GNAI2_RAT
ID GNAI2_RAT Reviewed; 355 AA.
AC P04897;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Guanine nucleotide-binding protein G(i) subunit alpha-2;
DE AltName: Full=Adenylate cyclase-inhibiting G alpha protein;
GN Name=Gnai2; Synonyms=Gnai-2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3086867; DOI=10.1073/pnas.83.11.3776;
RA Itoh H., Kozasa T., Nagata S., Nakamura S., Katada T., Ui M., Iwai S.,
RA Ohtsuka E., Kawasaki H., Suzuki K., Kaziro Y.;
RT "Molecular cloning and sequence determination of cDNAs for alpha subunits
RT of the guanine nucleotide-binding proteins Gs, Gi, and Go from rat brain.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:3776-3780(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2820999; DOI=10.1016/s0021-9258(18)47929-x;
RA Jones D.T., Reed R.R.;
RT "Molecular cloning of five GTP-binding protein cDNA species from rat
RT olfactory neuroepithelium.";
RL J. Biol. Chem. 262:14241-14249(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 12-126.
RX PubMed=2159473; DOI=10.1016/s0021-9258(19)39064-7;
RA Linder M.E., Ewald D.A., Miller R.J., Gilman A.G.;
RT "Purification and characterization of Go alpha and three types of Gi alpha
RT after expression in Escherichia coli.";
RL J. Biol. Chem. 265:8243-8251(1990).
RN [5]
RP INTERACTION WITH GPSM1.
RX PubMed=11121039; DOI=10.1073/pnas.97.26.14364;
RA de Vries L., Fischer T., Tronchere H., Brothers G.M., Strockbine B.,
RA Siderovski D.P., Farquhar M.G.;
RT "Activator of G protein signaling 3 is a guanine dissociation inhibitor for
RT Galpha i subunits.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:14364-14369(2000).
RN [6]
RP INTERACTION WITH RGS12 AND RGS14.
RX PubMed=11387333; DOI=10.1074/jbc.m103208200;
RA Kimple R.J., De Vries L., Tronchere H., Behe C.I., Morris R.A.,
RA Gist Farquhar M., Siderovski D.P.;
RT "RGS12 and RGS14 GoLoco motifs are G alpha(i) interaction sites with
RT guanine nucleotide dissociation inhibitor activity.";
RL J. Biol. Chem. 276:29275-29281(2001).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=16870394; DOI=10.1016/j.cellsig.2006.06.002;
RA Shu F.J., Ramineni S., Amyot W., Hepler J.R.;
RT "Selective interactions between Gi alpha1 and Gi alpha3 and the GoLoco/GPR
RT domain of RGS14 influence its dynamic subcellular localization.";
RL Cell. Signal. 19:163-176(2007).
RN [8]
RP MUTAGENESIS OF MET-82; VAL-85; LYS-86; ASN-90; GLN-92; ALA-96; PRO-98;
RP GLN-99; SER-111; CYS-112; PRO-121 AND GLU-122.
RX PubMed=15337739; DOI=10.1074/jbc.m407409200;
RA Mittal V., Linder M.E.;
RT "The RGS14 GoLoco domain discriminates among Galphai isoforms.";
RL J. Biol. Chem. 279:46772-46778(2004).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=17635935; DOI=10.1083/jcb.200604114;
RA Cho H., Kehrl J.H.;
RT "Localization of Gi alpha proteins in the centrosomes and at the midbody:
RT implication for their role in cell division.";
RL J. Cell Biol. 178:245-255(2007).
RN [10]
RP INTERACTION WITH CCDC88A.
RX PubMed=19211784; DOI=10.1073/pnas.0900294106;
RA Garcia-Marcos M., Ghosh P., Farquhar M.G.;
RT "GIV is a nonreceptor GEF for G alpha i with a unique motif that regulates
RT Akt signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:3178-3183(2009).
RN [11]
RP INTERACTION WITH NUCB1.
