Q5T6X5 (GPC6A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
G-protein coupled receptor family C group 6 member A
Short name=hGPRC6A

Alternative name(s):
G-protein coupled receptor GPCR33
Short name=hGPCR33

Gene names

Name:

GPRC6A

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	926 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor activated by amino acids with a preference for basic amino acids such as L-Lys, L-Arg and L-ornithine but also by small and polar amino acids. The L-alpha amino acids respond is augmented by divalent cations Ca2+ and Mg2+. Activated by extracellular calcium and osteocalin. Seems to act through a G(q)/G11 and G(i)-coupled pathway. Mediates the non-genomic effects of androgens in multiple tissue. May coordinates nutritional and hormonal anabolic signals through the sensing of extracellular amino acids, osteocalcin, divalents ions and its responsiveness to anabolic steroids. Ref.6 Ref.7
Subunit structure	Homodimer; disulfide-linked By similarity.
Subcellular location	Cell membrane; Multi-pass membrane protein By similarity.
Tissue specificity	Isoform 1 is expressed at high level in brain, skeletal muscle, testis, bone, calvaria, osteoblasts and leukocytes. Expressed at intermediate level in liver, heart, kidney and spleen. Expressed at low level in lung, pancreas, placenta and ovary. Not detected in thymus, prostate, small intestine, tongue and colon. Isoform 1 and isoform 2 are expressed in kidney at the same level. Isoform 2 is expressed at lower level than isoform 1 in the other tissues. Ref.1
Post-translational modification	N-glycosylated By similarity.
Sequence similarities	Belongs to the G-protein coupled receptor 3 family.
Sequence caution	The sequence BAC05904.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal 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	calcium-mediated signaling Inferred from electronic annotation. Source: Compara response to amino acid stimulus Inferred from direct assay PubMed 17478059. Source: UniProtKB
Cellular_component	cell surface Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	G-protein coupled receptor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q5T6X5-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Note: Major isoform.

Isoform 2 (identifier: Q5T6X5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     271-445: Missing.

Isoform 3 (identifier: Q5T6X5-3)

