CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-009296
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
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
314AFLGAKFKTSAQHALubiquitination[1, 2]
331VSRGSSLKILSKGKRubiquitination[1, 2, 3]
Reference
 [1] 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]
 [2] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [3] 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
MSIPLPLLQI YTSDNYTEEM GSGDYDSMKE PCFREENANF NKIFLPTIYS IIFLTGIVGN 60
GLVILVMGYQ KKLRSMTDKY RLHLSVADLL FVITLPFWAV DAVANWYFGN FLCKAVHVIY 120
TVNLYSSVLI LAFISLDRYL AIVHATNSQR PRKLLAEKVV YVGVWIPALL LTIPDFIFAN 180
VSEADDRYIC DRFYPNDLWV VVFQFQHIMV GLILPGIVIL SCYCIIISKL SHSKGHQKRK 240
ALKTTVILIL AFFACWLPYY IGISIDSFIL LEIIKQGCEF ENTVHKWISI TEALAFFHCC 300
LNPILYAFLG AKFKTSAQHA LTSVSRGSSL KILSKGKRGG HSSVSTESES SSFHSS 356 
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.