CCR5_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: CCR5_HUMAN
• UniProt AC: P51681
• Protein Name: C-C chemokine receptor type 5
• Gene Name: CCR5
• Organism: Homo sapiens (Human).
• Sequence Length: 352
• Subcellular Localization: Cell membrane ; Multi-pass membrane protein .
• Protein Description: Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May play a role in the control of granulocytic lineage proliferation or differentiation.; (Microbial infection) Acts as a coreceptor (CD4 being the primary receptor) of human immunodeficiency virus-1/HIV-1..
• Protein Sequence: MDYQVSSPIYDINYYTSEPCQKINVKQIAARLLPPLYSLVFIFGFVGNMLVILILINCKRLKSMTDIYLLNLAISDLFFLLTVPFWAHYAAAQWDFGNTMCQLLTGLYFIGFFSGIFFIILLTIDRYLAVVHAVFALKARTVTFGVVTSVITWVVAVFASLPGIIFTRSQKEGLHYTCSSHFPYSQYQFWKNFQTLKIVILGLVLPLLVMVICYSGILKTLLRCRNEKKRHRAVRLIFTIMIVYFLFWAPYNIVLLLNTFQEFFGLNNCSSSNRLDQAMQVTETLGMTHCCINPIIYAFVGEKFRNYLLVFFQKHIAKRFCKCCSIFQQEAPERASSVYTRSTGEQEISVGL

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
3	Sulfation	-----MDYQVSSPIY -----CCCCCCCCCC	14.98	10089882
3	Sulfation	-----MDYQVSSPIY -----CCCCCCCCCC	14.98	-
6	O-linked_Glycosylation	--MDYQVSSPIYDIN --CCCCCCCCCCCCC	18.18	11733580
6	O-linked_Glycosylation	--MDYQVSSPIYDIN --CCCCCCCCCCCCC	18.18	11733580
7	O-linked_Glycosylation	-MDYQVSSPIYDINY -CCCCCCCCCCCCCC	19.23	10089882
10	Sulfation	YQVSSPIYDINYYTS CCCCCCCCCCCCCCC	17.72	21763489
10	Sulfation	YQVSSPIYDINYYTS CCCCCCCCCCCCCCC	17.72	-
14	Sulfation	SPIYDINYYTSEPCQ CCCCCCCCCCCCCCC	14.41	-
14	Sulfation	SPIYDINYYTSEPCQ CCCCCCCCCCCCCCC	14.41	21763489
15	Sulfation	PIYDINYYTSEPCQK CCCCCCCCCCCCCCC	10.17	-
15	Sulfation	PIYDINYYTSEPCQK CCCCCCCCCCCCCCC	10.17	10089882
16	O-linked_Glycosylation	IYDINYYTSEPCQKI CCCCCCCCCCCCCCC	19.09	UniProtKB CARBOHYD
17	O-linked_Glycosylation	YDINYYTSEPCQKIN CCCCCCCCCCCCCCC	24.34	UniProtKB CARBOHYD
195	Phosphorylation	QFWKNFQTLKIVILG HHHHHHHHHHHHHHH	26.36	-
321	S-palmitoylation	KHIAKRFCKCCSIFQ HHHHHHHHHHHHHHH	3.71	11323418
323	S-palmitoylation	IAKRFCKCCSIFQQE HHHHHHHHHHHHHHH	2.01	11323418
324	S-palmitoylation	AKRFCKCCSIFQQEA HHHHHHHHHHHHHHC	1.82	11323418
325	Phosphorylation	KRFCKCCSIFQQEAP HHHHHHHHHHHHHCH	35.59	27080861
336	Phosphorylation	QEAPERASSVYTRST HHCHHHHCCCEECCC	26.93	10085131
337	Phosphorylation	EAPERASSVYTRSTG HCHHHHCCCEECCCC	20.40	28857561
339	Phosphorylation	PERASSVYTRSTGEQ HHHHCCCEECCCCCE	9.81	16809330
340	Phosphorylation	ERASSVYTRSTGEQE HHHCCCEECCCCCEE	18.91	27080861
342	Phosphorylation	ASSVYTRSTGEQEIS HCCCEECCCCCEEEE	32.72	29978859
343	Phosphorylation	SSVYTRSTGEQEISV CCCEECCCCCEEEEC	41.25	29978859
349	Phosphorylation	STGEQEISVGL---- CCCCEEEECCC----	14.91	11323418

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
336	S	Phosphorylation	Kinase	BARK1	P25098	Uniprot
336	S	Phosphorylation	Kinase	ARBK2	P35626	PhosphoELM
336	S	Phosphorylation	Kinase	GRK-SUBFAMILY	-	GPS
336	S	Phosphorylation	Kinase	GRK_GROUP	-	PhosphoELM
337	S	Phosphorylation	Kinase	BARK1	P25098	Uniprot
337	S	Phosphorylation	Kinase	ARBK2	P35626	PhosphoELM
337	S	Phosphorylation	Kinase	GRK-SUBFAMILY	-	GPS
337	S	Phosphorylation	Kinase	GRK_GROUP	-	PhosphoELM
342	S	Phosphorylation	Kinase	BARK1	P25098	Uniprot
342	S	Phosphorylation	Kinase	ARBK2	P35626	PhosphoELM
342	S	Phosphorylation	Kinase	GRK-SUBFAMILY	-	GPS
342	S	Phosphorylation	Kinase	GRK_GROUP	-	PhosphoELM
349	S	Phosphorylation	Kinase	BARK1	P25098	Uniprot
349	S	Phosphorylation	Kinase	GRK3	P35626	PSP
349	S	Phosphorylation	Kinase	GRK-SUBFAMILY	-	GPS
349	S	Phosphorylation	Kinase	GRK_GROUP	-	PhosphoELM