RX PubMed=21653697; DOI=10.1074/jbc.m110.204099;
RA Garcia-Marcos M., Kietrsunthorn P.S., Wang H., Ghosh P., Farquhar M.G.;
RT "G Protein binding sites on Calnuc (nucleobindin 1) and NUCB2 (nucleobindin
RT 2) define a new class of G(alpha)i-regulatory motifs.";
RL J. Biol. Chem. 286:28138-28149(2011).
CC -!- FUNCTION: Guanine nucleotide-binding proteins (G proteins) are involved
CC as modulators or transducers in various transmembrane signaling
CC systems. The G(i) proteins are involved in hormonal regulation of
CC adenylate cyclase: they inhibit the cyclase in response to beta-
CC adrenergic stimuli. May play a role in cell division.
CC -!- SUBUNIT: G proteins are composed of 3 units; alpha, beta and gamma. The
CC alpha chain contains the guanine nucleotide binding site. In this
CC context, interacts with GNB2 (By similarity). Interacts with UNC5B (By
CC similarity). Interacts with GPSM1 (PubMed:11121039). Interacts with
CC RGS12 and RGS14 (PubMed:11387333). Interacts (inactive GDP-bound form)
CC with NUCB1 (via GBA motif); the interaction leads to activation of
CC GNAI3 (PubMed:21653697). Interacts (inactive GDP-bound form) with
CC CCDC88C/DAPLE (via GBA motif) (By similarity). Interacts (inactive GDP-
CC bound form) with CCDC8A/GIV (via GBA motif) (PubMed:19211784).
CC {ECO:0000250|UniProtKB:P04899, ECO:0000269|PubMed:11121039,
CC ECO:0000269|PubMed:11387333, ECO:0000269|PubMed:19211784,
CC ECO:0000269|PubMed:21653697}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome.
CC Membrane {ECO:0000250|UniProtKB:P04899}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P04899}. Note=Localizes in the centrosomes of
CC interphase and mitotic cells. Detected at the cleavage furrow and/or
CC the midbody (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the G-alpha family. G(i/o/t/z) subfamily.
CC {ECO:0000305}.
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DR EMBL; M12672; AAA41260.1; -; mRNA.
DR EMBL; M17528; AAA40824.1; -; mRNA.
DR EMBL; BC078806; AAH78806.1; -; mRNA.
DR PIR; D27423; RGRTI2.
DR RefSeq; NP_112297.1; NM_031035.3.
DR RefSeq; XP_006243920.1; XM_006243858.1.
DR AlphaFoldDB; P04897; -.
DR SMR; P04897; -.
DR BioGRID; 249564; 3.
DR CORUM; P04897; -.
DR DIP; DIP-607N; -.
DR IntAct; P04897; 3.
DR MINT; P04897; -.
DR STRING; 10116.ENSRNOP00000022550; -.
DR ChEMBL; CHEMBL4524034; -.
DR iPTMnet; P04897; -.
DR PhosphoSitePlus; P04897; -.
DR SwissPalm; P04897; -.
DR jPOST; P04897; -.
DR PaxDb; P04897; -.
DR PRIDE; P04897; -.
DR Ensembl; ENSRNOT00000022550; ENSRNOP00000022550; ENSRNOG00000016592.
DR GeneID; 81664; -.
DR KEGG; rno:81664; -.
DR UCSC; RGD:620243; rat.
DR CTD; 2771; -.
DR RGD; 620243; Gnai2.
DR eggNOG; KOG0082; Eukaryota.
DR GeneTree; ENSGT00940000155125; -.
DR HOGENOM; CLU_014184_6_0_1; -.
DR InParanoid; P04897; -.
DR OMA; GMGCTVS; -.
DR OrthoDB; 754573at2759; -.
DR PhylomeDB; P04897; -.
DR TreeFam; TF300673; -.
DR Reactome; R-RNO-170670; Adenylate cyclase inhibitory pathway.
DR Reactome; R-RNO-392170; ADP signalling through P2Y purinoceptor 12.
DR Reactome; R-RNO-400042; Adrenaline,noradrenaline inhibits insulin secretion.
DR Reactome; R-RNO-418594; G alpha (i) signalling events.
DR Reactome; R-RNO-9009391; Extra-nuclear estrogen signaling.
