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 10-JUN-2026, entry version 237. DE RecName: Full=Guanine nucleotide-binding protein G(o) subunit alpha; DE EC=3.6.5.- {ECO:0000250|UniProtKB:P18872}; 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] {ECO:0007744|PDB:6G79} RP STRUCTURE BY ELECTRON MICROSCOPY (3.78 ANGSTROMS) IN COMPLEX WITH HTR1B; RP GNB1 AND GNG2, FUNCTION, AND SUBUNIT. RX PubMed=29925951; DOI=10.1038/s41586-018-0241-9; RA Garcia-Nafria J., Nehme R., Edwards P.C., Tate C.G.; RT "Cryo-EM structure of the serotonin 5-HT1B receptor coupled to RT heterotrimeric Go."; RL Nature 558:620-623(2018). RN [7] {ECO:0007744|PDB:7D76, ECO:0007744|PDB:7D77} RP STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS) OF 4-354, INTERACTION RP WITH ADGRG3, PALMITOYLATION AT CYS-351, AND MUTAGENESIS OF CYS-351. RX PubMed=33408414; DOI=10.1038/s41586-020-03083-w; RA Ping Y.Q., Mao C., Xiao P., Zhao R.J., Jiang Y., Yang Z., An W.T., RA Shen D.D., Yang F., Zhang H., Qu C., Shen Q., Tian C., Li Z.J., Li S., RA Wang G.Y., Tao X., Wen X., Zhong Y.N., Yang J., Yi F., Yu X., Xu H.E., RA Zhang Y., Sun J.P.; RT "Structures of the glucocorticoid-bound adhesion receptor GPR97-Go RT complex."; RL Nature 589:620-626(2021). RN [8] {ECO:0007744|PDB:8TZQ, ECO:0007744|PDB:8U02} RP STRUCTURE BY ELECTRON MICROSCOPY (3.20 ANGSTROMS) OF MUTANT GLU-46 IN RP COMPLEX WITH DRD2; GNB1; GNG2 AND DOPAMINE, FUNCTION, SUBUNIT, AND RP MUTAGENESIS OF LYS-46. RX PubMed=39103320; DOI=10.1038/s41467-024-50964-z; RA Knight K.M., Krumm B.E., Kapolka N.J., Ludlam W.G., Cui M., Mani S., RA Prytkova I., Obarow E.G., Lefevre T.J., Wei W., Ma N., Huang X.P., RA Fay J.F., Vaidehi N., Smrcka A.V., Slesinger P.A., Logothetis D.E., RA Martemyanov K.A., Roth B.L., Dohlman H.G.; RT "A neurodevelopmental disorder mutation locks G proteins in the transitory RT pre-activated state."; RL Nat. Commun. 15:6643-6643(2024). RN [9] 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 [10] 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 [11] 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 [12] 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 [13] 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 [14] 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 [15] 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 [16] 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 [17] 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 [18] 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 [19] 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) function as CC transducers downstream of G protein-coupled receptors (GPCRs) in CC numerous signaling cascades (PubMed:29925951, PubMed:33408414, CC PubMed:39103320). The alpha chain contains the guanine nucleotide CC binding site and alternates between an active, GTP-bound state and an CC inactive, GDP-bound state (PubMed:39103320). Signaling by an activated CC GPCR promotes GDP release and GTP binding (PubMed:39103320). The alpha CC subunit has a low GTPase activity that converts bound GTP to GDP, CC thereby terminating the signal (By similarity). Both GDP release and CC GTP hydrolysis are modulated by numerous regulatory proteins (By CC similarity). Signaling is mediated via effector proteins, such as CC adenylate cyclase (By similarity). Inhibits adenylate cyclase activity, CC leading to decreased intracellular cAMP levels (By similarity). CC {ECO:0000250|UniProtKB:P18872, ECO:0000269|PubMed:29925951, CC ECO:0000269|PubMed:33408414, ECO:0000269|PubMed:39103320}. CC -!