CCR2_HUMAN
ID CCR2_HUMAN Reviewed; 374 AA.
AC P41597; A0AVQ3; B2RMT0; O95950; Q4VBL2;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=C-C chemokine receptor type 2;
DE Short=C-C CKR-2;
DE Short=CC-CKR-2;
DE Short=CCR-2;
DE Short=CCR2;
DE AltName: Full=Monocyte chemoattractant protein 1 receptor;
DE Short=MCP-1-R;
DE AltName: CD_antigen=CD192;
GN Name=CCR2; Synonyms=CMKBR2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=8146186; DOI=10.1073/pnas.91.7.2752;
RA Charo I.F., Myers S.J., Herman A., Franci C., Connolly A.J., Coughlin S.R.;
RT "Molecular cloning and functional expression of two monocyte
RT chemoattractant protein 1 receptors reveals alternative splicing of the
RT carboxyl-terminal tails.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:2752-2756(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=8048929; DOI=10.1006/bbrc.1994.2049;
RA Yamagami S., Tokuda Y., Ishii K., Tamaka H., Endo N.;
RT "cDNA cloning and functional expression of a human monocyte chemoattractant
RT protein 1 receptor.";
RL Biochem. Biophys. Res. Commun. 202:1156-1162(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8995400; DOI=10.1074/jbc.272.2.1038;
RA Wong L.-M., Myers S.J., Tsou C.-L., Gosling J., Arai H., Charo I.F.;
RT "Organization and differential expression of the human monocyte
RT chemoattractant protein 1 receptor gene. Evidence for the role of the
RT carboxyl-terminal tail in receptor trafficking.";
RL J. Biol. Chem. 272:1038-1045(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-64 AND GLU-355.
RG SeattleSNPs variation discovery resource;
RL Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thymus, and Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A AND B).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 221-374 (ISOFORM B), ALTERNATIVE SPLICING,
RP TISSUE SPECIFICITY, AND INDUCTION BY IL2.
RX PubMed=9058802;
RA Polentarutti N., Allavena P., Bianchi G., Giardina G., Basile A.,
RA Sozzani S., Mantovani A., Introna M.;
RT "IL-2-Regulated Expression of the Monocyte Chemotactic Protein-1 Receptor
RT (CCR2) in Human NK Cells.";
RL J. Immunol. 158:2689-2694(1997).
RN [10]
RP PHOSPHORYLATION AT TYR-139 BY JAK2.
RX PubMed=9670957;
RA Mellado M., Rodriguez-Frade J.M., Aragay A., del Real G., Martin A.M.,
RA Vila-Coro A.J., Serrano A., Mayor F. Jr., Martinez-A C.;
RT "The chemokine monocyte chemotactic protein 1 triggers Janus kinase 2
RT activation and tyrosine phosphorylation of the CCR2B receptor.";
RL J. Immunol. 161:805-813(1998).
RN [11]
RP INTERACTION WITH ARRB1.
RX PubMed=9501202; DOI=10.1073/pnas.95.6.2985;
RA Aragay A.M., Mellado M., Frade J.M., Martin A.M., Jimenez-Sainz M.C.,
RA Martinez-A C., Mayor F. Jr.;
RT "Monocyte chemoattractant protein-1-induced CCR2B receptor desensitization
RT mediated by the G protein-coupled receptor kinase 2.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:2985-2990(1998).
RN [12]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HIV-1 TAT (MICROBIAL
RP INFECTION).
RX PubMed=9789057; DOI=10.1073/pnas.95.22.13153;
RA Albini A., Ferrini S., Benelli R., Sforzini S., Giunciuglio D.,
RA Aluigi M.G., Proudfoot A.E.I., Alouani S., Wells T.N.C., Mariani G.,
RA Rabin R.L., Farber J.M., Noonan D.M.;
RT "HIV-1 Tat protein mimicry of chemokines.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:13153-13158(1998).
RN [13]
RP SULFATION AT TYR-26, AND GLYCOSYLATION.
