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Protein

G-protein coupled receptor family C group 6 member A

Gene

GPRC6A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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)/G(11) 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.2 Publications

GO - Molecular functioni

GO - Biological processi

  • calcium-mediated signaling Source: Ensembl
  • response to amino acid Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-HSA-416476. G alpha (q) signalling events.
R-HSA-420499. Class C/3 (Metabotropic glutamate/pheromone receptors).

Protein family/group databases

TCDBi9.A.14.7.3. the g-protein-coupled receptor (gpcr) family.

Names & Taxonomyi

Protein namesi
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 namesi
Name:GPRC6A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:18510. GPRC6A.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini19 – 594ExtracellularSequence analysisAdd BLAST576
Transmembranei595 – 615Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini616 – 631CytoplasmicSequence analysisAdd BLAST16
Transmembranei632 – 652Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini653 – 669ExtracellularSequence analysisAdd BLAST17
Transmembranei670 – 690Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini691 – 704CytoplasmicSequence analysisAdd BLAST14
Transmembranei705 – 725Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini726 – 748ExtracellularSequence analysisAdd BLAST23
Transmembranei749 – 769Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini770 – 782CytoplasmicSequence analysisAdd BLAST13
Transmembranei783 – 803Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini804 – 810ExtracellularSequence analysis7
Transmembranei811 – 831Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini832 – 926CytoplasmicSequence analysisAdd BLAST95

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi149S → A: Loss of function. 1 Publication1
Mutagenesisi172T → A: Loss of function. 1 Publication1

Organism-specific databases

DisGeNETi222545.
OpenTargetsiENSG00000173612.
PharmGKBiPA38342.

Chemistry databases

GuidetoPHARMACOLOGYi55.

Polymorphism and mutation databases

BioMutaiGPRC6A.
DMDMi74745292.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000004319619 – 926G-protein coupled receptor family C group 6 member AAdd BLAST908

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi332N-linked (GlcNAc...)Sequence analysis1
Glycosylationi567N-linked (GlcNAc...)Sequence analysis1
Glycosylationi590N-linked (GlcNAc...)Sequence analysis1
Glycosylationi733N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ5T6X5.
PeptideAtlasiQ5T6X5.
PRIDEiQ5T6X5.

PTM databases

iPTMnetiQ5T6X5.
PhosphoSitePlusiQ5T6X5.

Expressioni

Tissue specificityi

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.1 Publication

Gene expression databases

BgeeiENSG00000173612.
CleanExiHS_GPRC6A.
GenevisibleiQ5T6X5. HS.

Organism-specific databases

HPAiCAB004591.

Interactioni

Subunit structurei

Homodimer; disulfide-linked.By similarity

Protein-protein interaction databases

STRINGi9606.ENSP00000309493.

Structurei

3D structure databases

ProteinModelPortaliQ5T6X5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1056. Eukaryota.
ENOG410XR6W. LUCA.
GeneTreeiENSGT00760000118974.
HOGENOMiHOG000063697.
HOVERGENiHBG096042.
InParanoidiQ5T6X5.
KOiK04622.
OMAiETHWAPV.
OrthoDBiEOG091G01NA.
PhylomeDBiQ5T6X5.
TreeFamiTF331269.

