ID   GNAO_HUMAN              Reviewed;         354 AA.
AC   P09471; P29777; Q8TD72; Q9UMV4;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 4.
DT   27-MAR-2024, entry version 228.
DE   RecName: Full=Guanine nucleotide-binding protein G(o) subunit alpha;
GN   Name=GNAO1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING.
RX   PubMed=1901650; DOI=10.1073/pnas.88.8.2974;
RA   Tsukamoto T., Toyama R., Itoh H., Kozasa T., Matsuoka M., Kaziro Y.;
RT   "Structure of the human gene and two rat cDNAs encoding the alpha chain of
RT   GTP-binding regulatory protein Go: two different mRNAs are generated by
RT   alternative splicing.";
RL   Proc. Natl. Acad. Sci. U.S.A. 88:2974-2978(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX   PubMed=3124840; DOI=10.1016/0006-291x(88)90463-9;
RA   Lavu S., Clark J., Swarup R., Matshushima K., Paturu K., Moss J.,
RA   Kung H.-F.;
RT   "Molecular cloning and DNA sequence analysis of the human guanine
RT   nucleotide-binding protein Go alpha.";
RL   Biochem. Biophys. Res. Commun. 150:811-815(1988).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS ALPHA-1 AND ALPHA-2).
RC   TISSUE=Brain;
RA   Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT   "cDNA clones of human proteins involved in signal transduction sequenced by
RT   the Guthrie cDNA resource center (www.cdna.org).";
RL   Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 246-354 (ISOFORM ALPHA-2).
RC   TISSUE=Myometrium;
RX   PubMed=10330115; DOI=10.1095/biolreprod60.6.1528;
RA   Duc-Goiran P., Bourgeois C., Mignot T.M., Robert B., Tanguy G., Ferre F.;
RT   "Identification and expression of GO1 and 2 alpha-subunit transcripts in
RT   human myometrium in relation to pregnancy.";
RL   Biol. Reprod. 60:1528-1535(1999).
RN   [5]
RP   MYRISTOYLATION AT GLY-2, CLEAVAGE OF INITIATOR METHIONINE, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=25255805; DOI=10.1038/ncomms5919;
RA   Thinon E., Serwa R.A., Broncel M., Brannigan J.A., Brassat U., Wright M.H.,
RA   Heal W.P., Wilkinson A.J., Mann D.J., Tate E.W.;
RT   "Global profiling of co- and post-translationally N-myristoylated proteomes
RT   in human cells.";
RL   Nat. Commun. 5:4919-4919(2014).
RN   [6]
RP   VARIANTS DEE17 GLY-174; 191-THR--PHE-197 DEL; ARG-203 AND ASN-279,
RP   CHARACTERIZATION OF VARIANTS DEE17 GLY-174; 191-THR--PHE-197 DEL; ARG-203
RP   AND ASN-279, AND INVOLVEMENT IN DEE17.
RX   PubMed=23993195; DOI=10.1016/j.ajhg.2013.07.014;
RA   Nakamura K., Kodera H., Akita T., Shiina M., Kato M., Hoshino H.,
RA   Terashima H., Osaka H., Nakamura S., Tohyama J., Kumada T., Furukawa T.,
RA   Iwata S., Shiihara T., Kubota M., Miyatake S., Koshimizu E., Nishiyama K.,
RA   Nakashima M., Tsurusaki Y., Miyake N., Hayasaka K., Ogata K., Fukuda A.,
RA   Matsumoto N., Saitsu H.;
RT   "De Novo mutations in GNAO1, encoding a Galphao subunit of heterotrimeric G
RT   proteins, cause epileptic encephalopathy.";
RL   Am. J. Hum. Genet. 93:496-505(2013).
RN   [7]
RP   VARIANT DEE17 ARG-40.
RX   PubMed=26485252; DOI=10.1016/j.cca.2015.10.011;
RA   Law C.Y., Chang S.T., Cho S.Y., Yau E.K., Ng G.S., Fong N.C., Lam C.W.;
RT   "Clinical whole-exome sequencing reveals a novel missense pathogenic
RT   variant of GNAO1 in a patient with infantile-onset epilepsy.";
RL   Clin. Chim. Acta 451:292-296(2015).
RN   [8]
RP   VARIANT NEDIM HIS-209.
RX   PubMed=26060304; DOI=10.1177/0883073815587945;
RA   Kulkarni N., Tang S., Bhardwaj R., Bernes S., Grebe T.A.;
RT   "Progressive movement disorder in brothers carrying a GNAO1 mutation
RT   responsive to deep brain stimulation.";
RL   J. Child Neurol. 31:211-214(2016).
RN   [9]
RP   VARIANTS NEDIM HIS-209 AND LEU-209.
RX   PubMed=27625011; DOI=10.1177/0883073816666474;
RA   Menke L.A., Engelen M., Alders M., Odekerken V.J., Baas F., Cobben J.M.;
RT   "Recurrent GNAO1 mutations associated with developmental delay and a
RT   movement disorder.";
RL   J. Child Neurol. 31:1598-1601(2016).
RN   [10]
RP   VARIANTS NEDIM GLY-209; HIS-209 AND LYS-246.
RX   PubMed=27068059; DOI=10.1016/j.pediatrneurol.2016.02.018;
RA   Ananth A.L., Robichaux-Viehoever A., Kim Y.M., Hanson-Kahn A., Cox R.,
RA   Enns G.M., Strober J., Willing M., Schlaggar B.L., Wu Y.W., Bernstein J.A.;
RT   "Clinical course of six children with GNAO1 mutations causing a severe and
RT   distinctive movement disorder.";
RL   Pediatr. Neurol. 59:81-84(2016).
RN   [11]
RP   VARIANT DEE17 ASN-279.
RX   PubMed=27476654; DOI=10.1016/j.ajhg.2016.06.003;
RG   Epi4K Consortium;
RT   "De novo mutations in SLC1A2 and CACNA1A are important causes of epileptic
RT   encephalopathies.";
RL   Am. J. Hum. Genet. 99:287-298(2016).
RN   [12]
RP   INVOLVEMENT IN NEDIM, VARIANTS NEDIM CYS-209; VAL-227 AND LYS-246, AND
RP   VARIANT DEE17 ARG-203.
RX   PubMed=25966631; DOI=10.1038/ejhg.2015.92;
RA   Saitsu H., Fukai R., Ben-Zeev B., Sakai Y., Mimaki M., Okamoto N.,
RA   Suzuki Y., Monden Y., Saito H., Tziperman B., Torio M., Akamine S.,
RA   Takahashi N., Osaka H., Yamagata T., Nakamura K., Tsurusaki Y.,
RA   Nakashima M., Miyake N., Shiina M., Ogata K., Matsumoto N.;
RT   "Phenotypic spectrum of GNAO1 variants: epileptic encephalopathy to
RT   involuntary movements with severe developmental delay.";
RL   Eur. J. Hum. Genet. 24:129-134(2016).
RN   [13]
RP   VARIANT DEE17 CYS-209.
RX   PubMed=27864847; DOI=10.1002/humu.23149;
RG   Clinical Study Group;
RA   Parrini E., Marini C., Mei D., Galuppi A., Cellini E., Pucatti D.,
RA   Chiti L., Rutigliano D., Bianchini C., Virdo S., De Vita D., Bigoni S.,
RA   Barba C., Mari F., Montomoli M., Pisano T., Rosati A., Guerrini R.;
RT   "Diagnostic targeted resequencing in 349 patients with drug-resistant
RT   pediatric epilepsies identifies causative mutations in 30 different
RT   genes.";
RL   Hum. Mutat. 38:216-225(2017).
RN   [14]
RP   VARIANTS NEDIM ARG-40; GLY-47; THR-56; CYS-209 AND GLY-246.
RX   PubMed=28357411; DOI=10.1212/nxg.0000000000000143;
RA   Danti F.R., Galosi S., Romani M., Montomoli M., Carss K.J., Raymond F.L.,
RA   Parrini E., Bianchini C., McShane T., Dale R.C., Mohammad S.S., Shah U.,
RA   Mahant N., Ng J., McTague A., Samanta R., Vadlamani G., Valente E.M.,
RA   Leuzzi V., Kurian M.A., Guerrini R.;
RT   "GNAO1 encephalopathy: Broadening the phenotype and evaluating treatment
RT   and outcome.";
RL   Neurol. Genet. 3:E143-E143(2017).
RN   [15]
RP   VARIANTS TRP-40 AND PRO-52.
RX   PubMed=29390993; DOI=10.1186/s12920-018-0320-7;
RA   Rim J.H., Kim S.H., Hwang I.S., Kwon S.S., Kim J., Kim H.W., Cho M.J.,
RA   Ko A., Youn S.E., Kim J., Lee Y.M., Chung H.J., Lee J.S., Kim H.D.,
RA   Choi J.R., Lee S.T., Kang H.C.;
RT   "Efficient strategy for the molecular diagnosis of intractable early-onset
RT   epilepsy using targeted gene sequencing.";
RL   BMC Med. Genomics 11:6-6(2018).
RN   [16]
RP   VARIANT DEE17 ARG-52, CHARACTERIZATION OF VARIANT DEE17 ARG-52,
RP   CHARACTERIZATION OF VARIANT PRO-52, INTERACTION WITH RGS19, INTERACTION
RP   WITH GNB1 AND GNG3, AND SUBCELLULAR LOCATION.