RX PubMed=11046064; DOI=10.4049/jimmunol.165.9.5295;
RA Preobrazhensky A.A., Dragan S., Kawano T., Gavrilin M.A., Gulina I.V.,
RA Chakravarty L., Kolattukudy P.E.;
RT "Monocyte chemotactic protein-1 receptor CCR2B is a glycoprotein that has
RT tyrosine sulfation in a conserved extracellular N-terminal region.";
RL J. Immunol. 165:5295-5303(2000).
RN [14]
RP FUNCTION, INTERACTION WITH NUP85, AND SUBCELLULAR LOCATION.
RX PubMed=15995708; DOI=10.1038/ni1222;
RA Terashima Y., Onai N., Murai M., Enomoto M., Poonpiriya V., Hamada T.,
RA Motomura K., Suwa M., Ezaki T., Haga T., Kanegasaki S., Matsushima K.;
RT "Pivotal function for cytoplasmic protein FROUNT in CCR2-mediated monocyte
RT chemotaxis.";
RL Nat. Immunol. 6:827-835(2005).
RN [15]
RP SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=18587271; DOI=10.3858/emm.2008.40.3.332;
RA Sung H.J., Kim Y.S., Kang H., Ko J.;
RT "Human LZIP induces monocyte CC chemokine receptor 2 expression leading to
RT enhancement of monocyte chemoattractant protein 1/CCL2-induced cell
RT migration.";
RL Exp. Mol. Med. 40:332-338(2008).
RN [16]
RP FUNCTION, AND SULFATION.
RX PubMed=23408426; DOI=10.1074/jbc.m112.447359;
RA Tan J.H., Ludeman J.P., Wedderburn J., Canals M., Hall P., Butler S.J.,
RA Taleski D., Christopoulos A., Hickey M.J., Payne R.J., Stone M.J.;
RT "Tyrosine sulfation of chemokine receptor CCR2 enhances interactions with
RT both monomeric and dimeric forms of the chemokine monocyte chemoattractant
RT protein-1 (MCP-1).";
RL J. Biol. Chem. 288:10024-10034(2013).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BETA-DEFENSIN
RP DEFB106A/DEFB106B.
RX PubMed=23938203; DOI=10.1016/j.jmb.2013.08.001;
RA De Paula V.S., Gomes N.S., Lima L.G., Miyamoto C.A., Monteiro R.Q.,
RA Almeida F.C., Valente A.P.;
RT "Structural basis for the interaction of human beta-defensin 6 and its
RT putative chemokine receptor CCR2 and breast cancer microvesicles.";
RL J. Mol. Biol. 425:4479-4495(2013).
RN [18]
RP STRUCTURE BY NMR OF 310-325 (ISOFORM B), INTERACTION WITH NUP85, AND
RP MUTAGENESIS OF ISOFORM B.
RX PubMed=25283965; DOI=10.1111/febs.13096;
RA Esaki K., Yoshinaga S., Tsuji T., Toda E., Terashima Y., Saitoh T.,
RA Kohda D., Kohno T., Osawa M., Ueda T., Shimada I., Matsushima K.,
RA Terasawa H.;
RT "Structural basis for the binding of the membrane-proximal C-terminal
RT region of chemokine receptor CCR2 with the cytosolic regulator FROUNT.";
RL FEBS J. 281:5552-5566(2014).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.81 ANGSTROMS) OF 2-328 (ISOFORM B), AND DISULFIDE
RP BOND.
RX PubMed=27926736; DOI=10.1038/nature20605;
RA Zheng Y., Qin L., Zacarias N.V., de Vries H., Han G.W., Gustavsson M.,
RA Dabros M., Zhao C., Cherney R.J., Carter P., Stamos D., Abagyan R.,
RA Cherezov V., Stevens R.C., Ijzerman A.P., Heitman L.H., Tebben A.,
RA Kufareva I., Handel T.M.;
RT "Structure of CC chemokine receptor 2 with orthosteric and allosteric
RT antagonists.";
RL Nature 540:458-461(2016).
RN [20]
RP VARIANT ILE-64.