- CATALYTIC ACTIVITY: CC Reaction=GTP + H2O = GDP + phosphate + H(+); Xref=Rhea:RHEA:19669, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; CC Evidence={ECO:0000269|PubMed:39103320}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670; CC Evidence={ECO:0000250|UniProtKB:P18872}; CC -!- ACTIVITY REGULATION: The GTPase activity is promoted by GTPAse CC activators, such as RGS14, RGS16 and RGS19 (By similarity). CC {ECO:0000250|UniProtKB:P18872}. CC -!- SUBUNIT: G proteins are composed of 3 units; alpha, beta and gamma CC (PubMed:29925951, PubMed:39103320, PubMed:34685729). The alpha chain CC contains the guanine nucleotide binding site (PubMed:29925951, CC PubMed:39103320). Forms a complex with GNB1 and GNG3 (PubMed:34685729). CC Forms a complex with GNB1 and GNG2; this complex associates with Mu- CC type opioid receptor OPRM1, D(2) dopamine receptor DRD2, neurotensin CC receptor type 1 NTSR1 and beta-2 adrenergic receptor ADRB2 CC (PubMed:39103320). Interacts with RGS14 (By similarity). Interacts with CC RGS16 (By similarity). Interacts with RGS19 (PubMed:34685729). CC Interacts (when palmitoylated) with ADGRG3 (PubMed:33408414). CC {ECO:0000250|UniProtKB:P18872, ECO:0000269|PubMed:29925951, CC ECO:0000269|PubMed:33408414, 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; Q9NPQ8: RIC8A; NbExp=2; IntAct=EBI-715087, EBI-717509; CC P09471; P51812: RPS6KA3; NbExp=3; IntAct=EBI-715087, EBI-1046616; CC P09471; Q96PV0: SYNGAP1; NbExp=4; IntAct=EBI-715087, EBI-2682386; CC P09471; P37173: TGFBR2; NbExp=3; IntAct=EBI-715087, EBI-296151; CC P09471; P55072: VCP; NbExp=5; IntAct=EBI-715087, EBI-355164; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:34685729}; CC Peripheral membrane protein {ECO:0000269|PubMed:33408414}; Cytoplasmic CC side {ECO:0000269|PubMed:33408414}. Note=Associated to the plasma CC membrane via lipid-anchor. {ECO:0000269|PubMed:33408414}. 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 -!- PTM: Palmitoylated at Cys-351, leading to binding to ADGRG3. CC {ECO:0000269|PubMed:33408414}. 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. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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_020988.3. [P09471-1] DR RefSeq; NP_620073.2; NM_138736.3. [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; 8IEC; EM; 3.18 A; C=1-56, C=182-354. DR PDB; 8IED; EM; 3.33 A; C=1-56, C=182-354. DR PDB; 8IY9; EM; 3.37 A; A=6-55, A=182-354. DR PDB; 8IYH; EM; 3.30 A; B=6-53, B=182-354. DR PDB; 8IYW; EM; 3.45 A; B=6-53, B=182-354. DR PDB; 8J6D; EM; 3.10 A; A=4-57, A=182-354. DR PDB; 8JER; EM; 3.45 A; A=6-57, A=183-354. DR PDB; 8JHN; EM; 3.75 A; A=4-57, A=183-354. DR PDB; 8JZP; EM; 3.45 A; B=4-57, B=182-354. DR PDB; 8JZZ; EM; 3.31 A; C=4-57, C=182-354. DR PDB; 8TZQ; EM; 3.20 A; B=1-354. DR PDB; 8U02; EM; 3.28 A; B=1-354. DR PDB; 8XWV; EM; 3.07 A; A=6-53, A=182-354. DR PDB; 8XX3; EM; 3.38 A; A=6-57, A=182-354. DR PDB; 8XX6; EM; 2.99 A; A=4-57, A=182-354. DR PDB; 8XX7; EM; 3.32 A; A/F=4-57, A/F=182-354. DR PDB; 8XXH; EM; 2.80 A; A=4-57, A=182-354. DR PDB; 8XXR; EM; 3.17 A; A=4-57, A=182-354. DR PDB; 8XXX; EM; 3.17 A; A=4-57, A=182-354. DR PDB; 8XXZ; EM; 3.30 A; A=4-57, A=182-354. DR PDB; 8XYK; EM; 3.03 A; A=4-57, A=182-354. DR PDB; 8Y0N; EM; 3.07 A; A=4-57, A=182-354. DR PDB; 8YN7; EM; 2.77 A; A=4-354. DR PDB; 8YN8; EM; 2.77 A; A=4-354. DR PDB; 9BSB; EM; 2.32 A; A=1-354. DR PDB; 9DYD; EM; 2.96 A; A=1-354. DR PDB; 9DYE; EM; 2.90 A; A=1-354. DR PDB; 9F33; EM; 3.05 