GNAL_HUMAN
ID GNAL_HUMAN Reviewed; 381 AA.
AC P38405; B7ZA26; Q86XU3;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1994, sequence version 1.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Guanine nucleotide-binding protein G(olf) subunit alpha;
DE AltName: Full=Adenylate cyclase-stimulating G alpha protein, olfactory type;
GN Name=GNAL;
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 [MRNA] (ISOFORM 1).
RC TISSUE=Insulinoma;
RX PubMed=8243272; DOI=10.1210/endo.133.6.8243272;
RA Zigman J.M., Westermark G.T., Lamendola J., Boel E., Steiner D.F.;
RT "Human G(olf) alpha: complementary deoxyribonucleic acid structure and
RT expression in pancreatic islets and other tissues outside the olfactory
RT neuroepithelium and central nervous system.";
RL Endocrinology 133:2508-2514(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Vuoristo J.T., Berrettini W.H., Overhauser J., Prockop D.J., Ferraro T.N.,
RA Ala-Kokko L.;
RT "The gene for the human G protein Golf alpha.";
RL Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [8]
RP INTERACTION WITH GAS2L2.
RX PubMed=23994616; DOI=10.1016/j.bbamcr.2013.08.009;
RA Wu Y.C., Lai H.L., Chang W.C., Lin J.T., Liu Y.J., Chern Y.;
RT "A novel Galphas-binding protein, Gas-2 like 2, facilitates the signaling
RT of the A2A adenosine receptor.";
RL Biochim. Biophys. Acta 1833:3145-3154(2013).
RN [9]
RP VARIANTS DYT25 102-PRO--VAL-104 DEL; MET-137 AND LYS-155, VARIANT PHE-16,
RP AND CHARACTERIZATION OF VARIANTS DYT25 MET-137 AND LYS-155.
RX PubMed=23222958; DOI=10.1038/ng.2496;
RA Fuchs T., Saunders-Pullman R., Masuho I., Luciano M.S., Raymond D.,
RA Factor S., Lang A.E., Liang T.W., Trosch R.M., White S., Ainehsazan E.,
RA Herve D., Sharma N., Ehrlich M.E., Martemyanov K.A., Bressman S.B.,
RA Ozelius L.J.;
RT "Mutations in GNAL cause primary torsion dystonia.";
RL Nat. Genet. 45:88-92(2013).
CC -!- FUNCTION: Guanine nucleotide-binding proteins (G proteins) are involved
CC as modulators or transducers in various transmembrane signaling
CC systems. G(olf) alpha mediates signal transduction within the olfactory
CC neuroepithelium and the basal ganglia. May be involved in some aspect
CC of visual transduction, and in mediating the effect of one or more
CC hormones/neurotransmitters.
CC -!- SUBUNIT: G proteins are composed of 3 units; alpha, beta and gamma. The
CC alpha chain contains the guanine nucleotide binding site. Interacts
CC with GAS2L2 (PubMed:23994616). {ECO:0000269|PubMed:23994616}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P38405-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P38405-2; Sequence=VSP_043050;
CC Name=3;
CC IsoId=P38405-3; Sequence=VSP_045130;
CC -!- TISSUE SPECIFICITY: Detected in olfactory neuroepithelium, brain,
CC testis, and to a lower extent in retina, lung alveoli, spleen. Trace
CC amounts where seen in kidney, adrenal gland and liver. Found to be
CC expressed in all the insulinomas examined.
CC -!- DISEASE: Dystonia 25 (DYT25) [MIM:615073]: A form of dystonia, a
CC disorder defined by the presence of sustained involuntary muscle
CC contraction, often leading to abnormal postures. DYT25 is an autosomal
CC dominant neurologic disorder characterized by adult onset of focal
CC dystonia, usually involving the neck. The dystonia most often
CC progresses to involve other regions, particularly the face and
CC laryngeal muscles, and less commonly the trunk and limbs.
CC {ECO:0000269|PubMed:23222958}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the G-alpha family. G(s) subfamily.
CC {ECO:0000305}.
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DR EMBL; L10665; AAC37535.1; -; mRNA.
DR EMBL; U55184; AAD00085.1; -; Genomic_DNA.
DR EMBL; U55180; AAD00085.1; JOINED; Genomic_DNA.
DR EMBL; U55181; AAD00085.1; JOINED; Genomic_DNA.