RX PubMed=9252328; DOI=10.1126/science.277.5328.959;
RA Smith M.W., Dean M., Carrington M., Winkler C., Huttley G.A., Lomb D.A.,
RA Goedert J.J., O'Brien T.R., Jacobson L.P., Kaslow R., Buchbinder S.,
RA Vittinghoff E., Vlahov D., Hoots K., Hilgartner M.W., O'Brien S.J.;
RT "Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection
RT and disease progression.";
RL Science 277:959-965(1997).
RN [21]
RP VARIANT ILE-64.
RX PubMed=9662369; DOI=10.1038/nm0798-786;
RA Mummidi S., Ahuja S.S., Gonzalez E., Anderson S.A., Santiago E.N.,
RA Stephan K.T., Craig F.E., O'Connell P., Tryon V., Clark R.A., Dolan M.J.,
RA Ahuja S.K.;
RT "Genealogy of the CCR5 locus and chemokine system gene variants associated
RT with altered rates of HIV-1 disease progression.";
RL Nat. Med. 4:786-793(1998).
CC -!- FUNCTION: Key functional receptor for CCL2 but can also bind CCL7 and
CC CCL12 (PubMed:8146186, PubMed:8048929, PubMed:23408426). Its binding
CC with CCL2 on monocytes and macrophages mediates chemotaxis and
CC migration induction through the activation of the PI3K cascade, the
CC small G protein Rac and lamellipodium protrusion (Probable). Also acts
CC as a receptor for the beta-defensin DEFB106A/DEFB106B
CC (PubMed:23938203). Regulates the expression of T-cell inflammatory
CC cytokines and T-cell differentiation, promoting the differentiation of
CC T-cells into T-helper 17 cells (Th17) during inflammation (By
CC similarity). Facilitates the export of mature thymocytes by enhancing
CC directional movement of thymocytes to sphingosine-1-phosphate
CC stimulation and up-regulation of S1P1R expression; signals through the
CC JAK-STAT pathway to regulate FOXO1 activity leading to an increased
CC expression of S1P1R (By similarity). Plays an important role in
CC mediating peripheral nerve injury-induced neuropathic pain (By
CC similarity). Increases NMDA-mediated synaptic transmission in both
CC dopamine D1 and D2 receptor-containing neurons, which may be caused by
CC MAPK/ERK-dependent phosphorylation of GRIN2B/NMDAR2B (By similarity).
CC Mediates the recruitment of macrophages and monocytes to the injury
CC site following brain injury (By similarity).
CC {ECO:0000250|UniProtKB:P51683, ECO:0000269|PubMed:23408426,
CC ECO:0000269|PubMed:23938203, ECO:0000269|PubMed:8048929,
CC ECO:0000269|PubMed:8146186, ECO:0000305|PubMed:15995708}.
CC -!- FUNCTION: (Microbial infection) Alternative coreceptor with CD4 for
CC HIV-1 infection. {ECO:0000269|PubMed:9789057}.
CC -!- SUBUNIT: Interacts with ARRB1 (PubMed:9501202). Interacts (via
CC extracellular N-terminal region) with beta-defensin DEFB106A/DEFB106B;
CC this interaction may preferentially require specific tyrosine sulfation
CC on CCR2 (PubMed:23938203). Interacts with NUP85; the interaction is
CC required for CCR2 clusters formation on the cell membrane and CCR2
CC signaling (PubMed:15995708, PubMed:25283965).
CC {ECO:0000269|PubMed:15995708, ECO:0000269|PubMed:23938203,
CC ECO:0000269|PubMed:25283965, ECO:0000269|PubMed:9501202}.
CC -!- SUBUNIT: (Microbial infection) Binds to HIV-1 Tat.
CC {ECO:0000269|PubMed:9789057}.
CC -!- INTERACTION:
CC P41597-2; Q9BW27: NUP85; NbExp=3; IntAct=EBI-14807859, EBI-716392;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15995708,
CC ECO:0000269|PubMed:18587271}; Multi-pass membrane protein
CC {ECO:0000255}. Note=The chemoattractant receptors are distributed
CC throughout the cell surface; after stimulation with a ligand, such as
CC CCL2, they are rapidly recruited into microdomain clusters at the cell
CC membrane. {ECO:0000269|PubMed:15995708}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A {ECO:0000303|PubMed:9058802};
CC IsoId=P41597-1; Sequence=Displayed;
CC Name=B {ECO:0000303|PubMed:9058802};
CC IsoId=P41597-2; Sequence=VSP_001893;
CC -!- TISSUE SPECIFICITY: Expressed by monocytes and IL2-activated NK cells.
