O08556 (CCR5_RAT) 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

Alternative name(s):
MIP-1 alpha receptor
CD_antigen=CD195

Gene names

Name:	Ccr5
Synonyms:	Cmkbr5

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	354 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript 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 By similarity.
Subunit structure	Interacts with PRAF2. 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 By similarity.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Post-translational modification	Sulfated on at least 2 of the N-terminal tyrosines. Sulfation is required for efficient binding of the chemokines, CCL3 and CCL4 By similarity. O-glycosylated, but not N-glycosylated. Ser-6 appears to be the major site. Also sialylated glycans present which contribute to chemokine binding. Ser-17 may also be glycosylated and, if so, with small moieties such as a T-antigen By similarity. Palmitoylation in the C-terminal is important for cell surface expression By similarity. Phosphorylation on serine residues in the C-terminal is stimulated by binding CC chemokines especially by APO-RANTES By similarity.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate Phosphoprotein Sulfation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	aging Inferred from expression pattern PubMed 16369869. Source: RGD chemotaxis Inferred from electronic annotation. Source: InterPro defense response to bacterium Inferred from expression pattern Ref.1. Source: RGD elevation of cytosolic calcium ion concentration Inferred from electronic annotation. Source: InterPro fat cell differentiation Inferred from expression pattern PubMed 17286602. Source: RGD forebrain development Inferred from expression pattern PubMed 16516309. Source: RGD inflammatory response to antigenic stimulus Inferred from expression pattern PubMed 14674010. Source: RGD leukocyte migration Traceable author statement PubMed 12403770. Source: RGD negative regulation of axon extension Inferred from mutant phenotype PubMed 16537566. Source: RGD negative regulation of cAMP biosynthetic process Inferred from electronic annotation. Source: InterPro negative regulation of cell migration Inferred from mutant phenotype PubMed 20940264. Source: RGD negative regulation of neural precursor cell proliferation Inferred from mutant phenotype PubMed 20940264. Source: RGD neuron death Inferred from mutant phenotype PubMed 20940264. Source: RGD positive regulation of apoptotic process by virus Inferred from mutant phenotype PubMed 19034668. Source: RGD positive regulation of cell-cell adhesion Inferred from mutant phenotype PubMed 16622027. Source: RGD positive regulation of fever generation Inferred from mutant phenotype PubMed 15066130. Source: RGD positive regulation of gene expression Inferred from mutant phenotype PubMed 19559698PubMed 20940264. Source: RGD positive regulation of interleukin-1 beta secretion Inferred from mutant phenotype PubMed 16790532. Source: RGD positive regulation of interleukin-6 production Inferred from mutant phenotype PubMed 16790532. Source: RGD positive regulation of neuron differentiation Inferred from mutant phenotype PubMed 19559698. Source: RGD positive regulation of tumor necrosis factor production Inferred from mutant phenotype PubMed 16790532. Source: RGD response to ionizing radiation Inferred from expression pattern PubMed 16937495. Source: RGD response to lipopolysaccharide Inferred from mutant phenotype PubMed 17604006. Source: RGD
Cellular_component	cell surface Inferred from direct assay PubMed 16320322. Source: RGD endosome Inferred from direct assay PubMed 12004163. Source: RGD integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	C-C chemokine binding Inferred from mutant phenotype PubMed 17604006. Source: RGD C-C chemokine receptor activity Inferred from mutant phenotype PubMed 17604006. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 354	354	C-C chemokine receptor type 5		PRO_0000069280
Regions
	Topological domain	1 – 32	32	Extracellular Potential
	Transmembrane	33 – 60	28	Helical; Name=1; Potential
	Topological domain	61 – 70	10	Cytoplasmic Potential
	Transmembrane	71 – 91	21	Helical; Name=2; Potential
	Topological domain	92 – 104	13	Extracellular Potential
	Transmembrane	105 – 126	22	Helical; Name=3; Potential
	Topological domain	127 – 143	17	Cytoplasmic Potential
	Transmembrane	144 – 168	25	Helical; Name=4; Potential
	Topological domain	169 – 200	32	Extracellular Potential
	Transmembrane	201 – 220	20	Helical; Name=5; Potential
	Topological domain	221 – 237	17	Cytoplasmic Potential
	Transmembrane	238 – 262	25	Helical; Name=6; Potential
	Topological domain	263 – 279	17	Extracellular Potential
	Transmembrane	280 – 303	24	Helical; Name=7; Potential
	Topological domain	304 – 354	51	Cytoplasmic Potential
Amino acid modifications
	Modified residue	10	1	Sulfotyrosine Potential
	Modified residue	16	1	Sulfotyrosine Potential
	Modified residue	338	1	Phosphoserine; by BARK1 By similarity
	Modified residue	339	1	Phosphoserine; by BARK1 By similarity
	Modified residue	344	1	Phosphoserine; by BARK1 By similarity
	Modified residue	351	1	Phosphoserine; by BARK1 By similarity
	Lipidation	323	1	S-palmitoyl cysteine By similarity
	Lipidation	326	1	S-palmitoyl cysteine By similarity
	Glycosylation	6	1	O-linked (GalNAc...) By similarity
	Glycosylation	19	1	O-linked (GalNAc...) Potential
	Disulfide bond	103 ↔ 180		By similarity

