CCR5 (C-C motif chemokine receptor 5)

Gene

• Entrez ID: 1234
• Gene name: C-C motif chemokine receptor 5
• Gene symbol: CCR5
• Synonyms: CC-CKR-5, CCCKR5, CCR-5, CD195, CKR-5, CKR5, CMKBR5, IDDM22
• Chromosome: 3
• Chromosome location: 3p21.31
• Summary: This gene encodes a member of the beta chemokine receptor family, which is predicted to be a seven transmembrane protein similar to G protein-coupled receptors. This protein is expressed by T cells and macrophages, and is known to be an important co-receptor for macrophage-tropic virus, including HIV, to enter host cells. Defective alleles of this gene have been associated with the HIV infection resistance. The ligands of this receptor include monocyte chemoattractant protein 2 (MCP-2), macrophage inflammatory protein 1 alpha (MIP-1 alpha), macrophage inflammatory protein 1 beta (MIP-1 beta) and regulated on activation normal T expressed and secreted protein (RANTES). Expression of this gene was also detected in a promyeloblastic cell line, suggesting that this protein may play a role in granulocyte lineage proliferation and differentiation. This gene is located at the chemokine receptor gene cluster region. An allelic polymorphism in this gene results in both functional and non-functional alleles; the reference genome represents the functional allele. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2015]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT620741	hsa-miR-510-3p	HITS-CLIP	23824327
MIRT620742	hsa-miR-6873-3p	HITS-CLIP	23824327
MIRT620743	hsa-miR-6867-3p	HITS-CLIP	23824327
MIRT620744	hsa-miR-203a-3p	HITS-CLIP	23824327
MIRT620745	hsa-miR-6817-3p	HITS-CLIP	23824327
MIRT620746	hsa-miR-7110-3p	HITS-CLIP	23824327
MIRT620747	hsa-miR-6845-3p	HITS-CLIP	23824327
MIRT620748	hsa-miR-4685-3p	HITS-CLIP	23824327
MIRT620749	hsa-miR-4287	HITS-CLIP	23824327
MIRT620750	hsa-miR-7113-3p	HITS-CLIP	23824327
MIRT620751	hsa-miR-4469	HITS-CLIP	23824327
MIRT620752	hsa-miR-6769b-3p	HITS-CLIP	23824327
MIRT620753	hsa-miR-4723-3p	HITS-CLIP	23824327
MIRT620754	hsa-miR-3183	HITS-CLIP	23824327
MIRT620755	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT620756	hsa-miR-6800-3p	HITS-CLIP	23824327
MIRT620757	hsa-miR-548z	HITS-CLIP	23824327
MIRT620758	hsa-miR-548h-3p	HITS-CLIP	23824327
MIRT620759	hsa-miR-548d-3p	HITS-CLIP	23824327
MIRT620760	hsa-miR-548bb-3p	HITS-CLIP	23824327
MIRT620761	hsa-miR-548ac	HITS-CLIP	23824327
MIRT620762	hsa-miR-6868-3p	HITS-CLIP	23824327
MIRT620763	hsa-miR-3182	HITS-CLIP	23824327
MIRT620764	hsa-miR-7157-3p	HITS-CLIP	23824327
MIRT620765	hsa-miR-6737-3p	HITS-CLIP	23824327
MIRT620766	hsa-miR-5008-3p	HITS-CLIP	23824327
MIRT620767	hsa-miR-6889-3p	HITS-CLIP	23824327
MIRT620768	hsa-miR-1248	HITS-CLIP	23824327
MIRT620769	hsa-miR-1237-3p	HITS-CLIP	23824327
MIRT620770	hsa-miR-660-3p	HITS-CLIP	23824327
MIRT620771	hsa-miR-5193	HITS-CLIP	23824327
MIRT641337	hsa-miR-211-5p	HITS-CLIP	23824327
MIRT641338	hsa-miR-204-5p	HITS-CLIP	23824327