The sequence of this isoform differs from the canonical sequence as follows:
     446-516: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Potential
	Chain	19 – 926	908	G-protein coupled receptor family C group 6 member A		PRO_0000043196
Regions
	Topological domain	19 – 594	576	Extracellular Potential
	Transmembrane	595 – 615	21	Helical; Name=1; Potential
	Topological domain	616 – 631	16	Cytoplasmic Potential
	Transmembrane	632 – 652	21	Helical; Name=2; Potential
	Topological domain	653 – 669	17	Extracellular Potential
	Transmembrane	670 – 690	21	Helical; Name=3; Potential
	Topological domain	691 – 704	14	Cytoplasmic Potential
	Transmembrane	705 – 725	21	Helical; Name=4; Potential
	Topological domain	726 – 748	23	Extracellular Potential
	Transmembrane	749 – 769	21	Helical; Name=5; Potential
	Topological domain	770 – 782	13	Cytoplasmic Potential
	Transmembrane	783 – 803	21	Helical; Name=6; Potential
	Topological domain	804 – 810	7	Extracellular Potential
	Transmembrane	811 – 831	21	Helical; Name=7; Potential
	Topological domain	832 – 926	95	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	332	1	N-linked (GlcNAc...) Potential
	Glycosylation	567	1	N-linked (GlcNAc...) Potential
	Glycosylation	590	1	N-linked (GlcNAc...) Potential
	Glycosylation	733	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	271 – 445	175	Missing in isoform 2.		VSP_016454
	Alternative sequence	446 – 516	71	Missing in isoform 3.		VSP_016455
	Natural variant	91	1	P → S. Ref.1 Ref.2 Corresponds to variant rs2274911 [ dbSNP | Ensembl ].		VAR_023966
	Natural variant	144	1	I → R. Corresponds to variant rs28360548 [ dbSNP | Ensembl ].		VAR_049283
	Natural variant	599	1	I → T. Corresponds to variant rs35937022 [ dbSNP | Ensembl ].		VAR_061203
Experimental info
	Mutagenesis	149	1	S → A: Loss of function. Ref.6
	Mutagenesis	172	1	T → A: Loss of function. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 21, 2004. Version 1. Checksum: 2019C884FF092EEF	FASTA	926	104,753
	10 20 30 40 50 60 MAFLIILITC FVIILATSQP CQTPDDFVAA TSPGHIIIGG LFAIHEKMLS SEDSPRRPQI 70 80 90 100 110 120 QECVGFEISV FLQTLAMIHS IEMINNSTLL PGVKLGYEIY DTCTEVTVAM AATLRFLSKF 130 140 150 160 170 180 NCSRETVEFK CDYSSYMPRV KAVIGSGYSE ITMAVSRMLN LQLMPQVGYE STAEILSDKI 190 200 210 220 230 240 RFPSFLRTVP SDFHQIKAMA HLIQKSGWNW IGIITTDDDY GRLALNTFII QAEANNVCIA 250 260 270 280 290 300 FKEVLPAFLS DNTIEVRINR TLKKIILEAQ VNVIVVFLRQ FHVFDLFNKA IEMNINKMWI 310 320 330 340 350 360 ASDNWSTATK ITTIPNVKKI GKVVGFAFRR GNISSFHSFL QNLHLLPSDS HKLLHEYAMH 370 380 390 400 410 420 LSACAYVKDT DLSQCIFNHS QRTLAYKANK AIERNFVMRN DFLWDYAEPG LIHSIQLAVF 430 440 450 460 470 480 ALGYAIRDLC QARDCQNPNA FQPWELLGVL KNVTFTDGWN SFHFDAHGDL NTGYDVVLWK 490 500 510 520 530 540 EINGHMTVTK MAEYDLQNDV FIIPDQETKN EFRNLKQIQS KCSKECSPGQ MKKTTRSQHI 550 560 570 580 590 600 CCYECQNCPE NHYTNQTDMP HCLLCNNKTH WAPVRSTMCF EKEVEYLNWN DSLAILLLIL 610 620 630 640 650 660 SLLGIIFVLV VGIIFTRNLN TPVVKSSGGL RVCYVILLCH FLNFASTSFF IGEPQDFTCK 670 680 690 700 710 720 TRQTMFGVSF TLCISCILTK SLKILLAFSF DPKLQKFLKC LYRPILIIFT CTGIQVVICT 730 740 750 760 770 780 LWLIFAAPTV EVNVSLPRVI ILECEEGSIL AFGTMLGYIA ILAFICFIFA FKGKYENYNE 790 800 810 820 830 840 AKFITFGMLI YFIAWITFIP IYATTFGKYV PAVEIIVILI SNYGILYCTF IPKCYVIICK 850 860 870 880 890 900 QEINTKSAFL KMIYSYSSHS VSSIALSPAS LDSMSGNVTM TNPSSSGKSA TWQKSKDLQA 910 920 QAFAHICREN ATSVSKTLPR KRMSSI
