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Protein

Guanine nucleotide-binding protein G(s) subunit alpha isoforms short

Gene

Gnas

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Guanine nucleotide-binding proteins (G proteins) function as transducers in numerous signaling pathways controlled by G protein-coupled receptors (GPCRs). Signaling involves the activation of adenylyl cyclases, resulting in increased levels of the signaling molecule cAMP. GNAS functions downstream of several GPCRs, including beta-adrenergic receptors. Stimulates the Ras signaling pathway via RAPGEF2.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi54MagnesiumBy similarity1
Metal bindingi204MagnesiumBy similarity1
Binding sitei366GTP; via amide nitrogenBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi47 – 55GTPBy similarity9
Nucleotide bindingi197 – 204GTPBy similarity8
Nucleotide bindingi223 – 227GTPBy similarity5
Nucleotide bindingi292 – 295GTPBy similarity4

GO - Molecular functioni

GO - Biological processi

  • adenylate cyclase-activating adrenergic receptor signaling pathway Source: UniProtKB
  • adenylate cyclase-activating dopamine receptor signaling pathway Source: MGI
  • adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: MGI
  • bone development Source: MGI
  • cartilage development Source: MGI
  • cognition Source: MGI
  • developmental growth Source: MGI
  • DNA methylation Source: MGI
  • embryonic cranial skeleton morphogenesis Source: MGI
  • embryonic hindlimb morphogenesis Source: MGI
  • endochondral ossification Source: MGI
  • energy reserve metabolic process Source: MGI
  • genetic imprinting Source: MGI
  • G-protein coupled receptor signaling pathway Source: MGI
  • hair follicle placode formation Source: MGI
  • multicellular organism growth Source: MGI
  • platelet aggregation Source: MGI
  • positive regulation of cAMP biosynthetic process Source: UniProtKB
  • positive regulation of cAMP-mediated signaling Source: UniProtKB
  • positive regulation of GTPase activity Source: UniProtKB
  • positive regulation of osteoblast differentiation Source: MGI
  • positive regulation of osteoclast differentiation Source: MGI
  • post-embryonic body morphogenesis Source: MGI
  • post-embryonic development Source: MGI
  • regulation of parathyroid hormone secretion Source: MGI
  • regulation of signal transduction Source: MGI
  • response to drug Source: MGI
  • response to parathyroid hormone Source: MGI
  • skeletal system development Source: MGI
  • skin development Source: MGI
  • tissue homeostasis Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Transducer

Keywords - Ligandi

GTP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-163359. Glucagon signaling in metabolic regulation.
R-MMU-164378. PKA activation in glucagon signalling.
R-MMU-381676. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
R-MMU-392851. Prostacyclin signalling through prostacyclin receptor.
R-MMU-418555. G alpha (s) signalling events.
R-MMU-420092. Glucagon-type ligand receptors.
R-MMU-432040. Vasopressin regulates renal water homeostasis via Aquaporins.
R-MMU-5610787. Hedgehog 'off' state.

Names & Taxonomyi

Protein namesi
Recommended name:
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
Alternative name(s):
Adenylate cyclase-stimulating G alpha protein
Gene namesi
Name:Gnas
Synonyms:Gnas1
ORF Names:MNCb-5546
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:95777. Gnas.

Subcellular locationi

  • Cell membrane 1 Publication; Lipid-anchor 1 Publication

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi3C → S: Abolishes S-palmitoylation. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002037231 – 394Guanine nucleotide-binding protein G(s) subunit alpha isoforms shortAdd BLAST394

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-palmitoyl glycineBy similarity1
Lipidationi3S-palmitoyl cysteine1 Publication1
Cross-linki300Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei352PhosphoserineBy similarity1

Keywords - PTMi

Isopeptide bond, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP63094.
MaxQBiP63094.
PeptideAtlasiP63094.
PRIDEiP63094.

PTM databases

iPTMnetiP63094.
PhosphoSitePlusiP63094.
SwissPalmiP63094.

Expressioni

Gene expression databases

BgeeiENSMUSG00000027523.
ExpressionAtlasiP63094. baseline and differential.
GenevisibleiP63094. MM.

