Q99527 (GPER_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
G-protein coupled estrogen receptor 1

Alternative name(s):
Chemoattractant receptor-like 2
Flow-induced endothelial G-protein coupled receptor 1
Short name=FEG-1
G-protein coupled receptor 30
GPCR-BR
IL8-related receptor DRY12
Lymphocyte-derived G-protein coupled receptor
Short name=LYGPR
Membrane estrogen receptor
Short name=mER

Gene names

Name:	GPER
Synonyms:	CEPR, CMKRL2, DRY12, GPR30

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	375 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Receptor for estrogen. Ref.14 Ref.15
Subcellular location	Cell membrane; Multi-pass membrane protein. Endoplasmic reticulum membrane; Multi-pass membrane protein By similarity. Golgi apparatus membrane; Multi-pass membrane protein By similarity. Note: Protein has been detected in the cell membrane, endoplasmic reticulum and Golgi apparatus. It is currently unclear whether this is a cell surface or intracellular receptor. Ref.15 Ref.16 Ref.17
Tissue specificity	Ubiquitously expressed, but is most abundant in placenta. In brain regions, expressed as a 2.8 kb transcript in basal forebrain, frontal cortex, thalamus, hippocampus, caudate and putamen.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Endoplasmic reticulum Golgi apparatus 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)
Cellular_component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	G-protein coupled receptor activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 375	375	G-protein coupled estrogen receptor 1		PRO_0000069310
Regions
	Topological domain	1 – 62	62	Extracellular Potential
	Transmembrane	63 – 84	22	Helical; Name=1; Potential
	Topological domain	85 – 96	12	Cytoplasmic Potential
	Transmembrane	97 – 120	24	Helical; Name=2; Potential
	Topological domain	121 – 132	12	Extracellular Potential
	Transmembrane	133 – 153	21	Helical; Name=3; Potential
	Topological domain	154 – 175	22	Cytoplasmic Potential
	Transmembrane	176 – 194	19	Helical; Name=4; Potential
	Topological domain	195 – 220	26	Extracellular Potential
	Transmembrane	221 – 236	16	Helical; Name=5; Potential
	Topological domain	237 – 259	23	Cytoplasmic Potential
	Transmembrane	260 – 280	21	Helical; Name=6; Potential
	Topological domain	281 – 306	26	Extracellular Potential
	Transmembrane	307 – 327	21	Helical; Name=7; Potential
	Topological domain	328 – 375	48	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	25	1	N-linked (GlcNAc...) Potential
	Glycosylation	32	1	N-linked (GlcNAc...) Potential
	Glycosylation	44	1	N-linked (GlcNAc...) Potential
	Disulfide bond	130 ↔ 207		Potential
Natural variations
	Natural variant	16	1	P → L. Ref.10 Ref.13 Corresponds to variant rs11544331 [ dbSNP | Ensembl ].		VAR_033319
Experimental info
	Sequence conflict	20 – 21	2	QP → HA in AAC52027. Ref.6
	Sequence conflict	32 – 49	18	Missing in AAB02736. Ref.7
	Sequence conflict	104	1	A → G in AAB02736. Ref.7
	Sequence conflict	140 – 146	7	NMYSSVF → QHVQAASS in AAB02736. Ref.7
	Sequence conflict	179	1	G → A in AAB02736. Ref.7
	Sequence conflict	184	1	A → S in AAB02736. Ref.7
	Sequence conflict	312	1	A → T in AAC51173. Ref.2
	Sequence conflict	320	1	N → T in AAB02736. Ref.7
	Sequence conflict	355	1	A → V in AAB02736. Ref.7
	Sequence conflict	358	1	A → V in AAB02736. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Q99527 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 0A54EED8A698F075	FASTA	375	42,248
	10 20 30 40 50 60 MDVTSQARGV GLEMYPGTAQ PAAPNTTSPE LNLSHPLLGT ALANGTGELS EHQQYVIGLF 70 80 90 100 110 120 LSCLYTIFLF PIGFVGNILI LVVNISFREK MTIPDLYFIN LAVADLILVA DSLIEVFNLH 130 140 150 160 170 180 ERYYDIAVLC TFMSLFLQVN MYSSVFFLTW MSFDRYIALA RAMRCSLFRT KHHARLSCGL 190 200 210 220 230 240 IWMASVSATL VPFTAVHLQH TDEACFCFAD VREVQWLEVT LGFIVPFAII GLCYSLIVRV 250 260 270 280 290 300 LVRAHRHRGL RPRRQKALRM ILAVVLVFFV CWLPENVFIS VHLLQRTQPG AAPCKQSFRH 310 320 330 340 350 360 AHPLTGHIVN LAAFSNSCLN PLIYSFLGET FRDKLRLYIE QKTNLPALNR FCHAALKAVI 370 PDSTEQSDVR FSSAV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of human cDNA encoding a novel heptahelix receptor expressed in Burkitt's lymphoma and widely distributed in brain and peripheral tissues." Owman C.S.O., Blay P., Nilsson C., Lolait S.J. Biochem. Biophys. Res. Commun. 228:285-292(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning of a novel member of the G protein-coupled receptor family related to peptide receptors." Feng Y., Gregor P. Biochem. Biophys. Res. Commun. 231:651-654(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Cloning of cDNAs encoding G protein-coupled receptor expressed in human endothelial cells exposed to fluid shear stress." Takada Y., Kato C., Kondo S., Korenaga R., Ando J. Biochem. Biophys. Res. Commun. 