CC {ECO:0000269|PubMed:9058802}.
CC -!- INDUCTION: Up-regulated by CREB3 (PubMed:18587271). In NK cells,
CC induced by IL2 (PubMed:9058802). {ECO:0000269|PubMed:18587271,
CC ECO:0000269|PubMed:9058802}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:11046064}.
CC -!- PTM: Sulfation increases the affinity for both monomeric and dimeric
CC CCL2 with stronger binding to the monomeric form (PubMed:11046064,
CC PubMed:23408426). Binding of sulfated CCR2 to CCL2 promotes conversion
CC of CCL2 from dimer to monomer (PubMed:11046064, PubMed:23408426).
CC {ECO:0000269|PubMed:11046064, ECO:0000269|PubMed:23408426}.
CC -!- POLYMORPHISM: Variations in CCR2 are associated with relative
CC resistance to immunodeficiency virus type 1 (resistance to HIV-1)
CC [MIM:609423]. {ECO:0000269|PubMed:9252328}.
CC -!- MISCELLANEOUS: [Isoform B]: Mutagenesis of Leu-316 to Thr as well as
CC Phe-320 to Asp decrease interaction with NUP85.
CC {ECO:0000269|PubMed:27926736}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=CC chemokine receptors entry;
CC URL="https://en.wikipedia.org/wiki/CC_chemokine_receptors";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/ccr2/";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CCR2ID964ch3p21.html";
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DR EMBL; U03882; AAA19119.1; -; mRNA.
DR EMBL; U03905; AAA19120.1; -; mRNA.
DR EMBL; D29984; BAA06253.1; -; mRNA.
DR EMBL; U80924; AAC51637.1; -; Genomic_DNA.
DR EMBL; U80924; AAC51636.1; -; Genomic_DNA.
DR EMBL; AF545480; AAN16400.1; -; Genomic_DNA.
DR EMBL; AK292685; BAF85374.1; -; mRNA.
DR EMBL; AK292920; BAF85609.1; -; mRNA.
DR EMBL; U95626; AAB57791.1; -; Genomic_DNA.
DR EMBL; U95626; AAB57792.1; -; Genomic_DNA.
DR EMBL; CH471055; EAW64760.1; -; Genomic_DNA.
DR EMBL; BC074751; AAH74751.1; -; mRNA.
DR EMBL; BC095540; AAH95540.1; -; mRNA.
DR EMBL; BC126452; AAI26453.1; -; mRNA.
DR EMBL; BC136396; AAI36397.1; -; mRNA.
DR EMBL; X95583; CAA64835.1; -; mRNA.
DR CCDS; CCDS43078.1; -. [P41597-1]
DR CCDS; CCDS46813.1; -. [P41597-2]
DR PIR; I38450; I38450.
DR PIR; JC2443; JC2443.
DR RefSeq; NP_001116513.2; NM_001123041.2. [P41597-1]
DR RefSeq; NP_001116868.1; NM_001123396.1. [P41597-2]
DR RefSeq; XP_011532371.1; XM_011534069.1. [P41597-2]
DR PDB; 2MLO; NMR; -; A=310-318.
DR PDB; 2MLQ; NMR; -; A=310-318.
DR PDB; 5T1A; X-ray; 2.81 A; A=2-313.
DR PDB; 7P8X; X-ray; 1.40 A; M=25-29.
DR PDBsum; 2MLO; -.
DR PDBsum; 2MLQ; -.
DR PDBsum; 5T1A; -.
DR PDBsum; 7P8X; -.
DR AlphaFoldDB; P41597; -.
DR SMR; P41597; -.
DR BioGRID; 609634; 45.
DR DIP; DIP-5833N; -.
