CXCR3
C-X-C chemokine receptor type 3
Also known as: CD183, CKR-L2, CMKAR3, CXCR3_HUMAN, GPR9, IP10-R, MigR
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P49682
- Gene
- CXCR3
- Ensembl
- ENSG00000186810
- Chromosome
- X
- Canonical length
- 368 aa
- Protein class
- CD markers, G-protein coupled receptors, Predicted membrane proteins
OverviewNCBI Gene
This gene encodes a G protein-coupled receptor with selectivity for three chemokines, termed CXCL9/Mig (monokine induced by interferon-g), CXCL10/IP10 (interferon-g-inducible 10 kDa protein) and CXCL11/I-TAC (interferon-inducible T cell a-chemoattractant). Binding of chemokines to this protein induces cellular responses that are involved in leukocyte traffic, most notably integrin activation, cytoskeletal changes and chemotactic migration. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. One of the isoforms (CXCR3-B) shows high affinity binding to chemokine, CXCL4/PF4 (PMID:12782716). [provided by RefSeq, Jun 2011]
Canonical amino-acid sequenceUniProt
368 residues, UniProt reviewed canonical sequence.
>P49682|CXCR3
1 MVLEVSDHQV LNDAEVAALL ENFSSSYDYG ENESDSCCTS PPCPQDFSLN FDRAFLPALY
61 SLLFLLGLLG NGAVAAVLLS RRTALSSTDT FLLHLAVADT LLVLTLPLWA VDAAVQWVFG
121 SGLCKVAGAL FNINFYAGAL LLACISFDRY LNIVHATQLY RRGPPARVTL TCLAVWGLCL
181 LFALPDFIFL SAHHDERLNA THCQYNFPQV GRTALRVLQL VAGFLLPLLV MAYCYAHILA
241 VLLVSRGQRR LRAMRLVVVV VVAFALCWTP YHLVVLVDIL MDLGALARNC GRESRVDVAK
301 SVTSGLGYMH CCLNPLLYAF VGVKFRERMW MLLLRLGCPN QRGLQRQPSS SRRDSSWSET
361 SEASYSGLLocalizationUniProt · AlphaFold · HPA
Whether an antibody against CXCR3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 7
- Mean surface accessibility (rSASA)
- 0.36
- Highest tissue expression
- 15 nTPM
Expression across tissuesHPA
Tissue
- lymph node: 15 nTPM
- spleen: 7.1 nTPM
- bone marrow: 6.8 nTPM
- small intestine: 6 nTPM
- appendix: 5.5 nTPM
- duodenum: 5.1 nTPM
Single-cell type
- pdcs: 110 nCPM
- t-cells: 40 nCPM
- enterocytes: 15 nCPM
- plasma cells: 14 nCPM
- nk-cells: 11 nCPM
- b-cells: 6.9 nCPM
Immune cell
- plasmacytoid DC: 307 nTPM
- NK-cell: 200 nTPM
- memory CD8 T-cell: 125 nTPM
- memory CD4 T-cell: 91 nTPM
- T-reg: 90 nTPM
- gdT-cell: 81 nTPM
Brain region
- cerebral cortex: 1.5 nTPM
- medulla oblongata: 1.2 nTPM
- cerebellum: 1.1 nTPM
- hippocampal formation: 1.1 nTPM
- amygdala: 1 nTPM
- thalamus: 1 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about CXCR3.
Disease | ImmuneIEDB
Conditions an epitope on CXCR3 was assayed in.
- systemic scleroderma B cell
ReferencesPubMed · IEDB
Publications for CXCR3 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
4 publications
- Disruption of CXCR3 function impedes the development of Sjögren's syndrome-like xerostomia in non-obese diabetic mice.
2018 · Lab Invest · RCR 1 · 22 citations - The role of CXCR3 and its ligands expression in Brucellar spondylitis.
2020 · BMC Immunol · RCR 0.3 · 4 citations - Targeting anti-CXCR3 autoantibodies as potential cardioprotective therapy: promises and challenges.
2023 · Eur Heart J · RCR 0.3 · 3 citations - Regulatory antibodies against GPCR in women ten years after early-onset preeclampsia.
2019 · Front Biosci (Landmark Ed) · RCR 0.1 · 3 citations
Reference: B cellIEDB
1 publication
- Autoantibodies in Serum of Systemic Scleroderma Patients: Peptide-Based Epitope Mapping Indicates Increased Binding to Cytoplasmic Domains of CXCR3.
2018 · Front Immunol · RCR 0.6 · 15 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.97
- gnomAD pLI
- 0.18
- gnomAD missense Z
- 1.74
- DepMap mean gene effect
- 0
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- adenylate cyclase-activating G protein-coupled receptor signaling pathway
- angiogenesis
- apoptotic process
- calcium-mediated signaling
- cell adhesion
- cell chemotaxis
- cell surface receptor signaling pathway
- chemotaxis
- G protein-coupled receptor signaling pathway
- immune response
- inflammatory response
- negative regulation of angiogenesis
- negative regulation of endothelial cell proliferation
- negative regulation of execution phase of apoptosis
- positive regulation of angiogenesis
- positive regulation of cell population proliferation
- positive regulation of chemotaxis
- positive regulation of cytosolic calcium ion concentration
- positive regulation of execution phase of apoptosis
- positive regulation of release of sequestered calcium ion into cytosol
- positive regulation of transcription by RNA polymerase II
- regulation of cell adhesion
- regulation of leukocyte migration
- T cell chemotaxis
Molecular functions
- C-C chemokine binding
- C-C chemokine receptor activity
- C-X-C chemokine binding
- C-X-C chemokine receptor activity
- chemokine binding
- chemokine receptor activity
- signaling receptor activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of CXCR3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads CXCR3 as an antibody target. Whether an autoantibody or antibody against CXCR3 could matter depends on whether native CXCR3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CXCR3 is annotated at the cell surface, where native CXCR3 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label CXCR3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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