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 02-SEP-2026, entry version 231. 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; DOI=10.4049/jimmunol.158.6.2689; 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 INTERACTION WITH KAPOSI VIRUS PROTEIN VCCL2 (MICROBIAL INFECTION). RX PubMed=9287217; DOI=10.1126/science.277.5332.1656; RA Kledal T.N., Rosenkilde M.M., Coulin F., Simmons G., Johnsen A.H., RA Alouani S., Power C.A., Luettichau H.R., Gerstoft J., Clapham P.R., RA Clark-Lewis I., Wells T.N., Schwartz T.W.; RT "A broad-spectrum chemokine antagonist encoded by Kaposi's sarcoma- RT associated herpesvirus."; RL Science 277:1656-1659(1997). RN [11] RP PHOSPHORYLATION AT TYR-139 BY JAK2. RX PubMed=9670957; DOI=10.4049/jimmunol.161.2.805; 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 [12] 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 [13] 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 [14] 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 [15] 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 [16] 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 [17] 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 [18] 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 [19] 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 [20] 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 [21] {ECO:0007744|PDB:7XA3} RP STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS), AND INTERACTION WITH RP GNAI1. RX PubMed=35570218; DOI=10.1038/s41421-022-00403-4; RA Shao Z., Tan Y., Shen Q., Hou L., Yao B., Qin J., Xu P., Mao C., Chen L.N., RA Zhang H., Shen D.D., Zhang C., Li W., Du X., Li F., Chen Z.H., Jiang Y., RA Xu H.E., Ying S., Ma H., Zhang Y., Shen H.; RT "Molecular insights into ligand recognition and activation of chemokine RT receptors CCR2 and CCR3."; RL Cell Discov. 8:44-44(2022). RN [22] 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 [23] 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). RN [24] RP INVOLVEMENT IN PCLUD, VARIANTS PCLUD ARG-61; ARG-119; 214-PRO-LEU-215 DEL RP AND ASN-296, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, RP CHARACTERIZATION OF VARIANTS PCLUD ARG-61; ARG-119; 214-PRO-LEU-215 DEL AND RP ASN-296, VARIANTS ILE-64; PHE-133; LEU-316 AND ASP-355, AND RP CHARACTERIZATION OF VARIANTS ILE-64; PHE-133; LEU-316 AND ASP-355. RX PubMed=38157855; DOI=10.1016/j.cell.2023.11.036; RA Neehus A.L., Carey B., Landekic M., Panikulam P., Deutsch G., Ogishi M., RA Arango-Franco C.A., Philippot Q., Modaresi M., Mohammadzadeh I., RA Corcini Berndt M., Rinchai D., Le Voyer T., Rosain J., Momenilandi M., RA Martin-Fernandez M., Khan T., Bohlen J., Han J.E., Deslys A., Bernard M., RA Gajardo-Carrasco T., Soudee C., Le Floc'h C., Migaud M., Seeleuthner Y., RA Jang M.S., Nikolouli E., Seyedpour S., Begueret H., Emile J.F., Le Guen P., RA Tavazzi G., Colombo C.N.J., Marzani F.C., Angelini M., Trespidi F., RA Ghirardello S., Alipour N., Molitor A., Carapito R., Mazloomrezaei M., RA Rokni-Zadeh H., Changi-Ashtiani M., Brouzes C., Vargas P., Borghesi A., RA Lachmann N., Bahram S., Crestani B., Pahari S., Schlesinger L.S., Marr N., RA Bugonovic D., Boisson-Dupuis S., Beziat V., Abel L., Borie R., Young L.R., RA Deterding R., Shahrooei M., Rezaei N., Parvaneh N., Craven D., Gros P., RA Malo D., Sepulveda F.E., Nogee L.M., Aladjidi N., Trapnell B.C., RA Casanova J.L., Bustamante J.; RT "Human inherited CCR2 deficiency underlies progressive polycystic lung RT disease."; RL Cell 187:390-408(2024). CC -!- FUNCTION: Key functional receptor for CCL2 but can also bind CCL7, and CC CCL12 (PubMed:23408426, PubMed:38157855, PubMed:8048929, CC PubMed:8146186). Also transduces signaling mediated by CCL13 CC (PubMed:38157855). Its binding with CCL2 on monocytes and macrophages CC mediates chemotaxis and migration induction through the activation of CC the PI3K cascade, the small G protein Rac and lamellipodium protrusion CC (PubMed:38157855). Also acts as a receptor for the beta-defensin CC DEFB106A/DEFB106B (PubMed:23938203). Regulates the expression of T-cell CC inflammatory cytokines and T-cell differentiation, promoting the CC differentiation of T-cells into T-helper 17 cells (Th17) during CC inflammation (By similarity). Facilitates the export of mature CC thymocytes by enhancing directional movement of thymocytes to CC sphingosine-1-phosphate stimulation and up-regulation of S1P1R CC expression; signals through the JAK-STAT pathway to regulate FOXO1 CC activity leading to an increased expression of S1P1R (By similarity). CC Plays an important role in mediating peripheral nerve injury-induced CC neuropathic pain (By