P51681 (CCR5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
C-C chemokine receptor type 5
Short name=C-C CKR-5
Short name=CC-CKR-5
Short name=CCR-5
Short name=CCR5

Alternative name(s):
CHEMR13
HIV-1 fusion coreceptor
CD_antigen=CD195

Gene names

Name:	CCR5
Synonyms:	CMKBR5

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	352 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for a number of inflammatory CC-chemokines including MIP-1-alpha, 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. Acts as a coreceptor (CD4 being the primary receptor) for HIV-1 R5 isolates. Ref.1 Ref.2 Ref.3 Ref.11 Ref.12 Ref.16
Subunit structure	Interacts with PRAF2. Interacts with HIV-1 surface protein gp120. Efficient ligand binding to CCL3/MIP-1alpha and CCL4/MIP-1beta requires sulfation, O-glycosylation and sialic acid modifications. Glycosylation on Ser-6 is required for efficient binding of CCL4. Interacts with ADRBK1. Interacts with ARRB1 and ARRB2. Ref.2 Ref.3 Ref.13 Ref.15 Ref.17 Ref.18 Ref.19 Ref.20
Subcellular location	Cell membrane; Multi-pass membrane protein Ref.16.
Tissue specificity	Highly expressed in spleen, thymus, in the myeloid cell line THP-1, in the promyeloblastic cell line KG-1A and on CD4+ and CD8+ T-cells. Medium levels in peripheral blood leukocytes and in small intestine. Low levels in ovary and lung. Ref.1 Ref.2
Post-translational modification	Sulfated on at least 2 of the N-terminal tyrosines. Sulfation contributes to the efficiency of HIV-1 entry and is required for efficient binding of the chemokines, CCL3 and CCL4. O-glycosylated, but not N-glycosylated. Ser-6 appears to be the major site. Also sialylated glycans present which contribute to chemokine binding. Thr-16 and Ser-17 may also be glycosylated and, if so, with small moieties such as a T-antigen. Ref.14 Ref.18 Palmitoylation in the C-terminal is important for cell surface expression, and to a lesser extent, for HIV entry. Phosphorylation on serine residues in the C-terminal is stimulated by binding CC chemokines especially by APO-RANTES.
Polymorphism	Variations in CCR5 are associated with resistance or susceptibility to immunodeficiency virus type 1 (resistance or susceptibility to HIV-1) [MIM:609423]. Variations in CCR5 gene also influence the rate of progression to AIDS after infection. Ser-60 variant, a naturally occurring mutation in a conserved residue in the first intracellular domain of CCR5, results in reduced amounts of the protein in the membrane and consequently may be associated with reduced susceptibility to infection by microbes that depend on these molecules as their receptors. Variations in CCR5 are associated with susceptibility to West Nile virus (WNV) infection [MIM:610379].
Involvement in disease	Genetic variation in CCR5 is associated with suseptibility to diabetes mellitus insulin-dependent type 22 (IDDM22) [MIM:612522]. A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. Ref.27
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Diabetes mellitus
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate Phosphoprotein Sulfation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell-cell signaling Traceable author statement. Source: ProtInc cellular defense response Traceable author statement. Source: ProtInc dendritic cell chemotaxis Traceable author statement. Source: BHF-UCL elevation of cytosolic calcium ion concentration Traceable author statement. Source: ProtInc entry into host cell Traceable author statement. Source: Reactome immune response Traceable author statement. Source: ProtInc inflammatory response Traceable author statement. Source: ProtInc initiation of viral infection Traceable author statement. Source: Reactome
Cellular component	endosome Traceable author statement. Source: ProtInc external side of plasma membrane Inferred from direct assay. Source: MGI integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	C-C chemokine receptor activity Non-traceable author statement Ref.1. Source: UniProtKB actin binding Inferred from direct assay. Source: UniProtKB coreceptor activity Traceable author statement. Source: ProtInc phosphatidylinositol phospholipase C activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 352

