Reviewed, UniProtKB/Swiss-Prot P41597 (CCR2_HUMAN)

Names and origin

Protein names

Recommended name:
    C-C chemokine receptor type 2
      Short name=C-C CKR-2
      Short name=CC-CKR-2
      Short name=CCR-2
      Short name=CCR2
Alternative name(s):
    Monocyte chemoattractant protein 1 receptor
      Short name=MCP-1-R
    CD_antigen=CD192

Gene names

Name:	CCR2
Synonyms:	CMKBR2

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	374 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Receptor for the MCP-1, MCP-3 and MCP-4 chemokines. Transduces a signal by increasing the intracellular calcium ions level. Alternative coreceptor with CD4 for HIV-1 infection.
Subunit structure	Binds to HIV-1 Tat.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Post-translational modification	N-glycosylated.
Polymorphism	Variations in CCR2 are associated with relative resistance to immunodeficiency virus type 1 (resistance to HIV-1) [MIM:609423].
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	Alternative splicing Polymorphism
Domain	Transmembrane
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Glycoprotein Sulfation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	G-protein coupled receptor protein signaling pathway Inferred from electronic annotation. Source: InterPro JAK-STAT cascade Traceable author statement. Source: ProtInc cellular defense response Traceable author statement. Source: ProtInc chemotaxis Traceable author statement. Source: ProtInc cytokine and chemokine mediated signaling pathway Inferred from direct assay. Source: MGI elevation of cytosolic calcium ion concentration Traceable author statement. Source: ProtInc immune response Traceable author statement. Source: ProtInc inflammatory response Traceable author statement. Source: ProtInc interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of adenylate cyclase activity Ref.3 Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from direct assay. Source: MGI integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc soluble fraction Ref.3 Traceable author statement. Source: ProtInc
Molecular function	C-C chemokine receptor activity Inferred from electronic annotation. Source: InterPro CCR2 chemokine receptor binding Inferred from direct assay. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform A (identifier: P41597-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform B (identifier: P41597-2)

The sequence of this isoform differs from the canonical sequence as follows:
     314-374: SLFHIALGCR...EASLQDKEGA → RYLSVFFRKH...TGEQEVSAGL

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 374

374

C-C chemokine receptor type 2

PRO_0000069232

Regions

Topological domain

1 – 42

42

Extracellular Potential

Transmembrane

43 – 70

28

1 Potential

Topological domain

71 – 80

10

Cytoplasmic Potential

Transmembrane

81 – 100

20

2 Potential

Topological domain

101 – 114

14

Extracellular Potential

Transmembrane

115 – 136

22

3 Potential

Topological domain

137 – 153

17

Cytoplasmic Potential

Transmembrane

154 – 178

25

4 Potential

Topological domain

179 – 206

28

Extracellular Potential

Transmembrane

207 – 226

20

5 Potential

Topological domain

227 – 243

17

Cytoplasmic Potential

Transmembrane

244 – 268

25

6 Potential

Topological domain

269 – 285

17

Extracellular Potential

Transmembrane

286 – 309

24

7 Potential

Topological domain

310 – 374

65

Cytoplasmic Potential

Amino acid modifications

Modified residue

26

1

Sulfotyrosine

Glycosylation

14

1

N-linked (GlcNAc...) Potential

Disulfide bond

32 ↔ 277

Disulfide bond

113 ↔ 190

Natural variations

Alternative sequence

314 – 374

61

SLFHI…DKEGA → RYLSVFFRKHITKRFCKQCP VFYRETVDGVTSTNTPSTGE QEVSAGL in isoform B.

VSP_001893

Natural variant

45

1

L → V: dbSNP rs4987052.

VAR_020066

Natural variant

64

1

V → I Confers relative resistance to infection by HIV-1; delay in disease progression in African Americans but not in Caucasians. dbSNP rs1799864.

VAR_014339

Natural variant

355

1

G → E: dbSNP rs3918387.

VAR_014340

Secondary structure

1

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374

Helix Strand Turn

Details...