similarity). Increases NMDA-mediated synaptic CC transmission in both dopamine D1 and D2 receptor-containing neurons, CC which may be caused by MAPK/ERK-dependent phosphorylation of CC GRIN2B/NMDAR2B (By similarity). Mediates the recruitment of macrophages CC and monocytes to the injury site following brain injury (By CC similarity). {ECO:0000250|UniProtKB:P51683, CC ECO:0000269|PubMed:23408426, ECO:0000269|PubMed:23938203, CC ECO:0000269|PubMed:38157855, 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). Interacts with GNAI1 CC (PubMed:35570218). {ECO:0000269|PubMed:15995708, CC ECO:0000269|PubMed:23938203, ECO:0000269|PubMed:25283965, CC ECO:0000269|PubMed:35570218, ECO:0000269|PubMed:9501202}. CC -!- SUBUNIT: (Microbial infection) Binds to HIV-1 Tat. CC {ECO:0000269|PubMed:9789057}. CC -!- SUBUNIT: (Microbial infection) Interacts with Kaposi virus protein CC vCCL2. {ECO:0000269|PubMed:9287217}. CC -!- INTERACTION: CC P41597; Q6S8J3: POTEE; NbExp=2; IntAct=EBI-16580134, EBI-4289913; CC P41597; O60895: RAMP2; NbExp=3; IntAct=EBI-16580134, EBI-9009040; CC P41597; O60896: RAMP3; NbExp=2; IntAct=EBI-16580134, EBI-720447; 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, ECO:0000269|PubMed:38157855}; Multi-pass CC membrane protein {ECO:0000255}. Note=The chemoattractant receptors are CC distributed throughout the cell surface; after stimulation with a CC ligand, such as CCL2, they are rapidly recruited into microdomain CC clusters at the cell 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 (PubMed:9058802). Abundantly expressed on CD14+/CD16- monocytes and CC weakly on CD14+/CD16+ monocytes, type 2 dendritic cells (DCs) and CC plasmacytoid DCs (at protein level) (PubMed:38157855). CC {ECO:0000269|PubMed:38157855, 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 -!- DISEASE: Polycystic lung disease (PCLUD) [MIM:219600]: An autosomal CC recessive disease characterized by pulmonary alveolar proteinosis, CC marked peribronchovascular and parenchymal lymphocytosis, CC peribronchiolar pulmonary fibrosis, progressive diffuse parenchymal CC lung cyst formation and enlargement, progressive obstructive airflow CC limitation, and recurrent secondary infections. Additional features may CC include digital clubbing, allergies, and atopic dermatitis. CC {ECO:0000269|PubMed:38157855}. Note=The disease is caused by variants CC affecting the gene represented in this entry. 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=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_001123041.3. [P41597-1] DR RefSeq; NP_001116868.1; NM_001123396.4. [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=2-318. DR PDB; 6GPS; X-ray; 3.30 A; A=2-231, A=235-374. DR PDB; 6GPX; X-ray; 2.70 A; A/B=29-231, A/B=235-321. DR PDB; 7P8X; X-ray; 1.40 A; M=25-29. DR PDB; 7XA3; EM; 2.90 A; R=1-318. DR AlphaFoldDB; P41597; -. DR EMDB; EMD-33086; -. DR MDRepo; P41597; -. DR SMR; P41597; -. DR BioGRID; 609634; 45. DR CORUM; P41597; -. DR DIP; DIP-5833N; -. DR FunCoup; P41597; 631. DR IntAct; P41597; 47. DR MINT; P41597; -. DR NDEx; IQUERY-CP-CCR2; 14 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000292301; -. DR BindingDB; P41597; -. DR ChEMBL; CHEMBL4015; -. DR DrugBank; DB16240; BMS-813160. DR DrugBank; DB05159; CCX915. DR DrugBank; DB11758; Cenicriviroc. DR DrugBank; DB16066; Ilacirnon. DR DrugBank; DB05130; INCB3284. DR DrugBank; DB11990; MK-0812. DR DrugBank; DB05383; Pimagedine. DR DrugBank; DB12520; Plozalizumab. DR DrugBank; DB28444; RAP-103. DR DrugBank; DB15748; Viral Macrophage-Inflammatory Protein. 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 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; 945 antibodies from 44 providers. DR DNASU; 729230; -. DR Ensembl; ENST00000400888.2; ENSP00000383681.2; ENSG00000121807.8. [P41597-1] DR Ensembl; ENST00000445132.3; ENSP00000399285.2; ENSG00000121807.8. [P41597-2] DR Ensembl; ENST00000908302.1; ENSP00000578361.1; ENSG00000121807.8. [P41597-2] DR Ensembl; ENST00000963442.1; ENSP00000633501.1; ENSG00000121807.8. [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 ClinPGx; PA26167; -. 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; 219600; phenotype. DR MIM; 601267; gene. DR MIM; 609423; phenotype. DR OpenTargets; ENSG00000121807; -. 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; 9876908at2759; -. DR PAN-GO; P41597; 9 GO annotations based on evolutionary models. DR PhylomeDB; P41597; -. 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 Agora; ENSG00000121807; -. DR BioGRID-ORCS; 729230; 10 hits in 1144 CRISPR screens. DR EvolutionaryTrace; P41597; -. 