RX   PubMed=34685729; DOI=10.3390/cells10102749;
RA   Solis G.P., Kozhanova T.V., Koval A., Zhilina S.S., Mescheryakova T.I.,
RA   Abramov A.A., Ishmuratov E.V., Bolshakova E.S., Osipova K.V.,
RA   Ayvazyan S.O., Lebon S., Kanivets I.V., Pyankov D.V., Troccaz S.,
RA   Silachev D.N., Zavadenko N.N., Prityko A.G., Katanaev V.L.;
RT   "Pediatric Encephalopathy: Clinical, Biochemical and Cellular Insights into
RT   the Role of Gln52 of GNAO1 and GNAI1 for the Dominant Disease.";
RL   Cells 10:0-0(2021).
CC   -!- FUNCTION: Guanine nucleotide-binding proteins (G proteins) are involved
CC       as modulators or transducers in various transmembrane signaling
CC       systems. The G(o) protein function is not clear. Stimulated by RGS14.
CC   -!- SUBUNIT: G proteins are composed of 3 units; alpha, beta and gamma. The
CC       alpha chain contains the guanine nucleotide binding site. Forms a
CC       complex with GNB1 and GNG3 (PubMed:34685729). Interacts with RGS14 (By
CC       similarity). Interacts with RGS19 (PubMed:34685729).
CC       {ECO:0000250|UniProtKB:P18872, ECO:0000269|PubMed:34685729}.
CC   -!- INTERACTION:
CC       P09471; P28288-2: ABCD3; NbExp=3; IntAct=EBI-715087, EBI-25889034;
CC       P09471; P27797: CALR; NbExp=3; IntAct=EBI-715087, EBI-1049597;
CC       P09471; P45973: CBX5; NbExp=3; IntAct=EBI-715087, EBI-78219;
CC       P09471; P36957: DLST; NbExp=3; IntAct=EBI-715087, EBI-351007;
CC       P09471; P42858: HTT; NbExp=7; IntAct=EBI-715087, EBI-466029;
CC       P09471; Q8TDX7: NEK7; NbExp=3; IntAct=EBI-715087, EBI-1055945;
CC       P09471; P51812: RPS6KA3; NbExp=3; IntAct=EBI-715087, EBI-1046616;
CC       P09471; P37173: TGFBR2; NbExp=3; IntAct=EBI-715087, EBI-296151;
CC       P09471; P55072: VCP; NbExp=3; IntAct=EBI-715087, EBI-355164;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:34685729}.
CC       Membrane {ECO:0000305}; Lipid-anchor {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=Alpha-1;
CC         IsoId=P09471-1; Sequence=Displayed;
CC       Name=Alpha-2;
CC         IsoId=P09471-2, P29777-1; Sequence=VSP_031250;
CC   -!- PTM: Histaminylated at Gln-205 residues by TGM2.
CC       {ECO:0000250|UniProtKB:P18872}.
CC   -!- DISEASE: Developmental and epileptic encephalopathy 17 (DEE17)
CC       [MIM:615473]: A severe neurologic disorder characterized by onset of
CC       intractable seizures in the first weeks or months of life and usually
CC       associated with EEG abnormalities. Affected infants have very poor
CC       psychomotor development and may have brain abnormalities, such as
CC       cerebral atrophy or thin corpus callosum. Some patients may show
CC       involuntary movements. {ECO:0000269|PubMed:23993195,
CC       ECO:0000269|PubMed:25966631, ECO:0000269|PubMed:26485252,
CC       ECO:0000269|PubMed:27476654, ECO:0000269|PubMed:27864847,
CC       ECO:0000269|PubMed:34685729}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Neurodevelopmental disorder with involuntary movements (NEDIM)
CC       [MIM:617493]: A neurodevelopmental disorder manifesting with a wide
CC       range of clinical symptoms. Clinical features range from severe motor
CC       and cognitive impairment with marked choreoathetosis, self-injurious
CC       behavior and epileptic encephalopathy, to a milder phenotype featuring
CC       moderate developmental delay associated with complex stereotypies,
CC       mainly facial dyskinesia, and mild epilepsy. Hyperkinetic movements are
CC       often exacerbated by specific triggers, such as illness, emotion and
CC       high ambient temperature. Some patients have brain abnormalities, such
CC       as cerebral atrophy or thin corpus callosum.
CC       {ECO:0000269|PubMed:25966631, ECO:0000269|PubMed:26060304,
CC       ECO:0000269|PubMed:27068059, ECO:0000269|PubMed:27625011,
CC       ECO:0000269|PubMed:28357411}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the G-alpha family. G(i/o/t/z) subfamily.
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DR   EMBL; M60164; AAA52585.1; -; Genomic_DNA.
