CXCR4_MOUSE
ID CXCR4_MOUSE Reviewed; 359 AA.
AC P70658; O09059; O09062; P70233; P70346; Q4KMW1;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=C-X-C chemokine receptor type 4;
DE Short=CXC-R4;
DE Short=CXCR-4;
DE AltName: Full=Fusin {ECO:0000303|PubMed:8955194};
DE AltName: Full=Leukocyte-derived seven transmembrane domain receptor;
DE Short=LESTR {ECO:0000303|PubMed:9295051};
DE AltName: Full=Pre-B-cell-derived chemokine receptor;
DE Short=PB-CKR;
DE AltName: Full=Stromal cell-derived factor 1 receptor;
DE Short=SDF-1 receptor;
DE AltName: CD_antigen=CD184;
GN Name=Cxcr4; Synonyms=Cmkar4, Lestr, Sdf1r;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM CXCR4-B).
RC STRAIN=129/Sv, and C57BL/6J; TISSUE=Peritoneal exudate;
RX PubMed=8955194;
RA Heesen M., Berman M.A., Benson J.D., Gerard C., Dorf M.E.;
RT "Cloning of the mouse fusin gene, homologue to a human HIV-1 co-factor.";
RL J. Immunol. 157:5455-5460(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CXCR4-B), FUNCTION, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Pre-B cell;
RX PubMed=8962122; DOI=10.1073/pnas.93.25.14726;
RA Nagasawa T., Nakajima T., Tachibana K., Iizasa H., Bleul C.C., Yoshie O.,
RA Matsushima K., Yoshida N., Springer T.A., Kishimoto T.;
RT "Molecular cloning and characterization of a murine pre-B-cell growth-
RT stimulating factor/stromal cell-derived factor 1 receptor, a murine homolog
RT of the human immunodeficiency virus 1 entry coreceptor fusin.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:14726-14729(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CXCR4-B).
RC STRAIN=129/Sv; TISSUE=Thymus;
RA Schubel A., Burgstahler R., Lipp M.;
RL Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS CXCR4-A AND CXCR4-B),
RP AND FUNCTION.
RC STRAIN=C57BL/6J X CBA/J; TISSUE=Thymus;
RX PubMed=9295051; DOI=10.1002/eji.1830270839;
RA Moepps B., Frodl R., Rodewald H.-R., Baggiolini M., Gierschik P.;
RT "Two murine homologues of the human chemokine receptor CXCR4 mediating
RT stromal cell-derived factor 1alpha activation of Gi2 are differentially
RT expressed in vivo.";
RL Eur. J. Immunol. 27:2102-2112(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS CXCR4-A AND CXCR4-B), AND
RP FUNCTION.
RX PubMed=9103415;
RA Heesen M., Berman M.A., Hoepken U.E., Gerard N.P., Dorf M.E.;
RT "Alternate splicing of mouse fusin/CXC chemokine receptor-4: stromal cell-
RT derived factor-1alpha is a ligand for both CXC chemokine receptor-4
RT isoforms.";
RL J. Immunol. 158:3561-3564(1997).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CXCR4-B).
RC STRAIN=C57BL/6J; TISSUE=Thymus;
RA Suzuki G., Nakata Y., Uzawa A., Shirasawa T., Saito T., Mita K.;
RL Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CXCR4-B).
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 ALTERNATIVE SPLICING.
RX PubMed=9879064; DOI=10.3109/10799899809047750;
RA Frodl R., Gierschik P., Moepps B.;
RT "Genomic organization and expression of the CXCR4 gene in mouse and man:
RT absence of a splice variant corresponding to mouse CXCR4-B in human
RT tissues.";
RL J. Recept. Signal Transduct. 18:321-344(1998).
RN [9]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=9634237; DOI=10.1038/31261;
RA Tachibana K., Hirota S., Iizasa H., Yoshida H., Kawabata K., Kataoka Y.,
RA Kitamura Y., Matsushima K., Yoshida N., Nishikawa S., Kishimoto T.,
RA Nagasawa T.;
RT "The chemokine receptor CXCR4 is essential for vascularization of the
RT gastrointestinal tract.";
RL Nature 393:591-594(1998).