352

C-C chemokine receptor type 5

PRO_0000069257

Regions

Topological domain

1 – 30

30

Extracellular Potential

Transmembrane

31 – 58

28

Helical; Name=1; Potential

Topological domain

59 – 68

10

Cytoplasmic Potential

Transmembrane

69 – 89

21

Helical; Name=2; Potential

Topological domain

90 – 102

13

Extracellular Potential

Transmembrane

103 – 124

22

Helical; Name=3; Potential

Topological domain

125 – 141

17

Cytoplasmic Potential

Transmembrane

142 – 166

25

Helical; Name=4; Potential

Topological domain

167 – 198

32

Extracellular Potential

Transmembrane

199 – 218

20

Helical; Name=5; Potential

Topological domain

219 – 235

17

Cytoplasmic Potential

Transmembrane

236 – 260

25

Helical; Name=6; Potential

Topological domain

261 – 277

17

Extracellular Potential

Transmembrane

278 – 301

24

Helical; Name=7; Potential

Topological domain

302 – 352

51

Cytoplasmic Potential

Amino acid modifications

Modified residue

3

1

Sulfotyrosine Ref.14

Modified residue

10

1

Sulfotyrosine Potential

Modified residue

14

1

Sulfotyrosine Potential

Modified residue

15

1

Sulfotyrosine Potential

Modified residue

336

1

Phosphoserine; by BARK1 Ref.15

Modified residue

337

1

Phosphoserine; by BARK1 Ref.15

Modified residue

342

1

Phosphoserine; by BARK1 Ref.15

Modified residue

349

1

Phosphoserine; by BARK1 Ref.15

Lipidation

321

1

S-palmitoyl cysteine Ref.16

Lipidation

323

1

S-palmitoyl cysteine Ref.16

Lipidation

324

1

S-palmitoyl cysteine Ref.16

Glycosylation

6

1

O-linked (GalNAc...) Ref.18

Glycosylation

7

1

O-linked (GalNAc...) Probable

Glycosylation

16

1

O-linked (GalNAc...) Potential

Glycosylation

17

1

O-linked (GalNAc...) Potential

Disulfide bond

101 ↔ 178

By similarity

Natural variations

Natural variant

10

1

Y → D in INCCR5-71A) (No sulfation and greatly decreased binding CCL4 and CCL5; when associated with D-3; D-10 and D-15. Restored most CCL4 binding; when associated with D-3 and D-15. Ref.18

VAR_003481

Natural variant

12

1

I → L. Ref.25

VAR_024066

Natural variant

20

1

C → S. Ref.25

VAR_024067

Natural variant

29

1

A → S. Ref.25
Corresponds to variant rs1800939 [ dbSNP | Ensembl ].

VAR_011839

Natural variant

31

1

R → H in INCCR5-72A.
Corresponds to variant rs56340326 [ dbSNP | Ensembl ].

VAR_003482

Natural variant

34

1

P → L in TZCCR5-179.

VAR_003483

Natural variant

42

1

I → F. Ref.25

VAR_024068

Natural variant

55

1

L → Q. Ref.24 Ref.25
Corresponds to variant rs1799863 [ dbSNP | Ensembl ].

VAR_011840

Natural variant

60

1

R → S Associated with susceptibility to HIV-1; reduced surface expression and function of CCR5 protein. Ref.25 Ref.26
Corresponds to variant rs1800940 [ dbSNP | Ensembl ].

VAR_011841

Natural variant

62

1

K → R in UGCCR5-145B.

VAR_003484

Natural variant

68

1

Y → H in ZWCCR5-7.

VAR_003485

Natural variant

73

1

A → V. Ref.25
Corresponds to variant rs56198941 [ dbSNP | Ensembl ].

VAR_024069

Natural variant

95

1

D → N in MWCCR5-107.

VAR_003486

Natural variant

97

1

G → E in INCCR5-467.

VAR_003487

Natural variant

122

1

L → P in ZWCCR5-7.

VAR_003488

Natural variant

158

1

F → S in UGCCR5-145A.

VAR_003489

Natural variant

176

1

Y → C in KECCR5-116.

VAR_003490

Natural variant

177

1

T → A in INCCR5-45C.

VAR_003491

Natural variant

178

1

C → R Found in a HIV-resistant individiual. Ref.7

VAR_012481

Natural variant

185

1

S → N in UGCCR5-145A.

VAR_003492

Natural variant

210

1

M → V in ZWCCR5-7.