DR   EMBL; M60156; AAA52585.1; JOINED; Genomic_DNA.
DR   EMBL; M60157; AAA52585.1; JOINED; Genomic_DNA.
DR   EMBL; M60158; AAA52585.1; JOINED; Genomic_DNA.
DR   EMBL; M60159; AAA52585.1; JOINED; Genomic_DNA.
DR   EMBL; M60160; AAA52585.1; JOINED; Genomic_DNA.
DR   EMBL; M60163; AAA52585.1; JOINED; Genomic_DNA.
DR   EMBL; M60162; AAA52586.1; -; Genomic_DNA.
DR   EMBL; M60156; AAA52586.1; JOINED; Genomic_DNA.
DR   EMBL; M60157; AAA52586.1; JOINED; Genomic_DNA.
DR   EMBL; M60158; AAA52586.1; JOINED; Genomic_DNA.
DR   EMBL; M60159; AAA52586.1; JOINED; Genomic_DNA.
DR   EMBL; M60160; AAA52586.1; JOINED; Genomic_DNA.
DR   EMBL; M60161; AAA52586.1; JOINED; Genomic_DNA.
DR   EMBL; M19182; AAA52584.1; -; mRNA.
DR   EMBL; M19184; AAA52584.1; JOINED; Genomic_DNA.
DR   EMBL; AF493894; AAM12608.1; -; mRNA.
DR   EMBL; AF493895; AAM12609.1; -; mRNA.
DR   EMBL; Y18213; CAB46639.1; -; mRNA.
DR   CCDS; CCDS10756.1; -. [P09471-1]
DR   CCDS; CCDS10757.1; -. [P09471-2]
DR   PIR; A40436; RGHUO1.
DR   PIR; B40436; RGHUO2.
DR   RefSeq; NP_066268.1; NM_020988.2. [P09471-1]
DR   RefSeq; NP_620073.2; NM_138736.2. [P09471-2]
DR   PDB; 6FUF; X-ray; 3.12 A; B=18-354.
DR   PDB; 6G79; EM; 3.78 A; A=4-57, A=276-354.
DR   PDB; 6K41; EM; 2.90 A; A=1-354.
DR   PDB; 6OIK; EM; 3.60 A; A=1-354.
DR   PDB; 6WWZ; EM; 3.34 A; A=4-57, A=182-354.
DR   PDB; 7D76; EM; 3.10 A; A=4-354.
DR   PDB; 7D77; EM; 2.90 A; A=4-354.
DR   PDB; 7EJ0; EM; 3.20 A; A=1-354.
DR   PDB; 7EJ8; EM; 3.00 A; A=1-354.
DR   PDB; 7EJA; EM; 3.60 A; A=1-354.
DR   PDB; 7EJK; EM; 3.40 A; A=1-354.
DR   PDB; 7QVM; EM; 3.25 A; A=1-57, A=182-353.
DR   PDB; 7T8X; EM; 3.21 A; B=1-354.
DR   PDB; 7T90; EM; 3.32 A; B=1-354.
DR   PDB; 7T94; EM; 3.16 A; B=1-354.
DR   PDB; 7T96; EM; 3.22 A; B=1-354.
DR   PDB; 7W2Z; EM; 2.80 A; A=182-354.
DR   PDB; 7W6P; EM; 3.47 A; A=1-354.
DR   PDB; 7W7E; EM; 3.40 A; A=1-354.
DR   PDB; 7XJJ; EM; 3.30 A; A=1-57, A=182-354.
DR   PDB; 7Y24; EM; 3.25 A; A=5-57, A=182-354.
DR   PDB; 8DZQ; EM; 2.82 A; B=1-354.
DR   PDB; 8E9X; EM; 2.70 A; B=136-354.
DR   PDB; 8FN1; EM; 2.88 A; B=1-57, B=182-354.
DR   PDB; 8HPT; EM; 3.39 A; B=4-57, B=182-354.
DR   PDB; 8HQC; EM; 3.89 A; B=4-57, B=182-354.
DR   PDB; 8I95; EM; 2.88 A; A=4-57, A=182-354.
DR   PDB; 8I97; EM; 3.19 A; A=4-57, A=182-354.
DR   PDB; 8I9L; EM; 3.18 A; A=4-57, A=182-354.
DR   PDB; 8I9S; EM; 3.26 A; A=4-57, A=182-354.
DR   PDB; 8IA2; EM; 3.21 A; B=4-57, B=182-354.
DR   PDB; 8J6D; EM; 3.10 A; A=4-57, A=182-354.
DR   PDB; 8JZZ; EM; 3.31 A; C=4-57, C=182-354.
DR   PDBsum; 6FUF; -.
DR   PDBsum; 6G79; -.
DR   PDBsum; 6K41; -.
