-induced chemotaxis." FT /evidence="ECO:0000269|PubMed:16847335" FT MUTAGEN 293 FT /note="E->A: Reduces binding to CXCL10 and CXCL9- and FT CXCL11-induced chemotaxis. Abolishes binding to CXCL11 and FT CXCL10-induced chemotaxis." FT /evidence="ECO:0000269|PubMed:16847335" FT MUTAGEN 293 FT /note="E->K: Abolishes binding to CXCL10 and CXCL11 and FT CXCL9-, CXCL10- and CXCL11-induced chemotaxis." FT /evidence="ECO:0000269|PubMed:16847335" FT CONFLICT 75 FT /note="A -> R (in Ref. 4; CAB02143)" FT /evidence="ECO:0000305" FT CONFLICT 157 FT /note="T -> I (in Ref. 6; BAG36429)" FT /evidence="ECO:0000305" SQ SEQUENCE 368 AA; 40660 MW; F08A3B44B2BBAD04 CRC64; MVLEVSDHQV LNDAEVAALL ENFSSSYDYG ENESDSCCTS PPCPQDFSLN FDRAFLPALY SLLFLLGLLG NGAVAAVLLS RRTALSSTDT FLLHLAVADT LLVLTLPLWA VDAAVQWVFG SGLCKVAGAL FNINFYAGAL LLACISFDRY LNIVHATQLY RRGPPARVTL TCLAVWGLCL LFALPDFIFL SAHHDERLNA THCQYNFPQV GRTALRVLQL VAGFLLPLLV MAYCYAHILA VLLVSRGQRR LRAMRLVVVV VVAFALCWTP YHLVVLVDIL MDLGALARNC GRESRVDVAK SVTSGLGYMH CCLNPLLYAF VGVKFRERMW MLLLRLGCPN QRGLQRQPSS SRRDSSWSET SEASYSGL //