VAR_003493

Natural variant

214

1

Y → C in KECCR5-3B.

VAR_003494

Natural variant

215

1

S → L. Ref.24

VAR_024070

Natural variant

223

1

R → Q. Ref.24 Ref.25
Corresponds to variant rs1800452 [ dbSNP | Ensembl ].

VAR_011842

Natural variant

228

1

Missing.

VAR_024071

Natural variant

239

1

T → S in INCCR5-71A.

VAR_003495

Natural variant

246

1

L → P in UGCCR5-145A.

VAR_003496

Natural variant

288

1

T → M in INCCR5-72A.

VAR_003497

Natural variant

301

1

G → V. Ref.25
Corresponds to variant rs1800943 [ dbSNP | Ensembl ].

VAR_011843

Natural variant

302

1

E → G in TZCCR5-179.

VAR_003498

Natural variant

303

1

K → E in THCCR5-5.

VAR_003499

Natural variant

306

1

N → S in MWCCR5-1567.

VAR_003500

Natural variant

322

1

K → R in THCCR5-5.

VAR_003501

Natural variant

333

1

E → G in THCCR5-2.

VAR_003502

Natural variant

335

1

A → V in MWCCR5-1567, MWCCR5-1568, ZWCCR5-14 and ZWCCR5-112. Ref.24 Ref.25
Corresponds to variant rs1800944 [ dbSNP | Ensembl ].

VAR_003503

Natural variant

339

1

Y → F in TZCCR5-181A and MWCCR5-107. Ref.24 Ref.25
Corresponds to variant rs1800945 [ dbSNP | Ensembl ].

VAR_003504

Natural variant

345

1

E → G in UGCCR5-145C.

VAR_003505

Experimental info

Mutagenesis

3

1

Y → D: No sulfation and greatly decreased binding CCL4 and CCL5; when associated with D-10; D-14 and D-15. Restored most CCL4 binding; when associated with D-10 and D-15. Ref.14 Ref.18

Mutagenesis

3

1

Y → F: No sulfation and greatly decreases binding of CCL4 and CCL5; when associated with F-10; F-14 and F-15. Ref.14 Ref.18

Mutagenesis

6

1

S → A: No change in glycosylation status and greatly decreased CCL4 binding. Loss of molecular mass of about 2 kDa as compared to wild type. Dramatically reduced binding of CCL4; when associated with A-7; A-16; A-17. Similar molecular mass loss. Dramatically reduced binding of CCL4; when associated with A-7 only. Ref.18

Mutagenesis

7

1

S → A: No change in glycosylation status and binds CCL4 as efficiently as wild type. Loss of molecular mass of about 2 kDa as compared to wild type. Dramatically reduced binding of CCL4; when associated with A-6; A-16; A-17. Similar molecular mass loss. Dramatically reduced binding of CCL4; when associated with A-6 only. Ref.18

Mutagenesis

10

1

Y → F: No sulfation and greatly decreases binding of CCL4 and CCL5; when associated with F-3; F-14 and F-15. Small loss of sulfation; when associated with F-14 and F-15. Ref.14 Ref.18

Mutagenesis

14

1

Y → D: No sulfation and greatly decreased binding CCL4 and CCL5; when associated with D-3; D-10 and D-14. No restoration of CCL4 binding; when associated with D-10 and D-15. Ref.14 Ref.18

Mutagenesis

14

1

Y → F: No sulfation and greatly decreases binding of CCL4 and CCL5; when associated with F-3; F-10; and F-15. Small loss of sulfation; when associated with F-10 and F-15. Ref.14 Ref.18

Mutagenesis

15

1

Y → D: No sulfation and greatly decreased binding CCL4 and CCL5; when associated with D-3; D-10 and D-14. Restored most CCL4 binding; when associated with D-3 and D-10. Ref.14 Ref.18

Mutagenesis

15

1

Y → F: No sulfation and greatly decreases binding of CCL4 and CCL5; when associated with F-3; F-10 and F-14. Small loss of sulfation; when associated with F-10 and F-14. Ref.14 Ref.18

Mutagenesis

16

1

T → A: Similar decrease in molecular mass when treated with O-glycosidase as for wild type; when associated with A-17. Ref.18