DR   PDBsum; 6OIK; -.
DR   PDBsum; 6WWZ; -.
DR   PDBsum; 7D76; -.
DR   PDBsum; 7D77; -.
DR   PDBsum; 7EJ0; -.
DR   PDBsum; 7EJ8; -.
DR   PDBsum; 7EJA; -.
DR   PDBsum; 7EJK; -.
DR   PDBsum; 7QVM; -.
DR   PDBsum; 7T8X; -.
DR   PDBsum; 7T90; -.
DR   PDBsum; 7T94; -.
DR   PDBsum; 7T96; -.
DR   PDBsum; 7W2Z; -.
DR   PDBsum; 7W6P; -.
DR   PDBsum; 7W7E; -.
DR   PDBsum; 7XJJ; -.
DR   PDBsum; 7Y24; -.
DR   PDBsum; 8DZQ; -.
DR   PDBsum; 8E9X; -.
DR   PDBsum; 8FN1; -.
DR   PDBsum; 8HPT; -.
DR   PDBsum; 8HQC; -.
DR   PDBsum; 8I95; -.
DR   PDBsum; 8I97; -.
DR   PDBsum; 8I9L; -.
DR   PDBsum; 8I9S; -.
DR   PDBsum; 8IA2; -.
DR   PDBsum; 8J6D; -.
DR   PDBsum; 8JZZ; -.
DR   AlphaFoldDB; P09471; -.
DR   EMDB; EMD-14180; -.
DR   EMDB; EMD-20079; -.
DR   EMDB; EMD-21950; -.
DR   EMDB; EMD-25748; -.
DR   EMDB; EMD-25749; -.
DR   EMDB; EMD-25751; -.
DR   EMDB; EMD-25752; -.
DR   EMDB; EMD-26597; -.
DR   EMDB; EMD-26598; -.
DR   EMDB; EMD-26599; -.
DR   EMDB; EMD-27805; -.
DR   EMDB; EMD-27967; -.
DR   EMDB; EMD-29303; -.
DR   EMDB; EMD-30602; -.
DR   EMDB; EMD-30603; -.
DR   EMDB; EMD-31147; -.
DR   EMDB; EMD-31156; -.
DR   EMDB; EMD-31157; -.
DR   EMDB; EMD-31162; -.
DR   EMDB; EMD-32268; -.
DR   EMDB; EMD-32331; -.
DR   EMDB; EMD-32342; -.
DR   EMDB; EMD-33229; -.
DR   EMDB; EMD-33585; -.
DR   EMDB; EMD-34943; -.
DR   EMDB; EMD-34947; -.
DR   EMDB; EMD-35257; -.
DR   EMDB; EMD-35259; -.
DR   EMDB; EMD-35275; -.
DR   EMDB; EMD-35282; -.
DR   EMDB; EMD-35292; -.
DR   EMDB; EMD-36001; -.
DR   EMDB; EMD-36755; -.
DR   EMDB; EMD-4358; -.
DR   EMDB; EMD-9911; -.
DR   SMR; P09471; -.
DR   BioGRID; 109037; 84.
DR   ELM; P09471; -.
DR   IntAct; P09471; 37.
DR   MINT; P09471; -.
DR   STRING; 9606.ENSP00000262494; -.
DR   BindingDB; P09471; -.
DR   ChEMBL; CHEMBL4742; -.
DR   iPTMnet; P09471; -.
DR   PhosphoSitePlus; P09471; -.
DR   SwissPalm; P09471; -.
DR   BioMuta; GNAO1; -.
DR   DMDM; 232133; -.
DR   EPD; P09471; -.
DR   jPOST; P09471; -.
DR   MassIVE; P09471; -.
DR   MaxQB; P09471; -.
DR   PaxDb; 9606-ENSP00000262494; -.
DR   PeptideAtlas; P09471; -.
DR   ProteomicsDB; 52224; -. [P09471-1]
DR   ProteomicsDB; 52225; -. [P09471-2]
DR   Pumba; P09471; -.
DR   Antibodypedia; 3649; 299 antibodies from 34 providers.
DR   DNASU; 2775; -.
DR   Ensembl; ENST00000262493.12; ENSP00000262493.6; ENSG00000087258.16. [P09471-1]
DR   Ensembl; ENST00000262494.13; ENSP00000262494.7; ENSG00000087258.16. [P09471-2]
DR   Ensembl; ENST00000638705.1; ENSP00000491223.1; ENSG00000087258.16. [P09471-1]
DR   GeneID; 2775; -.
DR   KEGG; hsa:2775; -.
DR   MANE-Select; ENST00000262493.12; ENSP00000262493.6; NM_020988.3; NP_066268.1.
DR   UCSC; uc002eit.5; human. [P09471-1]
DR   AGR; HGNC:4389; -.