DR SABIO-RK; P04897; -.
DR PRO; PR:P04897; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Bgee; ENSRNOG00000016592; Expressed in spleen and 19 other tissues.
DR ExpressionAtlas; P04897; baseline and differential.
DR Genevisible; P04897; RN.
DR GO; GO:0044297; C:cell body; ISO:RGD.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0030425; C:dendrite; ISO:RGD.
DR GO; GO:0005834; C:heterotrimeric G-protein complex; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0030496; C:midbody; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:GOC.
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:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IMP:RGD.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; ISO:RGD.
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:0008283; P:cell population proliferation; ISO:RGD.
DR GO; GO:0007213; P:G protein-coupled acetylcholine receptor signaling pathway; ISO:RGD.
DR GO; GO:0001973; P:G protein-coupled adenosine receptor signaling pathway; IDA:RGD.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:RGD.
DR GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; IDA:RGD.
DR GO; GO:0140199; P:negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process; IDA:RGD.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; IMP:RGD.
DR GO; GO:0045955; P:negative regulation of calcium ion-dependent exocytosis; IMP:RGD.
DR GO; GO:1903614; P:negative regulation of protein tyrosine phosphatase activity; IMP:RGD.
DR GO; GO:0050805; P:negative regulation of synaptic transmission; IDA:RGD.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:RGD.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; IMP:RGD.
DR GO; GO:0033864; P:positive regulation of NAD(P)H oxidase activity; IMP:RGD.
DR GO; GO:2000179; P:positive regulation of neural precursor cell proliferation; IMP:RGD.
DR GO; GO:0035815; P:positive regulation of renal sodium excretion; IMP:RGD.
DR GO; GO:0032930; P:positive regulation of superoxide anion generation; IMP:RGD.
DR GO; GO:0035810; P:positive regulation of urine volume; IMP:RGD.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IMP:RGD.
DR GO; GO:0051924; P:regulation of calcium ion transport; IDA:RGD.
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 Cell cycle; Cell division; Cell membrane; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; 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:0000250|UniProtKB:P04899"
FT CHAIN 2..355
FT /note="Guanine nucleotide-binding protein G(i) subunit
FT alpha-2"
FT /id="PRO_0000203682"
FT DOMAIN 32..355
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 325..330
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 327
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:P04899"
FT LIPID 3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT VARIANT 166..167
FT /note="SD -> PN (in tryptic peptides)"
FT MUTAGEN 82
FT /note="M->I: Increases sensitivity to RGS14 GTPase
FT activity; when associated with I-85; R-86; R-90; K-92; G-
FT 96; A-98; A-99; A-111; G-112; T-121 and A-122. Does not
FT increase sensitivity to RGS14 GTPase activity; when
FT associated with I-85 and A-111."
FT /evidence="ECO:0000269|PubMed:15337739"
FT MUTAGEN 85
FT /note="V->I: Increases sensitivity to RGS14 GTPase
FT activity; when associated with I-82; R-86; R-90; K-92; G-
FT 96; A-98; A-99; A-111; G-112; T-121 and A-122. Does not
FT increase sensitivity to RGS14 GTPase activity; when
FT associated with I-82 and A-111."
FT /evidence="ECO:0000269|PubMed:15337739"
FT MUTAGEN 86
FT /note="K->R: Increases sensitivity to RGS14 GTPase
FT activity; when associated with I-82; I-85; R-90; K-92; G-
FT 96; A-98; A-99; A-111; G-112; T-121 and A-122."
FT /evidence="ECO:0000269|PubMed:15337739"
FT MUTAGEN 90
FT /note="N->R: Increases sensitivity to RGS14 GTPase
FT activity; when associated with I-82; I-85; R-86; K-92; G-
FT 96; A-98; A-99; A-111; G-112; T-121 and A-122."
FT /evidence="ECO:0000269|PubMed:15337739"
FT MUTAGEN 92
FT /note="Q->K: Increases sensitivity to RGS14 GTPase
FT activity; when associated with I-82; I-85; R-86; R-90; G-
FT 96; A-98; A-99; A-111; G-112; T-121 and A-122."