Turn

2 – 6

5

Beta strand

12 – 14

3

Turn

20 – 23

4

Turn

37 – 40

4

Helix

41 – 69

29

Helix

77 – 93

17

Helix

95 – 101

7

Helix

109 – 143

35

Turn

145 – 148

4

Helix

156 – 177

22

Turn

185 – 188

4

Beta strand

191 – 193

3

Helix

194 – 196

3

Helix

202 – 210

9

Helix

212 – 224

13

Beta strand

234 – 236

3

Helix

239 – 255

17

Helix

258 – 265

8

Beta strand

283 – 285

3

Helix

293 – 300

8

Helix

301 – 304

4

Helix

305 – 316

12

Helix

318 – 328

11

Beta strand

333 – 335

3

Helix

340 – 343

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform A [UniParc]. Last modified November 1, 1995. Version 1. Checksum: F865E0D39E74CF0F	FASTA	374	41,915
	10 20 30 40 50 60 MLSTSRSRFI RNTNESGEEV TTFFDYDYGA PCHKFDVKQI GAQLLPPLYS LVFIFGFVGN 70 80 90 100 110 120 MLVVLILINC KKLKCLTDIY LLNLAISDLL FLITLPLWAH SAANEWVFGN AMCKLFTGLY 130 140 150 160 170 180 HIGYFGGIFF IILLTIDRYL AIVHAVFALK ARTVTFGVVT SVITWLVAVF ASVPGIIFTK 190 200 210 220 230 240 CQKEDSVYVC GPYFPRGWNN FHTIMRNILG LVLPLLIMVI CYSGILKTLL RCRNEKKRHR 250 260 270 280 290 300 AVRVIFTIMI VYFLFWTPYN IVILLNTFQE FFGLSNCEST SQLDQATQVT ETLGMTHCCI 310 320 330 340 350 360 NPIIYAFVGE KFRSLFHIAL GCRIAPLQKP VCGGPGVRPG KNVKVTTQGL LDGRGKGKSI 370 GRAPEASLQD KEGA
	Isoform B [UniParc]. Checksum: EA352636D724D470		360	41,064
	10 20 30 40 50 60 MLSTSRSRFI RNTNESGEEV TTFFDYDYGA PCHKFDVKQI GAQLLPPLYS LVFIFGFVGN 70 80 90 100 110 120 MLVVLILINC KKLKCLTDIY LLNLAISDLL FLITLPLWAH SAANEWVFGN AMCKLFTGLY 130 140 150 160 170 180 HIGYFGGIFF IILLTIDRYL AIVHAVFALK ARTVTFGVVT SVITWLVAVF ASVPGIIFTK 190 200 210 220 230 240 CQKEDSVYVC GPYFPRGWNN FHTIMRNILG LVLPLLIMVI CYSGILKTLL RCRNEKKRHR 250 260 270 280 290 300 AVRVIFTIMI VYFLFWTPYN IVILLNTFQE FFGLSNCEST SQLDQATQVT ETLGMTHCCI 310 320 330 340 350 360 NPIIYAFVGE KFRRYLSVFF RKHITKRFCK QCPVFYRETV DGVTSTNTPS TGEQEVSAGL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and functional expression of two monocyte chemoattractant protein 1 receptors reveals alternative splicing of the carboxyl-terminal tails." Charo I.F., Myers S.J., Herman A., Franci C., Connolly A.J., Coughlin S.R. Proc. Natl. Acad. Sci. U.S.A. 91:2752-2756(1994) [PubMed: 8146186] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"cDNA cloning and functional expression of a human monocyte chemoattractant protein 1 receptor." Yamagami S., Tokuda Y., Ishii K., Tamaka H., Endo N. Biochem. Biophys. Res. Commun. 202:1156-1162(1994) [PubMed: 8048929] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Organization and differential expression of the human monocyte chemoattractant protein 1 receptor gene. Evidence for the role of the carboxyl-terminal tail in receptor trafficking." Wong L.-M., Myers S.J., Tsou C.-L., Gosling J., Arai H., Charo I.F. J. Biol. Chem. 272:1038-1045(1997) [PubMed: 8995400] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	SeattleSNPs program for genomic applications Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ILE-64 AND GLU-355.
[5]	"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].
[6]	"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] (ISOFORM A).
[7]	"HIV-1 Tat protein mimicry of chemokines." Albini A., Ferrini S., Benelli R., Sforzini S., Giunciuglio D., Aluigi M.G., Proudfoot A.E.I., Alouani S., Wells T.N.C., Mariani G., Rabin R.L., Farber J.M., Noonan D.M. Proc. Natl. Acad. Sci. U.S.A. 95:13153-13158(1998) [PubMed: 9789057] [Abstract] Cited for: INTERACTION WITH HIV-1 TAT.
[8]	"Monocyte chemotactic protein-1 receptor CCR2B is a glycoprotein that has tyrosine sulfation in a conserved extracellular N-terminal region." Preobrazhensky A.A., Dragan S., Kawano T., Gavrilin M.A., Gulina I.V., Chakravarty L., Kolattukudy P.E. J. Immunol. 165:5295-5303(2000) [PubMed: 11046064] [Abstract] Cited for: SULFATION AT TYR-26, GLYCOSYLATION.
[9]	"Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression." Smith M.W., Dean M., Carrington M., Winkler C., Huttley G.A., Lomb D.A., Goedert J.J., O'Brien T.R., Jacobson L.P., Kaslow R., Buchbinder S., Vittinghoff E., Vlahov D., Hoots K., Hilgartner M.W., O'Brien S.J. Science 277:959-965(1997) [PubMed: 9252328] [Abstract] Cited for: VARIANT ILE-64.
[10]	"Genealogy of the CCR5 locus and chemokine system gene variants associated with altered rates of HIV-1 disease progression." Mummidi S., Ahuja S.S., Gonzalez E., Anderson S.A., Santiago E.N., Stephan K.T., Craig F.E., O'Connell P., Tryon V., Clark R.A., Dolan M.J., Ahuja S.K. Nat. Med. 4:786-793(1998) [PubMed: 9662369] [Abstract] Cited for: VARIANT ILE-64.
+	Additional computationally mapped references.

Web resources

Wikipedia

CC chemokine receptors entry

SeattleSNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	U03882 mRNA. Translation: AAA19119.1. U03905 mRNA. Translation: AAA19120.1. D29984 mRNA. Translation: BAA06253.1. U80924 Genomic DNA. Translation: AAC51637.1. U80924 Genomic DNA. Translation: AAC51636.1. AF545480 Genomic DNA. Translation: AAN16400.1. U95626 Genomic DNA. Translation: AAB57791.1. U95626 Genomic DNA. Translation: AAB57792.1. BC074751 mRNA. Translation: AAH74751.1. BC126452 mRNA. Translation: AAI26453.1.
PIR	I38450. JC2443.
RefSeq	NP_000638.1. NP_000639.1. NP_001116513.2.
UniGene	Hs.511794 Hs.644637