DR   CTD; 2775; -.
DR   DisGeNET; 2775; -.
DR   GeneCards; GNAO1; -.
DR   GeneReviews; GNAO1; -.
DR   HGNC; HGNC:4389; GNAO1.
DR   HPA; ENSG00000087258; Tissue enhanced (brain, retina).
DR   MalaCards; GNAO1; -.
DR   MIM; 139311; gene.
DR   MIM; 615473; phenotype.
DR   MIM; 617493; phenotype.
DR   neXtProt; NX_P09471; -.
DR   OpenTargets; ENSG00000087258; -.
DR   Orphanet; 1934; Early infantile epileptic encephalopathy.
DR   Orphanet; 592564; GNAO1-related developmental delay-seizures-movement disorder spectrum.
DR   PharmGKB; PA28771; -.
DR   VEuPathDB; HostDB:ENSG00000087258; -.
DR   eggNOG; KOG0082; Eukaryota.
DR   GeneTree; ENSGT00940000155883; -.
DR   HOGENOM; CLU_014184_6_0_1; -.
DR   InParanoid; P09471; -.
DR   OMA; TDAKMVF; -.
DR   OrthoDB; 2897309at2759; -.
DR   PhylomeDB; P09471; -.
DR   TreeFam; TF300673; -.
DR   PathwayCommons; P09471; -.
DR   Reactome; R-HSA-4086398; Ca2+ pathway.
DR   SignaLink; P09471; -.
DR   SIGNOR; P09471; -.
DR   BioGRID-ORCS; 2775; 11 hits in 1143 CRISPR screens.
DR   ChiTaRS; GNAO1; human.
DR   GeneWiki; GNAO1; -.
DR   GenomeRNAi; 2775; -.
DR   Pharos; P09471; Tbio.
DR   PRO; PR:P09471; -.
DR   Proteomes; UP000005640; Chromosome 16.
DR   RNAct; P09471; Protein.
DR   Bgee; ENSG00000087258; Expressed in cortical plate and 187 other cell types or tissues.
DR   ExpressionAtlas; P09471; baseline and differential.
DR   GO; GO:0005834; C:heterotrimeric G-protein complex; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0051430; F:corticotropin-releasing hormone receptor 1 binding; IBA:GO_Central.
DR   GO; GO:0031821; F:G protein-coupled serotonin receptor binding; IBA:GO_Central.
DR   GO; GO:0031683; F:G-protein beta/gamma-subunit complex binding; IBA:GO_Central.
DR   GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR   GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0031852; F:mu-type opioid receptor binding; IBA:GO_Central.
DR   GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0007212; P:dopamine receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0006936; P:muscle contraction; TAS:ProtInc.
DR   CDD; cd00066; G-alpha; 1.
DR   Gene3D; 1.10.400.10; GI Alpha 1, domain 2-like; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR   InterPro; IPR001408; Gprotein_alpha_I.
DR   InterPro; IPR001019; Gprotein_alpha_su.
DR   InterPro; IPR011025; GproteinA_insert.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   PANTHER; PTHR10218; GTP-BINDING PROTEIN ALPHA SUBUNIT; 1.
DR   PANTHER; PTHR10218:SF355; GUANINE NUCLEOTIDE-BINDING PROTEIN G(O) SUBUNIT ALPHA; 1.
DR   Pfam; PF00503; G-alpha; 1.
DR   PRINTS; PR00318; GPROTEINA.
DR   PRINTS; PR00441; GPROTEINAI.
DR   SMART; SM00275; G_alpha; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR   SUPFAM; SSF47895; Transducin (alpha subunit), insertion domain; 1.
DR   PROSITE; PS51882; G_ALPHA; 1.
DR   Genevisible; P09471; HS.