DR EMBL; U55182; AAD00085.1; JOINED; Genomic_DNA.
DR EMBL; U55183; AAD00085.1; JOINED; Genomic_DNA.
DR EMBL; AF493893; AAM12607.1; -; mRNA.
DR EMBL; AK316141; BAH14512.1; -; mRNA.
DR EMBL; AP001120; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001269; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP005137; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471113; EAX01573.1; -; Genomic_DNA.
DR EMBL; BC050021; AAH50021.1; -; mRNA.
DR CCDS; CCDS11851.1; -. [P38405-2]
DR CCDS; CCDS11852.1; -. [P38405-1]
DR CCDS; CCDS58614.1; -. [P38405-3]
DR PIR; I53271; I53271.
DR RefSeq; NP_001135811.1; NM_001142339.2. [P38405-1]
DR RefSeq; NP_001248372.1; NM_001261443.1. [P38405-1]
DR RefSeq; NP_001248373.1; NM_001261444.1. [P38405-3]
DR RefSeq; NP_892023.1; NM_182978.3. [P38405-2]
DR AlphaFoldDB; P38405; -.
DR SMR; P38405; -.
DR BioGRID; 109036; 15.
DR IntAct; P38405; 15.
DR STRING; 9606.ENSP00000334051; -.
DR iPTMnet; P38405; -.
DR PhosphoSitePlus; P38405; -.
DR SwissPalm; P38405; -.
DR BioMuta; GNAL; -.
DR DMDM; 585178; -.
DR EPD; P38405; -.
DR jPOST; P38405; -.
DR MassIVE; P38405; -.
DR MaxQB; P38405; -.
DR PaxDb; P38405; -.
DR PeptideAtlas; P38405; -.
DR PRIDE; P38405; -.
DR ProteomicsDB; 55293; -. [P38405-1]
DR ProteomicsDB; 55294; -. [P38405-2]
DR ProteomicsDB; 7052; -.
DR Antibodypedia; 4227; 182 antibodies from 27 providers.
DR DNASU; 2774; -.
DR Ensembl; ENST00000269162.9; ENSP00000269162.4; ENSG00000141404.17. [P38405-1]
DR Ensembl; ENST00000334049.11; ENSP00000334051.5; ENSG00000141404.17. [P38405-2]
DR Ensembl; ENST00000423027.8; ENSP00000408489.2; ENSG00000141404.17. [P38405-1]
DR Ensembl; ENST00000535121.5; ENSP00000439023.1; ENSG00000141404.17. [P38405-1]
DR Ensembl; ENST00000602628.1; ENSP00000473600.1; ENSG00000141404.17. [P38405-3]
DR GeneID; 2774; -.
DR KEGG; hsa:2774; -.
DR MANE-Select; ENST00000334049.11; ENSP00000334051.5; NM_182978.4; NP_892023.1. [P38405-2]
DR UCSC; uc002kqc.4; human. [P38405-1]
DR CTD; 2774; -.
DR DisGeNET; 2774; -.
DR GeneCards; GNAL; -.
DR GeneReviews; GNAL; -.
DR HGNC; HGNC:4388; GNAL.
DR HPA; ENSG00000141404; Tissue enriched (brain).
DR MalaCards; GNAL; -.
DR MIM; 139312; gene.
DR MIM; 615073; phenotype.
DR neXtProt; NX_P38405; -.
DR OpenTargets; ENSG00000141404; -.
DR Orphanet; 329466; Autosomal dominant focal dystonia, DYT25 type.
DR PharmGKB; PA28770; -.
DR VEuPathDB; HostDB:ENSG00000141404; -.
DR eggNOG; KOG0099; Eukaryota.
DR GeneTree; ENSGT00940000155271; -.
DR HOGENOM; CLU_014184_3_0_1; -.
DR InParanoid; P38405; -.
DR OMA; KEFFEHA; -.
DR OrthoDB; 754573at2759; -.
DR PhylomeDB; P38405; -.
DR TreeFam; TF300673; -.
DR PathwayCommons; P38405; -.
DR Reactome; R-HSA-170660; Adenylate cyclase activating pathway.
DR Reactome; R-HSA-170670; Adenylate cyclase inhibitory pathway.
DR Reactome; R-HSA-381753; Olfactory Signaling Pathway.