240:737-741(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"A novel putative G-protein-coupled receptor expressed in lung, heart and lymphoid tissue." Kvingedal A.M., Smeland E.B. FEBS Lett. 407:59-62(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Identification of a gene (GPR30) with homology to the G-protein-coupled receptor superfamily associated with estrogen receptor expression in breast cancer." Carmeci C., Thompson D.A., Ring H.Z., Francke U., Weigel R.J. Genomics 45:607-617(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	"Discovery of three novel G-protein-coupled receptor genes." O'Dowd B.F., Nguyen T., Marchese A., Cheng R., Lynch K.R., Heng H.H.Q., Kolakowski L.F. Jr., George S.R. Genomics 47:310-313(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"Cloning of novel IL8-related receptors from human hepatic tissue." McCoy R.L., Perlmutter D.H. Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[8]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[9]	"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: Placenta.
[10]	"Human protein factory for converting the transcriptome into an in vitro-expressed proteome." Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N. Nat. Methods 5:1011-1017(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LEU-16.
[11]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[12]	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].
[13]	"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], VARIANT LEU-16. Tissue: Uterus.
[14]	"Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF." Filardo E.J., Quinn J.A., Bland K.I., Frackelton A.R. Jr. Mol. Endocrinol. 14:1649-1660(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[15]	"Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells." Thomas P., Pang Y., Filardo E.J., Dong J. Endocrinology 146:624-632(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[16]	"A transmembrane intracellular estrogen receptor mediates rapid cell signaling." Revankar C.M., Cimino D.F., Sklar L.A., Arterburn J.B., Prossnitz E.R. Science 307:1625-1630(2005) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[17]	"Activation of the novel estrogen receptor G protein-coupled receptor 30 (GPR30) at the plasma membrane." Filardo E., Quinn J., Pang Y., Graeber C., Shaw S., Dong J., Thomas P. Endocrinology 148:3236-3245(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	Y08162 mRNA. Translation: CAA69354.1. U77827 Genomic DNA. Translation: AAC51173.1. AF015257 mRNA. Translation: AAC51904.1. X98510 mRNA. Translation: CAA67133.1. U63917 mRNA. Translation: AAB88017.1. AF027956 Genomic DNA. Translation: AAC52027.1. U58828 mRNA. Translation: AAB02736.1. CR541741 mRNA. Translation: CAG46541.1. AK291590 mRNA. Translation: BAF84279.1. AB451427 mRNA. Translation: BAG70241.1. CH236953 Genomic DNA. Translation: EAL23938.1. CH471144 Genomic DNA. Translation: EAW87194.1. BC011634 mRNA. Translation: AAH11634.1.
IPI	IPI00016025.
PIR	G02670. JC5069.
RefSeq	NP_001035055.1. NM_001039966.1. NP_001091671.1. NM_001098201.1. NP_001496.1. NM_001505.2.
UniGene	Hs.20961.
3D structure databases
ProteinModelPortal	Q99527.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q99527. 1 interaction.
Protein family/group databases
GPCRDB	Search...
Polymorphism databases
DMDM	3023539.
Proteomic databases
PaxDb	Q99527.
PRIDE	Q99527.
Protocols and materials databases
DNASU	2852.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000297469; ENSP00000297469; ENSG00000164850. ENST00000397088; ENSP00000380277; ENSG00000164850. ENST00000397092; ENSP00000380281; ENSG00000164850. ENST00000401670; ENSP00000385151; ENSG00000164850.
GeneID	2852.
KEGG	hsa:2852.
UCSC	uc003sjz.1. human.
Organism-specific databases
CTD	2852.
GeneCards	GC07P001121.
H-InvDB	HIX0167652.
HGNC	HGNC:4485. GPER.
HPA	HPA027052.
MIM	601805. gene.
neXtProt	NX_Q99527.
PharmGKB	PA28873.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG151076.
HOVERGEN	HBG005351.
KO	K04246.
OMA	QHARLSC.
OrthoDB	EOG43TZVP.
PhylomeDB	Q99527.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	Q99527.
Bgee	Q99527.
CleanEx	HS_GPER.
Genevestigator	Q99527.
GermOnline	ENSG00000164850. Homo sapiens.
Family and domain databases
InterPro	IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00237. GPCRRHODOPSN.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q99527.
ChEMBL	CHEMBL5872.
GenomeRNAi	2852.
NextBio	11247.
SOURCE	Search...

Entry information

Entry name

GPER_HUMAN

Accession

Primary (citable) accession number: Q99527
Secondary accession number(s): A8K6C5 , B5BUJ1, O00143, O43494, Q13631, Q6FHL1, Q96F42, Q99981

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	May 1, 1997
Last modified:	May 29, 2013
This is version 124 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.