C5AR2_HUMAN
ID C5AR2_HUMAN Reviewed; 337 AA.
AC Q9P296; B2RA09;
DT 05-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=C5a anaphylatoxin chemotactic receptor 2;
DE AltName: Full=Complement component 5a receptor 2;
DE AltName: Full=G-protein coupled receptor 77;
GN Name=C5AR2; Synonyms=C5L2, GPR77;
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 TISSUE SPECIFICITY.
RC TISSUE=Placenta;
RX PubMed=11090875; DOI=10.1016/s0161-5890(00)00067-5;
RA Ohno M., Hirata T., Enomoto M., Araki T., Ishimaru H., Takahashi T.A.;
RT "A putative chemoattractant receptor, C5L2, is expressed in granulocyte and
RT immature dendritic cells, but not in mature dendritic cells.";
RL Mol. Immunol. 37:407-412(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX PubMed=11165367; DOI=10.1016/s0169-328x(00)00242-4;
RA Lee D.K., George S.R., Cheng R., Nguyen T., Liu Y., Brown M., Lynch K.R.,
RA O'Dowd B.F.;
RT "Identification of four novel human G protein-coupled receptors expressed
RT in the brain.";
RL Brain Res. Mol. Brain Res. 86:13-22(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Kopatz S.A., Aronstam R.S., Sharma S.V.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [8]
RP FUNCTION.
RC TISSUE=Brain;
RX PubMed=11773063; DOI=10.1074/jbc.c100714200;
RA Cain S.A., Monk P.N.;
RT "The orphan receptor C5L2 has high affinity binding sites for complement
RT fragments C5a and C5a des Arg(74).";
RL J. Biol. Chem. 277:7165-7169(2002).
RN [9]
RP INTERACTION WITH C3 ADIOPOGENIC PEPTIDE ASP.
RX PubMed=12540846; DOI=10.1074/jbc.m206169200;
RA Kalant D., Cain S.A., Maslowska M., Sniderman A.D., Cianflone K.,
RA Monk P.N.;
RT "The chemoattractant receptor-like protein C5L2 binds the C3a des-
RT Arg77/acylation-stimulating protein.";
RL J. Biol. Chem. 278:11123-11129(2003).
RN [10]
RP FUNCTION AS A RECEPTOR FOR THE C3 ADIOPOGENIC PEPTIDE ASP.
RX PubMed=15833747; DOI=10.1074/jbc.m406921200;
RA Kalant D., MacLaren R., Cui W., Samanta R., Monk P.N., Laporte S.A.,
RA Cianflone K.;
RT "C5L2 is a functional receptor for acylation-stimulating protein.";
RL J. Biol. Chem. 280:23936-23944(2005).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANT ILE-323.
RX PubMed=19615750; DOI=10.1016/j.molimm.2009.06.007;
RA Cui W., Simaan M., Laporte S., Lodge R., Cianflone K.;
RT "C5a- and ASP-mediated C5L2 activation, endocytosis and recycling are lost
RT in S323I-C5L2 mutation.";
RL Mol. Immunol. 46:3086-3098(2009).
RN [12]
RP VARIANT ILE-323.
RX PubMed=16627811; DOI=10.1161/01.atv.0000222907.72985.0b;
RA Marcil M., Vu H., Cui W., Dastani Z., Engert J.C., Gaudet D.,
RA Castro-Cabezas M., Sniderman A.D., Genest J. Jr., Cianflone K.;
RT "Identification of a novel C5L2 variant (S323I) in a French Canadian family
RT with familial combined hyperlipemia.";
RL Arterioscler. Thromb. Vasc. Biol. 26:1619-1625(2006).
RN [13]
RP VARIANT LEU-233.
RX PubMed=21698200; DOI=10.1371/journal.pone.0020984;
RA Zheng Y.Y., Xie X., Ma Y.T., Yang Y.N., Fu Z.Y., Li X.M., Ma X., Chen B.D.,
RA Liu F.;
RT "Relationship between a novel polymorphism of the C5L2 gene and coronary
RT artery disease.";
RL PLoS ONE 6:E20984-E20984(2011).
CC -!- FUNCTION: Receptor for the chemotactic and inflammatory C3a, C4a and
CC C5a anaphylatoxin peptides and also for their dearginated forms
CC ASP/C3adesArg, C4adesArg and C5adesArg respectively. Couples weakly to
CC G(i)-mediated signaling pathways. {ECO:0000269|PubMed:11773063,
CC ECO:0000269|PubMed:15833747, ECO:0000269|PubMed:19615750}.
CC -!- SUBUNIT: Interacts with C3 (the anaphylatoxin peptide C3a and the
CC adipogenic hormone ASP); the interaction occurs with higher affinity
CC for ASP, enhancing the phosphorylation and activation of GPR77,
CC recruitment of ARRB2 to the cell surface and endocytosis of GRP77.
CC {ECO:0000269|PubMed:12540846}.
CC -!- INTERACTION:
CC Q9P296; Q9UHG0: DCDC2; NbExp=3; IntAct=EBI-2874691, EBI-10303987;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19615750};
CC Multi-pass membrane protein {ECO:0000269|PubMed:19615750}.
CC -!- TISSUE SPECIFICITY: Frontal cortex, hippocampus, hypothalamus, pons and
CC liver. {ECO:0000269|PubMed:11090875, ECO:0000269|PubMed:11165367}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AB038237; BAA95414.1; -; mRNA.
DR EMBL; AF317655; AAK12640.1; -; Genomic_DNA.
DR EMBL; AY268430; AAP23197.1; -; Genomic_DNA.
DR EMBL; AK313994; BAG36706.1; -; mRNA.
DR EMBL; AC008754; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471126; EAW57472.1; -; Genomic_DNA.
DR EMBL; BC067478; AAH67478.1; -; mRNA.
DR CCDS; CCDS12699.1; -.
DR RefSeq; NP_001258678.1; NM_001271749.1.
DR RefSeq; NP_001258679.1; NM_001271750.1.
DR RefSeq; NP_060955.1; NM_018485.2.
DR RefSeq; XP_011525038.1; XM_011526736.2.
DR AlphaFoldDB; Q9P296; -.
DR SMR; Q9P296; -.
DR BioGRID; 118077; 309.
DR IntAct; Q9P296; 71.
DR MINT; Q9P296; -.
DR STRING; 9606.ENSP00000472620; -.
DR ChEMBL; CHEMBL4523478; -.
DR GuidetoPHARMACOLOGY; 33; -.
DR GlyGen; Q9P296; 1 site.
DR iPTMnet; Q9P296; -.
DR PhosphoSitePlus; Q9P296; -.
DR BioMuta; C5AR2; -.
DR DMDM; 20137533; -.
DR MassIVE; Q9P296; -.
DR PaxDb; Q9P296; -.
DR PeptideAtlas; Q9P296; -.
DR PRIDE; Q9P296; -.
DR ProteomicsDB; 83760; -.
DR Antibodypedia; 2937; 414 antibodies from 36 providers.
DR DNASU; 27202; -.
DR Ensembl; ENST00000595464.3; ENSP00000472620.1; ENSG00000134830.6.
DR Ensembl; ENST00000600626.1; ENSP00000471184.1; ENSG00000134830.6.
DR GeneID; 27202; -.
DR KEGG; hsa:27202; -.
DR MANE-Select; ENST00000595464.3; ENSP00000472620.1; NM_001271749.2; NP_001258678.1.
DR UCSC; uc002pgk.3; human.
DR CTD; 27202; -.
DR DisGeNET; 27202; -.
DR GeneCards; C5AR2; -.
DR HGNC; HGNC:4527; C5AR2.
DR HPA; ENSG00000134830; Tissue enhanced (lymphoid).
DR MIM; 609949; gene.
DR neXtProt; NX_Q9P296; -.
DR OpenTargets; ENSG00000134830; -.
DR PharmGKB; PA28920; -.
DR VEuPathDB; HostDB:ENSG00000134830; -.
DR eggNOG; ENOG502R35Z; Eukaryota.
DR GeneTree; ENSGT01020000230336; -.
DR HOGENOM; CLU_009579_8_0_1; -.
DR InParanoid; Q9P296; -.
