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P09471 (GNAO_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 152. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | 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:
Guanine nucleotide-binding protein G(o) subunit alpha
Gene names
Name:GNAO1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length354 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(o) protein function is not clear. Stimulated by RGS14.

Subunit structure

Interacts with RGS14 By similarity. G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site.

Subcellular location

Cell membrane By similarity.

Involvement in disease

Epileptic encephalopathy, early infantile, 17 (EIEE17) [MIM:615473]: A severe neurologic disorder characterized by onset of intractable seizures in the first weeks or months of life and usually associated with EEG abnormalities. Affected infants have very poor psychomotor development and may have brain abnormalities, such as cerebral atrophy or thin corpus callosum. Some patients may show involuntary movements.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5

Sequence similarities

Belongs to the G-alpha family. G(i/o/t/z) subfamily.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
Epilepsy
   LigandGTP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionTransducer
   PTMADP-ribosylation
Lipoprotein
Myristate
Palmitate
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadenylate cyclase-modulating G-protein coupled receptor signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

aging

Inferred from electronic annotation. Source: Ensembl

dopamine receptor signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

forebrain development

Inferred from electronic annotation. Source: Ensembl

locomotory behavior

Inferred from electronic annotation. Source: Ensembl

muscle contraction

Traceable author statement PubMed 9050846. Source: ProtInc

negative regulation of calcium ion transport

Inferred from electronic annotation. Source: Ensembl

neuron projection development

Inferred from electronic annotation. Source: Ensembl

positive regulation of GTPase activity

Inferred from electronic annotation. Source: Ensembl

regulation of heart contraction

Inferred from electronic annotation. Source: Ensembl

response to cytokine

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to hydrogen peroxide

Inferred from electronic annotation. Source: Ensembl

response to morphine

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentextrinsic component of cytoplasmic side of plasma membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

heterotrimeric G-protein complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

neuron projection

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionG-protein beta/gamma-subunit complex binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

G-protein coupled serotonin receptor binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

GTP binding

Inferred from electronic annotation. Source: UniProtKB-KW

GTPase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

signal transducer activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Alpha-1 (identifier: P09471-1)

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.
Isoform Alpha-2 (identifier: P09471-2)

The sequence of this isoform differs from the canonical sequence as follows:
     249-354: MLFDSICNNK...ANNLRGCGLY → KLFDSICNNK...AKNLRGCGLY

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 354353Guanine nucleotide-binding protein G(o) subunit alpha
PRO_0000203702

Regions

Nucleotide binding40 – 478GTP By similarity
Nucleotide binding176 – 1827GTP By similarity
Nucleotide binding201 – 2055GTP By similarity
Nucleotide binding270 – 2734GTP By similarity

Sites

Metal binding471Magnesium By similarity
Metal binding1821Magnesium By similarity
Binding site3261GTP; via amide nitrogen By similarity

Amino acid modifications

Modified residue1791ADP-ribosylarginine; by cholera toxin By similarity
Modified residue3511ADP-ribosylcysteine; by pertussis toxin By similarity
Lipidation21N-myristoyl glycine By similarity
Lipidation31S-palmitoyl cysteine By similarity

Natural variations

Alternative sequence249 – 354106MLFDS…GCGLY → KLFDSICNNKWFTDTSIILF LNKKDIFEEKIKKSPLTICF PEYTGPSAFTEAVAYIQAQY ESKNKSAHKEIYTHVTCATD TNNIQFVFDAVTDVIIAKNL RGCGLY in isoform Alpha-2.
VSP_031250
Natural variant1741D → G in EIEE17; somatic mosaic mutation; the mutant protein has some abnormal cytoplasmic localization; has impaired current inhibition after norepinephrine application compared to wild-type. Ref.5
VAR_070864
Natural variant191 – 1977Missing in EIEE17; the mutant protein accumulates in the cytoplasmic compartment; increased calcium-current density compared to wild-type before norepinephrine application; mild reduction in calcium current compared to wild-type after application of norepinephrine.
VAR_070865
Natural variant2031G → R in EIEE17; the mutant protein localizes normally to the cell periphery; has impaired current inhibition after norepinephrine application compared to wildt-ype. Ref.5
VAR_070866
Natural variant2791I → N in EIEE17; the mutant protein has some abnormal cytoplasmic localization. Ref.5
VAR_070867

Experimental info

Sequence conflict161S → G in AAA52584. Ref.2
Sequence conflict1711T → L in AAA52584. Ref.2
Sequence conflict2181D → E in AAA52584. Ref.2

Sequences

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

Last modified January 23, 2007. Version 4.
Checksum: 4F182926A8106E3E

FASTA35440,051
        10         20         30         40         50         60 
MGCTLSAEER AALERSKAIE KNLKEDGISA AKDVKLLLLG AGESGKSTIV KQMKIIHEDG 

        70         80         90        100        110        120 
FSGEDVKQYK PVVYSNTIQS LAAIVRAMDT LGIEYGDKER KADAKMVCDV VSRMEDTEPF 

       130        140        150        160        170        180 
SAELLSAMMR LWGDSGIQEC FNRSREYQLN DSAKYYLDSL DRIGAADYQP TEQDILRTRV 

       190        200        210        220        230        240 
KTTGIVETHF TFKNLHFRLF DVGGQRSERK KWIHCFEDVT AIIFCVALSG YDQVLHEDET 

       250        260        270        280        290        300 
TNRMHESLML FDSICNNKFF IDTSIILFLN KKDLFGEKIK KSPLTICFPE YTGPNTYEDA 

       310        320        330        340        350 
AAYIQAQFES KNRSPNKEIY CHMTCATDTN NIQVVFDAVT DIIIANNLRG CGLY 

« Hide

Isoform Alpha-2 [UniParc] [UniParc].