Interactioni

Subunit structurei

Heterotrimeric G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site (By similarity). Interacts with CRY1; the interaction may block GPCR-mediated regulation of cAMP concentrations. Interacts with ADCY6 and stimulates its adenylyl cyclase activity (By similarity). Interacts with ADCY2 and ADCY5 (By similarity). Stimulates the ADCY5 adenylyl cyclase activity (By similarity).By similarity

Protein-protein interaction databases

BioGridi199972. 2 interactors.
IntActiP63094. 4 interactors.
MINTiMINT-1522537.

Structurei

3D structure databases

ProteinModelPortaliP63094.
SMRiP63094.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the G-alpha family. G(s) subfamily.Curated

Phylogenomic databases

GeneTreeiENSGT00770000120503.
HOVERGENiHBG063184.
KOiK04632.

Family and domain databases

CDDicd00066. G-alpha. 1 hit.
Gene3Di1.10.400.10. 1 hit.
3.40.50.300. 2 hits.
InterProiIPR000367. Gprotein_alpha_S.
IPR001019. Gprotein_alpha_su.
IPR011025. GproteinA_insert.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR10218. PTHR10218. 2 hits.
PfamiPF00503. G-alpha. 1 hit.
[Graphical view]
PRINTSiPR00318. GPROTEINA.
PR00443. GPROTEINAS.
SMARTiSM00275. G_alpha. 1 hit.
[Graphical view]
SUPFAMiSSF47895. SSF47895. 1 hit.
SSF52540. SSF52540. 2 hits.

Sequences (9)i

Sequence statusi: Complete.

This entry describes 9 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Gnas-1 (identifier: P63094-1) [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
MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE
60 70 80 90 100
SGKSTIVKQM RILHVNGFNG EGGEEDPQAA RSNSDGEKAT KVQDIKNNLK
110 120 130 140 150
EAIETIVAAM SNLVPPVELA NPENQFRVDY ILSVMNVPNF DFPPEFYEHA
160 170 180 190 200
KALWEDEGVR ACYERSNEYQ LIDCAQYFLD KIDVIKQADY VPSDQDLLRC
210 220 230 240 250
RVLTSGIFET KFQVDKVNFH MFDVGGQRDE RRKWIQCFND VTAIIFVVAS
260 270 280 290 300
SSYNMVIRED NQTNRLQEAL NLFKSIWNNR WLRTISVILF LNKQDLLAEK
310 320 330 340 350
VLAGKSKIED YFPEFARYTT PEDATPEPGE DPRVTRAKYF IRDEFLRIST
360 370 380 390
ASGDGRHYCY PHFTCAVDTE NIRRVFNDCR DIIQRMHLRQ YELL
Length:394
Mass (Da):45,664
Last modified:August 13, 1987 - v1
Checksum:i20341187BE4412ED
GO
Isoform Gnas-2 (identifier: P63094-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     71-86: EGGEEDPQAARSNSDG → DS

Show »
Length:380
Mass (Da):44,265
Checksum:i2EB8B1E1C4EBC61A
GO
Isoform Gnas-3 (identifier: P63094-3) [UniParc]FASTAAdd to basket
Also known as: NTas

The sequence of this isoform differs from the canonical sequence as follows:
     1-46: MGCLGNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLL → MGDSVQILLVFMDK

Show »
Length:362
Mass (Da):41,818
Checksum:i0642A708B3DFCA15
GO
Isoform XLas-1 (identifier: Q6R0H7-1) [UniParc]FASTAAdd to basket
Also known as: XXL
The sequence of this isoform can be found in the external entry Q6R0H7.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:1,133
Mass (Da):121,505
GO
Isoform XLas-2 (identifier: Q6R0H7-2) [UniParc]FASTAAdd to basket
Also known as: XXLb1
The sequence of this isoform can be found in the external entry Q6R0H7.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:876
Mass (Da):91,094
GO
Isoform XLas-3 (identifier: Q6R0H7-3) [UniParc]FASTAAdd to basket
Also known as: XXLb2
The sequence of this isoform can be found in the external entry Q6R0H7.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:827
Mass (Da):85,918
GO
Isoform XLas-4 (identifier: Q6R0H7-4) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry Q6R0H7.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:1,119
Mass (Da):120,107
GO
Isoform Nesp55-1 (identifier: Q9Z0F1-1) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry Q9Z0F1.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Shares no sequence similarity with other isoforms (except isoform Nesp55-2) due to a novel first exon containing the entire reading frame spliced to shared exon 2 so that exons 2-13 make up the 3'-UTR.
Length:257
Mass (Da):29,301
GO
Isoform Nesp55-2 (identifier: Q9Z0F1-2) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry Q9Z0F1.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Shares no sequence similarity with other isoforms (except isoform Nesp55-1) due to a novel first exon containing the entire reading frame spliced to shared exon 2 so that exons 2-13 make up the 3'-UTR.
Length:253
Mass (Da):28,930
GO