DR OMA; CHGALLC; -.
DR OrthoDB; 978188at2759; -.
DR PhylomeDB; Q9P296; -.
DR TreeFam; TF330976; -.
DR PathwayCommons; Q9P296; -.
DR Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR Reactome; R-HSA-977606; Regulation of Complement cascade.
DR SignaLink; Q9P296; -.
DR SIGNOR; Q9P296; -.
DR BioGRID-ORCS; 27202; 8 hits in 1058 CRISPR screens.
DR ChiTaRS; C5AR2; human.
DR GeneWiki; GPR77; -.
DR GenomeRNAi; 27202; -.
DR Pharos; Q9P296; Tbio.
DR PRO; PR:Q9P296; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9P296; protein.
DR Bgee; ENSG00000134830; Expressed in monocyte and 91 other tissues.
DR Genevisible; Q9P296; HS.
DR GO; GO:0045177; C:apical part of cell; IDA:UniProtKB.
DR GO; GO:0009925; C:basal plasma membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0004878; F:complement component C5a receptor activity; IBA:GO_Central.
DR GO; GO:0004875; F:complement receptor activity; IBA:GO_Central.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0006935; P:chemotaxis; IEA:InterPro.
DR GO; GO:0002430; P:complement receptor mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IMP:UniProtKB.
DR GO; GO:0090024; P:negative regulation of neutrophil chemotaxis; IMP:UniProtKB.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IMP:UniProtKB.
DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IBA:GO_Central.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IEA:InterPro.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:InterPro.
DR GO; GO:0032677; P:regulation of interleukin-8 production; IMP:UniProtKB.
DR InterPro; IPR001274; Anaphtx_C5AR1/C5AR2.
DR InterPro; IPR027809; Anaphtx_C5AR2.
DR InterPro; IPR000826; Formyl_rcpt-rel.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR PANTHER; PTHR24225; PTHR24225; 1.
DR PANTHER; PTHR24225:SF1; PTHR24225:SF1; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00426; C5ANPHYLTXNR.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein;
KW Membrane; Phosphoprotein; Receptor; Reference proteome; Transducer;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..337
FT /note="C5a anaphylatoxin chemotactic receptor 2"
FT /id="PRO_0000069216"
FT TOPO_DOM 1..38
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 39..61
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 62..72
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 73..95
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 96..114
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 115..137
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 138..149
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 150..172
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 173..202
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 203..225
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 226..237
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 238..260
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 261..274
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 275..294
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 295..337
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOD_RES 320
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q695P6"
FT CARBOHYD 3
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 107..186
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VARIANT 233
FT /note="P -> L (in dbSNP:rs149572881)"
FT /evidence="ECO:0000269|PubMed:21698200"
FT /id="VAR_068748"
FT VARIANT 323
FT /note="S -> I (found in a family with familial combined
FT hyperlipemia; unknown pathological significance; associated
FT with increased plasma triglyceride, plasma cholesterol,
FT low-density lipoprotein cholesterol, apolipoprotein B and
FT ASP; dbSNP:rs150599989)"
FT /evidence="ECO:0000269|PubMed:16627811,
FT ECO:0000269|PubMed:19615750"
FT /id="VAR_068749"
SQ SEQUENCE 337 AA; 36080 MW; 53AF41B129FE8FE6 CRC64;
MGNDSVSYEY GDYSDLSDRP VDCLDGACLA IDPLRVAPLP LYAAIFLVGV PGNAMVAWVA
GKVARRRVGA TWLLHLAVAD LLCCLSLPIL AVPIARGGHW PYGAVGCRAL PSIILLTMYA
SVLLLAALSA DLCFLALGPA WWSTVQRACG VQVACGAAWT LALLLTVPSA IYRRLHQEHF
PARLQCVVDY GGSSSTENAV TAIRFLFGFL GPLVAVASCH SALLCWAARR CRPLGTAIVV
GFFVCWAPYH LLGLVLTVAA PNSALLARAL RAEPLIVGLA LAHSCLNPML FLYFGRAQLR
RSLPAACHWA LRESQGQDES VDSKKSTSHD LVSEMEV
