CXCR4
C-X-C chemokine receptor type 4
Also known as: CD184, CXCR4_HUMAN, D2S201E, fusin, HM89, HSY3RR, LESTR, NPY3R, NPYR, NPYY3R
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P61073
- Gene
- CXCR4
- Ensembl
- ENSG00000121966
- Chromosome
- 2
- Canonical length
- 352 aa
- Protein class
- Cancer-related genes, CD markers, Disease related genes, FDA approved drug targets, G-protein coupled receptors, Human disease related genes, Predicted membrane proteins, Transporters
- Quaternary structure
- Homodimer
OverviewNCBI Gene
This gene encodes a CXC chemokine receptor specific for stromal cell-derived factor-1. The protein has 7 transmembrane regions and is located on the cell surface. It acts with the CD4 protein to support HIV entry into cells and is also highly expressed in breast cancer cells. Mutations in this gene have been associated with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
352 residues, UniProt reviewed canonical sequence.
>P61073|CXCR4
1 MEGISIYTSD NYTEEMGSGD YDSMKEPCFR EENANFNKIF LPTIYSIIFL TGIVGNGLVI
61 LVMGYQKKLR SMTDKYRLHL SVADLLFVIT LPFWAVDAVA NWYFGNFLCK AVHVIYTVNL
121 YSSVLILAFI SLDRYLAIVH ATNSQRPRKL LAEKVVYVGV WIPALLLTIP DFIFANVSEA
181 DDRYICDRFY PNDLWVVVFQ FQHIMVGLIL PGIVILSCYC IIISKLSHSK GHQKRKALKT
241 TVILILAFFA CWLPYYIGIS IDSFILLEII KQGCEFENTV HKWISITEAL AFFHCCLNPI
301 LYAFLGAKFK TSAQHALTSV SRGSSLKILS KGKRGGHSSV STESESSSFH SSLocalizationUniProt · AlphaFold · HPA
Whether an antibody against CXCR4 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)
- 0.34
- Highest tissue expression
- 1,175 nTPM
Expression across tissuesHPA
Tissue
- bone marrow: 1,175 nTPM
- tonsil: 523 nTPM
- thymus: 464 nTPM
- lymph node: 379 nTPM
- spleen: 337 nTPM
- appendix: 300 nTPM
Single-cell type
- innate lymphoid cells: 1,590 nCPM
- t-cells: 1,588 nCPM
- b-cells: 1,507 nCPM
- neutrophils: 1,115 nCPM
- nk-cells: 960 nCPM
- cdc: 462 nCPM
Immune cell
- naive B-cell: 168 nTPM
- neutrophil: 145 nTPM
- eosinophil: 120 nTPM
- memory B-cell: 117 nTPM
- naive CD4 T-cell: 114 nTPM
- naive CD8 T-cell: 110 nTPM
Brain region
- white matter: 72 nTPM
- medulla oblongata: 44 nTPM
- cerebral cortex: 36 nTPM
- hypothalamus: 35 nTPM
- choroid plexus: 35 nTPM
- spinal cord: 28 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about CXCR4.
Disease | AllUniProt
Conditions CXCR4 is implicated in, by any mechanism.
- WHIM syndrome 1 (WHIMS1) MIM:193670
Disease | GeneticClinVar
40 pathogenic / likely-pathogenic of 239 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- WHIM syndrome 1
- Warts, hypogammaglobulinemia, infections, and myelokathexis
- Neoplasm
- Inherited Immunodeficiency Diseases
ReferencesPubMed · IEDB
Publications for CXCR4 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
3 publications
- Antibodies against chemokine receptors CXCR3 and CXCR4 predict progressive deterioration of lung function in patients with systemic sclerosis.
2018 · Arthritis Res Ther · RCR 2 · 45 citations - Autoantibodies against C5aR1, C3aR1, CXCR3, and CXCR4 are decreased in primary Sjogren's syndrome.
2021 · Mol Immunol · RCR 0.5 · 8 citations - Human anti-CXCR4 antibodies undergo VH replacement, exhibit functional V-region sulfation, and define CXCR4 antigenic heterogeneity.
2007 · J Immunol · RCR 0.4 · 18 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. 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)
- 1.05
- gnomAD pLI
- 0.02
- gnomAD missense Z
- 1.66
- DepMap mean gene effect
- -0.01
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
- apoptotic process
- brain development
- calcium-mediated signaling
- cell chemotaxis
- cellular response to cytokine stimulus
- CXCL12-activated CXCR4 signaling pathway
- dendritic cell chemotaxis
- G protein-coupled receptor signaling pathway
- immune response
- inflammatory response
- myelin maintenance
- neurogenesis
- positive regulation of cell migration
- positive regulation of cold-induced thermogenesis
- positive regulation of cytosolic calcium ion concentration
- positive regulation of macrophage migration inhibitory factor signaling pathway
- positive regulation of oligodendrocyte differentiation
- positive regulation of vasculature development
- regulation of cell adhesion
- response to hypoxia
- response to virus
Molecular functions
- actin binding
- C-C chemokine binding
- C-C chemokine receptor activity
- C-X-C chemokine receptor activity
- coreceptor activity
- G protein-coupled receptor activity
- myosin light chain binding
- ubiquitin binding
- ubiquitin protein ligase binding
- virus receptor activity
- C-X-C motif chemokine 12 receptor activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
- G protein-coupled receptor, rhodopsin-like
- Chemokine receptor family
- CXC chemokine receptor 4/atypical chemokine receptor 2
- GPCR, rhodopsin-like, 7TM
- C-C chemokine receptor type 1-9-like
- 7 transmembrane receptor (rhodopsin family)
- CXC chemokine receptor 4 N-terminal domain
- CXCR4 Chemokine receptor N terminal
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of CXCR4 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 CXCR4 as an antibody target. Whether an autoantibody or antibody against CXCR4 could matter depends on whether native CXCR4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CXCR4 is annotated at the cell surface, where native CXCR4 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 CXCR4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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