A; A=1-354. DR PDB; 9F34; EM; 3.09 A; A=1-354. DR PDB; 9K20; EM; 2.65 A; B=4-57, B=182-354. DR PDB; 9KUG; EM; 3.07 A; B=4-57, B=182-354. DR PDB; 9KUT; EM; 3.29 A; A=4-57, A=182-354. DR PDB; 9KV6; EM; 2.88 A; A=4-57, A=182-354. DR PDB; 9KV8; EM; 3.17 A; A=4-57, A=182-354. DR PDB; 9KVP; EM; 2.79 A; A=4-57, A=182-354. DR PDB; 9KWG; EM; 3.15 A; B=4-57, B=182-354. DR PDB; 9KWX; EM; 3.13 A; B=6-53, B=182-354. DR PDB; 9KX6; EM; 3.11 A; B=6-53, B=182-354. DR PDB; 9KXS; EM; 3.31 A; B=4-53, B=182-354. DR PDB; 9KZ2; EM; 3.43 A; A=4-57, A=182-354. DR PDB; 9KZ8; EM; 3.30 A; A=4-57, A=182-354. DR PDB; 9KZK; EM; 3.54 A; A=4-57, A=182-354. DR PDB; 9L0H; EM; 3.57 A; A=4-57, A=182-354. DR PDB; 9PLO; EM; 2.74 A; A=1-354. DR PDB; 9UMJ; EM; 3.38 A; A=4-53, A=182-354. DR PDB; 9UMR; EM; 3.15 A; B=4-57, B=182-354. DR PDB; 9UMX; EM; 3.20 A; B=4-57, B=182-354. DR PDB; 9VJ5; EM; 2.69 A; B=1-354. DR PDB; 9VJE; EM; 2.47 A; B=1-354. DR PDB; 9VMY; EM; 2.86 A; B=1-354. DR PDB; 9VNF; EM; 2.74 A; B=1-354. 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; 8IEC; -. DR PDBsum; 8IED; -. DR PDBsum; 8IY9; -. DR PDBsum; 8IYH; -. DR PDBsum; 8IYW; -. DR PDBsum; 8J6D; -. DR PDBsum; 8JER; -. DR PDBsum; 8JHN; -. DR PDBsum; 8JZP; -. DR PDBsum; 8JZZ; -. DR PDBsum; 8TZQ; -. DR PDBsum; 8U02; -. DR PDBsum; 8XWV; -. DR PDBsum; 8XX3; -. DR PDBsum; 8XX6; -. DR PDBsum; 8XX7; -. DR PDBsum; 8XXH; -. DR PDBsum; 8XXR; -. DR PDBsum; 8XXX; -. DR PDBsum; 8XXZ; -. DR PDBsum; 8XYK; -. DR PDBsum; 8Y0N; -. DR PDBsum; 8YN7; -. DR PDBsum; 8YN8; -. DR PDBsum; 9BSB; -. DR PDBsum; 9DYD; -. DR PDBsum; 9DYE; -. DR PDBsum; 9F33; -. DR PDBsum; 9F34; -. DR PDBsum; 9K20; -. DR PDBsum; 9KUG; -. DR PDBsum; 9KUT; -. DR PDBsum; 9KV6; -. DR PDBsum; 9KV8; -. DR PDBsum; 9KVP; -. DR PDBsum; 9KWG; -. DR PDBsum; 9KWX; -. DR PDBsum; 9KX6; -. DR PDBsum; 9KXS; -. DR PDBsum; 9KZ2; -. DR PDBsum; 9KZ8; -. DR PDBsum; 9KZK; -. DR PDBsum; 9L0H; -. DR PDBsum; 9PLO; -. DR PDBsum; 9UMJ; -. DR PDBsum; 9UMR; -. DR PDBsum; 9UMX; -. DR PDBsum; 9VJ5; -. DR PDBsum; 9VJE; -. DR PDBsum; 9VMY; -. DR PDBsum; 9VNF; -. 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-35378; -. DR EMDB; EMD-35380; -. DR EMDB; EMD-35817; -. DR EMDB; EMD-35822; -. DR EMDB; EMD-35831; -. DR EMDB; EMD-36001; -. DR EMDB; EMD-36193; -. DR EMDB; EMD-36280; -. DR EMDB; EMD-36750; -. DR EMDB; EMD-36755; -. DR EMDB; EMD-38743; -. DR EMDB; EMD-38744; -. DR EMDB; EMD-38747; -. DR EMDB; EMD-38748; -. DR EMDB; EMD-38749; -. DR EMDB; EMD-38759; -. DR EMDB; EMD-38764; -. DR EMDB; EMD-38766; -. DR EMDB; EMD-38776; -. DR EMDB; EMD-38809; -. DR EMDB; EMD-39417; -. DR EMDB; EMD-39418; -. DR EMDB; EMD-41766; -. DR EMDB; EMD-41776; -. DR EMDB; EMD-44866; -. DR EMDB; EMD-47300; -. DR EMDB; EMD-47301; -. DR EMDB; EMD-50168; -. DR EMDB; EMD-50169; -. DR EMDB; EMD-61986; -. DR EMDB; EMD-62578; -. DR EMDB; EMD-62580; -. DR EMDB; EMD-62586; -. DR EMDB; EMD-62588; -. DR EMDB; EMD-62598; -. DR EMDB; EMD-62610; -. DR EMDB; EMD-62619; -. DR EMDB; EMD-62624; -. DR EMDB; EMD-62626; -. DR EMDB; EMD-62651; -. DR EMDB; EMD-62654; -. DR EMDB; EMD-62665; -. DR EMDB; EMD-62712; -. DR EMDB; EMD-64276; -. DR EMDB; EMD-64291; -. DR EMDB; EMD-64325; -. DR EMDB; EMD-65104; -. DR EMDB; EMD-65110; -. DR EMDB; EMD-65196; -. DR EMDB; EMD-65210; -. DR EMDB; EMD-71719; -. DR EMDB; EMD-9911; -. DR SMR; P09471; -. DR BioGRID; 109037; 91. DR ELM; P09471; -. DR FunCoup; P09471; 1538. DR IntAct; P09471; 66. DR MINT; P09471; -. DR NDEx; IQUERY-CP-GNAO1; 24 NDEx IQuery Curated Pathways. 