Mutagenesis

17

1

S → A: Similar decrease in molecular mass when treated with O-glycosidase as for wild type; when associated with A-16. Ref.18

Mutagenesis

321

1

C → A: Small reduction in palmitoylation. Cell surface expression reduced by 50%. Greatly reduced palmitoylation. Cell surface expression greatly reduced; when associated with A-323 or A-324. No palmitoylation. Cell surface expression greatly reduced. HIV entry reduced by 50%; when associated with A-323 and A-324. Ref.16

Mutagenesis

323

1

C → A: Small reduction in palmitoylation. Cell surface expression reduced by 50%. Greatly reduced palmitoylation. Cell surface expression greatly reduced; when associated with A-321 or A-324. No palmitoylation. Cell surface expression greatly reduced. HIV entry reduced by 50%; when associated with A-321 and A-324. Ref.16

Mutagenesis

324

1

C → A: Small reduction in palmitoylation. Cell surface expression reduced by 50%. Greatly reduced palmitoylation. Cell surface expression greatly reduced; when associated with A-321 or A-323. No palmitoylation. Cell surface expression greatly reduced. HIV entry reduced by 50%; when associated with A-321 and A-323. Ref.16

Mutagenesis

336

1

S → A: APO-RANTES-stimulated phosphorylation reduced by 15%; APO-RANTES-stimulated phosphorylation reduced by 30-50%; when associated with A-337 or A-342 or A-349; APO-RANTES-stimulated phosphorylation reduced by 80%; when associated with A-337 and A-342 or A-349; No APO-RANTES-stimulated phosphorylation; when associated with A-337; A-342 and A349; abolishes interaction with ARRB2; when associated with S-337; S-342 and S-349. Ref.15 Ref.17

Mutagenesis

337

1

S → A: APO-RANTES-stimulated phosphorylation reduced by 18%; APO-RANTES-stimulated phosphorylation reduced by 30-50% on APO-RANTES stimulation; when associated with A-336 or A-342 or A-349; APO-RANTES-stimulated phosphorylation reduced by 80%; when associated with A-336 and A-342 or A-349; No APO-RANTES-stimulated phosphorylation; when associated with A-336; A-342 and A349; abolishes interaction with ARRB2; when associated with S-336; S-342 and S-349. Ref.15 Ref.17

Mutagenesis

342

1

S → A: APO-RANTES-stimulated phosphorylation reduced by 42%. Phosphorylation reduced by 50% on APO-RANTES stimulation; when associated with A-336 or A-337 or A-349; APO-RANTES-stimulated phosphorylation reduced by 80% when associated with A-336 and A-337 or A-349; No APO-RANTES-stimulated phosphorylation; when associated with A-336; A-337 and A349; abolishes interaction with ARRB2; when associated with S-336; S-337 and S-349. Ref.15 Ref.17

Mutagenesis

349

1

S → A: APO-RANTES-stimulated phosphorylation reduced by 43%; APO-RANTES-stimulated phosphorylation reduced by 30-50%; when associated with A-336 or A-337 or A-342; APO-RANTES-stimulated phosphorylation reduced by 80%; when associated with A-336 and A-337 or A-342; No APO-RANTES-stimulated phosphorylation stimulation; when associated with A-336; A-337 and A347; abolishes interaction with ARRB2; when associated with S-336; S-337 and S-342. Ref.15 Ref.17

Secondary structure

1

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352

Helix Strand Turn

Details...

