GNAI3_MOUSE
ID GNAI3_MOUSE Reviewed; 354 AA.
AC Q9DC51; A2AE36; Q3TGV1; Q61019;
DT 17-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Guanine nucleotide-binding protein G(i) subunit alpha-3;
DE AltName: Full=G(i) alpha-3;
GN Name=Gnai3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Heart, Kidney, and Lung;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N;
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 [4]
RP PROTEIN SEQUENCE OF 36-46; 55-67; 181-192; 198-205 AND 249-257, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 248-322.
RC STRAIN=CF-1 / Harlan;
RX PubMed=8858601;
RX DOI=10.1002/(sici)1098-2795(199607)44:3<315::aid-mrd5>3.0.co;2-p;
RA Williams C.J., Schultz R.M., Kopf G.S.;
RT "G protein gene expression during mouse oocyte growth and maturation, and
RT preimplantation embryo development.";
RL Mol. Reprod. Dev. 44:315-323(1996).
RN [6]
RP INTERACTION WITH GPSM1.
RX PubMed=16009138; DOI=10.1016/j.cell.2005.05.009;
RA Sanada K., Tsai L.-H.;
RT "G protein betagamma subunits and AGS3 control spindle orientation and
RT asymmetric cell fate of cerebral cortical progenitors.";
RL Cell 122:119-131(2005).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Heterotrimeric guanine nucleotide-binding proteins (G
CC proteins) function as transducers downstream of G protein-coupled
CC receptors (GPCRs) in numerous signaling cascades. The alpha chain
CC contains the guanine nucleotide binding site and alternates between an
CC active, GTP-bound state and an inactive, GDP-bound state. Signaling by
CC an activated GPCR promotes GDP release and GTP binding. The alpha
CC subunit has a low GTPase activity that converts bound GTP to GDP,
CC thereby terminating the signal. Both GDP release and GTP hydrolysis are
CC modulated by numerous regulatory proteins. Signaling is mediated via
CC effector proteins, such as adenylate cyclase. Inhibits adenylate
CC cyclase activity, leading to decreased intracellular cAMP levels.
CC Stimulates the activity of receptor-regulated K(+) channels. The active
CC GTP-bound form prevents the association of RGS14 with centrosomes and
CC is required for the translocation of RGS14 from the cytoplasm to the
CC plasma membrane. May play a role in cell division.
CC {ECO:0000250|UniProtKB:P08754}.
CC -!- SUBUNIT: Heterotrimeric G proteins are composed of 3 units; alpha, beta
CC and gamma. The alpha subunit contains the guanine nucleotide binding
CC site. GTP binding causes dissociation of the heterotrimer, liberating
CC the individual subunits so that they can interact with downstream
CC effector proteins (By similarity). Forms a complex with CCDC88A/GIV and
CC EGFR which leads to enhanced EGFR signaling and triggering of cell
CC migration; ligand stimulation is required for recruitment of GNAI3 to
CC the complex (By similarity). Interacts (inactive GDP-bound form) with
CC CCDC88A/GIV (via GBA motif); the interaction leads to activation of
CC GNAI3 (By similarity). Interacts (inactive GDP-bound form) with
CC CCDC88C/DAPLE (via GBA motif); the interaction leads to activation of
CC GNAI3 (By similarity). Interacts (inactive GDP-bound form) with NUCB1
CC (via GBA motif) and NUCB2 (via GBA motif); the interaction leads to
CC activation of GNAI3 (By similarity). Interacts (inactive GDP-bound
CC form) with PLCD4 (via GBA motif); the interaction leads to activation
CC of GNAI3 (By similarity). Interacts with INSR; the interaction is
CC probably mediated by CCDC88A/GIV (By similarity). Interacts with GPSM1
CC (PubMed:16009138). Interacts (GDP-bound form) with GPSM2 (via GoLoco
CC domains). Does not interact with RGS2. Interacts with RGS8 and RGS10;
CC this strongly enhances the intrinsic GTPase activity. Interacts with
CC RGS16; this strongly enhances the intrinsic GTPase activity (By
CC similarity). Interacts with RGS12 (By similarity). Interacts (via
CC active GTP- or inactive GDP-bound form) with RGS14 (By similarity).
CC {ECO:0000250|UniProtKB:P08753, ECO:0000250|UniProtKB:P08754,
CC ECO:0000269|PubMed:16009138}.
CC -!- INTERACTION:
CC Q9DC51; P09405: Ncl; NbExp=4; IntAct=EBI-641852, EBI-641864;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P08754}. Cell
CC membrane {ECO:0000250|UniProtKB:P08754}; Lipid-anchor {ECO:0000305}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000250|UniProtKB:P08754}. Note=Localizes in the centrosomes of
CC interphase and mitotic cells. Detected at the cleavage furrow and/or
CC the midbody. {ECO:0000250|UniProtKB:P08754}.
CC -!- SIMILARITY: Belongs to the G-alpha family. G(i/o/t/z) subfamily.
CC {ECO:0000305}.
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DR EMBL; AK004566; BAB23377.1; -; mRNA.
DR EMBL; AK077490; BAC36828.1; -; mRNA.
DR EMBL; AK133749; BAE21821.1; -; mRNA.
DR EMBL; AK168578; BAE40447.1; -; mRNA.
DR EMBL; AK169067; BAE40854.1; -; mRNA.
DR EMBL; AK169285; BAE41043.1; -; mRNA.
DR EMBL; AL671854; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC041107; AAH41107.1; -; mRNA.
DR EMBL; U38502; AAB01733.1; -; mRNA.
DR CCDS; CCDS17751.1; -.