DR SignaLink; P38405; -.
DR SIGNOR; P38405; -.
DR BioGRID-ORCS; 2774; 10 hits in 1072 CRISPR screens.
DR ChiTaRS; GNAL; human.
DR GeneWiki; GNAL; -.
DR GenomeRNAi; 2774; -.
DR Pharos; P38405; Tbio.
DR PRO; PR:P38405; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; P38405; protein.
DR Bgee; ENSG00000141404; Expressed in lateral globus pallidus and 193 other tissues.
DR ExpressionAtlas; P38405; baseline and differential.
DR Genevisible; P38405; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005834; C:heterotrimeric G-protein complex; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0001664; F:G protein-coupled 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:0007191; P:adenylate cyclase-activating dopamine receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007606; P:sensory perception of chemical stimulus; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR CDD; cd00066; G-alpha; 1.
DR Gene3D; 1.10.400.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR000367; Gprotein_alpha_S.
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; PR00443; GPROTEINAS.
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 ADP-ribosylation; Alternative splicing; Disease variant; Dystonia;
KW GTP-binding; Lipoprotein; Magnesium; Metal-binding; Nucleotide-binding;
KW Palmitate; Phosphoprotein; Reference proteome; Transducer.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..381
FT /note="Guanine nucleotide-binding protein G(olf) subunit
FT alpha"
FT /id="PRO_0000203732"
FT DOMAIN 41..381
FT /note="G-alpha"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 44..57
FT /note="G1 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 183..191
FT /note="G2 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 206..215
FT /note="G3 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 275..282
FT /note="G4 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 351..356
FT /note="G5 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT BINDING 49..56
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 56
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 185..191
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 191
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 210..214
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 279..282
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 353
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT MOD_RES 178
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8CGK7"
FT MOD_RES 188
FT /note="ADP-ribosylarginine; by cholera toxin"
FT /evidence="ECO:0000250"
FT LIPID 2
FT /note="N-palmitoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:P04896"
FT LIPID 3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..207
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045130"
FT VAR_SEQ 1..41
FT /note="MGCLGGNSKTTEDQGVDEKERREANKKIEKQLQKERLAYKA -> MGLCYSL
FT RPLLFGGPGDDPCAASEPPVEDAQPAPAPALAPVRAAARDTARTLLPRGGEGSPACARP
FT KADKPKEKRQRTEQLSAEEREAAKEREAVKEARKVSRGIDRMLRDQKRDLQQ (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_043050"
FT VARIANT 16
FT /note="V -> F (in dbSNP:rs1039372506)"
FT /evidence="ECO:0000269|PubMed:23222958"
FT /id="VAR_069329"
FT VARIANT 102..104
FT /note="Missing (in DYT25)"
FT /evidence="ECO:0000269|PubMed:23222958"
FT /id="VAR_069330"
FT VARIANT 137
FT /note="V -> M (in DYT25; loss of function mutation;
FT dbSNP:rs398122923)"
FT /evidence="ECO:0000269|PubMed:23222958"
FT /id="VAR_069331"
FT VARIANT 155
FT /note="E -> K (in DYT25; loss of function mutation;
FT dbSNP:rs398122925)"
FT /evidence="ECO:0000269|PubMed:23222958"
FT /id="VAR_069332"
SQ SEQUENCE 381 AA; 44308 MW; 9A73D2982FF9C9A3 CRC64;
MGCLGGNSKT TEDQGVDEKE RREANKKIEK QLQKERLAYK ATHRLLLLGA GESGKSTIVK
QMRILHVNGF NPEEKKQKIL DIRKNVKDAI VTIVSAMSTI IPPVPLANPE NQFRSDYIKS
IAPITDFEYS QEFFDHVKKL WDDEGVKACF ERSNEYQLID CAQYFLERID SVSLVDYTPT
DQDLLRCRVL TSGIFETRFQ VDKVNFHMFD VGGQRDERRK WIQCFNDVTA IIYVAACSSY
NMVIREDNNT NRLRESLDLF ESIWNNRWLR TISIILFLNK QDMLAEKVLA GKSKIEDYFP
EYANYTVPED ATPDAGEDPK VTRAKFFIRD LFLRISTATG DGKHYCYPHF TCAVDTENIR
RVFNDCRDII QRMHLKQYEL L