Beta strand

3 – 6

4

Turn

21 – 24

4

Beta strand

28 – 32

5

Helix

33 – 58

26

Helix

69 – 82

14

Helix

84 – 89

6

Turn

92 – 94

3

Turn

99 – 103

5

Helix

105 – 123

19

Beta strand

144 – 147

4

Helix

152 – 157

6

Turn

158 – 160

3

Helix

162 – 164

3

Turn

165 – 167

3

Beta strand

169 – 172

4

Beta strand

175 – 177

3

Helix

200 – 204

5

Turn

205 – 207

3

Helix

208 – 216

9

Beta strand

227 – 230

4

Beta strand

233 – 235

3

Helix

236 – 259

24

Beta strand

275 – 277

3

Helix

279 – 286

8

Helix

289 – 297

9

Beta strand

307 – 309

3

Turn

310 – 312

3

Sequences

	Sequence		Length	Mass (Da)
	P51681 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 88ECE1F38E6D45A7	FASTA	352	40,524
	10 20 30 40 50 60 MDYQVSSPIY DINYYTSEPC QKINVKQIAA RLLPPLYSLV FIFGFVGNML VILILINCKR 70 80 90 100 110 120 LKSMTDIYLL NLAISDLFFL LTVPFWAHYA AAQWDFGNTM CQLLTGLYFI GFFSGIFFII 130 140 150 160 170 180 LLTIDRYLAV VHAVFALKAR TVTFGVVTSV ITWVVAVFAS LPGIIFTRSQ KEGLHYTCSS 190 200 210 220 230 240 HFPYSQYQFW KNFQTLKIVI LGLVLPLLVM VICYSGILKT LLRCRNEKKR HRAVRLIFTI 250 260 270 280 290 300 MIVYFLFWAP YNIVLLLNTF QEFFGLNNCS SSNRLDQAMQ VTETLGMTHC CINPIIYAFV 310 320 330 340 350 GEKFRNYLLV FFQKHIAKRF CKCCSIFQQE APERASSVYT RSTGEQEISV GL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and functional expression of a new human CC-chemokine receptor gene." Samson M., Labbe O., Mollereau C., Vassart G., Parmentier M. Biochemistry 35:3362-3367(1996) [PubMed: 8639485] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, TISSUE SPECIFICITY.
[2]	"Molecular cloning and functional characterization of a novel human CC chemokine receptor (CCR5) for RANTES, MIP-1beta, and MIP-1alpha." Raport C.J., Gosling J., Schweichart V.L., Gray P.W., Charo I.F. J. Biol. Chem. 271:17161-17166(1996) [PubMed: 8663314] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH CCL4 AND CCL5, TISSUE SPECIFICITY. Tissue: Macrophage.
[3]	"Cloning and functional expression of CC CKR5, a human monocyte CC chemokine receptor selective for MIP-1(alpha), MIP-1(beta), and RANTES." Combadiere C., Ahuja S.K., Tiffany H.L., Murphy P.M. J. Leukoc. Biol. 60:147-152(1996) [PubMed: 8699119] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH CCL3; CCL4 AND CCL5.
[4]	"Polymorphisms in the CCR5 genes of African green monkeys and mice implicate specific amino acids in infections by simian and human immunodeficiency viruses." Kuhmann S.E., Platt E.J., Kozak S.L., Kabat D. J. Virol. 71:8642-8656(1997) [PubMed: 9343222] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"HIV type 1 subtypes, coreceptor usage, and CCR5 polymorphism." Zhang L., Carruthers C.D., He T., Huang Y., Cao Y., Wang G., Hahn B., Ho D.D. AIDS Res. Hum. Retroviruses 13:1357-1366(1997) [PubMed: 9359654] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], POLYMORPHISM.
[6]	"The human CC chemokine receptor 5 (CCR5) gene. Multiple transcripts with 5'-end heterogeneity, dual promoter usage, and evidence for polymorphisms within the regulatory regions and noncoding exons." Mummidi S., Ahuja S.S., McDaniel B.L., Ahuja S.K. J. Biol. Chem. 272:30662-30671(1997) [PubMed: 9388201] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	Magierowska M., Barre-Sinoussi F., Issafras H., Theodorou I., Debre P. Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ARG-178.
[8]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." Kopatz S.A., Aronstam R.S., Sharma S.V. Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[9]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed: 16641997] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"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].
[11]	"Identification of a major co-receptor for primary isolates of HIV-1." Deng H., Liu R., Ellmeier W., Choe S., Unutmaz D., Burkhart M., di Marzio P., Marmon S., Sutton R.E., Hill C.M., Davis C.B., Peiper S.C., Schall T.J., Littman D.R., Landau N.R. Nature 381:661-666(1996) [PubMed: 8649511] [Abstract] Cited for: FUNCTION AS A HIV-1 CORECEPTOR.
[12]	"HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5." Dragic T., Litwin V., Allaway G.P., Martin S.R., Huang Y., Nagashima K.A., Cayanan C., Maddon P.J., Koup R.A., Moore J.P., Paxton W.A. Nature 381:667-673(1996) [PubMed: 8649512] [Abstract] Cited for: FUNCTION AS A HIV-1 CORECEPTOR.
[13]	"A conserved HIV gp120 glycoprotein structure involved in chemokine receptor binding." Rizzuto C.D., Wyatt R., Hernandez-Ramos N., Sun Y., Kwong P.D., Hendrickson W.A., Sodroski J. Science 280:1949-1953(1998) [PubMed: 9632396] [Abstract] Cited for: INTERACTION WITH HIV-1 SURFACE PROTEIN GP120.