Sequence cautioni

The sequence BAB93551 differs from that shown.Curated
The sequence CAM24410 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1 – 15MGCLG…DQRNE → MAARGAAGLRGGG in AAA37745 (PubMed:3092218).CuratedAdd BLAST15
Sequence conflicti64H → L in BAE35187 (PubMed:16141072).Curated1
Sequence conflicti97N → H in BAE35187 (PubMed:16141072).Curated1
Sequence conflicti130Y → C in AAI06134 (PubMed:15489334).Curated1
Sequence conflicti137V → L in AAA37745 (PubMed:3092218).Curated1
Sequence conflicti137V → L in AAD11807 (Ref. 3) Curated1
Sequence conflicti139N → D in CAA68695 (PubMed:2826231).Curated1
Sequence conflicti160R → P in BAB93551 (Ref. 7) Curated1
Sequence conflicti326P → L in BAE40795 (PubMed:16141072).Curated1
Sequence conflicti326P → L in AAI06134 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti389R → P in unc mutant; uncouples receptors from adenylyl cyclases. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0211531 – 46MGCLG…RLLLL → MGDSVQILLVFMDK in isoform Gnas-3. 1 PublicationAdd BLAST46
Alternative sequenceiVSP_01156771 – 86EGGEE…SNSDG → DS in isoform Gnas-2. 3 PublicationsAdd BLAST16

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y00703 mRNA. Translation: CAA68695.1.
M13964 mRNA. Translation: AAA37745.1.
AF107848 mRNA. Translation: AAD11807.1.
AK147051 mRNA. Translation: BAE27636.1.
AK159563 mRNA. Translation: BAE35187.1.
AK168996 mRNA. Translation: BAE40795.1.
AL593857 Genomic DNA. Translation: CAM24410.1. Sequence problems.
AL593857 Genomic DNA. Translation: CAM24411.1.
AL593857 Genomic DNA. Translation: CAM24412.1.
BC038067 mRNA. Translation: AAH38067.1.
BC048834 mRNA. Translation: AAH48834.1.
BC061496 mRNA. Translation: AAH61496.1.
BC062654 mRNA. Translation: AAH62654.1.
BC080816 mRNA. Translation: AAH80816.1.
BC092055 mRNA. Translation: AAH92055.1.
BC106133 mRNA. Translation: AAI06134.1.
AB041808 mRNA. Translation: BAB93551.1. Sequence problems.
CCDSiCCDS38356.1. [P63094-1]
CCDS38357.1. [P63094-2]
PIRiA25889. RGMSA1.
S03075. RGMSA2.
RefSeqiNP_001070978.1. NM_001077510.4. [P63094-2]
NP_001297012.1. NM_001310083.1. [P63094-1]
NP_963910.1. NM_201616.2. [P63094-1]
UniGeneiMm.125770.
Mm.394046.

Genome annotation databases

EnsembliENSMUST00000087871; ENSMUSP00000085179; ENSMUSG00000027523. [P63094-1]
ENSMUST00000109085; ENSMUSP00000104713; ENSMUSG00000027523. [P63094-2]
ENSMUST00000109087; ENSMUSP00000104715; ENSMUSG00000027523. [P63094-1]
GeneIDi14683.
KEGGimmu:14683.
UCSCiuc008oey.1. mouse. [P63094-1]
uc033hrs.1. mouse. [P63094-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y00703 mRNA. Translation: CAA68695.1.
M13964 mRNA. Translation: AAA37745.1.
AF107848 mRNA. Translation: AAD11807.1.
AK147051 mRNA. Translation: BAE27636.1.
AK159563 mRNA. Translation: BAE35187.1.
AK168996 mRNA. Translation: BAE40795.1.
AL593857 Genomic DNA. Translation: CAM24410.1. Sequence problems.
AL593857 Genomic DNA. Translation: CAM24411.1.
AL593857 Genomic DNA. Translation: CAM24412.1.
BC038067 mRNA. Translation: AAH38067.1.
BC048834 mRNA. Translation: AAH48834.1.
BC061496 mRNA. Translation: AAH61496.1.
BC062654 mRNA. Translation: AAH62654.1.
BC080816 mRNA. Translation: AAH80816.1.
BC092055 mRNA. Translation: AAH92055.1.
BC106133 mRNA. Translation: AAI06134.1.
AB041808 mRNA. Translation: BAB93551.1. Sequence problems.
CCDSiCCDS38356.1. [P63094-1]
CCDS38357.1. [P63094-2]
PIRiA25889. RGMSA1.
S03075. RGMSA2.
RefSeqiNP_001070978.1. NM_001077510.4. [P63094-2]
NP_001297012.1. NM_001310083.1. [P63094-1]
NP_963910.1. NM_201616.2. [P63094-1]
UniGeneiMm.125770.
Mm.394046.

