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Q5T6X5 (GPC6A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 90. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length926 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Chain19 – 926908G-protein coupled receptor family C group 6 member A
PRO_0000043196

Regions

Topological domain19 – 594576Extracellular Potential
Transmembrane595 – 61521Helical; Name=1; Potential
Topological domain616 – 63116Cytoplasmic Potential
Transmembrane632 – 65221Helical; Name=2; Potential
Topological domain653 – 66917Extracellular Potential
Transmembrane670 – 69021Helical; Name=3; Potential
Topological domain691 – 70414Cytoplasmic Potential
Transmembrane705 – 72521Helical; Name=4; Potential
Topological domain726 – 74823Extracellular Potential
Transmembrane749 – 76921Helical; Name=5; Potential
Topological domain770 – 78213Cytoplasmic Potential
Transmembrane783 – 80321Helical; Name=6; Potential
Topological domain804 – 8107Extracellular Potential
Transmembrane811 – 83121Helical; Name=7; Potential
Topological domain832 – 92695Cytoplasmic Potential

Amino acid modifications

Glycosylation3321N-linked (GlcNAc...) Potential
Glycosylation5671N-linked (GlcNAc...) Potential
Glycosylation5901N-linked (GlcNAc...) Potential
Glycosylation7331N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence271 – 445175Missing in isoform 2.
VSP_016454
Alternative sequence446 – 51671Missing in isoform 3.
VSP_016455
Natural variant911P → S. Ref.1 Ref.2
Corresponds to variant rs2274911 [ dbSNP | Ensembl ].
VAR_023966
Natural variant1441I → R.
Corresponds to variant rs28360548 [ dbSNP | Ensembl ].
VAR_049283
Natural variant5991I → T.
Corresponds to variant rs35937022 [ dbSNP | Ensembl ].
VAR_061203

Experimental info

Mutagenesis1491S → A: Loss of function. Ref.6
Mutagenesis1721T → A: Loss of function. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 21, 2004. Version 1.
Checksum: 2019C884FF092EEF

FASTA926104,753
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 0A5019AAB24393D8
Show »

FASTA75184,565
Isoform 3 [UniParc].

Checksum: 0C93431762234E38
Show »

FASTA85596,526

References

« Hide '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. expand/collapse author list , 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.
RefSeqNP_001273283.1. NM_001286354.1.
NP_001273284.1. NM_001286355.1.
NP_683766.2. NM_148963.3.
UniGeneHs.266745.

3D structure databases

ProteinModelPortalQ5T6X5.
SMRQ5T6X5. Positions 29-584.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000309493.

Chemistry

GuidetoPHARMACOLOGY55.

Protein family/group databases

TCDB9.A.14.7.3. the g-protein-coupled receptor (gpcr) family.
GPCRDBSearch...

PTM databases

PhosphoSiteQ5T6X5.

Polymorphism databases

DMDM74745292.

Proteomic databases

PaxDbQ5T6X5.
PRIDEQ5T6X5.

Protocols and materials databases

DNASU222545.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000310357; ENSP00000309493; ENSG00000173612. [Q5T6X5-1]
ENST00000368549; ENSP00000357537; ENSG00000173612. [Q5T6X5-3]
ENST00000530250; ENSP00000433465; ENSG00000173612. [Q5T6X5-2]
GeneID222545.
KEGGhsa:222545.
UCSCuc003pxj.1. human. [Q5T6X5-1]
uc003pxk.1. human. [Q5T6X5-2]
uc003pxl.1. human. [Q5T6X5-3]

Organism-specific databases

CTD222545.
GeneCardsGC06M117158.
H-InvDBHIX0032801.
HGNCHGNC:18510. GPRC6A.
HPAHPA038428.
MIM613572. gene.
neXtProtNX_Q5T6X5.
PharmGKBPA38342.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG295353.
HOGENOMHOG000063697.
HOVERGENHBG096042.
InParanoidQ5T6X5.
KOK04622.
OMAETHWAPV.
OrthoDBEOG7DZ8J8.
PhylomeDBQ5T6X5.
TreeFamTF331269.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeQ5T6X5.
CleanExHS_GPRC6A.
GenevestigatorQ5T6X5.

Family and domain databases

InterProIPR001828. ANF_lig-bd_rcpt.
IPR000337. GPCR_3.
IPR011500. GPCR_3_9-Cys_dom.
IPR017978. GPCR_3_C.
IPR017979. GPCR_3_CS.
IPR028082. Peripla_BP_I.
[Graphical view]
PfamPF00003. 7tm_3. 1 hit.
PF01094. ANF_receptor. 1 hit.
PF07562. NCD3G. 1 hit.
[Graphical view]
PRINTSPR00248. GPCRMGR.
SUPFAMSSF53822. SSF53822. 1 hit.
PROSITEPS00980. G_PROTEIN_RECEP_F3_2. 1 hit.
PS50259. G_PROTEIN_RECEP_F3_4. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiGPRC6A.
GenomeRNAi222545.
NextBio91619.
PROQ5T6X5.
SOURCESearch...

Entry information

Entry nameGPC6A_HUMAN
AccessionPrimary (citable) accession number: Q5T6X5
Secondary accession number(s): Q6JK43 expand/collapse secondary AC list , Q6JK44, Q8NGU8, Q8NHZ9, Q8TDT6
Entry history
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: December 21, 2004
Last modified: March 19, 2014
This is version 90 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries