Q9P296 (C5ARL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
C5a anaphylatoxin chemotactic receptor C5L2

Alternative name(s):
G-protein coupled receptor 77

Gene names

Name:	GPR77
Synonyms:	C5L2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	337 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for the chemotactic and inflammatory C3a, C4a and C5a anaphylatoxin peptides and also for their dearginated forms ASP/C3adesArg, C4adesArg and C5adesArg respectively. Couples weakly to G(i)-mediated signaling pathways. Ref.7 Ref.9 Ref.10
Subunit structure	Interacts with C3 (the anaphylatoxin peptide C3a and the adipogenic hormone ASP); the interaction occurs with higher affinity for ASP, enhancing the phosphorylation and activation of GPR77, recruitment of ARRB2 to the cell surface and endocytosis of GRP77. Ref.8
Subcellular location	Cell membrane; Multi-pass membrane protein Ref.10.
Tissue specificity	Frontal cortex, hippocampus, hypothalamus, pons and liver. Ref.1 Ref.2
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	chemotaxis Inferred from electronic annotation. Source: InterPro negative regulation of interleukin-6 secretion Inferred from mutant phenotype PubMed 16204243. Source: UniProtKB negative regulation of neutrophil chemotaxis Inferred from mutant phenotype PubMed 16204243. Source: UniProtKB negative regulation of tumor necrosis factor production Inferred from mutant phenotype PubMed 16204243. Source: UniProtKB regulation of interleukin-8 secretion Inferred from mutant phenotype PubMed 22496247. Source: UniProtKB
Cellular_component	apical part of cell Inferred from direct assay PubMed 22496247. Source: UniProtKB basal plasma membrane Inferred from direct assay PubMed 22960554. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	C5a anaphylatoxin receptor activity Inferred from electronic annotation. Source: InterPro N-formyl peptide receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 337	337	C5a anaphylatoxin chemotactic receptor C5L2		PRO_0000069216
Regions
	Topological domain	1 – 38	38	Extracellular Potential
	Transmembrane	39 – 61	23	Helical; Name=1; Potential
	Topological domain	62 – 72	11	Cytoplasmic Potential
	Transmembrane	73 – 95	23	Helical; Name=2; Potential
	Topological domain	96 – 114	19	Extracellular Potential
	Transmembrane	115 – 137	23	Helical; Name=3; Potential
	Topological domain	138 – 149	12	Cytoplasmic Potential
	Transmembrane	150 – 172	23	Helical; Name=4; Potential
	Topological domain	173 – 202	30	Extracellular Potential
	Transmembrane	203 – 225	23	Helical; Name=5; Potential
	Topological domain	226 – 237	12	Cytoplasmic Potential
	Transmembrane	238 – 260	23	Helical; Name=6; Potential
	Topological domain	261 – 274	14	Extracellular Potential
	Transmembrane	275 – 294	20	Helical; Name=7; Potential
	Topological domain	295 – 337	43	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	3	1	N-linked (GlcNAc...) Potential
	Disulfide bond	107 ↔ 186		By similarity
Natural variations
	Natural variant	233	1	P → L. Ref.12 Corresponds to variant rs149572881 [ dbSNP | Ensembl ].		VAR_068748
	Natural variant	323	1	S → I Rare polymorphism found in a family with familial combined hyperlipemia; associated with increased plasma triglyceride, plasma cholesterol, low-density lipoprotein cholesterol, apolipoprotein B and ASP. Ref.10 Ref.11 Corresponds to variant rs150599989 [ dbSNP | Ensembl ].		VAR_068749

