Reviewed, UniProtKB/Swiss-Prot P70658 (CXCR4_MOUSE)

Names and origin

Protein names

Recommended name:
    C-X-C chemokine receptor type 4
      Short name=CXC-R4
      Short name=CXCR-4
Alternative name(s):
    Stromal cell-derived factor 1 receptor
      Short name=SDF-1 receptor
    Fusin
    Leukocyte-derived seven transmembrane domain receptor
      Short name=LESTR
    Pre-B-cell-derived chemokine receptor
      Short name=PB-CKR
    CD_antigen=CD184

Gene names

Name:	Cxcr4
Synonyms:	Cmkar4, Lestr, Sdf1r

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	359 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Receptor for the C-X-C chemokine CXCL12/SDF-1. Transduces a signal by increasing the intracellular calcium ions level. Involved in B-cell lymphopoiesis, bone-marrow myelopoiesis and in cardiac ventricular septum formation. Plays also an essential role in vascularization of the gastrointestinal tract, probably by regulating vascular branching and/or remodeling processes in endothelial cells. Involved in cerebellar neuronal layer formation, preventing premature migration of proliferating granule cells from the external granule layer inwards. In the CNS, could mediate hippocampal-neuron survival. Ref.9 Ref.10
Subunit structure	Monomer. Can form dimers By similarity.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Lymphocytes, macrophages, neutrophils, microglial cells and astrocytes. Found in spleen, thymus, bone marrow, lymph nodes and, at lower levels in brain, small intestine, stomach and kidney. CXCR4-A is predominant in all tissues tested.
Developmental stage	High expression during embryonic development does not seem to be associated with the differentiation of any particular cell type, but is widely utilized when there is a requirement for cell movement. Frequently associated with less differentiated cell types and down-regulated with subsequent differentiation. Detected in sites with haemopoietic potential: the yolk sac (7.5, 8.5 and 12.5 dpc) and fetal liver (12.5 dpc). During gastrulation, at 7.2 to 7.8 dpc, expressed in the mesoderm and the definitive endoderm. As gastrulation pattern fades (8.5 dpc), expression in the mesoderm is down-regulated, while it becomes predominant in neural ectoderm. Endodermal expression is retained in the foregut and later in a subset of foregut derivatives, including the stomach (10.5 dpc), the cystic ducts of the gall bladder and the lung epithelium (12.5 dpc). In neuronal tissue: at 10.5 and 12.5 dpc, expressed in the dorsal root ganglia, in the ventral mantle layer of the spinal cord (or basal plates), in the hindbrain. At 14.5 dpc, expression more tightly confined to the neural epithelium lining the ventricular space and to the external granular layer of the ventral rhombic lip (the developing cerebellum). Expressed in the outpocketing of the diencephalic floor at 10.5 dpc and in the developing thalamus and, to a lesser extent, the developing hypothalamus. At 14.5 dpc, restricted to the region where thalamus and hypothalamus meet. Detected in a discrete band of cells at the edge of the olfactory bulb. In the vascular system: expressed in the endothelium of numerous blood vessels, but not all, at 10.5, 11.5 and 12.5 dpc, such as vitelline/umbilical vessels, cardiac ventricular wall capillaries, facial vessels and, at 14.5 pdc, in the vasculature of the herniated gut. Expression seems to be associated with expanding vascular networks. In the heart development, expressed at 10.5 dpc in the precursor to the aortopulmonary (AP) septum. At 12.5 dpc, detected in the AP septum at the base of the outflow tract and in the atrioventricular valves. Detected in cranofacial ectoderm from 10.5 to 14.5 dpc. At 10.5 and 11.5 dpc, expressed in the Rathke pouch. Ref.11
Post-translational modification	Sulfation is required for efficient binding of CXCL12/SDF-1alpha and promotes its dimerization By similarity. O- and N-glycosylated. N-glycosylation can mask coreceptor function. The O-glycosylation chondroitin sulfate attachment does not affect interaction with CXCL12/SDF-1alpha nor its coreceptor activity By similarity.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Phosphoprotein Proteoglycan Sulfation
Gene Ontology (GO)
Biological process	G-protein coupled receptor protein signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW T cell proliferation Inferred from mutant phenotype. Source: MGI ameboidal cell migration Inferred from mutant phenotype. Source: MGI brain development Inferred from mutant phenotype. Source: MGI germ cell development Inferred from mutant phenotype. Source: MGI germ cell migration Inferred from mutant phenotype. Source: MGI motor axon guidance Inferred from mutant phenotype. Source: MGI neuron migration Inferred from direct assay. Source: MGI patterning of blood vessels Inferred from mutant phenotype. Source: MGI regulation of cell migration Inferred from mutant phenotype. Source: MGI
Cellular component	growth cone Inferred from direct assay. Source: MGI integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	C-C chemokine receptor activity Inferred from electronic annotation. Source: InterPro C-X-C chemokine receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform CXCR4-B (identifier: P70658-1)

Also known as: LESTR-B;

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.

