ID GNAI3_CAVPO Reviewed; 354 AA.
AC P38403;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 27-MAR-2024, entry version 156.
DE RecName: Full=Guanine nucleotide-binding protein G(i) subunit alpha-3;
DE AltName: Full=G(i) alpha-3;
GN Name=GNAI3;
OS Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Hartley; TISSUE=Lung;
RX PubMed=1482697; DOI=10.1016/0167-4889(92)90009-z;
RA Sakanaka C., Izumi T., Nakamura M., Honda Z., Watanabe T., Minami M.,
RA Mutoh H., Bito H., Seyama Y., Ui M., Shimizu T.;
RT "Three types of Gi alpha protein of the guinea-pig lung: cDNA cloning and
RT analysis of their tissue distribution.";
RL Biochim. Biophys. Acta 1175:61-66(1992).
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. Forms a complex with CCDC88A/GIV and EGFR which
CC leads to enhanced EGFR signaling and triggering of cell migration;
CC ligand stimulation is required for recruitment of GNAI3 to the complex
CC (By similarity). Interacts (inactive GDP-bound form) with CCDC88A/GIV
CC (via GBA motif); the interaction leads to activation of GNAI3 (By
CC similarity). Interacts (inactive GDP-bound form) with CCDC88C/DAPLE
CC (via GBA motif); the interaction leads to activation of GNAI3 (By
CC similarity). Interacts (inactive GDP-bound form) with NUCB1 (via GBA
CC motif) and NUCB2 (via GBA motif); the interaction leads to activation
CC of GNAI3 (By similarity). Interacts (inactive GDP-bound form) with
CC PLCD4 (via GBA motif); the interaction leads to activation of GNAI3 (By
CC similarity). Interacts with INSR; the interaction is probably mediated
CC by CCDC88A/GIV (By similarity). Interacts with GPSM1. Interacts (GDP-
CC bound form) with GPSM2 (via GoLoco domains). Does not interact with
CC RGS2. Interacts with RGS8 and RGS10; this strongly enhances the
CC intrinsic GTPase activity. Interacts with RGS12. Interacts with RGS16;
CC this strongly enhances the intrinsic GTPase activity. Interacts (via
CC active GTP- or inactive GDP-bound form) with RGS14.
CC {ECO:0000250|UniProtKB:P08753, ECO:0000250|UniProtKB:P08754,
CC ECO:0000250|UniProtKB:Q9DC51}.
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 -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:1482697}.
CC -!- SIMILARITY: Belongs to the G-alpha family. G(i/o/t/z) subfamily.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; D21234; BAA04766.1; -; mRNA.
DR PIR; S28159; S28159.
DR RefSeq; NP_001166426.1; NM_001172955.1.
DR RefSeq; XP_005007809.1; XM_005007752.2.
DR AlphaFoldDB; P38403; -.
DR BMRB; P38403; -.
DR SMR; P38403; -.
DR STRING; 10141.ENSCPOP00000010346; -.
DR Ensembl; ENSCPOT00000011611.3; ENSCPOP00000010346.2; ENSCPOG00000011504.4.
DR GeneID; 100135530; -.
DR KEGG; cpoc:100135530; -.
DR CTD; 2773; -.
DR VEuPathDB; HostDB:ENSCPOG00000011504; -.
DR eggNOG; KOG0082; Eukaryota.
DR GeneTree; ENSGT00940000153567; -.
DR HOGENOM; CLU_014184_6_0_1; -.
DR InParanoid; P38403; -.
DR OMA; RICAPNY; -.
DR OrthoDB; 2897309at2759; -.
DR TreeFam; TF300673; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR Bgee; ENSCPOG00000011504; Expressed in zone of skin and 13 other cell types or tissues.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:Ensembl.
DR GO; GO:0000139; C:Golgi membrane; IEA:Ensembl.
DR GO; GO:0030496; C:midbody; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0031683; F:G-protein beta/gamma-subunit complex binding; IEA:InterPro.
DR GO; GO:0019003; F:GDP binding; ISS:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; ISS:UniProtKB.
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:0046039; P:GTP metabolic process; ISS:UniProtKB.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IEA:Ensembl.
DR CDD; cd00066; G-alpha; 1.
DR Gene3D; 1.10.400.10; GI Alpha 1, domain 2-like; 1.
DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 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; GTP-BINDING PROTEIN ALPHA SUBUNIT; 1.
DR PANTHER; PTHR10218:SF230; GUANINE NUCLEOTIDE-BINDING PROTEIN G(I) SUBUNIT ALPHA-3; 1.
DR Pfam; PF00503; G-alpha; 1.
DR PRINTS; PR00318; GPROTEINA.
DR PRINTS; PR00441; GPROTEINAI.
DR SMART; SM00275; G_alpha; 1.
DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR SUPFAM; SSF47895; Transducin (alpha subunit), insertion domain; 1.
DR PROSITE; PS51882; G_ALPHA; 1.
PE 2: Evidence at transcript level;
KW Cell cycle; Cell division; Cell membrane; Cytoplasm; Cytoskeleton;
KW GTP-binding; Lipoprotein; Magnesium; Membrane; Metal-binding; Myristate;
KW Nucleotide-binding; 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_0000203690"
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; 40604 MW; CE913BFF010C5C30 CRC64;
MGCTLSAEDK AAVERSKMID RNLREDGEKA AKEVKLLLLG AGESGKSTIV KQMKIIHEDG
YSEEECKQYK VVVYSNTIQS IIAIIRAMGR LKIDFGEPAR ADDARQLFVL AGSAEEGLMT
SELAGVIRRL WRDGGVQACF SRSREYQLND SASYYLNDLD RISQTNYIPT QQDVLRTRVK
TTGIVETHFT FKDLYFKMFD VGGQRSERKK WIHCFEGVTA IIFCVALSDY DLVLAEDEEM
NRMHESMKLF DSICNNKWFT DTSIILFLNK KDLFEEKIKR SPLTICYPEY TGSNTYEEAA
AYIQCQFEDL NRRKDTKEIY THFTCATDTK NVQFVFDAVT DVIIKNNLKE CGLY
//
