CXCR4_HUMAN - dbPTM
CXCR4_HUMAN - PTM Information in dbPTM
Basic Information of Protein
UniProt ID CXCR4_HUMAN
UniProt AC P61073
Protein Name C-X-C chemokine receptor type 4
Gene Name CXCR4
Organism Homo sapiens (Human).
Sequence Length 352
Subcellular Localization Cell membrane
Multi-pass membrane protein. Cell junction. Early endosome. Late endosome. Lysosome. In unstimulated cells, diffuse pattern on plasma membrane. On agonist stimulation, colocalizes with ITCH at the plasma membrane where it becomes ubiqu
Protein 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.; (Microbial infection) Acts as a coreceptor (CD4 being the primary receptor) for human immunodeficiency virus-1/HIV-1 X4 isolates and as a primary receptor for some HIV-2 isolates. Promotes Env-mediated fusion of the virus. [PubMed: 9427609]
Protein Sequence MEGISIYTSDNYTEEMGSGDYDSMKEPCFREENANFNKIFLPTIYSIIFLTGIVGNGLVILVMGYQKKLRSMTDKYRLHLSVADLLFVITLPFWAVDAVANWYFGNFLCKAVHVIYTVNLYSSVLILAFISLDRYLAIVHATNSQRPRKLLAEKVVYVGVWIPALLLTIPDFIFANVSEADDRYICDRFYPNDLWVVVFQFQHIMVGLILPGIVILSCYCIIISKLSHSKGHQKRKALKTTVILILAFFACWLPYYIGISIDSFILLEIIKQGCEFENTVHKWISITEALAFFHCCLNPILYAFLGAKFKTSAQHALTSVSRGSSLKILSKGKRGGHSSVSTESESSSFHSS
Overview of Protein Modification Sites with Functional and Structural Information
Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations Modification Substrate Peptides
&
Secondary Structure		 ASA (%) Reference Orthologous
Protein Cluster
5Phosphorylation---MEGISIYTSDNY
---CCCCEEECCCCC		22.0220068231
7Phosphorylation-MEGISIYTSDNYTE
-CCCCEEECCCCCCC		8.0630576142
7Sulfation-MEGISIYTSDNYTE
-CCCCEEECCCCCCC		8.0618834145
7Sulfation-MEGISIYTSDNYTE
-CCCCEEECCCCCCC		8.06-
8PhosphorylationMEGISIYTSDNYTEE
CCCCEEECCCCCCCC		28.1220068231
9PhosphorylationEGISIYTSDNYTEEM
CCCEEECCCCCCCCC		13.5920068231
11N-linked_GlycosylationISIYTSDNYTEEMGS
CEEECCCCCCCCCCC		45.4510756055
12PhosphorylationSIYTSDNYTEEMGSG
EEECCCCCCCCCCCC		22.1020068231
12SulfationSIYTSDNYTEEMGSG
EEECCCCCCCCCCCC		22.10-
12SulfationSIYTSDNYTEEMGSG
EEECCCCCCCCCCCC		22.1018834145
13PhosphorylationIYTSDNYTEEMGSGD
EECCCCCCCCCCCCC		31.5524043423
18O-linked_GlycosylationNYTEEMGSGDYDSMK
CCCCCCCCCCCCCCC		27.4712034737
18PhosphorylationNYTEEMGSGDYDSMK
CCCCCCCCCCCCCCC		27.4730576142
18SulfoserineNYTEEMGSGDYDSMK
CCCCCCCCCCCCCCC		27.47-
18SulfationNYTEEMGSGDYDSMK
CCCCCCCCCCCCCCC		27.4712034737
21SulfationEEMGSGDYDSMKEPC
CCCCCCCCCCCCCCC		17.28-
21PhosphorylationEEMGSGDYDSMKEPC
CCCCCCCCCCCCCCC		17.2824043423
21SulfationEEMGSGDYDSMKEPC
CCCCCCCCCCCCCCC		17.2818834145
23PhosphorylationMGSGDYDSMKEPCFR
CCCCCCCCCCCCCCC		26.0620068231
135PhosphorylationAFISLDRYLAIVHAT
HHHCHHHHHHHHHHC		10.51-
157PhosphorylationLLAEKVVYVGVWIPA
HHHCHHHHHHCHHHH		8.4215615703
176N-linked_GlycosylationIPDFIFANVSEADDR
CCCHHCCCCCCCCCC		27.39UniProtKB CARBOHYD
310UbiquitinationAFLGAKFKTSAQHAL
HHHCCHHHCCHHHHH		40.6421890473
310UbiquitinationAFLGAKFKTSAQHAL
HHHCCHHHCCHHHHH		40.6421890473
310 (in isoform 1)Ubiquitination-40.6421890473
311PhosphorylationFLGAKFKTSAQHALT
HHCCHHHCCHHHHHH		32.2123403867
312PhosphorylationLGAKFKTSAQHALTS
