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 27-MAR-2024, entry version 221. 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="https://atlasgeneticsoncology.org/gene/964/CCR2"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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. 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 PDB; 7XA3; EM; 2.90 A; R=1-318. DR PDBsum; 2MLO; -. DR PDBsum; 2MLQ; -. DR PDBsum; 5T1A; -. DR PDBsum; 7P8X; -. DR PDBsum; 7XA3; -. DR AlphaFoldDB; P41597; -. DR EMDB; EMD-33086; -. DR SMR; P41597; -. DR BioGRID; 609634; 45. DR DIP; DIP-5833N; -. DR IntAct; P41597; 44. DR MINT; P41597; -. DR STRING; 9606.ENSP00000292301; -. DR BindingDB; P41597; -. DR ChEMBL; CHEMBL4015; -. DR DrugBank; DB05159; CCX915. DR DrugBank; DB11758; Cenicriviroc. DR DrugBank; DB05130; INCB3284. DR DrugBank; DB12520; Plozalizumab. DR DrugCentral; P41597; -. DR GuidetoPHARMACOLOGY; 59; -. DR GlyCosmos; P41597; 1 site, No reported glycans. 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; 9606-ENSP00000292301; -. DR PeptideAtlas; P41597; -. DR ProteomicsDB; 55474; -. [P41597-1] DR ProteomicsDB; 55475; -. [P41597-2] DR ABCD; P41597; 7 sequenced antibodies. DR Antibodypedia; 29661; 1087 antibodies from 39 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 AGR; HGNC:1603; -. DR CTD; 729230; -. DR DisGeNET; 729230; -. DR GeneCards; CCR2; -. DR HGNC; HGNC:1603; CCR2. DR HPA; ENSG00000121807; Tissue enhanced (lymphoid). DR MalaCards; CCR2; -. 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; YHIALGC; -. DR OrthoDB; 4604454at2759; -. 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 1144 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 cell types or tissues. DR ExpressionAtlas; P41597; baseline and differential. 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:0016020; C: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:HPA. 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:0035716; F:chemokine (C-C motif) ligand 12 binding; IEA:Ensembl. DR GO; GO:0035715; F:chemokine (C-C motif) ligand 2 binding; IEA:Ensembl. DR GO; GO:0035717; F:chemokine (C-C motif) ligand 7 binding; IEA:Ensembl. 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: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:0030097; P:hemopoiesis; IEA:Ensembl. DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; IEA:Ensembl. DR GO; GO:0006959; P:humoral immune response; IEA:Ensembl. 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:0006874; P:intracellular calcium ion homeostasis; ISS:BHF-UCL. DR GO; GO:0061756; P:leukocyte adhesion to vascular endothelial cell; IEA:Ensembl. DR GO; GO:1905517; P:macrophage migration; ISS:UniProtKB. DR GO; GO:0002548; P:monocyte chemotaxis; IEA:Ensembl. 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:0097350; P:neutrophil clearance; IEA:Ensembl. 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:0032743; P:positive regulation of interleukin-2 production; ISS:BHF-UCL. DR GO; GO:1903238; P:positive regulation of leukocyte tethering or rolling; IEA:Ensembl. 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:0032729; P:positive regulation of type II interferon 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:1905521; P:regulation of macrophage migration; IEA:Ensembl. 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 CDD; cd15184; 7tmA_CCR5_CCR2; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR002237; Chemokine_CCR2. DR InterPro; IPR000355; Chemokine_rcpt. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR PANTHER; PTHR10489:SF913; C-C CHEMOKINE RECEPTOR TYPE 2; 1. DR PANTHER; PTHR10489; CELL ADHESION MOLECULE; 1. 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 SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. DR Genevisible; P41597; HS. 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 TURN 72..74 FT /evidence="ECO:0007829|PDB:7XA3" 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 //