[14]	"Tyrosine sulfation of the amino terminus of CCR5 facilitates HIV-1 entry." Farzan M., Mirzabekov T., Kolchinsky P., Wyatt R., Cayabyab M., Gerard N.P., Gerard C., Sodroski J., Choe H. Cell 96:667-676(1999) [PubMed: 10089882] [Abstract] Cited for: SULFATION AT TYR-3, GLYCOSYLATION, MUTAGENESIS OF TYR-3; TYR-10; TYR-14 AND TYR-15.
[15]	"Differential effects of CC chemokines on CC chemokine receptor 5 (CCR5) phosphorylation and identification of phosphorylation sites on the CCR5 carboxyl terminus." Oppermann M., Mack M., Proudfoot A.E., Olbrich H. J. Biol. Chem. 274:8875-8885(1999) [PubMed: 10085131] [Abstract] Cited for: PHOSPHORYLATION AT SER-336; SER-337; SER-342 AND SER-349, MUTAGENESIS OF SER-336; SER-337; SER-342 AND SER-349, INTERACTION WITH ADRBK1.
[16]	"Palmitoylation of CCR5 is critical for receptor trafficking and efficient 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) [PubMed: 11323418] [Abstract] Cited for: PALMITOYLATION AT CYS-321; CYS-323 AND CYS-324, SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF CYS-321; CYS-323 AND CYS-324.
[17]	"Characterization of sequence determinants within the carboxyl-terminal domain of chemokine receptor CCR5 that regulate signaling and receptor internalization." Kraft K., Olbrich H., Majoul I., Mack M., Proudfoot A., Oppermann M. J. Biol. Chem. 276:34408-34418(2001) [PubMed: 11448957] [Abstract] Cited for: INTERACTION WITH ARRB2, MUTAGENESIS OF SER-336; SER-337; SER-342 AND SER-349.
[18]	"Sialylated O-glycans and sulfated tyrosines in the NH2-terminal domain of CC chemokine receptor 5 contribute to high affinity binding of chemokines." Bannert N., Craig S., Farzan M., Sogah D., Santo N.V., Choe H., Sodroski J. J. Exp. Med. 194:1661-1673(2001) [PubMed: 11733580] [Abstract] Cited for: SULFATION, GLYCOSYLATION AT SER-6, INTERACTION WITH CCL3; CCL4 AND CCL5, MUTAGENESIS OF TYR-3; SER-6; SER-7; TYR-10; TYR-14; TYR-15; THR-16 AND SER-17, CHARACTERIZATION OF VARIANT ASP-10.
[19]	"JM4 is a four-transmembrane protein binding to the CCR5 receptor." Schweneker M., Bachmann A.S., Moelling K. FEBS Lett. 579:1751-1758(2005) [PubMed: 15757671] [Abstract] Cited for: INTERACTION WITH PRAF2.
[20]	"G protein-coupled receptor kinases promote phosphorylation and beta-arrestin-mediated internalization of CCR5 homo- and hetero-oligomers." Huettenrauch F., Pollok-Kopp B., Oppermann M. J. Biol. Chem. 280:37503-37515(2005) [PubMed: 16144840] [Abstract] Cited for: INTERACTION WITH ARRB1 AND ARRB2.
[21]	"CCR5 deficiency increases risk of symptomatic West Nile virus infection." Glass W.G., McDermott D.H., Lim J.K., Lekhong S., Yu S.F., Frank W.A., Pape J., Cheshier R.C., Murphy P.M. J. Exp. Med. 203:35-40(2006) [PubMed: 16418398] [Abstract] Cited for: INVOLVEMENT IN WEST NILE VIRUS INFECTION SUSCEPTIBILITY.
[22]	"Structure modeling of the chemokine receptor CCR5: implications for ligand binding and selectivity." Paterlini M.G. Biophys. J. 83:3012-3031(2002) [PubMed: 12496074] [Abstract] Cited for: 3D-STRUCTURE MODELING.
[23]	"Structural and functional characterization of the human CCR5 receptor in complex with HIV gp120 envelope glycoprotein and CD4 receptor by molecular modeling studies." Liu S., Fan S., Sun Z. J. Mol. Model. 9:329-336(2003) [PubMed: 14517611] [Abstract] Cited for: 3D-STRUCTURE MODELING.
[24]	"The extent of genetic variation in the CCR5 gene." Ansari-Lari M.A., Liu X.-M., Metzker M.L., Rut A.R., Gibbs R.A. Nat. Genet. 16:221-222(1997) [PubMed: 9207783] [Abstract] Cited for: VARIANTS GLN-55; LEU-215; GLN-223; VAL-335 AND PHE-339.
[25]	"Novel alleles of the chemokine-receptor gene CCR5." Carrington M., Kissner T., Gerrard B., Ivanov S., O'Brien S.J., Dean M. Am. J. Hum. Genet. 61:1261-1267(1997) [PubMed: 9399903] [Abstract] Cited for: VARIANTS LEU-12; SER-20; SER-29; PHE-42; GLN-55; SER-60; VAL-73; GLN-223; LYS-228 DEL; VAL-301; VAL-335 AND PHE-339, ASSOCIATION WITH SUSCEPTIBILITY TO HIV-1.
[26]	"A homologous naturally occurring mutation in Duffy and CCR5 leading to reduced receptor expression." Tamasauskas D., Powell V., Saksela K., Yazdanbakhsh K. Blood 97:3651-3654(2001) [PubMed: 11369664] [Abstract] Cited for: CHARACTERIZATION OF VARIANT SER-60.
[27]	"Shared and distinct genetic variants in type 1 diabetes and celiac disease." Smyth D.J., Plagnol V., Walker N.M., Cooper J.D., Downes K., Yang J.H.M., Howson J.M.M., Stevens H., McManus R., Wijmenga C., Heap G.A., Dubois P.C., Clayton D.G., Hunt K.A., van Heel D.A., Todd J.A. N. Engl. J. Med. 359:2767-2777(2008) [PubMed: 19073967] [Abstract] Cited for: INVOLVEMENT IN IDDM22.
+	Additional computationally mapped references.