FT /evidence="ECO:0000269|PubMed:15337739"
FT MUTAGEN 96
FT /note="A->G: Increases sensitivity to RGS14 GTPase
FT activity; when associated with I-82; I-85; R-86; R-90; K-
FT 92; A-98; A-99; A-111; G-112; T-121 and A-122."
FT /evidence="ECO:0000269|PubMed:15337739"
FT MUTAGEN 98
FT /note="P->A: Increases sensitivity to RGS14 GTPase
FT activity; when associated with I-82; I-85; R-86; R-90; K-
FT 92; G-96; A-99; A-111; G-112; T-121 and A-122."
FT /evidence="ECO:0000269|PubMed:15337739"
FT MUTAGEN 99
FT /note="Q->A: Increases sensitivity to RGS14 GTPase
FT activity; when associated with I-82; I-85; R-86; R-90; K-
FT 92; G-96; A-98; A-111; G-112; T-121 and A-122."
FT /evidence="ECO:0000269|PubMed:15337739"
FT MUTAGEN 111
FT /note="S->A: Increases sensitivity to RGS14 GTPase
FT activity; when associated with I-82; I-85; R-86; R-90; K-
FT 92; G-96; A-98; A-99; G-112; T-121 and A-122. Does not
FT increase sensitivity to RGS14 GTPase activity; when
FT associated with G-112; T-121 and A-122. Does not increase
FT sensitivity to RGS14 GTPase activity; when associated with
FT I-82 and A-85."
FT /evidence="ECO:0000269|PubMed:15337739"
FT MUTAGEN 112
FT /note="C->G: Increases sensitivity to RGS14 GTPase
FT activity; when associated with I-82; I-85; R-86; R-90; K-
FT 92; G-96; A-98; A-99; A-111; T-121 and A-122. Does not
FT increase sensitivity to RGS14 GTPase activity; when
FT associated with G-111; T-121 and A-122."
FT /evidence="ECO:0000269|PubMed:15337739"
FT MUTAGEN 117
FT /note="Missing: Increases sensitivity to RGS14 GTPase
FT activity; when associated with I-82; I-85; R-86; R-90; K-
FT 92; G-96; A-98; A-99; A-111; G-112; T-121 and A-122. Does
FT not increase sensitivity to RGS14 GTPase activity; when
FT associated with G-111; G-112; T-121 and A-122."
FT MUTAGEN 121
FT /note="P->T: Increases sensitivity to RGS14 GTPase
FT activity; when associated with I-82; I-85; R-86; R-90; K-
FT 92; G-96; A-98; A-99; A-111; G-112 and A-122. Does not
FT increase sensitivity to RGS14 GTPase activity; when
FT associated with G-111; G-112 and A-122."
FT /evidence="ECO:0000269|PubMed:15337739"
FT MUTAGEN 122
FT /note="E->A: Increases sensitivity to RGS14 GTPase
FT activity; when associated with I-82; I-85; R-86; R-90; K-
FT 92; G-96; A-98; A-99; A-111; G-112 and T-121. Does not
FT increase sensitivity to RGS14 GTPase activity; when
FT associated with G-111; G-112 and T-121."
FT /evidence="ECO:0000269|PubMed:15337739"
SQ SEQUENCE 355 AA; 40499 MW; 9360ABAC6BDC493E CRC64;
MGCTVSAEDK AAAERSKMID KNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEDG
YSEEECRQYR AVVYSNTIQS IMAIVKAMGN LQIDFADPQR ADDARQLFAL SCAAEEQGML
PEDLSGVIRR LWADHGVQAC FGRSREYQLN DSAAYYLNDL ERIAQSDYIP TQQDVLRTRV
KTTGIVETHF TFKDLHFKMF DVGGQRSERK KWIHCFEGVT AIIFCVALSA YDLVLAEDEE
MNRMHESMKL FDSICNNKWF TDTSIILFLN KKDLFEEKIT QSPLTICFPE YTGANKYDEA
ASYIQSKFED LNKRKDTKEI YTHFTCATDT KNVQFVFDAV TDVIIKNNLK DCGLF