Family and domain databases

InterProiIPR001828. 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]
PfamiPF00003. 7tm_3. 1 hit.
PF01094. ANF_receptor. 1 hit.
PF07562. NCD3G. 1 hit.
[Graphical view]
PRINTSiPR00248. GPCRMGR.
SUPFAMiSSF53822. SSF53822. 1 hit.
PROSITEiPS00980. G_PROTEIN_RECEP_F3_2. 1 hit.
PS50259. G_PROTEIN_RECEP_F3_4. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q5T6X5-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAFLIILITC FVIILATSQP CQTPDDFVAA TSPGHIIIGG LFAIHEKMLS
60 70 80 90 100
SEDSPRRPQI QECVGFEISV FLQTLAMIHS IEMINNSTLL PGVKLGYEIY
110 120 130 140 150
DTCTEVTVAM AATLRFLSKF NCSRETVEFK CDYSSYMPRV KAVIGSGYSE
160 170 180 190 200
ITMAVSRMLN LQLMPQVGYE STAEILSDKI RFPSFLRTVP SDFHQIKAMA
210 220 230 240 250
HLIQKSGWNW IGIITTDDDY GRLALNTFII QAEANNVCIA FKEVLPAFLS
260 270 280 290 300
DNTIEVRINR TLKKIILEAQ VNVIVVFLRQ FHVFDLFNKA IEMNINKMWI
310 320 330 340 350
ASDNWSTATK ITTIPNVKKI GKVVGFAFRR GNISSFHSFL QNLHLLPSDS
360 370 380 390 400
HKLLHEYAMH LSACAYVKDT DLSQCIFNHS QRTLAYKANK AIERNFVMRN
410 420 430 440 450
DFLWDYAEPG LIHSIQLAVF ALGYAIRDLC QARDCQNPNA FQPWELLGVL
460 470 480 490 500
KNVTFTDGWN SFHFDAHGDL NTGYDVVLWK EINGHMTVTK MAEYDLQNDV
510 520 530 540 550
FIIPDQETKN EFRNLKQIQS KCSKECSPGQ MKKTTRSQHI CCYECQNCPE
560 570 580 590 600
NHYTNQTDMP HCLLCNNKTH WAPVRSTMCF EKEVEYLNWN DSLAILLLIL
610 620 630 640 650
SLLGIIFVLV VGIIFTRNLN TPVVKSSGGL RVCYVILLCH FLNFASTSFF
660 670 680 690 700
IGEPQDFTCK TRQTMFGVSF TLCISCILTK SLKILLAFSF DPKLQKFLKC
710 720 730 740 750
LYRPILIIFT CTGIQVVICT LWLIFAAPTV EVNVSLPRVI ILECEEGSIL
760 770 780 790 800
AFGTMLGYIA ILAFICFIFA FKGKYENYNE AKFITFGMLI YFIAWITFIP
810 820 830 840 850
IYATTFGKYV PAVEIIVILI SNYGILYCTF IPKCYVIICK QEINTKSAFL
860 870 880 890 900
KMIYSYSSHS VSSIALSPAS LDSMSGNVTM TNPSSSGKSA TWQKSKDLQA
910 920
QAFAHICREN ATSVSKTLPR KRMSSI
Note: Major isoform.
Length:926
Mass (Da):104,753
Last modified:December 21, 2004 - v1
Checksum:i2019C884FF092EEF
GO
Isoform 2 (identifier: Q5T6X5-2) [UniParc]FASTAAdd to basket

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

Show »
Length:751
Mass (Da):84,565
Checksum:i0A5019AAB24393D8
GO
Isoform 3 (identifier: Q5T6X5-3) [UniParc]FASTAAdd to basket

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

Show »
Length:855
Mass (Da):96,526
Checksum:i0C93431762234E38
GO

Sequence cautioni

The sequence BAC05904 differs from that shown. Reason: Erroneous gene model prediction.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02396691P → S.2 PublicationsCorresponds to variant rs2274911dbSNPEnsembl.1
Natural variantiVAR_049283144I → R.Corresponds to variant rs28360548dbSNPEnsembl.1
Natural variantiVAR_061203599I → T.Corresponds to variant rs35937022dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_016454271 – 445Missing in isoform 2. 1 PublicationAdd BLAST175
Alternative sequenceiVSP_016455446 – 516Missing in isoform 3. 1 PublicationAdd BLAST71

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS5112.1. [Q5T6X5-1]
CCDS69184.1. [Q5T6X5-3]
CCDS69185.1. [Q5T6X5-2]
RefSeqiNP_001273283.1. NM_001286354.1. [Q5T6X5-2]
NP_001273284.1. NM_001286355.1. [Q5T6X5-3]
NP_683766.2. NM_148963.3. [Q5T6X5-1]
UniGeneiHs.266745.