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
16	T	Glycosylation	Thr-16 and Ser-17 may also be glycosylated and, if so, with small moieties such as a T-antigen.	11733580
17	S	Glycosylation	Thr-16 and Ser-17 may also be glycosylated and, if so, with small moieties such as a T-antigen.	11733580

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of CCR5_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
ARRB1_HUMAN	ARRB1	physical	12065593
JAK2_HUMAN	JAK2	physical	11278738
STAT3_HUMAN	STAT3	physical	11350939
STA5B_HUMAN	STAT5B	physical	11350939
P85B_HUMAN	PIK3R2	physical	11350939
PSA5_HUMAN	PSMA5	physical	11877445
CST9L_HUMAN	CST9L	physical	21988832
CTBP2_HUMAN	CTBP2	physical	21988832
ETV5_HUMAN	ETV5	physical	21988832
IL24_HUMAN	IL24	physical	21988832

Drug and Disease Associations

• Kegg Disease
• There are no disease associations of PTM sites.
• OMIM Disease
• 612522: Diabetes mellitus, insulin-dependent, 22 (IDDM22)
• Kegg Drug
• D03210: Ancriviroc (USAN/INN)
• D06297: Vicriviroc maleate (USAN)
• D06557: Aplaviroc hydrochloride (USAN)
• D06670: Maraviroc (JAN/INN); Selzentry (TN)
• D09878: Cenicriviroc (USAN/INN)
• D09879: Cenicriviroc mesylate (USAN)
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

O-linked Glycosylation

"Sialylated O-glycans and sulfated tyrosines in the NH2-terminaldomain of CC chemokine receptor 5 contribute to high affinity bindingof chemokines.";
Bannert N., Craig S., Farzan M., Sogah D., Santo N.V., Choe H.,Sodroski J.;
J. Exp. Med. 194:1661-1673(2001).
Cited for: SULFATION, GLYCOSYLATION AT SER-6, INTERACTION WITH CCL3; CCL4 ANDCCL5, MUTAGENESIS OF TYR-3; SER-6; SER-7; TYR-10; TYR-14; TYR-15;THR-16 AND SER-17, AND CHARACTERIZATION OF VARIANT ASP-10.
PubMed: 11733580

Palmitoylation

"Palmitoylation of CCR5 is critical for receptor trafficking andefficient activation of intracellular signaling pathways.";
Blanpain C., Wittamer V., Vanderwinden J.-M., Boom A., Renneboog B.,Lee B., Le Poul E., El Asmar L., Govaerts C., Vassart G., Doms R.W.,Parmentier M.;
J. Biol. Chem. 276:23795-23804(2001).
Cited for: PALMITOYLATION AT CYS-321; CYS-323 AND CYS-324, SUBCELLULAR LOCATION,FUNCTION, AND MUTAGENESIS OF CYS-321; CYS-323 AND CYS-324.
PubMed: 11323418

Phosphorylation

"Differential effects of CC chemokines on CC chemokine receptor 5(CCR5) phosphorylation and identification of phosphorylation sites onthe CCR5 carboxyl terminus.";
Oppermann M., Mack M., Proudfoot A.E., Olbrich H.;
J. Biol. Chem. 274:8875-8885(1999).
Cited for: PHOSPHORYLATION AT SER-336; SER-337; SER-342 AND SER-349, MUTAGENESISOF SER-336; SER-337; SER-342 AND SER-349, AND INTERACTION WITH ADRBK1.
PubMed: 10085131

Sulfation

"The conformation and orientation of a 27-residue CCR5 peptide in aternary complex with HIV-1 gp120 and a CD4-mimic peptide.";
Schnur E., Noah E., Ayzenshtat I., Sargsyan H., Inui T., Ding F.X.,Arshava B., Sagi Y., Kessler N., Levy R., Scherf T., Naider F.,Anglister J.;
J. Mol. Biol. 410:778-797(2011).
Cited for: STRUCTURE BY NMR OF 1-27 IN COMPLEX WITH HIV-1 GP120 AND CD4 MIMICPEPTIDE, AND SULFATION AT TYR-10 AND TYR-14.
PubMed: 21763489

"Tyrosine sulfation of the amino terminus of CCR5 facilitates HIV-1entry.";
Farzan M., Mirzabekov T., Kolchinsky P., Wyatt R., Cayabyab M.,Gerard N.P., Gerard C., Sodroski J., Choe H.;
Cell 96:667-676(1999).
Cited for: SULFATION AT TYR-3, GLYCOSYLATION, AND MUTAGENESIS OF TYR-3; TYR-10;TYR-14 AND TYR-15.
PubMed: 10089882