RN [10]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=9634238; DOI=10.1038/31269;
RA Zou Y.-R., Kottmann A.H., Kuroda M., Taniuchi I., Littman D.R.;
RT "Function of the chemokine receptor CXCR4 in haematopoiesis and in
RT cerebellar development.";
RL Nature 393:595-599(1998).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=9689100; DOI=10.1073/pnas.95.16.9448;
RA Ma Q., Jones D., Borghesani P.R., Segal R.A., Nagasawa T., Kishimoto T.,
RA Bronson R.T., Springer T.A.;
RT "Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron
RT migration in CXCR4- and SDF-1-deficient mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:9448-9453(1998).
RN [12]
RP DEVELOPMENTAL STAGE.
RC STRAIN=ICR;
RX PubMed=10479460; DOI=10.1006/dbio.1999.9405;
RA McGrath K.E., Koniski A.D., Maltby K.M., McGann J.K., Palis J.;
RT "Embryonic expression and function of the chemokine SDF-1 and its receptor,
RT CXCR4.";
RL Dev. Biol. 213:442-456(1999).
RN [13]
RP INTERACTION WITH CD164.
RX PubMed=18227060; DOI=10.1074/jbc.m706730200;
RA Bae G.-U., Gaio U., Yang Y.-J., Lee H.-J., Kang J.-S., Krauss R.S.;
RT "Regulation of myoblast motility and fusion by the CXCR4-associated
RT sialomucin, CD164.";
RL J. Biol. Chem. 283:8301-8309(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-326, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces
CC a signal by increasing intracellular calcium ion levels and enhancing
CC MAPK1/MAPK3 activation (PubMed:8962122, PubMed:9295051,
CC PubMed:9103415). Involved in the AKT signaling cascade (By similarity).
CC Plays a role in regulation of cell migration, e.g. during wound
CC healing. Acts as a receptor for extracellular ubiquitin; leading to
CC enhanced intracellular calcium ions and reduced cellular cAMP levels.
CC Binds bacterial lipopolysaccharide (LPS) et mediates LPS-induced
CC inflammatory response, including TNF secretion by monocytes (By
CC similarity). Involved in hematopoiesis and in cardiac ventricular
CC septum formation (PubMed:9634237, PubMed:9634238, PubMed:9689100). Also
CC plays an essential role in vascularization of the gastrointestinal
CC tract, probably by regulating vascular branching and/or remodeling
CC processes in endothelial cells (PubMed:9634237). Involved in cerebellar
CC development. In the CNS, could mediate hippocampal-neuron survival
CC (PubMed:9634238, PubMed:9689100). {ECO:0000250|UniProtKB:P61073,
CC ECO:0000269|PubMed:8962122, ECO:0000269|PubMed:9103415,
CC ECO:0000269|PubMed:9295051, ECO:0000269|PubMed:9634237,
CC ECO:0000269|PubMed:9634238, ECO:0000269|PubMed:9689100}.
CC -!- SUBUNIT: Monomer. Can form homodimers. Interacts with CD164. Interacts
CC with ARRB2; the interaction is dependent on the C-terminal
CC phosphorylation of CXCR4 and allows activation of MAPK1 and MAPK3.
CC Interacts with ARR3; the interaction is dependent on the C-terminal
CC phosphorylation of CXCR4 and modulates calcium mobilization. Interacts
CC with RNF113A; the interaction, enhanced by CXCL12, promotes CXCR4
CC ubiquitination and subsequent degradation. Interacts (via the
CC cytoplasmic C-terminal) with ITCH (via the WW domains I and II); the
CC interaction, enhanced by CXCL12, promotes CXCR4 ubiquitination and
CC leads to its degradation. Interacts with extracellular ubiquitin.
CC Interacts with DBN1; this interaction is enhanced by antigenic
CC stimulation. Following LPS binding, may form a complex with GDF5,
CC HSP90AA1 and HSPA8. {ECO:0000250|UniProtKB:P61073}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:8962122,
CC ECO:0000269|PubMed:9295051}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P61073}. Cell junction {ECO:0000250}. Early
CC endosome {ECO:0000250}. Late endosome {ECO:0000250}. Lysosome
CC {ECO:0000250}. Note=In unstimulated cells, diffuse pattern on plasma
CC membrane. On agonist stimulation, colocalizes with ITCH at the plasma
CC membrane where it becomes ubiquitinated (By similarity). In the
CC presence of antigen, distributes to the immunological synapse forming
CC at the T-cell-APC contact area, where it localizes at the peripheral
CC and distal supramolecular activation cluster (SMAC) (By similarity).