Web resources

Wikipedia

CC chemokine receptors entry

Wikipedia

CCR5 receptor entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X91492 Genomic DNA. Translation: CAA62796.1.
U54994 mRNA. Translation: AAC50598.1.
U57840 mRNA. Translation: AAB17071.1.
U83326 Genomic DNA. Translation: AAC51797.1.
AF011500 mRNA. Translation: AAB65700.1.
AF011501 mRNA. Translation: AAB65701.1.
AF011502 mRNA. Translation: AAB65702.1.
AF011503 mRNA. Translation: AAB65703.1.
AF011505 mRNA. Translation: AAB65705.1.
AF011506 mRNA. Translation: AAB65706.1.
AF011507 mRNA. Translation: AAB65707.1.
AF011508 mRNA. Translation: AAB65708.1.
AF011509 mRNA. Translation: AAB65709.1.
AF011510 mRNA. Translation: AAB65710.1.
AF011511 mRNA. Translation: AAB65711.1.
AF011512 mRNA. Translation: AAB65712.1.
AF011513 mRNA. Translation: AAB65713.1.
AF011514 mRNA. Translation: AAB65714.1.
AF011515 mRNA. Translation: AAB65715.1.
AF011516 mRNA. Translation: AAB65716.1.
AF011517 mRNA. Translation: AAB65717.1.
AF011518 mRNA. Translation: AAB65718.1.
AF011519 mRNA. Translation: AAB65719.1.
AF011520 mRNA. Translation: AAB65720.1.
AF011521 mRNA. Translation: AAB65721.1.
AF011522 mRNA. Translation: AAB65722.1.
AF011523 mRNA. Translation: AAB65723.1.
AF011524 mRNA. Translation: AAB65724.1.
AF011525 mRNA. Translation: AAB65725.1.
AF011526 mRNA. Translation: AAB65726.1.
AF011527 mRNA. Translation: AAB65727.1.
AF011528 mRNA. Translation: AAB65728.1.
AF011529 mRNA. Translation: AAB65729.1.
AF011530 mRNA. Translation: AAB65730.1.
AF011531 mRNA. Translation: AAB65731.1.
AF011532 mRNA. Translation: AAB65732.1.
AF011533 mRNA. Translation: AAB65733.1.
AF011534 mRNA. Translation: AAB65734.1.
AF011535 mRNA. Translation: AAB65735.1.
AF011536 mRNA. Translation: AAB65736.1.
AF011537 mRNA. Translation: AAB65737.1.
AF031237 Genomic DNA. Translation: AAB94735.1.
AF052539 Genomic DNA. Translation: AAD18131.1.
AY221093 Genomic DNA. Translation: AAO65971.1.
U95626 Genomic DNA. Translation: AAB57793.1.
BC038398 mRNA. Translation: AAH38398.1.