Genome annotation databases

EnsembliENST00000310357; ENSP00000309493; ENSG00000173612. [Q5T6X5-1]
ENST00000368549; ENSP00000357537; ENSG00000173612. [Q5T6X5-3]
ENST00000530250; ENSP00000433465; ENSG00000173612. [Q5T6X5-2]
GeneIDi222545.
KEGGihsa:222545.
UCSCiuc003pxj.3. human. [Q5T6X5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS5112.1. [Q5T6X5-1]
CCDS69184.1. [Q5T6X5-3]
CCDS69185.1. [Q5T6X5-2]
RefSeqiNP_001273283.1. NM_001286354.1. [Q5T6X5-2]
NP_001273284.1. NM_001286355.1. [Q5T6X5-3]
NP_683766.2. NM_148963.3. [Q5T6X5-1]
UniGeneiHs.266745.

3D structure databases

ProteinModelPortaliQ5T6X5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000309493.

Chemistry databases

GuidetoPHARMACOLOGYi55.

Protein family/group databases

TCDBi9.A.14.7.3. the g-protein-coupled receptor (gpcr) family.
GPCRDBiSearch...

PTM databases

iPTMnetiQ5T6X5.
PhosphoSitePlusiQ5T6X5.

Polymorphism and mutation databases

BioMutaiGPRC6A.
DMDMi74745292.

Proteomic databases

PaxDbiQ5T6X5.
PeptideAtlasiQ5T6X5.
PRIDEiQ5T6X5.

Protocols and materials databases

DNASUi222545.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000310357; ENSP00000309493; ENSG00000173612. [Q5T6X5-1]
ENST00000368549; ENSP00000357537; ENSG00000173612. [Q5T6X5-3]
ENST00000530250; ENSP00000433465; ENSG00000173612. [Q5T6X5-2]
GeneIDi222545.
KEGGihsa:222545.
UCSCiuc003pxj.3. human. [Q5T6X5-1]

Organism-specific databases

CTDi222545.
DisGeNETi222545.
GeneCardsiGPRC6A.
H-InvDBHIX0032801.
HGNCiHGNC:18510. GPRC6A.
HPAiCAB004591.
MIMi613572. gene.
neXtProtiNX_Q5T6X5.
OpenTargetsiENSG00000173612.
PharmGKBiPA38342.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1056. Eukaryota.
ENOG410XR6W. LUCA.
GeneTreeiENSGT00760000118974.
HOGENOMiHOG000063697.
HOVERGENiHBG096042.
InParanoidiQ5T6X5.
KOiK04622.
OMAiETHWAPV.
OrthoDBiEOG091G01NA.
PhylomeDBiQ5T6X5.
TreeFamiTF331269.

Enzyme and pathway databases

ReactomeiR-HSA-416476. G alpha (q) signalling events.
R-HSA-420499. Class C/3 (Metabotropic glutamate/pheromone receptors).

Miscellaneous databases

GeneWikiiGPRC6A.
GenomeRNAii222545.
PROiQ5T6X5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000173612.
CleanExiHS_GPRC6A.
GenevisibleiQ5T6X5. HS.

Family and domain databases

InterProiIPR001828. 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]
PfamiPF00003. 7tm_3. 1 hit.
PF01094. ANF_receptor. 1 hit.
PF07562. NCD3G. 1 hit.
[Graphical view]
PRINTSiPR00248. GPCRMGR.
SUPFAMiSSF53822. SSF53822. 1 hit.
PROSITEiPS00980. G_PROTEIN_RECEP_F3_2. 1 hit.
PS50259. G_PROTEIN_RECEP_F3_4. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGPC6A_HUMAN
AccessioniPrimary (citable) accession number: Q5T6X5
Secondary accession number(s): Q6JK43
, Q6JK44, Q8NGU8, Q8NHZ9, Q8TDT6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: December 21, 2004
Last modified: November 30, 2016
This is version 112 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.