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=CXCR4-B; Synonyms=LESTR-B;
CC IsoId=P70658-1; Sequence=Displayed;
CC Name=CXCR4-A; Synonyms=LESTR-A;
CC IsoId=P70658-2; Sequence=VSP_001891;
CC -!- TISSUE SPECIFICITY: Lymphocytes, macrophages, neutrophils, microglial
CC cells and astrocytes. Found in spleen, thymus, bone marrow, lymph nodes
CC and, at lower levels in brain, small intestine, stomach and kidney.
CC CXCR4-A is predominant in all tissues tested. During embryonic
CC development, high levels are detected in the endothelium of developing
CC blood vessels and in many regions of the developing brain including the
CC olfactory epithelium, olfactory bulb, hippocampus, cerebellum and
CC spinal cord. {ECO:0000269|PubMed:9634237, ECO:0000269|PubMed:9634238}.
CC -!- DEVELOPMENTAL STAGE: High expression during embryonic development does
CC not seem to be associated with the differentiation of any particular
CC cell type, but is widely utilized when there is a requirement for cell
CC movement. Frequently associated with less differentiated cell types and
CC down-regulated with subsequent differentiation. Detected in sites with
CC hemopoietic potential: the yolk sac (7.5, 8.5 and 12.5 dpc) and fetal
CC liver (12.5 dpc). During gastrulation, at 7.2 to 7.8 dpc, expressed in
CC the mesoderm and the definitive endoderm. As gastrulation pattern fades
CC (8.5 dpc), expression in the mesoderm is down-regulated, while it
CC becomes predominant in neural ectoderm. Endodermal expression is
CC retained in the foregut and later in a subset of foregut derivatives,
CC including the stomach (10.5 dpc), the cystic ducts of the gall bladder
CC and the lung epithelium (12.5 dpc). In neuronal tissue: at 10.5 and
CC 12.5 dpc, expressed in the dorsal root ganglia, in the ventral mantle
CC layer of the spinal cord (or basal plates), in the hindbrain. At 14.5
CC dpc, expression more tightly confined to the neural epithelium lining
CC the ventricular space and to the external granular layer of the ventral
CC rhombic lip (the developing cerebellum). Expressed in the outpocketing
CC of the diencephalic floor at 10.5 dpc and in the developing thalamus
CC and, to a lesser extent, the developing hypothalamus. At 14.5 dpc,
CC restricted to the region where thalamus and hypothalamus meet. Detected
CC in a discrete band of cells at the edge of the olfactory bulb. In the
CC vascular system: expressed in the endothelium of numerous blood
CC vessels, but not all, at 10.5, 11.5 and 12.5 dpc, such as
CC vitelline/umbilical vessels, cardiac ventricular wall capillaries,
CC facial vessels and, at 14.5 dpc, in the vasculature of the herniated
CC gut. Expression seems to be associated with expanding vascular
CC networks. In the heart development, expressed at 10.5 dpc in the
CC precursor to the aortopulmonary (AP) septum. At 12.5 dpc, detected in
CC the AP septum at the base of the outflow tract and in the
CC atrioventricular valves. Detected in cranofacial ectoderm from 10.5 to
CC 14.5 dpc. At 10.5 and 11.5 dpc, expressed in the Rathke pouch.
CC {ECO:0000269|PubMed:10479460}.
CC -!- PTM: Phosphorylated on agonist stimulation. Rapidly phosphorylated on
CC serine and threonine residues in the C-terminal. Phosphorylation at
CC Ser-331 and Ser-332 leads to recruitment of ITCH, ubiquitination and
CC protein degradation. {ECO:0000250|UniProtKB:P61073}.
CC -!- PTM: Ubiquitinated after ligand binding, leading to its degradation.