IPI

IPI00743929.

PIR

A43113.

RefSeq

NP_000570.1. NM_000579.3.
NP_001093638.1. NM_001100168.1.

UniGene

Hs.450802.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ND8	model	-	A	1-352	[»]
1NE0	model	-	A	1-352	[»]
1OPN	model	-	A	1-352	[»]
1OPT	model	-	A	1-352	[»]
1OPW	model	-	A	1-352	[»]
2L87	NMR	-	A	1-27	[»]
2RLL	NMR	-	A	7-15	[»]

ProteinModelPortal

P51681.

SMR

P51681. Positions 32-314.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5866N.

IntAct

P51681. 9 interactions.

MINT

MINT-103024.

STRING

P51681.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P51681.

Polymorphism databases

DMDM

1705896.

Proteomic databases

PRIDE

P51681.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000292303; ENSP00000292303; ENSG00000160791.
ENST00000343801; ENSP00000343985; ENSG00000160791.
ENST00000400886; ENSP00000383680; ENSG00000160791.
ENST00000445772; ENSP00000404881; ENSG00000160791.

GeneID

1234.

KEGG

hsa:1234.

UCSC

uc003cpo.2. human.

Organism-specific databases

CTD

1234.

GeneCards

GC03P046386.

H-InvDB

HIX0030863.

HGNC

HGNC:1606. CCR5.

MIM

601373. gene.
609423. phenotype.
610379. phenotype.
612522. phenotype.

neXtProt

NX_P51681.

PharmGKB

PA26170.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

HBG106917.

InParanoid

P51681.

OMA

FGNTMCQ.

OrthoDB

EOG40S0GG.

PhylomeDB

P51681.

Enzyme and pathway databases

Pathway_Interaction_DB

il12_2pathway. IL12-mediated signaling events.

Reactome

REACT_111102. Signal Transduction.
REACT_6185. HIV Infection.

Gene expression databases

ArrayExpress

P51681.

Bgee

P51681.

Genevestigator

P51681.

GermOnline

ENSG00000160791. Homo sapiens.

Family and domain databases

InterPro

IPR000276. 7TM_GPCR_Rhodpsn.
IPR002240. Chemokine_CCR5.
IPR000355. Chemokine_rcpt.
IPR017452. GPCR_Rhodpsn_supfam.
[Graphical view]

KO

K04180.

Pfam

PF00001. 7tm_1. 1 hit.
[Graphical view]

PRINTS

PR00657. CCCHEMOKINER.
PR01110. CHEMOKINER5.
PR00237. GPCRRHODOPSN.

PROSITE

PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB04835. Maraviroc.

NextBio

5035.

SOURCE

Search...

Entry information

Entry name

CCR5_HUMAN

Accession

Primary (citable) accession number: P51681
Secondary accession number(s): O14692 , O14693, O14695, O14696, O14697, O14698, O14699, O14700, O14701, O14702, O14703, O14704, O14705, O14706, O14707, O14708, O15538, Q9UPA4

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	December 14, 2011
This is version 121 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.