	Isoform 2 [UniParc]. Checksum: 0A5019AAB24393D8	FASTA	751	84,565
	10 20 30 40 50 60 MAFLIILITC FVIILATSQP CQTPDDFVAA TSPGHIIIGG LFAIHEKMLS SEDSPRRPQI 70 80 90 100 110 120 QECVGFEISV FLQTLAMIHS IEMINNSTLL PGVKLGYEIY DTCTEVTVAM AATLRFLSKF 130 140 150 160 170 180 NCSRETVEFK CDYSSYMPRV KAVIGSGYSE ITMAVSRMLN LQLMPQVGYE STAEILSDKI 190 200 210 220 230 240 RFPSFLRTVP SDFHQIKAMA HLIQKSGWNW IGIITTDDDY GRLALNTFII QAEANNVCIA 250 260 270 280 290 300 FKEVLPAFLS DNTIEVRINR TLKKIILEAQ LLGVLKNVTF TDGWNSFHFD AHGDLNTGYD 310 320 330 340 350 360 VVLWKEINGH MTVTKMAEYD LQNDVFIIPD QETKNEFRNL KQIQSKCSKE CSPGQMKKTT 370 380 390 400 410 420 RSQHICCYEC QNCPENHYTN QTDMPHCLLC NNKTHWAPVR STMCFEKEVE YLNWNDSLAI 430 440 450 460 470 480 LLLILSLLGI IFVLVVGIIF TRNLNTPVVK SSGGLRVCYV ILLCHFLNFA STSFFIGEPQ 490 500 510 520 530 540 DFTCKTRQTM FGVSFTLCIS CILTKSLKIL LAFSFDPKLQ KFLKCLYRPI LIIFTCTGIQ 550 560 570 580 590 600 VVICTLWLIF AAPTVEVNVS LPRVIILECE EGSILAFGTM LGYIAILAFI CFIFAFKGKY 610 620 630 640 650 660 ENYNEAKFIT FGMLIYFIAW ITFIPIYATT FGKYVPAVEI IVILISNYGI LYCTFIPKCY 670 680 690 700 710 720 VIICKQEINT KSAFLKMIYS YSSHSVSSIA LSPASLDSMS GNVTMTNPSS SGKSATWQKS 730 740 750 KDLQAQAFAH ICRENATSVS KTLPRKRMSS I
	Isoform 3 [UniParc]. Checksum: 0C93431762234E38	FASTA	855	96,526
	10 20 30 40 50 60 MAFLIILITC FVIILATSQP CQTPDDFVAA TSPGHIIIGG LFAIHEKMLS SEDSPRRPQI 70 80 90 100 110 120 QECVGFEISV FLQTLAMIHS IEMINNSTLL PGVKLGYEIY DTCTEVTVAM AATLRFLSKF 130 140 150 160 170 180 NCSRETVEFK CDYSSYMPRV KAVIGSGYSE ITMAVSRMLN LQLMPQVGYE STAEILSDKI 190 200 210 220 230 240 RFPSFLRTVP SDFHQIKAMA HLIQKSGWNW IGIITTDDDY GRLALNTFII QAEANNVCIA 250 260 270 280 290 300 FKEVLPAFLS DNTIEVRINR TLKKIILEAQ VNVIVVFLRQ FHVFDLFNKA IEMNINKMWI 310 320 330 340 350 360 ASDNWSTATK ITTIPNVKKI GKVVGFAFRR GNISSFHSFL QNLHLLPSDS HKLLHEYAMH 370 380 390 400 410 420 LSACAYVKDT DLSQCIFNHS QRTLAYKANK AIERNFVMRN DFLWDYAEPG LIHSIQLAVF 430 440 450 460 470 480 ALGYAIRDLC QARDCQNPNA FQPWEQIQSK CSKECSPGQM KKTTRSQHIC CYECQNCPEN 490 500 510 520 530 540 HYTNQTDMPH CLLCNNKTHW APVRSTMCFE KEVEYLNWND SLAILLLILS LLGIIFVLVV 550 560 570 580 590 600 GIIFTRNLNT PVVKSSGGLR VCYVILLCHF LNFASTSFFI GEPQDFTCKT RQTMFGVSFT 610 620 630 640 650 660 LCISCILTKS LKILLAFSFD PKLQKFLKCL YRPILIIFTC TGIQVVICTL WLIFAAPTVE 670 680 690 700 710 720 VNVSLPRVII LECEEGSILA FGTMLGYIAI LAFICFIFAF KGKYENYNEA KFITFGMLIY 730 740 750 760 770 780 FIAWITFIPI YATTFGKYVP AVEIIVILIS NYGILYCTFI PKCYVIICKQ EINTKSAFLK 790 800 810 820 830 840 MIYSYSSHSV SSIALSPASL DSMSGNVTMT NPSSSGKSAT WQKSKDLQAQ AFAHICRENA 850 TSVSKTLPRK RMSSI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning, expression, and sequence analysis of GPRC6A, a novel family C G-protein-coupled receptor." Wellendorph P., Braeuner-Osborne H. Gene 335:37-46(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), TISSUE SPECIFICITY, VARIANT SER-91. Tissue: Kidney.
[2]	"Cloning of a metabotropic glutamate/pheromone receptor (GPRC6A)." Lorenz-Depiereux B., Dorner M., Strom T.M. Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT SER-91. Tissue: Kidney.
[3]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Genome-wide discovery and analysis of human seven transmembrane helix receptor genes." Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S., Tsutsumi S., Aburatani H., Asai K., Akiyama Y. Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 66-926.