Sequences

	Sequence		Length	Mass (Da)
	O08556 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: 77EDB368AA4C868D	FASTA	354	41,031
	10 20 30 40 50 60 MDFQGSIPTY IYDIDYSMSA PCQKVNVKQI AAQLLPPLYS LVFIFGFVGN MMVFLILISC 70 80 90 100 110 120 KKLKSMTDIY LFNLAISDLL FLLTLPFWAH YAANEWVFGN IMCKLFTGIY HIGYFGGIFF 130 140 150 160 170 180 IILLTIDRYL AIVHAVFAIK ARTVNFGVIT SVVTWVVAVF VSLPEIIFMR SQKEGSHYTC 190 200 210 220 230 240 SPHFLHIQYR FWKHFQTLKM VILSLILPLL VMVICYSGIL NTLFRCRNEK KRHRAVRLIF 250 260 270 280 290 300 AIMIVYFLFW TPYNIVLLLT TFQEYFGLNN CSSSNRLDQA MQVTETLGMT HCCLNPVIYA 310 320 330 340 350 FVGEKFRNYL SVFFRKHIVK RFCKHCSIFQ QVNPDRVSSV YTRSTGEQEV STGL

References

[1]	"Cloning of rat HIV-1-chemokine coreceptor CKR5 from microglia and upregulation of its mRNA in ischemic and endotoxinemic rat brain." Spleiss O., Gourmala N., Boddeke H.W.G.M., Sauter A., Fiebich B.L., Berger M., Gebicke-Haerter P.J. J. Neurosci. Res. 53:16-28(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Wistar. Tissue: Brain.
[2]	"Chemokine receptor expression in cultured glia and rat experimental allergic encephalomyelitis." Jiang Y., Salafranca M.N., Adhikari S., Xia Y., Feng L., Sonntag M.K., deFiebre C.M., Pennell N.A., Streit W.J., Harrison J.K. J. Neuroimmunol. 86:1-12(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Sprague-Dawley.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Y12009 mRNA. Translation: CAA72737.1. U77350 Genomic DNA. Translation: AAC03243.1.
IPI	IPI00193718.
RefSeq	NP_446412.2. NM_053960.3.
UniGene	Rn.10736.
3D structure databases
ProteinModelPortal	O08556.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000008871.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	O08556.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	117029.
KEGG	rno:117029.
UCSC	RGD:620596. rat.
Organism-specific databases
CTD	1234.
RGD	620596. Ccr5.
Phylogenomic databases
eggNOG	NOG148353.
HOGENOM	HOG000234122.
HOVERGEN	HBG106917.
InParanoid	O08556.
KO	K04180.
OrthoDB	EOG40S0GG.
Gene expression databases
ArrayExpress	O08556.
Genevestigator	O08556.
GermOnline	ENSRNOG00000006774. Rattus norvegicus.
Family and domain databases
InterPro	IPR002240. Chemokine_CCR5. IPR000355. Chemokine_rcpt. IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. [Graphical view]
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
BindingDB	O08556.
ChEMBL	CHEMBL1795146.
NextBio	619809.

Entry information

Entry name

CCR5_RAT

Accession

Primary (citable) accession number: O08556

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 1, 1997
Last modified:	May 1, 2013
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program