Checksum: 181B613AAF92F123
Show »

FASTA35440,087

References

« Hide 'large scale' references
[1]"Structure of the human gene and two rat cDNAs encoding the alpha chain of GTP-binding regulatory protein Go: two different mRNAs are generated by alternative splicing."
Tsukamoto T., Toyama R., Itoh H., Kozasa T., Matsuoka M., Kaziro Y.
Proc. Natl. Acad. Sci. U.S.A. 88:2974-2978(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING.
[2]"Molecular cloning and DNA sequence analysis of the human guanine nucleotide-binding protein Go alpha."
Lavu S., Clark J., Swarup R., Matshushima K., Paturu K., Moss J., Kung H.-F.
Biochem. Biophys. Res. Commun. 150:811-815(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[3]"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
Puhl H.L. III, Ikeda S.R., Aronstam R.S.
Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS ALPHA-1 AND ALPHA-2).
Tissue: Brain.
[4]"Identification and expression of GO1 and 2 alpha-subunit transcripts in human myometrium in relation to pregnancy."
Duc-Goiran P., Bourgeois C., Mignot T.M., Robert B., Tanguy G., Ferre F.
Biol. Reprod. 60:1528-1535(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 246-354 (ISOFORM ALPHA-2).
Tissue: Myometrium.
[5]"De Novo mutations in GNAO1, encoding a Galphao subunit of heterotrimeric G proteins, cause epileptic encephalopathy."
Nakamura K., Kodera H., Akita T., Shiina M., Kato M., Hoshino H., Terashima H., Osaka H., Nakamura S., Tohyama J., Kumada T., Furukawa T., Iwata S., Shiihara T., Kubota M., Miyatake S., Koshimizu E., Nishiyama K. expand/collapse author list , Nakashima M., Tsurusaki Y., Miyake N., Hayasaka K., Ogata K., Fukuda A., Matsumoto N., Saitsu H.
Am. J. Hum. Genet. 93:496-505(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EIEE17 GLY-174; 191-THR--PHE-197 DEL; ARG-203 AND ASN-279, CHARACTERIZATION OF VARIANTS EIEE17 GLY-174; 191-THR--PHE-197 DEL; ARG-203 AND ASN-279.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M60164 expand/collapse EMBL AC list , M60156, M60157, M60158, M60159, M60160, M60163 Genomic DNA. Translation: AAA52585.1.
M60162 expand/collapse EMBL AC list , M60156, M60157, M60158, M60159, M60160, M60161 Genomic DNA. Translation: AAA52586.1.
M19182, M19184 Genomic DNA. Translation: AAA52584.1.
AF493894 mRNA. Translation: AAM12608.1.
AF493895 mRNA. Translation: AAM12609.1.
Y18213 mRNA. Translation: CAB46639.1.
CCDSCCDS10756.1. [P09471-1]
CCDS10757.1. [P09471-2]
PIRRGHUO1. A40436.
RGHUO2. B40436.
RefSeqNP_066268.1. NM_020988.2. [P09471-1]
NP_620073.2. NM_138736.2. [P09471-2]
UniGeneHs.644524.

3D structure databases

ProteinModelPortalP09471.
SMRP09471. Positions 35-345.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109037. 20 interactions.
IntActP09471. 4 interactions.
MINTMINT-1203064.
STRING9606.ENSP00000262493.

Chemistry

BindingDBP09471.
ChEMBLCHEMBL4742.

PTM databases

PhosphoSiteP09471.

Polymorphism databases

DMDM232133.

Proteomic databases

MaxQBP09471.
PaxDbP09471.
PeptideAtlasP09471.
PRIDEP09471.

Protocols and materials databases

DNASU2775.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262493; ENSP00000262493; ENSG00000087258. [P09471-1]
ENST00000262494; ENSP00000262494; ENSG00000087258. [P09471-2]
GeneID2775.
KEGGhsa:2775.
UCSCuc002eit.4. human. [P09471-2]
uc002eiu.4. human. [P09471-1]

Organism-specific databases

CTD2775.
GeneCardsGC16P056277.
HGNCHGNC:4389. GNAO1.
HPACAB008387.
MIM139311. gene.
615473. phenotype.
neXtProtNX_P09471.
Orphanet1934. Early infantile epileptic encephalopathy.
PharmGKBPA28771.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG322962.
HOGENOMHOG000038730.
HOVERGENHBG063184.
KOK04534.
OMAPANPLHE.
PhylomeDBP09471.
TreeFamTF300673.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkP09471.

Gene expression databases

ArrayExpressP09471.
BgeeP09471.
CleanExHS_GNAO1.
GenevestigatorP09471.

Family and domain databases

Gene3D1.10.400.10. 1 hit.
3.40.50.300. 2 hits.
InterProIPR001408. Gprotein_alpha_I.
IPR001019. Gprotein_alpha_su.
IPR011025. GproteinA_insert.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERPTHR10218. PTHR10218. 1 hit.
PfamPF00503. G-alpha. 1 hit.
[Graphical view]
PRINTSPR00318. GPROTEINA.
PR00441. GPROTEINAI.
SMARTSM00275. G_alpha. 1 hit.
[Graphical view]
SUPFAMSSF47895. SSF47895. 1 hit.
SSF52540. SSF52540. 2 hits.
ProtoNetSearch...

Other

ChiTaRSGNAO1. human.
GeneWikiGNAO1.
GenomeRNAi2775.
NextBio10916.
PROP09471.
SOURCESearch...

Entry information

Entry nameGNAO_HUMAN
AccessionPrimary (citable) accession number: P09471
Secondary accession number(s): P29777, Q8TD72, Q9UMV4
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 152 of the entry and version 4 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 16

Human chromosome 16: entries, gene names and cross-references to MIM