Transcription factors

Transcription factor	Regulation	Reference
KLF2	Activation	22988032
NFKB1	Unknown	12745546;19469019;9840284
NR3C2	Activation	11751947
RELA	Unknown	12745546;19469019;9840284
YY1	Repression	12571248;15737629

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000165	Process	MAPK cascade	IEP	12032188
GO:0001618	Function	Virus receptor activity	IEA
GO:0002407	Process	Dendritic cell chemotaxis	TAS	16621978
GO:0003779	Function	Actin binding	IDA	12421915
GO:0004435	Function	Phosphatidylinositol phospholipase C activity	TAS	8663314
GO:0004950	Function	Chemokine receptor activity	TAS	10201901
GO:0005515	Function	Protein binding	IPI	10816381, 12421915, 15001559, 15660419, 18230715, 18632580, 23235831, 23480650, 23597562, 24405750, 28381538, 30542158, 32296183
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005768	Component	Endosome	IDA	10679098
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	TAS	10393923
GO:0006816	Process	Calcium ion transport	IDA	8699119
GO:0006935	Process	Chemotaxis	TAS	10741397
GO:0006954	Process	Inflammatory response	IBA	21873635
GO:0006955	Process	Immune response	IBA	21873635
GO:0006968	Process	Cellular defense response	TAS	10201901
GO:0007166	Process	Cell surface receptor signaling pathway	TAS	8639485
GO:0007186	Process	G protein-coupled receptor signaling pathway	IMP	19523456
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS
GO:0007204	Process	Positive regulation of cytosolic calcium ion concentration	IBA	21873635
GO:0007267	Process	Cell-cell signaling	IDA	10679098
GO:0009897	Component	External side of plasma membrane	IBA	21873635
GO:0009897	Component	External side of plasma membrane	IDA	10383387, 10679098, 11278962, 19523456
GO:0009986	Component	Cell surface	IDA	10521508
GO:0014808	Process	Release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	IDA	19523456
GO:0015026	Function	Coreceptor activity	TAS	10469138
GO:0016493	Function	C-C chemokine receptor activity	IBA	21873635
GO:0016493	Function	C-C chemokine receptor activity	IDA	10383387, 11278962
GO:0016493	Function	C-C chemokine receptor activity	NAS	8639485
GO:0019064	Process	Fusion of virus membrane with host plasma membrane	TAS
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS
GO:0019722	Process	Calcium-mediated signaling	IBA	21873635
GO:0019722	Process	Calcium-mediated signaling	IDA	10679098, 19523456
GO:0019957	Function	C-C chemokine binding	IBA	21873635
GO:0019957	Function	C-C chemokine binding	IPI	8699119, 10383387, 10679098
GO:0023052	Process	Signaling	IEP	12032188
GO:0042802	Function	Identical protein binding	IPI	18230715, 18632580, 23121557
GO:0060326	Process	Cell chemotaxis	IBA	21873635
GO:0070098	Process	Chemokine-mediated signaling pathway	IEA
GO:0070723	Process	Response to cholesterol	IMP	19523456
GO:0071222	Process	Cellular response to lipopolysaccharide	IEP	10679098
GO:0071791	Function	Chemokine (C-C motif) ligand 5 binding	IBA	21873635
GO:0071791	Function	Chemokine (C-C motif) ligand 5 binding	IPI	8699119

Other IDs

• MIM: 601373
• HGNC: 1606
• e!Ensembl: ENSG00000160791

Protein

• UniProt ID: P51681
• Protein name: C-C chemokine receptor type 5 (C-C CKR-5) (CC-CKR-5) (CCR-5) (CCR5) (CHEMR13) (HIV-1 fusion coreceptor) (CD antigen CD195)
• Protein function: 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. Participates in T-lymphocyte migration to the infection site by acting as a chemotactic receptor (PubMed:30713770). ; (Microbial infection) Acts as a coreceptor (CD4 being the primary receptor) of human immunodeficiency virus-1/HIV-1.
• PDB: 1ND8, 1NE0, 1OPN, 1OPT, 1OPW, 2L87, 2MZX, 2RLL, 2RRS, 4MBS, 5UIW, 5YD3, 5YD4, 5YD5, 5YY4, 6FGP, 6MEO, 6MET
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00001	7tm_1	47 → 297	7 transmembrane receptor (rhodopsin family)	Family