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:0030425; C:dendrite; ISS:BHF-UCL. DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central. 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:UniProtKB. DR GO; GO:0019957; F:C-C chemokine binding; IBA:GO_Central. DR GO; GO:0016493; F:C-C chemokine receptor activity; IDA:UniProt. 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:0007259; P:cell surface receptor signaling pathway via JAK-STAT; TAS:ProtInc. 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; IDA:UniProt. 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:0006874; P:intracellular calcium ion homeostasis; ISS:BHF-UCL. 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:1900451; P:positive regulation of glutamate receptor signaling pathway; ISS:ARUK-UCL. 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: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: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: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 CDD; cd15184; 7tmA_CCR5_CCR2; 1. DR FunFam; 1.20.1070.10:FF:000026; C-C chemokine receptor type 5; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR050119; CCR1-9-like. 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 PDBsum; 2MLO; -. DR PDBsum; 2MLQ; -. DR PDBsum; 5T1A; -. DR PDBsum; 6GPS; -. DR PDBsum; 6GPX; -. DR PDBsum; 7P8X; -. DR PDBsum; 7XA3; -. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Disease variant; KW Disulfide bond; G protein-coupled receptor; Glycoprotein; KW Host-virus interaction; Inflammatory response; Membrane; Phosphoprotein; KW Proteomics identification; Receptor; Reference proteome; Sulfation; KW Transducer; Transmembrane; 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 61 FT /note="M -> R (in PCLUD; likely pathogenic; loss of CCL2 or FT CCL13 cytokine-mediated signaling pathway; loss of FT expression at the cell surface; contrary to wild-type, does FT not rescue CCL2 cytokine-mediated calcium mobilization and FT cell migration, when transfected in CCR2-null monocytic FT THP-1 cells; dbSNP:rs752561542)" FT /evidence="ECO:0000269|PubMed:38157855" FT /id="VAR_089452" 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; no effect on expression at the cell FT surface, nor on CCL2 or CCL13 cytokine-mediated signaling FT pathway; dbSNP:rs1799864)" FT /evidence="ECO:0000269|PubMed:38157855, FT ECO:0000269|PubMed:9252328, ECO:0000269|PubMed:9662369, FT ECO:0000269|Ref.4" FT /id="VAR_014339" FT VARIANT 119 FT /note="L -> R (in PCLUD; likely pathogenic; loss of CCL2 or FT CCL13 cytokine-mediated signaling pathway; loss of FT expression at the cell surface; contrary to wild-type, does FT not rescue CCL2 or CCL13 cytokine-mediated calcium FT mobilization and cell migration, when transfected in FT CCR2-null monocytic THP-1 cells; dbSNP:rs113340633)" FT /evidence="ECO:0000269|PubMed:38157855" FT /id="VAR_089453" FT VARIANT 133 FT /note="L -> F (no effect on expression at the cell surface, FT nor on CCL2 or CCL13 cytokine-mediated signaling pathway; FT the nucleotide substitution creating this missense variant FT may lead to abnormally low levels of isoform A at the cell FT surface, while isoform B levels are similar to the FT wild-type protein)" FT /evidence="ECO:0000269|PubMed:38157855" FT /id="VAR_089454" FT VARIANT 214..215 FT /note="Missing (in PCLUD; likely pathogenic; loss of CCL2 FT or CCL13 cytokine-mediated signaling pathway; loss of FT expression at the cell surface; contrary to wild-type, does FT not rescue CCL2 cytokine-mediated calcium mobilization and FT cell migration, when transfected in CCR2-null monocytic FT THP-1 cells)" FT /evidence="ECO:0000269|PubMed:38157855" FT /id="VAR_089455" FT VARIANT 296 FT /note="T -> N (in PCLUD; likely pathogenic; loss of CCL2 or FT CCL13 cytokine-mediated signaling pathway; loss of FT expression at the cell surface; contrary to wild-type, does FT not rescue CCL2 cytokine-mediated calcium mobilization and FT cell migration, when transfected in CCR2-null monocytic FT THP-1 cells)" FT /evidence="ECO:0000269|PubMed:38157855" FT /id="VAR_089456" FT VARIANT 316 FT /note="F -> L (no effect on expression at the cell surface, FT nor on CCL2 or CCL13 cytokine-mediated signaling pathway; FT dbSNP:rs140816549)" FT /evidence="ECO:0000269|PubMed:38157855" FT /id="VAR_089457" FT VARIANT 355 FT /note="G -> D (no effect on expression at the cell surface, FT nor on CCL2 or CCL13 cytokine-mediated signaling pathway)" FT /evidence="ECO:0000269|PubMed:38157855" FT /id="VAR_089458" 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..207 FT /evidence="ECO:0007829|PDB:5T1A" FT HELIX 208..212 FT /evidence="ECO:0007829|PDB:5T1A" FT HELIX 213..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 //