DR RefSeq; NP_034436.1; NM_010306.3.
DR PDB; 3AB3; X-ray; 2.40 A; A/C=1-28.
DR PDBsum; 3AB3; -.
DR AlphaFoldDB; Q9DC51; -.
DR BMRB; Q9DC51; -.
DR SMR; Q9DC51; -.
DR BioGRID; 199968; 39.
DR DIP; DIP-49479N; -.
DR IntAct; Q9DC51; 6.
DR MINT; Q9DC51; -.
DR STRING; 10090.ENSMUSP00000000001; -.
DR iPTMnet; Q9DC51; -.
DR PhosphoSitePlus; Q9DC51; -.
DR SwissPalm; Q9DC51; -.
DR EPD; Q9DC51; -.
DR jPOST; Q9DC51; -.
DR MaxQB; Q9DC51; -.
DR PaxDb; Q9DC51; -.
DR PeptideAtlas; Q9DC51; -.
DR PRIDE; Q9DC51; -.
DR ProteomicsDB; 271412; -.
DR Antibodypedia; 20068; 236 antibodies from 32 providers.
DR DNASU; 14679; -.
DR Ensembl; ENSMUST00000000001; ENSMUSP00000000001; ENSMUSG00000000001.
DR GeneID; 14679; -.
DR KEGG; mmu:14679; -.
DR UCSC; uc008qyd.2; mouse.
DR CTD; 2773; -.
DR MGI; MGI:95773; Gnai3.
DR VEuPathDB; HostDB:ENSMUSG00000000001; -.
DR eggNOG; KOG0082; Eukaryota.
DR GeneTree; ENSGT00940000153567; -.
DR HOGENOM; CLU_014184_6_0_1; -.
DR InParanoid; Q9DC51; -.
DR OMA; MRIIHDV; -.
DR OrthoDB; 754573at2759; -.
DR PhylomeDB; Q9DC51; -.
DR TreeFam; TF300673; -.
DR Reactome; R-MMU-170670; Adenylate cyclase inhibitory pathway.
DR Reactome; R-MMU-392170; ADP signalling through P2Y purinoceptor 12.
DR Reactome; R-MMU-418594; G alpha (i) signalling events.
DR Reactome; R-MMU-9009391; Extra-nuclear estrogen signaling.
DR BioGRID-ORCS; 14679; 5 hits in 75 CRISPR screens.
DR ChiTaRS; Gnai3; mouse.
DR PRO; PR:Q9DC51; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q9DC51; protein.
DR Bgee; ENSMUSG00000000001; Expressed in placenta labyrinth and 260 other tissues.
DR Genevisible; Q9DC51; MM.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0000139; C:Golgi membrane; ISO:MGI.
DR GO; GO:0005834; C:heterotrimeric G-protein complex; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0030496; C:midbody; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0042588; C:zymogen granule; ISO:MGI.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IBA:GO_Central.
DR GO; GO:0031821; F:G protein-coupled serotonin receptor binding; ISO:MGI.
DR GO; GO:0031683; F:G-protein beta/gamma-subunit complex binding; IBA:GO_Central.
DR GO; GO:0019003; F:GDP binding; ISS:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0032794; F:GTPase activating protein binding; ISO:MGI.
DR GO; GO:0003924; F:GTPase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; ISS:UniProtKB.
DR GO; GO:0007212; P:dopamine receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:MGI.
DR GO; GO:0046039; P:GTP metabolic process; ISS:UniProtKB.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; ISO:MGI.
DR GO; GO:0016239; P:positive regulation of macroautophagy; ISO:MGI.
DR GO; GO:0033864; P:positive regulation of NAD(P)H oxidase activity; ISO:MGI.
DR GO; GO:0032930; P:positive regulation of superoxide anion generation; ISO:MGI.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0006906; P:vesicle fusion; ISO:MGI.
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; Cell cycle; Cell division; Cell membrane; Cytoplasm;
KW Cytoskeleton; Direct protein sequencing; GTP-binding; Lipoprotein;
KW Magnesium; Membrane; Metal-binding; Myristate; Nucleotide-binding;
KW Palmitate; Reference proteome; Transducer.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P08754"
FT CHAIN 2..354
FT /note="Guanine nucleotide-binding protein G(i) subunit
FT alpha-3"
FT /id="PRO_0000203693"
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 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 BINDING 43..48
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P08754"
FT BINDING 47
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P08754"
FT BINDING 150..151
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P08754"
FT BINDING 175..181
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P08754"
FT BINDING 181
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P08754"
FT BINDING 200..204
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P08754"
FT BINDING 269..272
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P08754"
FT BINDING 326
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P08754"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:P08754"
FT LIPID 3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
SQ SEQUENCE 354 AA; 40538 MW; A03C83CE5488C777 CRC64;
MGCTLSAEDK AAVERSKMID RNLREDGEKA AKEVKLLLLG AGESGKSTIV KQMKIIHEDG
YSEDECKQYK VVVYSNTIQS IIAIIRAMGR LKIDFGESAR ADDARQLFVL AGSAEEGVMT
SELAGVIKRL WRDGGVQACF SRSREYQLND SASYYLNDLD RISQTNYIPT QQDVLRTRVK
TTGIVETHFT FKELYFKMFD VGGQRSERKK WIHCFEGVTA IIFCVALSDY DLVLAEDEEM
NRMHESMKLF DSICNNKWFT DTSIILFLNK KDLFEEKIKR SPLTICYPEY TGSNTYEEAA
AYIQCQFEDL NRRKDTKEVY THFTCATDTK NVQFVFDAVT DVIIKNNLKE CGLY