3D structure databases

ProteinModelPortaliP63094.
SMRiP63094.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199972. 2 interactors.
IntActiP63094. 4 interactors.
MINTiMINT-1522537.

PTM databases

iPTMnetiP63094.
PhosphoSitePlusiP63094.
SwissPalmiP63094.

Proteomic databases

EPDiP63094.
MaxQBiP63094.
PeptideAtlasiP63094.
PRIDEiP63094.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000087871; ENSMUSP00000085179; ENSMUSG00000027523. [P63094-1]
ENSMUST00000109085; ENSMUSP00000104713; ENSMUSG00000027523. [P63094-2]
ENSMUST00000109087; ENSMUSP00000104715; ENSMUSG00000027523. [P63094-1]
GeneIDi14683.
KEGGimmu:14683.
UCSCiuc008oey.1. mouse. [P63094-1]
uc033hrs.1. mouse. [P63094-2]

Organism-specific databases

CTDi2778.
MGIiMGI:95777. Gnas.

Phylogenomic databases

GeneTreeiENSGT00770000120503.
HOVERGENiHBG063184.
KOiK04632.

Enzyme and pathway databases

ReactomeiR-MMU-163359. Glucagon signaling in metabolic regulation.
R-MMU-164378. PKA activation in glucagon signalling.
R-MMU-381676. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
R-MMU-392851. Prostacyclin signalling through prostacyclin receptor.
R-MMU-418555. G alpha (s) signalling events.
R-MMU-420092. Glucagon-type ligand receptors.
R-MMU-432040. Vasopressin regulates renal water homeostasis via Aquaporins.
R-MMU-5610787. Hedgehog 'off' state.

Miscellaneous databases

ChiTaRSiGnas. mouse.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000027523.
ExpressionAtlasiP63094. baseline and differential.
GenevisibleiP63094. MM.

Family and domain databases

CDDicd00066. G-alpha. 1 hit.
Gene3Di1.10.400.10. 1 hit.
3.40.50.300. 2 hits.
InterProiIPR000367. Gprotein_alpha_S.
IPR001019. Gprotein_alpha_su.
IPR011025. GproteinA_insert.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR10218. PTHR10218. 2 hits.
PfamiPF00503. G-alpha. 1 hit.
[Graphical view]
PRINTSiPR00318. GPROTEINA.
PR00443. GPROTEINAS.
SMARTiSM00275. G_alpha. 1 hit.
[Graphical view]
SUPFAMiSSF47895. SSF47895. 1 hit.
SSF52540. SSF52540. 2 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiGNAS2_MOUSE
AccessioniPrimary (citable) accession number: P63094
Secondary accession number(s): A2A611
, A2A612, A2A613, P04894, P08755, Q3KQM5, Q3TFV3, Q3TWS9, Q3UI70, Q58E62, Q6P7U9, Q80ZK6, Q8K5E1, Q9Z1R7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: August 13, 1987
Last modified: November 30, 2016
This is version 141 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

This protein is produced by a bicistronic gene which also produces the ALEX protein from an overlapping reading frame.
The GNAS locus is imprinted in a complex manner, giving rise to distinct paternally, maternally and biallelically expressed proteins. The XLas isoforms are paternally derived, the Gnas isoforms are biallelically derived and the Nesp55 isoforms are maternally derived.

Caution

It was found (PubMed:8227063) that in engineered, C3S-mutagenized sequence expressed in HEK293 cells there was no radiolabeling by either S- or N-palmitoylation. This result is incompatible with a prediction for N-palmitoylation unless N-palmitoylation depends on S-palmitoylation occurring first or N-palmitoylation did not occur in the experimental expression system.1 Publication

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.