DR IntAct; P41597; 42.
DR MINT; P41597; -.
DR STRING; 9606.ENSP00000292301; -.
DR BindingDB; P41597; -.
DR ChEMBL; CHEMBL4015; -.
DR DrugBank; DB05159; CCX915.
DR DrugBank; DB05130; INCB3284.
DR DrugBank; DB12520; Plozalizumab.
DR DrugCentral; P41597; -.
DR GuidetoPHARMACOLOGY; 59; -.
DR GlyGen; P41597; 1 site.
DR iPTMnet; P41597; -.
DR PhosphoSitePlus; P41597; -.
DR BioMuta; CCR2; -.
DR DMDM; 1168965; -.
DR jPOST; P41597; -.
DR MassIVE; P41597; -.
DR PaxDb; P41597; -.
DR PeptideAtlas; P41597; -.
DR PRIDE; P41597; -.
DR ProteomicsDB; 55474; -. [P41597-1]
DR ProteomicsDB; 55475; -. [P41597-2]
DR ABCD; P41597; 1 sequenced antibody.
DR Antibodypedia; 29661; 862 antibodies from 38 providers.
DR DNASU; 729230; -.
DR Ensembl; ENST00000400888.2; ENSP00000383681.2; ENSG00000121807.7. [P41597-1]
DR Ensembl; ENST00000445132.3; ENSP00000399285.2; ENSG00000121807.7. [P41597-2]
DR GeneID; 729230; -.
DR KEGG; hsa:729230; -.
DR MANE-Select; ENST00000445132.3; ENSP00000399285.2; NM_001123396.4; NP_001116868.1. [P41597-2]
DR UCSC; uc003cpm.5; human. [P41597-1]
DR CTD; 729230; -.
DR DisGeNET; 729230; -.
DR GeneCards; CCR2; -.
DR HGNC; HGNC:1603; CCR2.
DR HPA; ENSG00000121807; Tissue enhanced (lymphoid).
DR MIM; 601267; gene.
DR MIM; 609423; phenotype.
DR neXtProt; NX_P41597; -.
DR OpenTargets; ENSG00000121807; -.
DR PharmGKB; PA26167; -.
DR VEuPathDB; HostDB:ENSG00000121807; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01020000230359; -.
DR HOGENOM; CLU_009579_8_3_1; -.
DR InParanoid; P41597; -.
DR OMA; ACAPYFP; -.
DR OrthoDB; 937138at2759; -.
DR PhylomeDB; P41597; -.
DR TreeFam; TF330966; -.
DR PathwayCommons; P41597; -.
DR Reactome; R-HSA-1461957; Beta defensins.
DR Reactome; R-HSA-380108; Chemokine receptors bind chemokines.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR Reactome; R-HSA-6783783; Interleukin-10 signaling.
DR SignaLink; P41597; -.
DR SIGNOR; P41597; -.
DR BioGRID-ORCS; 729230; 10 hits in 1063 CRISPR screens.
DR GeneWiki; CCR2; -.
DR GenomeRNAi; 729230; -.
DR Pharos; P41597; Tchem.
DR PRO; PR:P41597; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P41597; protein.
DR Bgee; ENSG00000121807; Expressed in monocyte and 101 other tissues.
DR ExpressionAtlas; P41597; baseline and differential.
DR Genevisible; P41597; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISS:BHF-UCL.
DR GO; GO:0030425; C:dendrite; ISS:BHF-UCL.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0043025; C:neuronal cell body; ISS:BHF-UCL.
DR GO; GO:0043204; C:perikaryon; ISS:BHF-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0019957; F:C-C chemokine binding; IBA:GO_Central.
DR GO; GO:0016493; F:C-C chemokine receptor activity; IBA:GO_Central.
DR GO; GO:0031727; F:CCR2 chemokine receptor binding; IDA:MGI.
DR GO; GO:0004950; F:chemokine receptor activity; TAS:ProtInc.
DR GO; GO:0042802; F:identical protein binding; ISS:BHF-UCL.
DR GO; GO:0001974; P:blood vessel remodeling; ISS:BHF-UCL.