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 jPOST; P09471; -. DR MassIVE; P09471; -. DR PaxDb; 9606-ENSP00000262494; -. DR PeptideAtlas; P09471; -. DR ProteomicsDB; 52224; -. [P09471-1] DR ProteomicsDB; 52225; -. [P09471-2] DR Pumba; P09471; -. DR Antibodypedia; 3649; 263 antibodies from 35 providers. DR DNASU; 2775; -. DR Ensembl; ENST00000262493.12; ENSP00000262493.6; ENSG00000087258.18. [P09471-1] DR Ensembl; ENST00000262494.13; ENSP00000262494.7; ENSG00000087258.18. [P09471-2] DR Ensembl; ENST00000638705.1; ENSP00000491223.1; ENSG00000087258.18. [P09471-1] DR Ensembl; ENST00000640469.2; ENSP00000491875.2; ENSG00000087258.18. [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 ClinPGx; PA28771; -. 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 OpenTargets; ENSG00000087258; -. DR Orphanet; 1934; Early infantile developmental and epileptic encephalopathy. DR Orphanet; 592564; GNAO1-related developmental delay-seizures-movement disorder spectrum. DR VEuPathDB; HostDB:ENSG00000087258; -. DR eggNOG; KOG0082; Eukaryota. DR GeneTree; ENSGT00940000155883; -. DR HOGENOM; CLU_014184_6_0_1; -. DR InParanoid; P09471; -. DR OMA; GKKDYMP; -. DR OrthoDB; 5817230at2759; -. DR PAN-GO; P09471; 9 GO annotations based on evolutionary models. DR PhylomeDB; P09471; -. DR PathwayCommons; P09471; -. DR Reactome; R-HSA-4086398; Ca2+ pathway. DR SignaLink; P09471; -. DR SIGNOR; P09471; -. DR Agora; ENSG00000087258; -. DR BioGRID-ORCS; 2775; 11 hits in 1143 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. 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:0044297; C:cell body; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0030425; C:dendrite; IEA:Ensembl. DR GO; GO:0098982; C:GABA-ergic synapse; IEA:Ensembl. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0005834; C:heterotrimeric G-protein complex; IDA:UniProtKB. DR GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0045211; C:postsynaptic membrane; IEA:Ensembl. DR GO; GO:0042734; C:presynaptic membrane; IEA:Ensembl. DR GO; GO:0051430; F:corticotropin-releasing hormone receptor 1 binding; IBA:GO_Central. DR GO; GO:0003925; F:G protein activity; ISS:UniProt. 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:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IDA:UniProt. DR GO; GO:0007198; P:adenylate cyclase-inhibiting serotonin receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IBA:GO_Central. DR GO; GO:0007212; P:G protein-coupled dopamine receptor signaling pathway; IBA:GO_Central. DR GO; GO:0006936; P:muscle contraction; TAS:ProtInc. DR GO; GO:0046676; P:negative regulation of insulin secretion; IEA:Ensembl. DR GO; GO:0099170; P:postsynaptic modulation of chemical synaptic transmission; IEA:Ensembl. DR CDD; cd00066; G-alpha; 1. DR FunFam; 3.40.50.300:FF:003559; Guanine nucleotide-binding protein G(i) subunit alpha-1; 1. DR FunFam; 3.40.50.300:FF:002307; Guanine nucleotide-binding protein G(k) subunit alpha; 1. DR FunFam; 1.10.400.10:FF:000020; Guanine nucleotide-binding protein G(o) subunit 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:SF361; 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. PE 1: Evidence at protein level; KW 3D-structure; ADP-ribosylation; Alternative splicing; Cell membrane; KW Disease variant; Epilepsy; GTP-binding; Hydrolase; Lipoprotein; Magnesium; KW Membrane; Metal-binding; Myristate; Nucleotide-binding; Palmitate; KW Proteomics identification; 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 43 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P18872" FT BINDING 46 