PE   1: Evidence at protein level;
KW   3D-structure; ADP-ribosylation; Alternative splicing; Cell membrane;
KW   Disease variant; Epilepsy; GTP-binding; Lipoprotein; Magnesium; Membrane;
KW   Metal-binding; Myristate; Nucleotide-binding; Palmitate;
KW   Reference proteome; Transducer.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|PubMed:25255805"
FT   CHAIN           2..354
FT                   /note="Guanine nucleotide-binding protein G(o) subunit
FT                   alpha"
FT                   /id="PRO_0000203702"
FT   DOMAIN          32..354
FT                   /note="G-alpha"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT   REGION          35..48
FT                   /note="G1 motif"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT   REGION          174..182
FT                   /note="G2 motif"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT   REGION          197..206
FT                   /note="G3 motif"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT   REGION          266..273
FT                   /note="G4 motif"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT   REGION          324..329
FT                   /note="G5 motif"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT   BINDING         40..47
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250"
FT   BINDING         47
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   BINDING         176..182
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250"
FT   BINDING         182
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   BINDING         201..205
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250"
FT   BINDING         270..273
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250"
FT   BINDING         326
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         179
FT                   /note="ADP-ribosylarginine; by cholera toxin"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         205
FT                   /note="5-glutamyl histamine"
FT                   /evidence="ECO:0000250|UniProtKB:P18872"
FT   MOD_RES         351
FT                   /note="ADP-ribosylcysteine; by pertussis toxin"
FT                   /evidence="ECO:0000250"
FT   LIPID           2
FT                   /note="N-myristoyl glycine"
FT                   /evidence="ECO:0000269|PubMed:25255805"
FT   LIPID           3
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         249..354
FT                   /note="MLFDSICNNKFFIDTSIILFLNKKDLFGEKIKKSPLTICFPEYTGPNTYEDA
FT                   AAYIQAQFESKNRSPNKEIYCHMTCATDTNNIQVVFDAVTDIIIANNLRGCGLY -> K
FT                   LFDSICNNKWFTDTSIILFLNKKDIFEEKIKKSPLTICFPEYTGPSAFTEAVAYIQAQY
FT                   ESKNKSAHKEIYTHVTCATDTNNIQFVFDAVTDVIIAKNLRGCGLY (in isoform
FT                   Alpha-2)"
FT                   /evidence="ECO:0000303|PubMed:10330115, ECO:0000303|Ref.3"
FT                   /id="VSP_031250"
FT   VARIANT         40
FT                   /note="G -> R (in DEE17 and NEDIM; dbSNP:rs886041715)"
FT                   /evidence="ECO:0000269|PubMed:26485252,
FT                   ECO:0000269|PubMed:28357411"
FT                   /id="VAR_075416"
FT   VARIANT         40
FT                   /note="G -> W (found in a patient with intractable
FT                   early-onset epilepsy; likely pathogenic)"
FT                   /evidence="ECO:0000269|PubMed:29390993"
FT                   /id="VAR_087220"
FT   VARIANT         47
FT                   /note="S -> G (in NEDIM)"
FT                   /evidence="ECO:0000269|PubMed:28357411"
FT                   /id="VAR_079278"
FT   VARIANT         52
FT                   /note="Q -> P (found in a patient with intractable
FT                   early-onset epilepsy; likely pathogenic; loss of GTP
FT                   binding; decreased interaction with RGS19; decreased
FT                   interaction with heterodimers formed by GNB1 and GNG3;
FT                   strongly decreased localization to cell membrane)"
FT                   /evidence="ECO:0000269|PubMed:29390993,
FT                   ECO:0000269|PubMed:34685729"
FT                   /id="VAR_087221"
FT   VARIANT         52
FT                   /note="Q -> R (in DEE17; loss of GTP binding; decreased
FT                   interaction with RGS19; decreased interaction with
FT                   heterodimers formed by GNB1 and GNG3; strongly decreased
FT                   localization to cell membrane)"
FT                   /evidence="ECO:0000269|PubMed:34685729"
FT                   /id="VAR_087222"
FT   VARIANT         56
FT                   /note="I -> T (in NEDIM)"
FT                   /evidence="ECO:0000269|PubMed:28357411"
FT                   /id="VAR_079279"
FT   VARIANT         174
FT                   /note="D -> G (in DEE17; somatic mosaic mutation; the
FT                   mutant protein has some abnormal cytoplasmic localization;
FT                   dbSNP:rs587777055)"
FT                   /evidence="ECO:0000269|PubMed:23993195"
FT                   /id="VAR_070864"
FT   VARIANT         191..197