Isoform CXCR4-A (identifier: P70658-2)

Also known as: LESTR-A;

The sequence of this isoform differs from the canonical sequence as follows:
     6-7: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 359	359	C-X-C chemokine receptor type 4		PRO_0000069355
Regions
	Topological domain	1 – 41	41	Extracellular Potential
	Transmembrane	42 – 65	24	1 Potential
	Topological domain	66 – 81	16	Cytoplasmic Potential
	Transmembrane	82 – 101	20	2 Potential
	Topological domain	102 – 112	11	Extracellular Potential
	Transmembrane	113 – 134	22	3 Potential
	Topological domain	135 – 156	22	Cytoplasmic Potential
	Transmembrane	157 – 177	21	4 Potential
	Topological domain	178 – 207	30	Extracellular Potential
	Transmembrane	208 – 227	20	5 Potential
	Topological domain	228 – 247	20	Cytoplasmic Potential
	Transmembrane	248 – 268	21	6 Potential
	Topological domain	269 – 292	24	Extracellular Potential
	Transmembrane	293 – 312	20	7 Potential
	Topological domain	313 – 359	47	Cytoplasmic Potential
Amino acid modifications
	Modified residue	23	1	Sulfotyrosine By similarity
	Modified residue	326	1	Phosphoserine By similarity
	Modified residue	355	1	Phosphoserine By similarity
	Modified residue	358	1	Phosphoserine By similarity
	Glycosylation	13	1	N-linked (GlcNAc...) By similarity
	Glycosylation	20	1	O-linked (Xyl...) (chondroitin sulfate) By similarity
	Disulfide bond	111 ↔ 193		By similarity
Natural variations
	Alternative sequence	6 – 7	2	Missing in isoform CXCR4-A.		VSP_001891
Experimental info
	Sequence conflict	216	1	I → V Ref.4
	Sequence conflict	216	1	I → V Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform CXCR4-B (LESTR-B) [UniParc]. Last modified November 1, 1997. Version 2. Checksum: 33D1B5552A31595B	FASTA	359	40,426
	10 20 30 40 50 60 MEPISVSIYT SDNYSEEVGS GDYDSNKEPC FRDENVHFNR IFLPTIYFII FLTGIVGNGL 70 80 90 100 110 120 VILVMGYQKK LRSMTDKYRL HLSVADLLFV ITLPFWAVDA MADWYFGKFL CKAVHIIYTV 130 140 150 160 170 180 NLYSSVLILA FISLDRYLAI VHATNSQRPR KLLAEKAVYV GVWIPALLLT IPDFIFADVS 190 200 210 220 230 240 QGDISQGDDR YICDRLYPDS LWMVVFQFQH IMVGLILPGI VILSCYCIII SKLSHSKGHQ 250 260 270 280 290 300 KRKALKTTVI LILAFFACWL PYYVGISIDS FILLGVIKQG CDFESIVHKW ISITEALAFF 310 320 330 340 350 HCCLNPILYA FLGAKFKSSA QHALNSMSRG SSLKILSKGK RGGHSSVSTE SESSSFHSS
	Isoform CXCR4-A (LESTR-A). Checksum: 648C8835307AD5EC	FASTA	357	40,240
	10 20 30 40 50 60 MEPISIYTSD NYSEEVGSGD YDSNKEPCFR DENVHFNRIF LPTIYFIIFL TGIVGNGLVI 70 80 90 100 110 120 LVMGYQKKLR SMTDKYRLHL SVADLLFVIT LPFWAVDAMA DWYFGKFLCK AVHIIYTVNL 130 140 150 160 170 180 YSSVLILAFI SLDRYLAIVH ATNSQRPRKL LAEKAVYVGV WIPALLLTIP DFIFADVSQG 190 200 210 220 230 240 DISQGDDRYI CDRLYPDSLW MVVFQFQHIM VGLILPGIVI LSCYCIIISK LSHSKGHQKR 250 260 270 280 290 300 KALKTTVILI LAFFACWLPY YVGISIDSFI LLGVIKQGCD FESIVHKWIS ITEALAFFHC 310 320 330 340 350 CLNPILYAFL GAKFKSSAQH ALNSMSRGSS LKILSKGKRG GHSSVSTESE SSSFHSS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the mouse fusin gene, homologue to a human HIV-1 co-factor." Heesen M., Berman M.A., Benson J.D., Gerard C., Dorf M.E. J. Immunol. 157:5455-5460(1996) [PubMed: 8955194] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM CXCR4-B). Strain: 129/Sv and C57BL/6J. Tissue: Peritoneal exudate.
[2]	"Molecular cloning and characterization of a murine pre-B-cell growth-stimulating factor/stromal cell-derived factor 1 receptor, a murine homolog of the human immunodeficiency virus 1 entry coreceptor fusin." Nagasawa T., Nakajima T., Tachibana K., Iizasa H., Bleul C.C., Yoshie O., Matsushima K., Yoshida N., Springer T.A., Kishimoto T. Proc. Natl. Acad. Sci. U.S.A. 93:14726-14729(1996) [PubMed: 8962122] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CXCR4-B). Tissue: Pre-B cell.
[3]	Schubel A., Burgstahler R., Lipp M. Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CXCR4-B). Strain: 129/Sv. Tissue: Thymus.
