GNAO_HUMAN
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 03-AUG-2022, entry version 219.
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).
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: Interacts with RGS14 (By similarity). G proteins are composed
CC of 3 units; alpha, beta and gamma. The alpha chain contains the guanine
CC nucleotide binding site. {ECO:0000250|UniProtKB:P18872}.
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:0000250|UniProtKB:P18872}.
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;
CC 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}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC 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; 7W2Z; EM; 2.80 A; A=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; 7W2Z; -.
DR AlphaFoldDB; P09471; -.
DR SMR; P09471; -.
DR BioGRID; 109037; 75.
DR ELM; P09471; -.
DR IntAct; P09471; 34.
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; P09471; -.
DR PeptideAtlas; P09471; -.
DR PRIDE; P09471; -.
DR ProteomicsDB; 52224; -. [P09471-1]
DR ProteomicsDB; 52225; -. [P09471-2]
DR Antibodypedia; 3649; 269 antibodies from 34 providers.
DR DNASU; 2775; -.
DR Ensembl; ENST00000262493.12; ENSP00000262493.6; ENSG00000087258.16. [P09471-1]
DR Ensembl; ENST00000262494.12; 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 CTD; 2775; -.
DR DisGeNET; 2775; -.
DR GeneCards; 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; QVIWADA; -.
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; 10 hits in 1065 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 185 other tissues.
DR ExpressionAtlas; P09471; baseline and differential.
DR Genevisible; P09471; HS.
DR GO; GO:0005834; C:heterotrimeric G-protein complex; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0051430; F:corticotropin-releasing hormone receptor 1 binding; IBA:GO_Central.
DR GO; GO:0001664; F:G protein-coupled receptor 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; -; 1.
DR Gene3D; 3.40.50.300; -; 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; PTHR10218; 1.
DR Pfam; PF00503; G-alpha; 1.
DR PRINTS; PR00318; GPROTEINA.
DR PRINTS; PR00441; GPROTEINAI.
DR SMART; SM00275; G_alpha; 1.
DR SUPFAM; SSF47895; SSF47895; 1.
DR SUPFAM; SSF52540; SSF52540; 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; 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 47
FT /note="S -> G (in NEDIM)"
FT /evidence="ECO:0000269|PubMed:28357411"
FT /id="VAR_079278"
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 calcium-
FT 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..30
FT /evidence="ECO:0007829|PDB:6K41"
FT STRAND 33..38
FT /evidence="ECO:0007829|PDB:6K41"
FT STRAND 42..45
FT /evidence="ECO:0007829|PDB:6K41"
FT HELIX 46..52
FT /evidence="ECO:0007829|PDB:6K41"
FT STRAND 186..191
FT /evidence="ECO:0007829|PDB:7W2Z"
FT STRAND 196..201
FT /evidence="ECO:0007829|PDB:7W2Z"
FT HELIX 209..212
FT /evidence="ECO:0007829|PDB:7W2Z"
FT HELIX 213..216
FT /evidence="ECO:0007829|PDB:7W2Z"
FT STRAND 220..227
FT /evidence="ECO:0007829|PDB:7W2Z"
FT HELIX 228..231
FT /evidence="ECO:0007829|PDB:6K41"
FT HELIX 244..255
FT /evidence="ECO:0007829|PDB:7W2Z"
FT STRAND 258..262
FT /evidence="ECO:0007829|PDB:7D77"
FT STRAND 264..270
FT /evidence="ECO:0007829|PDB:7W2Z"
FT HELIX 272..281
FT /evidence="ECO:0007829|PDB:7W2Z"
FT TURN 284..287
FT /evidence="ECO:0007829|PDB:7W2Z"
FT STRAND 294..296
FT /evidence="ECO:0007829|PDB:6WWZ"
FT HELIX 297..309
FT /evidence="ECO:0007829|PDB:7W2Z"
FT STRAND 314..316
FT /evidence="ECO:0007829|PDB:7D76"
FT STRAND 319..322
FT /evidence="ECO:0007829|PDB:7W2Z"
FT STRAND 326..328
FT /evidence="ECO:0007829|PDB:7D77"
FT HELIX 331..350
FT /evidence="ECO:0007829|PDB:7W2Z"
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
