GNAT2_HUMAN
ID GNAT2_HUMAN Reviewed; 354 AA.
AC P19087;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 218.
DE RecName: Full=Guanine nucleotide-binding protein G(t) subunit alpha-2;
DE AltName: Full=Transducin alpha-2 chain;
GN Name=GNAT2; Synonyms=GNATC;
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].
RC TISSUE=Retina;
RX PubMed=2534964; DOI=10.1016/0896-6273(89)90261-4;
RA Lerea C.L., Bunt-Milam A.H., Hurley J.B.;
RT "Alpha transducin is present in blue-, green-, and red-sensitive cone
RT photoreceptors in the human retina.";
RL Neuron 3:367-376(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=1936270; DOI=10.1016/0014-5793(91)81294-i;
RA Kubo M., Hirano T., Kakinuma M.;
RT "Molecular cloning and sequence analysis of cDNA and genomic DNA for the
RT human cone transducin alpha subunit.";
RL FEBS Lett. 291:245-248(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8406495; DOI=10.1006/geno.1993.1345;
RA Morris A.T., Fong S.;
RT "Characterization of the gene encoding human cone transducin alpha-subunit
RT (GNAT2).";
RL Genomics 17:442-448(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 [6]
RP INVOLVEMENT IN ACHM4.
RX PubMed=12077706; DOI=10.1086/341835;
RA Kohl S., Baumann B., Rosenberg T., Kellner U., Lorenz B., Vadala M.,
RA Jacobson S.G., Wissinger B.;
RT "Mutations in the cone photoreceptor G-protein alpha-subunit gene GNAT2 in
RT patients with achromatopsia.";
RL Am. J. Hum. Genet. 71:422-425(2002).
RN [7]
RP VARIANTS ILE-107 AND MET-124.
RX PubMed=15712225; DOI=10.1002/humu.20142;
RA Nishiguchi K.M., Sandberg M.A., Gorji N., Berson E.L., Dryja T.P.;
RT "Cone cGMP-gated channel mutations and clinical findings in patients with
RT achromatopsia, macular degeneration, and other hereditary cone diseases.";
RL Hum. Mutat. 25:248-258(2005).
CC -!- FUNCTION: Guanine nucleotide-binding proteins (G proteins) are involved
CC as modulators or transducers in various transmembrane signaling
CC systems. Transducin is an amplifier and one of the transducers of a
CC visual impulse that performs the coupling between rhodopsin and cGMP-
CC phosphodiesterase.
CC -!- SUBUNIT: G proteins are composed of 3 units; alpha, beta and gamma. The
CC alpha chain contains the guanine nucleotide binding site.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium, photoreceptor outer
CC segment {ECO:0000250|UniProtKB:P50149}. Photoreceptor inner segment
CC {ECO:0000250|UniProtKB:P50149}. Note=Localizes mainly in the outer
CC segment in the dark-adapted state, whereas is translocated to the inner
CC part of the photoreceptors in the light-adapted state. During dark-
CC adapted conditions, in the presence of UNC119 mislocalizes from the
CC outer segment to the inner part of rod photoreceptors which leads to
CC decreased photoreceptor damage caused by light.
CC {ECO:0000250|UniProtKB:P50149}.
CC -!- TISSUE SPECIFICITY: Retinal rod outer segment.
CC -!- DISEASE: Achromatopsia 4 (ACHM4) [MIM:613856]: An ocular stationary
CC disorder due to the absence of functioning cone photoreceptors in the
CC retina. It is characterized by total colorblindness, low visual acuity,
CC photophobia and nystagmus. {ECO:0000269|PubMed:12077706}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the G-alpha family. G(i/o/t/z) subfamily.
CC {ECO:0000305}.
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DR EMBL; D10384; BAA01211.1; -; Genomic_DNA.
DR EMBL; Z18859; CAA79310.1; -; Genomic_DNA.
DR EMBL; AF493909; AAM12623.1; -; mRNA.
DR EMBL; BC000233; AAH00233.1; -; mRNA.
DR CCDS; CCDS803.1; -.
DR PIR; A47219; RGHUT2.
DR RefSeq; NP_005263.1; NM_005272.3.
DR RefSeq; XP_011539566.1; XM_011541264.2.
DR PDB; 6N84; X-ray; 1.75 A; A=331-354.
DR PDB; 6N85; X-ray; 2.50 A; M=331-354.
DR PDBsum; 6N84; -.
DR PDBsum; 6N85; -.
DR AlphaFoldDB; P19087; -.
DR SMR; P19087; -.
DR BioGRID; 109042; 19.
DR IntAct; P19087; 9.
DR STRING; 9606.ENSP00000251337; -.
DR iPTMnet; P19087; -.
DR PhosphoSitePlus; P19087; -.
DR SwissPalm; P19087; -.
DR BioMuta; GNAT2; -.
DR DMDM; 232151; -.
DR jPOST; P19087; -.
DR MassIVE; P19087; -.
DR PaxDb; P19087; -.
DR PeptideAtlas; P19087; -.
DR PRIDE; P19087; -.
DR ProteomicsDB; 53631; -.
DR Antibodypedia; 33764; 178 antibodies from 25 providers.
DR DNASU; 2780; -.
DR Ensembl; ENST00000351050.8; ENSP00000251337.3; ENSG00000134183.13.
DR Ensembl; ENST00000679935.1; ENSP00000505083.1; ENSG00000134183.13.
DR GeneID; 2780; -.
DR KEGG; hsa:2780; -.