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P18872" FT BINDING 47 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P18872" FT BINDING 47 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P18872" FT BINDING 48 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P18872" FT BINDING 152 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P18872" FT BINDING 176 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P18872" FT BINDING 177 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P18872" FT BINDING 178 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P18872" FT BINDING 179 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P18872" FT BINDING 182 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P18872" FT BINDING 270 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P18872" FT BINDING 273 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P18872" FT BINDING 325 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P18872" 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|UniProtKB:P59215" FT LIPID 351 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000269|PubMed:33408414" 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 MUTAGEN 46 FT /note="K->E: Abolishes guanine nucleotide binding and FT impairs responses of the associated receptors including FT OPRM1, DRD2, NTSR1 and ADRB2." FT /evidence="ECO:0000269|PubMed:39103320" FT MUTAGEN 351 FT /note="C->A: Strong loss of binding to ADGRG3." FT /evidence="ECO:0000269|PubMed:33408414" 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..15 FT /evidence="ECO:0007829|PDB:9K20" FT HELIX 20..30 FT /evidence="ECO:0007829|PDB:9K20" FT STRAND 31..39 FT /evidence="ECO:0007829|PDB:9K20" FT TURN 42..44 FT /evidence="ECO:0007829|PDB:8DZQ" FT HELIX 46..53 FT /evidence="ECO:0007829|PDB:9K20" FT HELIX 64..68 FT /evidence="ECO:0007829|PDB:8U02" FT HELIX 70..91 FT /evidence="ECO:0007829|PDB:8U02" FT HELIX 93..95 FT /evidence="ECO:0007829|PDB:8U02" FT HELIX 99..112 FT /evidence="ECO:0007829|PDB:8U02" FT HELIX 122..132 FT /evidence="ECO:0007829|PDB:8U02" FT HELIX 135..142 FT /evidence="ECO:0007829|PDB:8U02" FT TURN 143..146 FT /evidence="ECO:0007829|PDB:8U02" FT HELIX 151..158 FT /evidence="ECO:0007829|PDB:8U02" FT HELIX 160..165 FT /evidence="ECO:0007829|PDB:8U02" FT TURN 180..182 FT /evidence="ECO:0007829|PDB:8U02" FT STRAND 186..194 FT /evidence="ECO:0007829|PDB:9K20" FT STRAND 196..201 FT /evidence="ECO:0007829|PDB:9K20" FT HELIX 202..204 FT /evidence="ECO:0007829|PDB:8IA2" FT HELIX 209..211 FT /evidence="ECO:0007829|PDB:9K20" FT TURN 212..216 FT /evidence="ECO:0007829|PDB:9K20" FT STRAND 220..229 FT /evidence="ECO:0007829|PDB:9K20" FT STRAND 231..233 FT /evidence="ECO:0007829|PDB:7T94" FT TURN 236..238 FT /evidence="ECO:0007829|PDB:8TZQ" FT HELIX 242..255 FT /evidence="ECO:0007829|PDB:9K20" FT HELIX 258..260 FT /evidence="ECO:0007829|PDB:9K20" FT STRAND 261..263 FT /evidence="ECO:0007829|PDB:8I9L" FT STRAND 265..270 FT /evidence="ECO:0007829|PDB:9K20" FT HELIX 272..279 FT /evidence="ECO:0007829|PDB:9K20" FT HELIX 284..286 FT /evidence="ECO:0007829|PDB:9K20" FT STRAND 287..289 FT /evidence="ECO:0007829|PDB:7EJ8" FT STRAND 294..296 FT /evidence="ECO:0007829|PDB:6WWZ" FT HELIX 297..309 FT /evidence="ECO:0007829|PDB:9K20" FT STRAND 314..316 FT /evidence="ECO:0007829|PDB:8XYK" FT STRAND 320..323 FT /evidence="ECO:0007829|PDB:8E9X" FT STRAND 326..328 FT /evidence="ECO:0007829|PDB:7D77" FT HELIX 331..350 FT /evidence="ECO:0007829|PDB:9K20" 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 //