DR GO; GO:0019722; P:calcium-mediated signaling; IBA:GO_Central.
DR GO; GO:0060326; P:cell chemotaxis; IBA:GO_Central.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISS:BHF-UCL.
DR GO; GO:0006968; P:cellular defense response; TAS:ProtInc.
DR GO; GO:0019725; P:cellular homeostasis; ISS:BHF-UCL.
DR GO; GO:0070098; P:chemokine-mediated signaling pathway; ISS:BHF-UCL.
DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IDA:MGI.
DR GO; GO:0002407; P:dendritic cell chemotaxis; TAS:BHF-UCL.
DR GO; GO:0006955; P:immune response; IBA:GO_Central.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0090594; P:inflammatory response to wounding; ISS:UniProtKB.
DR GO; GO:1905517; P:macrophage migration; ISS:UniProtKB.
DR GO; GO:0035696; P:monocyte extravasation; ISS:UniProtKB.
DR GO; GO:0007194; P:negative regulation of adenylate cyclase activity; TAS:ProtInc.
DR GO; GO:0016525; P:negative regulation of angiogenesis; ISS:BHF-UCL.
DR GO; GO:0043310; P:negative regulation of eosinophil degranulation; ISS:BHF-UCL.
DR GO; GO:0002829; P:negative regulation of type 2 immune response; ISS:BHF-UCL.
DR GO; GO:0046641; P:positive regulation of alpha-beta T cell proliferation; ISS:BHF-UCL.
DR GO; GO:2000464; P:positive regulation of astrocyte chemotaxis; IDA:BHF-UCL.
DR GO; GO:2000451; P:positive regulation of CD8-positive, alpha-beta T cell extravasation; ISS:BHF-UCL.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IBA:GO_Central.
DR GO; GO:2000473; P:positive regulation of hematopoietic stem cell migration; ISS:BHF-UCL.
DR GO; GO:0090265; P:positive regulation of immune complex clearance by monocytes and macrophages; ISS:BHF-UCL.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISS:BHF-UCL.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; ISS:BHF-UCL.
DR GO; GO:0032743; P:positive regulation of interleukin-2 production; ISS:BHF-UCL.
DR GO; GO:0090026; P:positive regulation of monocyte chemotaxis; IDA:UniProtKB.
DR GO; GO:2000439; P:positive regulation of monocyte extravasation; ISS:BHF-UCL.
DR GO; GO:1904783; P:positive regulation of NMDA glutamate receptor activity; ISS:ARUK-UCL.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; ISS:UniProtKB.
DR GO; GO:0050870; P:positive regulation of T cell activation; ISS:BHF-UCL.
DR GO; GO:0010820; P:positive regulation of T cell chemotaxis; ISS:BHF-UCL.
DR GO; GO:0002827; P:positive regulation of T-helper 1 type immune response; ISS:BHF-UCL.
DR GO; GO:2000412; P:positive regulation of thymocyte migration; ISS:UniProtKB.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISS:BHF-UCL.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; TAS:ProtInc.
DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0002724; P:regulation of T cell cytokine production; ISS:UniProtKB.
DR GO; GO:0045580; P:regulation of T cell differentiation; ISS:UniProtKB.
DR GO; GO:0010574; P:regulation of vascular endothelial growth factor production; ISS:BHF-UCL.
DR GO; GO:0009611; P:response to wounding; TAS:ProtInc.
DR GO; GO:0019233; P:sensory perception of pain; ISS:UniProtKB.
DR GO; GO:0035705; P:T-helper 17 cell chemotaxis; ISS:BHF-UCL.
DR InterPro; IPR002237; Chemokine_CCR2.
DR InterPro; IPR000355; Chemokine_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00657; CCCHEMOKINER.