DR MANE-Select; ENST00000679935.1; ENSP00000505083.1; NM_001377295.2; NP_001364224.1.
DR CTD; 2780; -.
DR DisGeNET; 2780; -.
DR GeneCards; GNAT2; -.
DR GeneReviews; GNAT2; -.
DR HGNC; HGNC:4394; GNAT2.
DR HPA; ENSG00000134183; Tissue enriched (retina).
DR MalaCards; GNAT2; -.
DR MIM; 139340; gene.
DR MIM; 613856; phenotype.
DR neXtProt; NX_P19087; -.
DR OpenTargets; ENSG00000134183; -.
DR Orphanet; 49382; Achromatopsia.
DR Orphanet; 1871; Progressive cone dystrophy.
DR PharmGKB; PA28774; -.
DR VEuPathDB; HostDB:ENSG00000134183; -.
DR eggNOG; KOG0082; Eukaryota.
DR GeneTree; ENSGT00940000158399; -.
DR HOGENOM; CLU_014184_6_0_1; -.
DR InParanoid; P19087; -.
DR OMA; ICKPDYM; -.
DR OrthoDB; 754573at2759; -.
DR PhylomeDB; P19087; -.
DR TreeFam; TF300673; -.
DR PathwayCommons; P19087; -.
DR Reactome; R-HSA-4086398; Ca2+ pathway.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR SignaLink; P19087; -.
DR SIGNOR; P19087; -.
DR BioGRID-ORCS; 2780; 11 hits in 1066 CRISPR screens.
DR ChiTaRS; GNAT2; human.
DR GeneWiki; GNAT2; -.
DR GenomeRNAi; 2780; -.
DR Pharos; P19087; Tbio.
DR PRO; PR:P19087; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P19087; protein.
DR Bgee; ENSG00000134183; Expressed in oocyte and 101 other tissues.
DR ExpressionAtlas; P19087; baseline and differential.
DR Genevisible; P19087; HS.
DR GO; GO:0005834; C:heterotrimeric G-protein complex; IBA:GO_Central.
DR GO; GO:0001917; C:photoreceptor inner segment; IDA:UniProtKB.
DR GO; GO:0001750; C:photoreceptor outer segment; IDA:UniProtKB.
DR GO; GO:0042622; C:photoreceptor outer segment membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0008020; F:G protein-coupled photoreceptor activity; NAS:UniProtKB.
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; NAS:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0001580; P:detection of chemical stimulus involved in sensory perception of bitter taste; IBA:GO_Central.
DR GO; GO:0050908; P:detection of light stimulus involved in visual perception; IMP:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; NAS:UniProtKB.
DR GO; GO:0007602; P:phototransduction; NAS:UniProtKB.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IEA:Ensembl.
DR GO; GO:0009642; P:response to light intensity; IEA:Ensembl.
DR GO; GO:0046549; P:retinal cone cell development; IEA:Ensembl.
DR GO; GO:0007601; P:visual perception; NAS:UniProtKB.
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; Cell projection; GTP-binding; Lipoprotein;
KW Magnesium; Metal-binding; Myristate; Nucleotide-binding;
KW Reference proteome; Sensory transduction; Transducer; Vision.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..354
FT /note="Guanine nucleotide-binding protein G(t) subunit
FT alpha-2"
FT /id="PRO_0000203740"
FT DOMAIN 32..354
FT /note="G-alpha"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 35..48
FT /note="G1 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 173..181
FT /note="G2 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 196..205
FT /note="G3 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 265..272
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 COMPBIAS 8..27
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 175..181
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 181
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 200..204
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 269..272
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 178
FT /note="ADP-ribosylarginine; by cholera toxin"
FT /evidence="ECO:0000250"
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:0000250"
FT VARIANT 107
FT /note="L -> I (in dbSNP:rs3738766)"
FT /evidence="ECO:0000269|PubMed:15712225"
FT /id="VAR_047623"
FT VARIANT 124
FT /note="V -> M (in dbSNP:rs41280330)"
FT /evidence="ECO:0000269|PubMed:15712225"
FT /id="VAR_047624"
FT VARIANT 183
FT /note="G -> D (in dbSNP:rs1799940)"
FT /id="VAR_014783"
FT CONFLICT 106..107
FT /note="QL -> HV (in Ref. 1)"
FT /evidence="ECO:0000305"
FT HELIX 338..341
FT /evidence="ECO:0007829|PDB:6N84"
FT HELIX 348..350
FT /evidence="ECO:0007829|PDB:6N84"
SQ SEQUENCE 354 AA; 40176 MW; BFF8D50C024F18DA CRC64;
MGSGASAEDK ELAKRSKELE KKLQEDADKE AKTVKLLLLG AGESGKSTIV KQMKIIHQDG
YSPEECLEFK AIIYGNVLQS ILAIIRAMTT LGIDYAEPSC ADDGRQLNNL ADSIEEGTMP
PELVEVIRRL WKDGGVQACF ERAAEYQLND SASYYLNQLE RITDPEYLPS EQDVLRSRVK
TTGIIETKFS VKDLNFRMFD VGGQRSERKK WIHCFEGVTC IIFCAALSAY DMVLVEDDEV
NRMHESLHLF NSICNHKFFA ATSIVLFLNK KDLFEEKIKK VHLSICFPEY DGNNSYDDAG
NYIKSQFLDL NMRKDVKEIY SHMTCATDTQ NVKFVFDAVT DIIIKENLKD CGLF