HCCHHHCCHHHHHHH		26.9029396449
314UbiquitinationAKFKTSAQHALTSVS
CHHHCCHHHHHHHCC		23.3521890473
314 (in isoform 2)Ubiquitination-23.3521890473
314UbiquitinationAKFKTSAQHALTSVS
CHHHCCHHHHHHHCC		23.3521890473
318PhosphorylationTSAQHALTSVSRGSS
CCHHHHHHHCCCCCC		28.0623401153
319PhosphorylationSAQHALTSVSRGSSL
CHHHHHHHCCCCCCE		20.9522167270
321PhosphorylationQHALTSVSRGSSLKI
HHHHHHCCCCCCEEE		30.5922167270
322 (in isoform 2)Phosphorylation-47.0227251275
323 (in isoform 2)Phosphorylation-17.6824719451
324PhosphorylationLTSVSRGSSLKILSK
HHHCCCCCCEEEEEC		31.2425463755
325 (in isoform 2)Phosphorylation-36.1827251275
325PhosphorylationTSVSRGSSLKILSKG
HHCCCCCCEEEEECC		36.1825463755
327 (in isoform 1)Ubiquitination-43.4821890473
327UbiquitinationVSRGSSLKILSKGKR
CCCCCCEEEEECCCC		43.4821890473
327UbiquitinationVSRGSSLKILSKGKR
CCCCCCEEEEECCCC		43.482189047
328 (in isoform 2)Phosphorylation-6.7824719451
330PhosphorylationGSSLKILSKGKRGGH
CCCEEEEECCCCCCC		42.7226055452
331UbiquitinationSSLKILSKGKRGGHS
CCEEEEECCCCCCCC		66.0721890473
331UbiquitinationSSLKILSKGKRGGHS
CCEEEEECCCCCCCC		66.0721890473
331 (in isoform 2)Ubiquitination-66.0721890473
331UbiquitinationSSLKILSKGKRGGHS
CCEEEEECCCCCCCC		66.07-
333UbiquitinationLKILSKGKRGGHSSV
EEEEECCCCCCCCCC		52.16-
334MethylationKILSKGKRGGHSSVS
EEEECCCCCCCCCCC		66.06-
338PhosphorylationKGKRGGHSSVSTESE
CCCCCCCCCCCCCCC		35.3923401153
339PhosphorylationGKRGGHSSVSTESES
CCCCCCCCCCCCCCC		17.8923401153
341PhosphorylationRGGHSSVSTESESSS
CCCCCCCCCCCCCCC		28.5322167270
342PhosphorylationGGHSSVSTESESSSF
CCCCCCCCCCCCCCC		41.1822167270
344PhosphorylationHSSVSTESESSSFHS
CCCCCCCCCCCCCCC		42.7522167270
346PhosphorylationSVSTESESSSFHSS-
CCCCCCCCCCCCCC-		40.3325463755
347PhosphorylationVSTESESSSFHSS--
CCCCCCCCCCCCC--		32.7325463755
348PhosphorylationSTESESSSFHSS---
CCCCCCCCCCCC---		35.9425463755
351PhosphorylationSESSSFHSS------
CCCCCCCCC------		35.4125463755
352 (in isoform 2)Phosphorylation-35.3524719451
352PhosphorylationESSSFHSS-------
CCCCCCCC-------		35.3525463755
Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)
Modified Location Modified Residue Modification Type of Upstream Proteins Gene Name of Upstream Proteins UniProt AC of Upstream Proteins Sources
324SPhosphorylationKinaseGRK6P43250
Uniprot
324SPhosphorylationKinasePRKCDQ05655
GPS
324SPhosphorylationKinasePKC-FAMILY-GPS
324SPhosphorylationKinasePKC-Uniprot
325SPhosphorylationKinaseGRK6P43250
Uniprot
325SPhosphorylationKinasePRKCDQ05655
GPS
325SPhosphorylationKinasePKC-FAMILY-GPS
325SPhosphorylationKinasePKC-Uniprot
330SPhosphorylationKinaseGRK6P43250
Uniprot
330SPhosphorylationKinaseGRK6O70293
PSP
339SPhosphorylationKinaseGRK6P43250
Uniprot
339SPhosphorylationKinaseGRK6O70293
PSP
339SPhosphorylationKinasePIM1P11309
PSP
-KUbiquitinationE3 ubiquitin ligaseITCHQ96J02
PMID:14602072
-KUbiquitinationE3 ubiquitin ligaseRNF126Q9BV68
PMID:22199232
-KUbiquitinationE3 ubiquitin ligaseRNF115Q9Y4L5
PMID:22199232
-KUbiquitinationE3 ubiquitin ligaseWWP1Q9H0M0
PMID:22266093
Functions of PTM Sites
Modified Location Modified Residue Modification Function Reference
11NGlycosylation