DR PRINTS; PR01107; CHEMOKINER2.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR SMART; SM01381; 7TM_GPCR_Srsx; 1.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Host-virus interaction;
KW Inflammatory response; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Sulfation; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..374
FT /note="C-C chemokine receptor type 2"
FT /id="PRO_0000069232"
FT TOPO_DOM 1..42
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 43..70
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 71..80
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 81..100
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 101..114
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 115..136
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 137..153
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 154..178
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 179..206
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 207..226
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 227..243
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 244..268
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 269..285
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 286..309
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 310..374
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 348..374
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 26
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000269|PubMed:11046064"
FT MOD_RES 139
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000269|PubMed:9670957"
FT CARBOHYD 14
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 113..190
FT /evidence="ECO:0000269|PubMed:27926736"
FT VAR_SEQ 314..374
FT /note="SLFHIALGCRIAPLQKPVCGGPGVRPGKNVKVTTQGLLDGRGKGKSIGRAPE
FT ASLQDKEGA -> RYLSVFFRKHITKRFCKQCPVFYRETVDGVTSTNTPSTGEQEVSAG
FT L (in isoform B)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9058802"
FT /id="VSP_001893"
FT VARIANT 45
FT /note="L -> V (in dbSNP:rs4987052)"
FT /id="VAR_020066"
FT VARIANT 64
FT /note="V -> I (confers relative resistance to infection by
FT HIV-1; delay in disease progression in African Americans
FT but not in Caucasians; dbSNP:rs1799864)"
FT /evidence="ECO:0000269|PubMed:9252328,
FT ECO:0000269|PubMed:9662369, ECO:0000269|Ref.4"
FT /id="VAR_014339"
FT VARIANT 355
FT /note="G -> E (in dbSNP:rs3918387)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_014340"
FT HELIX 38..69
FT /evidence="ECO:0007829|PDB:5T1A"
FT HELIX 76..92
FT /evidence="ECO:0007829|PDB:5T1A"
FT HELIX 95..103
FT /evidence="ECO:0007829|PDB:5T1A"
FT HELIX 110..142
FT /evidence="ECO:0007829|PDB:5T1A"
FT HELIX 146..151
FT /evidence="ECO:0007829|PDB:5T1A"
FT HELIX 154..170
FT /evidence="ECO:0007829|PDB:5T1A"
FT HELIX 173..177
FT /evidence="ECO:0007829|PDB:5T1A"
FT STRAND 179..184
FT /evidence="ECO:0007829|PDB:5T1A"
FT STRAND 187..192
FT /evidence="ECO:0007829|PDB:5T1A"
FT HELIX 196..210
FT /evidence="ECO:0007829|PDB:5T1A"
FT HELIX 212..228
FT /evidence="ECO:0007829|PDB:5T1A"
FT HELIX 237..265
FT /evidence="ECO:0007829|PDB:5T1A"
FT TURN 266..268
FT /evidence="ECO:0007829|PDB:5T1A"
FT HELIX 269..272
FT /evidence="ECO:0007829|PDB:5T1A"
FT HELIX 279..295
FT /evidence="ECO:0007829|PDB:5T1A"
FT TURN 296..300
FT /evidence="ECO:0007829|PDB:5T1A"
FT HELIX 301..308
FT /evidence="ECO:0007829|PDB:5T1A"
FT HELIX 310..318
FT /evidence="ECO:0007829|PDB:5T1A"
SQ SEQUENCE 374 AA; 41915 MW; F865E0D39E74CF0F CRC64;
MLSTSRSRFI RNTNESGEEV TTFFDYDYGA PCHKFDVKQI GAQLLPPLYS LVFIFGFVGN
MLVVLILINC KKLKCLTDIY LLNLAISDLL FLITLPLWAH SAANEWVFGN AMCKLFTGLY
HIGYFGGIFF IILLTIDRYL AIVHAVFALK ARTVTFGVVT SVITWLVAVF ASVPGIIFTK
CQKEDSVYVC GPYFPRGWNN FHTIMRNILG LVLPLLIMVI CYSGILKTLL RCRNEKKRHR
AVRVIFTIMI VYFLFWTPYN IVILLNTFQE FFGLSNCEST SQLDQATQVT ETLGMTHCCI
NPIIYAFVGE KFRSLFHIAL GCRIAPLQKP VCGGPGVRPG KNVKVTTQGL LDGRGKGKSI
GRAPEASLQD KEGA
