UniProt Accession

 CXCR4_HUMAN; P61073; B2R5N0; O60835; P30991; P56438; Q53S69; Q9BXA0; Q9UKN2 

Genbank Protein ID

 L01639; M99293; X71635; L06797; D10924; AF005058; AF052572; AJ224869; AF025375; Y14739; AF147204; AF348491; AK312244; AY242129; BT006660; AY728138; AC068492; CH471058; BC020968 

Genbank Nucleotide ID

 AAA16594.1; AAA16617.1; CAA50641.1; AAA03209.1; BAA01722.1; AAB93982.1; AAC34581.1; CAA12166.1; AAB81970.1; CAA75034.1; AAF00130.1; AAK29630.1; BAG35177.1; AAO92296.1; AAP35306.1; AAU05775.1; AAY24044.1; EAX11616.1; AAH20968.1 

Protein Name

 C-X-C chemokine receptor type 4 

Protein Synonyms/Alias

 CXC-R4; CXCR-4; FB22; Fusin; HM89; LCR1; Leukocyte-derived seven transmembrane domain receptor; LESTR; NPYRL; Stromal cell-derived factor 1 receptor; SDF-1 receptor; CD184 

Gene Name

 CXCR4 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
310	AFLGAKFKTSAQHAL	ubiquitination	[1, 2, 3]
327	VSRGSSLKILSKGKR	ubiquitination	[1, 2, 3, 4, 5]
331	SSLKILSKGKRGGHS	ubiquitination	[1]

Reference

 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [4] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [5] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724] 

Functional Description

 Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Acts as a receptor for extracellular ubiquitin; leading to enhanced intracellular calcium ions and reduced cellular cAMP levels. Involved in hematopoiesis and in cardiac ventricular septum formation. Also plays an essential role in vascularization of the gastrointestinal tract, probably by regulating vascular branching and/or remodeling processes in endothelial cells. Involved in cerebellar development. In the CNS, could mediate hippocampal-neuron survival. Acts as a coreceptor (CD4 being the primary receptor) for HIV-1 X4 isolates and as a primary receptor for some HIV-2 isolates. Promotes Env-mediated fusion of the virus. 

Sequence Annotation

 REGION 1 21 Important for chemokine binding,
 REGION 94 97 Chemokine binding.
 REGION 113 117 Chemokine binding.
 REGION 135 147 Involved in dimerization; when bound to
 REGION 186 190 Chemokine binding, important for
 REGION 191 210 Involved in dimerization.
 REGION 266 268 Involved in dimerization.
 MOTIF 133 135 Important for signaling.
 BINDING 171 171 Chemokine.
 BINDING 288 288 Chemokine.
 MOD_RES 7 7 Sulfotyrosine; partial.
 MOD_RES 12 12 Sulfotyrosine; partial.
 MOD_RES 21 21 Sulfotyrosine.
 MOD_RES 319 319 Phosphoserine.
 MOD_RES 321 321 Phosphoserine.
 MOD_RES 324 324 Phosphoserine; by PKC and GRK6.
 MOD_RES 325 325 Phosphoserine; by PKC and GRK6.
 MOD_RES 330 330 Phosphoserine; by GRK6.
 MOD_RES 339 339 Phosphoserine; by GRK6.
 MOD_RES 348 348 Phosphoserine.
 MOD_RES 351 351 Phosphoserine.
 CARBOHYD 11 11 N-linked (GlcNAc...).
 CARBOHYD 18 18 O-linked (Xyl...) (chondroitin sulfate).
 CARBOHYD 176 176 N-linked (GlcNAc...) (Potential).
 DISULFID 28 274
 DISULFID 109 186  

Keyword

 3D-structure; Alternative splicing; Cell membrane; Complete proteome; Disulfide bond; G-protein coupled receptor; Glycoprotein; Host cell receptor for virus entry; Host-virus interaction; Membrane; Phosphoprotein; Proteoglycan; Receptor; Reference proteome; Sulfation; Transducer; Transmembrane; Transmembrane helix; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 352 AA 

Protein Sequence

Gene Ontology

 GO:0031252; C:cell leading edge; IDA:UniProtKB.
 GO:0009986; C:cell surface; IDA:UniProtKB.
 GO:0016023; C:cytoplasmic membrane-bounded vesicle; IDA:UniProtKB.
 GO:0009897; C:external side of plasma membrane; IEA:Compara.
 GO:0030426; C:growth cone; IEA:Compara.
 GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
 GO:0005886; C:plasma membrane; TAS:Reactome.
 GO:0003779; F:actin binding; IDA:UniProtKB.
 GO:0016494; F:C-X-C chemokine receptor activity; NAS:UniProtKB.
 GO:0015026; F:coreceptor activity; TAS:ProtInc.
 GO:0032027; F:myosin light chain binding; IDA:UniProtKB.
 GO:0043130; F:ubiquitin binding; IDA:UniProtKB.
 GO:0000187; P:activation of MAPK activity; TAS:ProtInc.
 GO:0001667; P:ameboidal cell migration; IEA:Compara.
 GO:0006915; P:apoptotic process; TAS:ProtInc.
 GO:0007420; P:brain development; IEA:Compara.
 GO:0019722; P:calcium-mediated signaling; IMP:MGI.
 GO:0002407; P:dendritic cell chemotaxis; TAS:BHF-UCL.
 GO:0007204; P:elevation of cytosolic calcium ion concentration; TAS:ProtInc.
 GO:0030260; P:entry into host cell; TAS:Reactome.
 GO:0007281; P:germ cell development; IEA:Compara.
 GO:0008354; P:germ cell migration; IEA:Compara.
 GO:0006954; P:inflammatory response; TAS:ProtInc.
 GO:0008045; P:motor neuron axon guidance; IEA:Compara.
 GO:0043217; P:myelin maintenance; ISS:BHF-UCL.
 GO:0061351; P:neural precursor cell proliferation; IEA:Compara.
 GO:0001764; P:neuron migration; IEA:Compara.
 GO:0042119; P:neutrophil activation; IEA:InterPro.
 GO:0001569; P:patterning of blood vessels; IEA:Compara.
 GO:0048714; P:positive regulation of oligodendrocyte differentiation; ISS:BHF-UCL.
 GO:0030334; P:regulation of cell migration; IEA:Compara.
 GO:0050920; P:regulation of chemotaxis; IMP:UniProtKB.
 GO:0001666; P:response to hypoxia; IEP:UniProtKB.
 GO:0009615; P:response to virus; TAS:ProtInc.
 GO:0042098; P:T cell proliferation; IEA:Compara.
 GO:0022415; P:viral reproductive process; TAS:Reactome.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 

Interpro

 IPR001277; Chemokine_CXCR4.
 IPR022726; Chemokine_CXCR4_N_dom.
 IPR000355; Chemokine_rcpt.
 IPR000276; GPCR_Rhodpsn.
 IPR017452; GPCR_Rhodpsn_7TM. 

Pfam

 PF00001; 7tm_1
 PF12109; CXCR4_N 

SMART

  

PROSITE

 PS00237; G_PROTEIN_RECEP_F1_1
 PS50262; G_PROTEIN_RECEP_F1_2 

PRINTS

 PR00657; CCCHEMOKINER.
 PR00645; CXCCHMKINER4.
 PR00237; GPCRRHODOPSN.