10756055
176NGlycosylation

10756055
324SPhosphorylation

19116316
324Subiquitylation

19116316
325SPhosphorylation

19116316
325Subiquitylation

19116316
Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location Modification Variant Position
(Distance <= 10) 		Residue Change SAP Related Disease Reference

Oops, there are no SNP-PTM records of CXCR4_HUMAN !!
Protein-Protein Interaction
Interacting Protein Gene Name Interaction Type PPI Reference Domain-Domain Interactions
CCR5_HUMANCCR5physical
12429730
JAK3_HUMANJAK3physical
10506573
JAK2_HUMANJAK2physical
10506573
PTN6_HUMANPTPN6physical
10506573
ITCH_HUMANITCHphysical
19116316
UBP14_HUMANUSP14physical
19106094
STAM1_HUMANSTAMphysical
20505072
ITCH_HUMANITCHphysical
22275353
STAM1_HUMANSTAMphysical
22275353
CAV1_HUMANCAV1physical
22275353
PTN11_HUMANPTPN11physical
11157475
SDF1_HUMANCXCL12physical
21757744
F10A1_HUMANST13physical
11751889
ENV_HV1H2envphysical
14592831
PDIA1_HUMANP4HBphysical
14592831
CD4_HUMANCD4physical
14592831
MYBB_HUMANMYBL2physical
21988832
ITCH_HUMANITCHphysical
24489825
B2MG_HUMANB2Mphysical
18083706
1B07_HUMANHLA-Bphysical
18083706
1B18_HUMANHLA-Bphysical
18083706
Drug and Disease Associations
Kegg Disease
H00097 Chemokine receptor defect, including the following disease: WHIM syndrome
OMIM Disease
193670WHIM syndrome (WHIMS)
Kegg Drug
D08971 Plerixafor (USAN/INN); Mozobil (TN)
DrugBank
There are no disease associations of PTM sites.
Regulatory Network of CXCR4_HUMAN