[4]	"Two murine homologues of the human chemokine receptor CXCR4 mediating stromal cell-derived factor 1alpha activation of Gi2 are differentially expressed in vivo." Moepps B., Frodl R., Rodewald H.-R., Baggiolini M., Gierschik P. Eur. J. Immunol. 27:2102-2112(1997) [PubMed: 9295051] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS CXCR4-A AND CXCR4-B). Strain: C57BL/6J X CBA/J. Tissue: Thymus.
[5]	"Alternate splicing of mouse fusin/CXC chemokine receptor-4: stromal cell-derived factor-1alpha is a ligand for both CXC chemokine receptor-4 isoforms." Heesen M., Berman M.A., Hoepken U.E., Gerard N.P., Dorf M.E. J. Immunol. 158:3561-3564(1997) [PubMed: 9103415] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS CXCR4-A AND CXCR4-B).
[6]	Suzuki G., Nakata Y., Uzawa A., Shirasawa T., Saito T., Mita K. Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CXCR4-B). Strain: C57BL/6. Tissue: Thymus.
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CXCR4-B). Strain: FVB/N. Tissue: Mammary gland.
[8]	"Genomic organization and expression of the CXCR4 gene in mouse and man: absence of a splice variant corresponding to mouse CXCR4-B in human tissues." Frodl R., Gierschik P., Moepps B. J. Recept. Signal Transduct. 18:321-344(1998) [PubMed: 9879064] [Abstract] Cited for: ALTERNATIVE SPLICING.
[9]	"The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract." Tachibana K., Hirota S., Iizasa H., Yoshida H., Kawabata K., Kataoka Y., Kitamura Y., Matsushima K., Yoshida N., Nishikawa S., Kishimoto T., Nagasawa T. Nature 393:591-594(1998) [PubMed: 9634237] [Abstract] Cited for: FUNCTION.
[10]	"Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development." Zou Y.-R., Kottmann A.H., Kuroda M., Taniuchi I., Littman D.R. Nature 393:595-599(1998) [PubMed: 9634238] [Abstract] Cited for: FUNCTION.
[11]	"Embryonic expression and function of the chemokine SDF-1 and its receptor, CXCR4." McGrath K.E., Koniski A.D., Maltby K.M., McGann J.K., Palis J. Dev. Biol. 213:442-456(1999) [PubMed: 10479460] [Abstract] Cited for: DEVELOPMENTAL STAGE. Strain: ICR.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U59760 mRNA. Translation: AAB07725.1. U65580 Genomic DNA. Translation: AAC52953.1. D87747 mRNA. Translation: BAA13451.1. Z80111 mRNA. Translation: CAB02201.1. Z80112 mRNA. Translation: CAB02202.1. X99581 Genomic DNA. Translation: CAA67893.1. X99582 mRNA. Translation: CAA67894.1. AB000803 mRNA. Translation: BAA19187.1. BC031665 mRNA. Translation: AAH31665.1. BC098322 mRNA. Translation: AAH98322.1.
IPI	IPI00111763. IPI00849797.
RefSeq	NP_034041.2.
UniGene	Mm.1401
3D structure databases
ModBase	Search...
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	P70658.
Proteomic databases
PRIDE	P70658.
Genome annotation databases
Ensembl	ENSMUSG00000045382. Mus musculus. [Contig view]
GeneID	12767.
KEGG	mmu:12767.
Organism-specific databases
MGI	MGI:109563. Cxcr4.
Phylogenomic databases
HOGENOM	P70658.
HOVERGEN	P70658.
Gene expression databases
ArrayExpress	P70658.
Bgee	P70658.
CleanEx	MM_CXCR4.
GermOnline	ENSMUSG00000045382. Mus musculus.
Family and domain databases
InterPro	IPR000276. 7TM_GPCR_Rhodpsn. IPR000355. Chmkine_rcpt. IPR001277. CXC_4_rcpt. IPR017452. GPCR_Rhodpsn_supfam. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00657. CCCHEMOKINER. PR00645. CXCCHMKINER4. PR00237. GPCRRHODOPSN.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	460845.
SOURCE	Search...

Entry information

Entry name

CXCR4_MOUSE

Accession

Primary (citable) accession number: P70658
Secondary accession number(s): O09059 , O09062, P70233, P70346, Q4KMW1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	June 16, 2009
This is version 86 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)