CC Ubiquitinated by ITCH at the cell membrane on agonist stimulation. The
CC ubiquitin-dependent mechanism, endosomal sorting complex required for
CC transport (ESCRT), then targets CXCR4 for lysosomal degradation. This
CC process is dependent also on prior Ser-/Thr-phosphorylation in the C-
CC terminal of CXCR4. Also binding of ARRB1 to STAM negatively regulates
CC CXCR4 sorting to lysosomes though modulating ubiquitination of SFR5S.
CC {ECO:0000250|UniProtKB:P61073}.
CC -!- PTM: Sulfation is required for efficient binding of CXCL12/SDF-1alpha
CC and promotes its dimerization. {ECO:0000250|UniProtKB:P61073}.
CC -!- PTM: O- and N-glycosylated. N-glycosylation can mask coreceptor
CC function. The O-glycosylation chondroitin sulfate attachment does not
CC affect interaction with CXCL12/SDF-1alpha nor its coreceptor activity.
CC {ECO:0000250|UniProtKB:P61073}.
CC -!- DISRUPTION PHENOTYPE: Half of the embryos die by 17.5 dpc-18.5 dpc and
CC neonates die within a few hours. Mutants display defective vascular
CC development, cerebellar development, B-lymphopoiesis, myelopoiesis, and
CC cardiogenesis with defective formation of the large vessels supplying
CC the gastrointestinal tract. {ECO:0000269|PubMed:9634237,
CC ECO:0000269|PubMed:9634238, ECO:0000269|PubMed:9689100}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; U59760; AAB07725.1; -; mRNA.
DR EMBL; U65580; AAC52953.1; -; Genomic_DNA.
DR EMBL; D87747; BAA13451.1; -; mRNA.
DR EMBL; Z80111; CAB02201.1; -; mRNA.
DR EMBL; Z80112; CAB02202.1; -; mRNA.
DR EMBL; X99581; CAA67893.1; -; Genomic_DNA.
DR EMBL; X99582; CAA67894.1; -; mRNA.
DR EMBL; AB000803; BAA19187.1; -; mRNA.
DR EMBL; BC031665; AAH31665.1; -; mRNA.
DR EMBL; BC098322; AAH98322.1; -; mRNA.
DR CCDS; CCDS15254.1; -. [P70658-1]
DR RefSeq; NP_034041.2; NM_009911.3.
DR AlphaFoldDB; P70658; -.
DR SMR; P70658; -.
DR BioGRID; 198767; 2.
DR IntAct; P70658; 4.
DR STRING; 10090.ENSMUSP00000053489; -.
DR BindingDB; P70658; -.
DR ChEMBL; CHEMBL1250365; -.
DR GuidetoPHARMACOLOGY; 71; -.
DR GlyGen; P70658; 2 sites.
DR iPTMnet; P70658; -.
DR PhosphoSitePlus; P70658; -.
DR EPD; P70658; -.
DR jPOST; P70658; -.
DR MaxQB; P70658; -.
DR PaxDb; P70658; -.
DR PeptideAtlas; P70658; -.
DR PRIDE; P70658; -.
DR ProteomicsDB; 279222; -. [P70658-1]
DR ProteomicsDB; 279223; -. [P70658-2]
DR DNASU; 12767; -.
DR GeneID; 12767; -.
DR KEGG; mmu:12767; -.
DR UCSC; uc007cls.1; mouse. [P70658-2]
DR UCSC; uc007clt.1; mouse. [P70658-1]
DR CTD; 7852; -.
DR MGI; MGI:109563; Cxcr4.
DR eggNOG; KOG3656; Eukaryota.
DR InParanoid; P70658; -.
DR OrthoDB; 773026at2759; -.
DR PhylomeDB; P70658; -.
DR TreeFam; TF330966; -.
DR Reactome; R-MMU-376176; Signaling by ROBO receptors.
DR Reactome; R-MMU-380108; Chemokine receptors bind chemokines.
DR Reactome; R-MMU-418594; G alpha (i) signalling events.
DR BioGRID-ORCS; 12767; 1 hit in 77 CRISPR screens.
DR ChiTaRS; Cxcr4; mouse.
DR PRO; PR:P70658; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P70658; protein.
DR GO; GO:0031252; C:cell leading edge; ISO:MGI.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; ISO:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0030426; C:growth cone; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0003779; F:actin binding; ISO:MGI.