FT                   /note="Missing (in DEE17; the mutant protein accumulates in
FT                   the cytoplasmic compartment; increased basal
FT                   calcium-current density compared to wild-type)"
FT                   /evidence="ECO:0000269|PubMed:23993195"
FT                   /id="VAR_070865"
FT   VARIANT         203
FT                   /note="G -> R (in DEE17; the mutant protein localizes
FT                   normally to the cell periphery; dbSNP:rs587777057)"
FT                   /evidence="ECO:0000269|PubMed:23993195,
FT                   ECO:0000269|PubMed:25966631"
FT                   /id="VAR_070866"
FT   VARIANT         209
FT                   /note="R -> C (in DEE17 and NEDIM; dbSNP:rs886039494)"
FT                   /evidence="ECO:0000269|PubMed:25966631,
FT                   ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:28357411"
FT                   /id="VAR_077337"
FT   VARIANT         209
FT                   /note="R -> G (in NEDIM; dbSNP:rs886039494)"
FT                   /evidence="ECO:0000269|PubMed:27068059"
FT                   /id="VAR_079280"
FT   VARIANT         209
FT                   /note="R -> H (in NEDIM; dbSNP:rs797044878)"
FT                   /evidence="ECO:0000269|PubMed:26060304,
FT                   ECO:0000269|PubMed:27068059, ECO:0000269|PubMed:27625011"
FT                   /id="VAR_079281"
FT   VARIANT         209
FT                   /note="R -> L (in NEDIM)"
FT                   /evidence="ECO:0000269|PubMed:27625011"
FT                   /id="VAR_079282"
FT   VARIANT         227
FT                   /note="A -> V (in NEDIM; dbSNP:rs797045599)"
FT                   /evidence="ECO:0000269|PubMed:25966631"
FT                   /id="VAR_077338"
FT   VARIANT         246
FT                   /note="E -> G (in NEDIM; dbSNP:rs1114167431)"
FT                   /evidence="ECO:0000269|PubMed:28357411"
FT                   /id="VAR_079283"
FT   VARIANT         246
FT                   /note="E -> K (in NEDIM; dbSNP:rs797044951)"
FT                   /evidence="ECO:0000269|PubMed:25966631,
FT                   ECO:0000269|PubMed:27068059"
FT                   /id="VAR_077339"
FT   VARIANT         279
FT                   /note="I -> N (in DEE17; the mutant protein has some
FT                   abnormal cytoplasmic localization; dbSNP:rs587777054)"
FT                   /evidence="ECO:0000269|PubMed:23993195,
FT                   ECO:0000269|PubMed:27476654"
FT                   /id="VAR_070867"
FT   CONFLICT        16
FT                   /note="S -> G (in Ref. 2; AAA52584)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        171
FT                   /note="T -> L (in Ref. 2; AAA52584)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        218
FT                   /note="D -> E (in Ref. 2; AAA52584)"
FT                   /evidence="ECO:0000305"
FT   HELIX           7..31
FT                   /evidence="ECO:0007829|PDB:8E9X"
FT   STRAND          34..45
FT                   /evidence="ECO:0007829|PDB:8E9X"
FT   HELIX           46..48
FT                   /evidence="ECO:0007829|PDB:8E9X"
FT   STRAND          49..51
FT                   /evidence="ECO:0007829|PDB:7D76"
FT   STRAND          186..194
FT                   /evidence="ECO:0007829|PDB:8E9X"
FT   STRAND          196..201
FT                   /evidence="ECO:0007829|PDB:8E9X"
FT   HELIX           209..211
FT                   /evidence="ECO:0007829|PDB:8E9X"
FT   HELIX           213..216
FT                   /evidence="ECO:0007829|PDB:8E9X"
FT   STRAND          220..229
FT                   /evidence="ECO:0007829|PDB:8E9X"
FT   TURN            230..232
FT                   /evidence="ECO:0007829|PDB:7W7E"
FT   HELIX           242..255
FT                   /evidence="ECO:0007829|PDB:8E9X"
FT   STRAND          258..262
FT                   /evidence="ECO:0007829|PDB:8E9X"
FT   STRAND          264..270
FT                   /evidence="ECO:0007829|PDB:8E9X"
FT   HELIX           272..281
FT                   /evidence="ECO:0007829|PDB:8E9X"
FT   TURN            284..287
FT                   /evidence="ECO:0007829|PDB:7W2Z"
FT   STRAND          294..296
FT                   /evidence="ECO:0007829|PDB:6WWZ"
FT   HELIX           297..310
FT                   /evidence="ECO:0007829|PDB:8E9X"
FT   STRAND          314..316
FT                   /evidence="ECO:0007829|PDB:7D76"
FT   STRAND          320..323
FT                   /evidence="ECO:0007829|PDB:8E9X"
FT   STRAND          326..328
FT                   /evidence="ECO:0007829|PDB:7D77"
FT   HELIX           332..350
FT                   /evidence="ECO:0007829|PDB:8E9X"
SQ   SEQUENCE   354 AA;  40051 MW;  4F182926A8106E3E CRC64;
     MGCTLSAEER AALERSKAIE KNLKEDGISA AKDVKLLLLG AGESGKSTIV KQMKIIHEDG
     FSGEDVKQYK PVVYSNTIQS LAAIVRAMDT LGIEYGDKER KADAKMVCDV VSRMEDTEPF
     SAELLSAMMR LWGDSGIQEC FNRSREYQLN DSAKYYLDSL DRIGAADYQP TEQDILRTRV
     KTTGIVETHF TFKNLHFRLF DVGGQRSERK KWIHCFEDVT AIIFCVALSG YDQVLHEDET
     TNRMHESLML FDSICNNKFF IDTSIILFLN KKDLFGEKIK KSPLTICFPE YTGPNTYEDA
     AAYIQAQFES KNRSPNKEIY CHMTCATDTN NIQVVFDAVT DIIIANNLRG CGLY
//