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Related Literatures of Post-Translational Modification
N-linked Glycosylation
ReferencePubMed
"N-linked glycosylation of CXCR4 masks coreceptor function for CCR5-dependent human immunodeficiency virus type 1 isolates.";
Chabot D.J., Chen H., Dimitrov D.S., Broder C.C.;
J. Virol. 74:4404-4413(2000).
Cited for: GLYCOSYLATION AT ASN-11, INTERACTION WITH HIV-1 ENV, SUBUNIT, ANDMUTAGENESIS OF ASN-11; THR-13 AND ASN-176.
O-linked Glycosylation
ReferencePubMed
"The role of post-translational modifications of the CXCR4 aminoterminus in stromal-derived factor 1 alpha association and HIV-1entry.";
Farzan M., Babcock G.J., Vasilieva N., Wright P.L., Kiprilov E.,Mirzabekov T., Choe H.;
J. Biol. Chem. 277:29484-29489(2002).
Cited for: GLYCOSYLATION AT SER-18, IDENTIFICATION OF PROTEOGLYCAN, INTERACTIONWITH CXCL12, SULFATION AT TYR-21, AND MUTAGENESIS OF TYR-7; THR-8;SER-9; TYR-12; SER-18 AND TYR-21.
Phosphorylation
ReferencePubMed
"Site-specific phosphorylation of CXCR4 is dynamically regulated bymultiple kinases and results in differential modulation of CXCR4signaling.";
Busillo J.M., Armando S., Sengupta R., Meucci O., Bouvier M.,Benovic J.L.;
J. Biol. Chem. 285:7805-7817(2010).
Cited for: PHOSPHORYLATION AT SER-321; SER-324; SER-325; SER-330; SER-339 ANDSER-351, INTERACTION WITH ARRB2 AND ARRC, FUNCTION, AND MASSSPECTROMETRY.
"The E3 ubiquitin ligase atrophin interacting protein 4 binds directlyto the chemokine receptor CXCR4 via a novel WW domain-mediatedinteraction.";
Bhandari D., Robia S.L., Marchese A.;
Mol. Biol. Cell 20:1324-1339(2009).
Cited for: INTERACTION WITH ITCH, SUBCELLULAR LOCATION, PHOSPHORYLATION ATSER-324 AND SER-325, AND MUTAGENESIS OF SER-324; SER-325 AND SER-330.
"A quantitative atlas of mitotic phosphorylation.";
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.;
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-319; SER-348 ANDSER-351, AND MASS SPECTROMETRY.
"Combining protein-based IMAC, peptide-based IMAC, and MudPIT forefficient phosphoproteomic analysis.";
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,Yates J.R. III;
J. Proteome Res. 7:1346-1351(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-319, AND MASSSPECTROMETRY.
Sulfation
ReferencePubMed
"Recognition of a CXCR4 sulfotyrosine by the chemokine stromal cell-derived factor-1alpha (SDF-1alpha/CXCL12).";
Veldkamp C.T., Seibert C., Peterson F.C., Sakmar T.P., Volkman B.F.;
J. Mol. Biol. 359:1400-1409(2006).
Cited for: STRUCTURE BY NMR OF 1-38, SULFATION AT TYR-21, MASS SPECTROMETRY, ANDINTERACTION WITH CXCL12.
"Sequential tyrosine sulfation of CXCR4 by tyrosylproteinsulfotransferases.";
Seibert C., Veldkamp C.T., Peterson F.C., Chait B.T., Volkman B.F.,Sakmar T.P.;
Biochemistry 47:11251-11262(2008).
Cited for: SULFATION AT TYR-7; TYR-12 AND TYR-21, AND INTERACTION WITH CXCL12.
"The role of post-translational modifications of the CXCR4 aminoterminus in stromal-derived factor 1 alpha association and HIV-1entry.";
Farzan M., Babcock G.J., Vasilieva N., Wright P.L., Kiprilov E.,Mirzabekov T., Choe H.;
J. Biol. Chem. 277:29484-29489(2002).
Cited for: GLYCOSYLATION AT SER-18, IDENTIFICATION OF PROTEOGLYCAN, INTERACTIONWITH CXCL12, SULFATION AT TYR-21, AND MUTAGENESIS OF TYR-7; THR-8;SER-9; TYR-12; SER-18 AND TYR-21.

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