• Sequence:

  MDYQVSSPIYDINYYTSEPCQKINVKQIAARLLPPLYSLVFIFGFVGNMLVILILINCKR
  LKSMTDIYLLNLAISDLFFLLTVPFWAHYAAAQWDFGNTMCQLLTGLYFIGFFSGIFFII
  LLTIDRYLAVVHAVFALKARTVTFGVVTSVITWVVAVFASLPGIIFTRSQKEGLHYTCSS
  HFPYSQYQFWKNFQTLKIVILGLVLPLLVMVICYSGILKTLLRCRNEKKRHRAVRLIFTI
  MIVYFLFWAPYNIVLLLNTFQEFFGLNNCSSSNRLDQAMQVTETLGMTHCCINPIIYAFV
  GEKFRNYLLVFFQKHIAKRFCKCCSIFQQEAPERASSVYTRSTGEQEISVGL

• Sequence length: 352

Pathways

KEGG:

Viral life cycle - HIV-1
Virion - Human immunodeficiency virus
Cytokine-cytokine receptor interaction
Viral protein interaction with cytokine and cytokine receptor
Chemokine signaling pathway
Endocytosis
Toxoplasmosis
Human cytomegalovirus infection
Kaposi sarcoma-associated herpesvirus infection
Human immunodeficiency virus 1 infection
Viral carcinogenesis

Reactome:

Binding and entry of HIV virion
Chemokine receptors bind chemokines
G alpha (i) signalling events
Interleukin-10 signaling