DR GO; GO:0019957; F:C-C chemokine binding; ISO:MGI.
DR GO; GO:0016493; F:C-C chemokine receptor activity; IBA:GO_Central.
DR GO; GO:0038147; F:C-X-C motif chemokine 12 receptor activity; ISS:UniProtKB.
DR GO; GO:0032027; F:myosin light chain binding; ISO:MGI.
DR GO; GO:0036094; F:small molecule binding; ISO:MGI.
DR GO; GO:0043130; F:ubiquitin binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0009887; P:animal organ morphogenesis; TAS:ProtInc.
DR GO; GO:0035904; P:aorta development; IMP:MGI.
DR GO; GO:0043534; P:blood vessel endothelial cell migration; IMP:MGI.
DR GO; GO:0007420; P:brain development; IMP:MGI.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IMP:MGI.
DR GO; GO:0019722; P:calcium-mediated signaling; ISO:MGI.
DR GO; GO:0060048; P:cardiac muscle contraction; ISO:MGI.
DR GO; GO:0060326; P:cell chemotaxis; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; ISO:MGI.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; IDA:MGI.
DR GO; GO:0038160; P:CXCL12-activated CXCR4 signaling pathway; IDA:MGI.
DR GO; GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; ISO:MGI.
DR GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; ISO:MGI.
DR GO; GO:0045446; P:endothelial cell differentiation; ISO:MGI.
DR GO; GO:0061154; P:endothelial tube morphogenesis; ISO:MGI.
DR GO; GO:0002064; P:epithelial cell development; ISO:MGI.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0048699; P:generation of neurons; IEP:DFLAT.
DR GO; GO:0007281; P:germ cell development; IMP:MGI.
DR GO; GO:0008354; P:germ cell migration; IMP:MGI.
DR GO; GO:0035701; P:hematopoietic stem cell migration; IMP:MGI.
DR GO; GO:0006955; P:immune response; IBA:GO_Central.
DR GO; GO:0001822; P:kidney development; IMP:MGI.
DR GO; GO:0008045; P:motor neuron axon guidance; IMP:MGI.
DR GO; GO:0043217; P:myelin maintenance; IMP:BHF-UCL.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0061351; P:neural precursor cell proliferation; IEP:DFLAT.
DR GO; GO:0022008; P:neurogenesis; ISO:MGI.
DR GO; GO:0001764; P:neuron migration; IDA:MGI.
DR GO; GO:0090280; P:positive regulation of calcium ion import; IDA:MGI.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:0050921; P:positive regulation of chemotaxis; ISO:MGI.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IBA:GO_Central.
DR GO; GO:1903861; P:positive regulation of dendrite extension; ISO:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:MGI.
DR GO; GO:2000448; P:positive regulation of macrophage migration inhibitory factor signaling pathway; ISO:MGI.
DR GO; GO:1905322; P:positive regulation of mesenchymal stem cell migration; ISO:MGI.
DR GO; GO:0050769; P:positive regulation of neurogenesis; ISO:MGI.
DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; IMP:BHF-UCL.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:MGI.
DR GO; GO:0035470; P:positive regulation of vascular wound healing; ISO:MGI.
DR GO; GO:0051924; P:regulation of calcium ion transport; ISO:MGI.
DR GO; GO:0030155; P:regulation of cell adhesion; ISO:MGI.
DR GO; GO:0030334; P:regulation of cell migration; IMP:MGI.
DR GO; GO:0050920; P:regulation of chemotaxis; ISO:MGI.
DR GO; GO:2001222; P:regulation of neuron migration; IMP:MGI.
DR GO; GO:0043067; P:regulation of programmed cell death; ISO:MGI.
DR GO; GO:0050792; P:regulation of viral process; ISO:MGI.
DR GO; GO:0014070; P:response to organic cyclic compound; ISO:MGI.
DR GO; GO:0042098; P:T cell proliferation; IMP:MGI.
DR GO; GO:0022029; P:telencephalon cell migration; ISO:MGI.
DR GO; GO:0003281; P:ventricular septum development; IMP:MGI.
DR InterPro; IPR022726; Chemokine_CXCR4_N_dom.