Sequences

	Sequence		Length	Mass (Da)
	Q9P296 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 53AF41B129FE8FE6	FASTA	337	36,080
	10 20 30 40 50 60 MGNDSVSYEY GDYSDLSDRP VDCLDGACLA IDPLRVAPLP LYAAIFLVGV PGNAMVAWVA 70 80 90 100 110 120 GKVARRRVGA TWLLHLAVAD LLCCLSLPIL AVPIARGGHW PYGAVGCRAL PSIILLTMYA 130 140 150 160 170 180 SVLLLAALSA DLCFLALGPA WWSTVQRACG VQVACGAAWT LALLLTVPSA IYRRLHQEHF 190 200 210 220 230 240 PARLQCVVDY GGSSSTENAV TAIRFLFGFL GPLVAVASCH SALLCWAARR CRPLGTAIVV 250 260 270 280 290 300 GFFVCWAPYH LLGLVLTVAA PNSALLARAL RAEPLIVGLA LAHSCLNPML FLYFGRAQLR 310 320 330 RSLPAACHWA LRESQGQDES VDSKKSTSHD LVSEMEV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A putative chemoattractant receptor, C5L2, is expressed in granulocyte and immature dendritic cells, but not in mature dendritic cells." Ohno M., Hirata T., Enomoto M., Araki T., Ishimaru H., Takahashi T.A. Mol. Immunol. 37:407-412(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Placenta.
[2]	"Identification of four novel human G protein-coupled receptors expressed in the brain." Lee D.K., George S.R., Cheng R., Nguyen T., Liu Y., Brown M., Lynch K.R., O'Dowd B.F. Brain Res. Mol. Brain Res. 86:13-22(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY.
[3]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." Kopatz S.A., Aronstam R.S., Sharma S.V. Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Trachea.
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	"The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des Arg(74)." Cain S.A., Monk P.N. J. Biol. Chem. 277:7165-7169(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION. Tissue: Brain.
[8]	"The chemoattractant receptor-like protein C5L2 binds the C3a des-Arg77/acylation-stimulating protein." Kalant D., Cain S.A., Maslowska M., Sniderman A.D., Cianflone K., Monk P.N. J. Biol. Chem. 278:11123-11129(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH C3 ADIOPOGENIC PEPTIDE ASP.
[9]	"C5L2 is a functional receptor for acylation-stimulating protein." Kalant D., MacLaren R., Cui W., Samanta R., Monk P.N., Laporte S.A., Cianflone K. J. Biol. Chem. 280:23936-23944(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS A RECEPTOR FOR THE C3 ADIOPOGENIC PEPTIDE ASP.
[10]	"C5a- and ASP-mediated C5L2 activation, endocytosis and recycling are lost in S323I-C5L2 mutation." Cui W., Simaan M., Laporte S., Lodge R., Cianflone K. Mol. Immunol. 46:3086-3098(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT ILE-323.
[11]	"Identification of a novel C5L2 variant (S323I) in a French Canadian family with familial combined hyperlipemia." Marcil M., Vu H., Cui W., Dastani Z., Engert J.C., Gaudet D., Castro-Cabezas M., Sniderman A.D., Genest J. Jr., Cianflone K. Arterioscler. Thromb. Vasc. Biol. 26:1619-1625(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ILE-323.
[12]	"Relationship between a novel polymorphism of the C5L2 gene and coronary artery disease." Zheng Y.Y., Xie X., Ma Y.T., Yang Y.N., Fu Z.Y., Li X.M., Ma X., Chen B.D., Liu F. PLoS ONE 6:E20984-E20984(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LEU-233.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB038237 mRNA. Translation: BAA95414.1. AF317655 Genomic DNA. Translation: AAK12640.1. AY268430 Genomic DNA. Translation: AAP23197.1. AK313994 mRNA. Translation: BAG36706.1. CH471126 Genomic DNA. Translation: EAW57472.1. BC067478 mRNA. Translation: AAH67478.1.
IPI	IPI00020543.
RefSeq	NP_001258678.1. NM_001271749.1. NP_001258679.1. NM_001271750.1. NP_060955.1. NM_018485.2.
UniGene	Hs.534412.
3D structure databases
ProteinModelPortal	Q9P296.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9P296. 1 interaction.
STRING	9606.ENSP00000257267.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	Q9P296.
Polymorphism databases
DMDM	20137533.
Proteomic databases
PRIDE	Q9P296.
Protocols and materials databases
DNASU	27202.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000257267; ENSP00000257267; ENSG00000134830. ENST00000595464; ENSP00000472620; ENSG00000134830. ENST00000600626; ENSP00000471184; ENSG00000134830.
GeneID	27202.
KEGG	hsa:27202.
UCSC	uc002pgk.1. human.
Organism-specific databases
CTD	27202.
GeneCards	GC19P047840.
HGNC	HGNC:4527. GPR77.
HPA	HPA016629.
MIM	609949. gene.
neXtProt	NX_Q9P296.
PharmGKB	PA28920.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG151055.
HOGENOM	HOG000234122.
HOVERGEN	HBG107547.
InParanoid	Q9P296.
KO	K04171.
OMA	AACHWAL.
OrthoDB	EOG4VQ9Q1.
PhylomeDB	Q9P296.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
Bgee	Q9P296.
CleanEx	HS_GPR77.
Genevestigator	Q9P296.
GermOnline	ENSG00000134830. Homo sapiens.
Family and domain databases
InterPro	IPR001274. C5A_anaphtx_rcpt. IPR000826. Formyl_pep_rcpt. IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. [Graphical view]
PANTHER	PTHR24225. PTHR24225. 1 hit.
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00426. C5ANPHYLTXNR. PR00237. GPCRRHODOPSN.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. False negative. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	27202.
NextBio	50076.
SOURCE	Search...

Entry information

Entry name

C5ARL_HUMAN

Accession

Primary (citable) accession number: Q9P296
Secondary accession number(s): B2RA09

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 5, 2002
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 101 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.