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Diabetes mellitus	DIABETES MELLITUS, INSULIN-DEPENDENT, 22 (disorder)	rs587776515, rs61730328, rs606231121, rs606231122, rs79020217, rs77625743, rs78378398, rs606231123, rs4402960, rs1362648752, rs3745368, rs3792267, rs3842570, rs5030952, rs2975760, rs119489103, rs7903146, rs12255372, rs11196205, rs104893649, rs80356624, rs80356616, rs80356625, rs80356611, rs104894237, rs80356613, rs137852740, rs137852786, rs387906407, rs151344623, rs28938469, rs28936371, rs137852672, rs80356637, rs80356642, rs80356653, rs137852673, rs137852674, rs80356634, rs80356651, rs193929360, rs137853334, rs137853335, rs137853336, rs-1, rs1600731198, rs137853338, rs121964882, rs121964883, rs387906511, rs121964884, rs121964885, rs2147483647, rs387906512, rs121964887, rs121964888, rs121964889, rs121964890, rs121964891, rs28934878, rs74315383, rs121964893, rs886037620, rs886037621, rs80356663, rs121434593, rs121913150, rs587776825, rs137853236, rs2135842335, rs137853237, rs137853238, rs2135818776, rs1566092470, rs1463923467, rs137853243, rs137853244, rs2135839114, rs137853245, rs2135847417, rs121918407, rs104894005, rs104894006, rs80356655, rs104894008, rs104894009, rs104894010, rs104894011, rs80356654, rs104894016, rs193929376, rs193929374, rs193929375, rs193929373, rs80356666, rs80356669, rs80356664, rs193929366, rs1048095, rs193929355, rs193929356, rs1259467443, rs104893642, rs387906777, rs387906779, rs141804752, rs182349376, rs184917682, rs193922396, rs193922400, rs193922401, rs137852676, rs193922407, rs193922638, rs193922257, rs193922258, rs193922259, rs193922260, rs193922261, rs193922262, rs193922263, rs193922264, rs193922265, rs193922268, rs193921338, rs193922269, rs193922272, rs193922273, rs193922275, rs193922278, rs193922279, rs193922280, rs193922281, rs193922282, rs193922283, rs193922284, rs193922286, rs193922287, rs193922289, rs193922291, rs193922295, rs193922297, rs193922300, rs193922302, rs193922303, rs193922308, rs193922313, rs193922314, rs144723656, rs193922315, rs193922316, rs193922317, rs148311934, rs193922319, rs193922320, rs193922326, rs193922329, rs193922330, rs193922331, rs193922335, rs193922336, rs193922338, rs193922340, rs193922341, rs193922471, rs193922475, rs193922476, rs193922479, rs193922355, rs193922356, rs193922576, rs193922578, rs193922582, rs193922588, rs193922592, rs193922594, rs193922596, rs386134267, rs193922598, rs193922599, rs193922600, rs193922604, rs193922605, rs397514580, rs397515519, rs267601516, rs587780343, rs587780345, rs587780346, rs587780347, rs587780357, rs148954387, rs61736969, rs587783673, rs587783672, rs587783669, rs786204676, rs794727236, rs151344624, rs794727775, rs794727839, rs199946797, rs869320673, rs796065047, rs759072800, rs797045595, rs797045209, rs797045207, rs797045213, rs797045623, rs863225280, rs149703259, rs864321656, rs139964066, rs777870079, rs878853246, rs769268803, rs886039380, rs886041392, rs886041391, rs886042610, rs143064649, rs1057516192, rs746480424, rs1057516281, rs576684889, rs754728827, rs1057520291, rs1057520779, rs893256143, rs1057520504, rs1057524790, rs1057524902, rs1057524904, rs1057524905, rs764232985, rs1064793998, rs1064794268, rs769086289, rs369429452, rs1085307913, rs1131691416, rs765432081, rs1131692182, rs748749585, rs1554335441, rs762263694, rs1312678560, rs767565869, rs1375656631, rs1554335391, rs1360415315, rs1554335616, rs1554335752, rs1554909277, rs769518471, rs757171524, rs768951263, rs762703502, rs1555212248, rs1555212359, rs1555813319, rs1555816654, rs371977235, rs76474829, rs200998587, rs1415041911, rs1554334894, rs1260178539, rs1554335421, rs1555211904, rs779184183, rs1554335564, rs200670692, rs1400535021, rs1554334872, rs1555212749, rs1553876668, rs1553878211, rs954727530, rs1554924035, rs372307320, rs925231098, rs1554913069, rs1554933565, rs766431403, rs746714109, rs751279984, rs770664202, rs1008906426, rs758844607, rs1554924540, rs1566092307, rs753998395, rs1565885935, rs1167124132, rs1376796469, rs556436603, rs1562715657, rs1486280029, rs1564869850, rs755259997, rs769569410, rs1172328722, rs1286294151, rs1375557127, rs1568731279, rs1562715426, rs556581174, rs1564865302, rs1565886545, rs776793516, rs1568724014, rs1392795567, rs781260712, rs1562719705, rs1382448285, rs1564977373, rs750586210, rs1598842892, rs1583592247, rs780612692, rs1593060859, rs1476637197, rs751279776, rs1593060890, rs1191912908, rs1167675604, rs1583601110, rs1593058932, rs778611627, rs753296261
Schizophrenia	Schizophrenia	rs74315508, rs74315509, rs13447324, rs1558507406, rs387906932, rs387906933, rs-1, rs863223354, rs863223355, rs776061422, rs863223349, rs748809996, rs759748655, rs863223353, rs863223350, rs863223356, rs781821239, rs863223348, rs863223346, rs863223347, rs863223351, rs863223352, rs61734270, rs797045205, rs869312829, rs869312830, rs770913157, rs869312832, rs869312831, rs781720548, rs1262969313	16513874
Dermatitis	Dermatitis, Atopic	rs61816761, rs150597413, rs138726443, rs201356558, rs149484917, rs372754256, rs747301529, rs567795279, rs745915174	18249437

Unknown
Disease name	Disease term	dbSNP ID	References
Eczema	Eczema, Infantile		18249437
Kidney failure	Kidney Failure, Acute		26055553
Nephritis	Nephritis		26055553
Acute kidney insufficiency	Acute Kidney Insufficiency		26055553