DR InterPro; IPR000355; Chemokine_rcpt.
DR InterPro; IPR001277; CXCR4/ACKR2.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR Pfam; PF12109; CXCR4_N; 1.
DR PRINTS; PR00657; CCCHEMOKINER.
DR PRINTS; PR00645; CXCCHMKINER4.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell junction; Cell membrane; Disulfide bond;
KW Endosome; G-protein coupled receptor; Glycoprotein; Isopeptide bond;
KW Lysosome; Membrane; Phosphoprotein; Proteoglycan; Receptor;
KW Reference proteome; Sulfation; Transducer; Transmembrane;
KW Transmembrane helix; Ubl conjugation.
FT CHAIN 1..359
FT /note="C-X-C chemokine receptor type 4"
FT /id="PRO_0000069355"
FT TOPO_DOM 1..40
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 41..65
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT TOPO_DOM 66..79
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 80..101
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT TOPO_DOM 102..112
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 113..132
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT TOPO_DOM 133..156
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 157..176
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT TOPO_DOM 177..202
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 203..223
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT TOPO_DOM 224..248
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 249..268
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT TOPO_DOM 269..289
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 290..309
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT TOPO_DOM 310..359
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 1..23
FT /note="Important for chemokine binding and signaling"
FT /evidence="ECO:0000250"
FT REGION 96..99
FT /note="Chemokine binding"
FT /evidence="ECO:0000250"
FT REGION 115..119
FT /note="Chemokine binding"
FT /evidence="ECO:0000250"
FT REGION 137..149
FT /note="Involved in dimerization; when bound to chemokine"
FT /evidence="ECO:0000250"
FT REGION 193..197
FT /note="Chemokine binding, important for signaling"
FT /evidence="ECO:0000250"
FT REGION 198..217
FT /note="Involved in dimerization"
FT /evidence="ECO:0000250"
FT REGION 273..275
FT /note="Involved in dimerization"
FT /evidence="ECO:0000250"
FT REGION 335..359
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 135..137
FT /note="Important for signaling"
FT /evidence="ECO:0000250"
FT COMPBIAS 342..359
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 173
FT /note="Chemokine binding"
FT /evidence="ECO:0000250"
FT SITE 295
FT /note="Chemokine binding"
FT /evidence="ECO:0000250"
FT MOD_RES 9
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT MOD_RES 14
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT MOD_RES 23
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT MOD_RES 326
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 328
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT MOD_RES 331
FT /note="Phosphoserine; by PKC and GRK6"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT MOD_RES 332
FT /note="Phosphoserine; by PKC and GRK6"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT MOD_RES 337
FT /note="Phosphoserine; by GRK6"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT MOD_RES 346
FT /note="Phosphoserine; by GRK6"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT MOD_RES 355
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT MOD_RES 358
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT CARBOHYD 13
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 20
FT /note="O-linked (Xyl...) (chondroitin sulfate) serine"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT DISULFID 30..281
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 111..193
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT CROSSLNK 338
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT VAR_SEQ 6..7
FT /note="Missing (in isoform CXCR4-A)"
FT /evidence="ECO:0000303|PubMed:9295051"
FT /id="VSP_001891"
FT CONFLICT 216
FT /note="I -> V (in Ref. 4; CAA67893 and 6; BAA19187)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 359 AA; 40426 MW; 33D1B5552A31595B CRC64;
MEPISVSIYT SDNYSEEVGS GDYDSNKEPC FRDENVHFNR IFLPTIYFII FLTGIVGNGL
VILVMGYQKK LRSMTDKYRL HLSVADLLFV ITLPFWAVDA MADWYFGKFL CKAVHIIYTV
NLYSSVLILA FISLDRYLAI VHATNSQRPR KLLAEKAVYV GVWIPALLLT IPDFIFADVS
QGDISQGDDR YICDRLYPDS LWMVVFQFQH IMVGLILPGI VILSCYCIII SKLSHSKGHQ
KRKALKTTVI LILAFFACWL PYYVGISIDS FILLGVIKQG CDFESIVHKW ISITEALAFF
HCCLNPILYA FLGAKFKSSA QHALNSMSRG SSLKILSKGK RGGHSSVSTE SESSSFHSS