[5]	"Identification of G protein-coupled receptor genes from the human genome sequence." Takeda S., Kadowaki S., Haga T., Takaesu H., Mitaku S. FEBS Lett. 520:97-101(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 559-926.
[6]	"Deorphanization of GPRC6A: a promiscuous L-alpha-amino acid receptor with preference for basic amino acids." Wellendorph P., Hansen K.B., Balsgaard A., Greenwood J.R., Egebjerg J., Brauener-Osborne H. Mol. Pharmacol. 67:589-597(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF SER-149 AND THR-172.
[7]	"GPRC6A mediates the non-genomic effects of steroids." Pi M., Parrill A.L., Quarles L.D. J. Biol. Chem. 285:39953-39964(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY435125 mRNA. Translation: AAS13465.1. AY435126 mRNA. Translation: AAS13466.1. AY435127 mRNA. Translation: AAS13467.1. AF502962 mRNA. Translation: AAM22230.1. AL354716 Genomic DNA. Translation: CAI16922.1. AB065680 Genomic DNA. Translation: BAC05904.1. Sequence problems. AB083615 Genomic DNA. Translation: BAB89328.1.
IPI	IPI00169389. IPI00426401. IPI00656032.
RefSeq	NP_683766.2. NM_148963.2.
UniGene	Hs.266745.
3D structure databases
ProteinModelPortal	Q5T6X5.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000309493.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	Q5T6X5.
Polymorphism databases
DMDM	74745292.
Proteomic databases
PaxDb	Q5T6X5.
PRIDE	Q5T6X5.
Protocols and materials databases
DNASU	222545.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000310357; ENSP00000309493; ENSG00000173612. ENST00000368549; ENSP00000357537; ENSG00000173612. ENST00000530250; ENSP00000433465; ENSG00000173612.
GeneID	222545.
KEGG	hsa:222545.
UCSC	uc003pxj.1. human. uc003pxk.1. human. uc003pxl.1. human.
Organism-specific databases
CTD	222545.
GeneCards	GC06M117158.
H-InvDB	HIX0032801.
HGNC	HGNC:18510. GPRC6A.
HPA	HPA038428.
MIM	613572. gene.
neXtProt	NX_Q5T6X5.
PharmGKB	PA38342.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG295353.
HOGENOM	HOG000063697.
HOVERGEN	HBG096042.
InParanoid	Q5T6X5.
KO	K04622.
OMA	ETHWAPV.
OrthoDB	EOG4NVZJP.
PhylomeDB	Q5T6X5.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
Bgee	Q5T6X5.
CleanEx	HS_GPRC6A.
Genevestigator	Q5T6X5.
GermOnline	ENSG00000173612. Homo sapiens.
Family and domain databases
InterPro	IPR001828. ANF_lig-bd_rcpt. IPR000337. GPCR_3. IPR011500. GPCR_3_9-Cys_dom. IPR017978. GPCR_3_C. IPR017979. GPCR_3_CS. [Graphical view]
Pfam	PF00003. 7tm_3. 1 hit. PF01094. ANF_receptor. 1 hit. PF07562. NCD3G. 1 hit. [Graphical view]
PRINTS	PR00248. GPCRMGR.
PROSITE	PS00979. G_PROTEIN_RECEP_F3_1. False negative. PS00980. G_PROTEIN_RECEP_F3_2. 1 hit. PS00981. G_PROTEIN_RECEP_F3_3. False negative. PS50259. G_PROTEIN_RECEP_F3_4. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	222545.
NextBio	91619.
SOURCE	Search...

Entry information

Entry name

GPC6A_HUMAN

Accession

Primary (citable) accession number: Q5T6X5
Secondary accession number(s): Q6JK43 , Q6JK44, Q8NGU8, Q8NHZ9, Q8TDT6

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 6, 2005
Last sequence update:	December 21, 2004
Last modified:	May 1, 2013
This is version 82 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.