GNA12_RAT
ID GNA12_RAT Reviewed; 379 AA.
AC Q63210;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Guanine nucleotide-binding protein subunit alpha-12;
DE Short=G alpha-12;
DE Short=G-protein subunit alpha-12;
GN Name=Gna12;
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].
RC TISSUE=Brain;
RA Mitsui H., Exton J.;
RT "Molecular cloning of rat G alpha 12.";
RL Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, INTERACTION WITH PPP5C, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP GLN-229.
RX PubMed=12176367; DOI=10.1016/s0960-9822(02)01034-5;
RA Yamaguchi Y., Katoh H., Mori K., Negishi M.;
RT "Galpha(12) and Galpha(13) interact with Ser/Thr protein phosphatase type 5
RT and stimulate its phosphatase activity.";
RL Curr. Biol. 12:1353-1358(2002).
RN [3]
RP FUNCTION.
RX PubMed=21212405; DOI=10.1161/atvbaha.110.218552;
RA Kim Y.M., Lim S.C., Han C.Y., Kay H.Y., Cho I.J., Ki S.H., Lee M.Y.,
RA Kwon H.M., Lee C.H., Kim S.G.;
RT "G(alpha)12/13 induction of CYR61 in association with arteriosclerotic
RT intimal hyperplasia: effect of sphingosine-1-phosphate.";
RL Arterioscler. Thromb. Vasc. Biol. 31:861-869(2011).
CC -!- FUNCTION: Guanine nucleotide-binding proteins (G proteins) are involved
CC as modulators or transducers in various transmembrane signaling systems
CC (PubMed:12176367, PubMed:21212405). Activates effector molecule RhoA by
CC binding and activating RhoGEFs (ARHGEF12/LARG) (By similarity). GNA12-
CC dependent Rho signaling subsequently regulates transcription factor AP-
CC 1 (activating protein-1) (PubMed:21212405). GNA12-dependent Rho
CC signaling also regulates protein phosphatese 2A activation causing
CC dephosphorylation of its target proteins (By similarity). Promotes
CC tumor cell invasion and metastasis by activating RhoA/ROCK signaling
CC pathway and up-regulating pro-inflammatory cytokine production.
CC Inhibits CDH1-mediated cell adhesion in process independent from Rho
CC activation (By similarity). Together with NAPA promotes CDH5
CC localization to plasma membrane (By similarity). May play a role in the
CC control of cell migration through the TOR signaling cascade
CC (PubMed:12176367). {ECO:0000250|UniProtKB:P27600,
CC ECO:0000250|UniProtKB:Q03113, ECO:0000269|PubMed:12176367,
CC ECO:0000269|PubMed:21212405}.
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 UBXD5. Interacts (in GTP-bound form) with PPP5C (via TPR repeats);
CC activates PPP5C phosphatase activity and translocates PPP5C to the cell
CC membrane. Interacts with RGS22. Interacts (via N-terminus) with NAPA;
CC the interaction promotes CDH5 localization to plasma membrane.
CC Interacts with CTNND1 (via N-terminus); the interaction regulates CDH1-
CC mediated cell-cell adhesion. Interacts with PPP2R1A; the interaction
CC promotes protein phosphatase 2A activation causing dephosphorylation of
CC MAPT. Interacts (in GTP-bound form) with ARHGEF1. Interacts (in GTP-
CC bound form) with ARHGEF11 (via RGS domain). Interacts (in GTP-bound
CC form) with ARHGEF12 (via RGS domain). {ECO:0000250|UniProtKB:P27600,
CC ECO:0000250|UniProtKB:Q03113}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12176367};
CC Lipid-anchor {ECO:0000269|PubMed:12176367}. Lateral cell membrane
CC {ECO:0000250|UniProtKB:Q03113}; Lipid-anchor
CC {ECO:0000269|PubMed:12176367}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q03113}. Note=CDH1 enhances cell membrane
CC localization. {ECO:0000250|UniProtKB:Q03113}.
CC -!- SIMILARITY: Belongs to the G-alpha family. G(12) subfamily.
CC {ECO:0000305}.
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DR EMBL; D85760; BAA12867.1; -; mRNA.
DR RefSeq; NP_112296.1; NM_031034.2.
DR AlphaFoldDB; Q63210; -.
DR SMR; Q63210; -.
DR STRING; 10116.ENSRNOP00000001654; -.
DR jPOST; Q63210; -.
DR PaxDb; Q63210; -.
DR PRIDE; Q63210; -.
DR Ensembl; ENSRNOT00000001654; ENSRNOP00000001654; ENSRNOG00000001235.
DR GeneID; 81663; -.
DR KEGG; rno:81663; -.
DR UCSC; RGD:71018; rat.
DR CTD; 2768; -.
DR RGD; 71018; Gna12.
DR eggNOG; KOG0082; Eukaryota.
DR GeneTree; ENSGT00940000157636; -.
DR HOGENOM; CLU_014184_3_1_1; -.
DR InParanoid; Q63210; -.
DR OMA; MVASNEY; -.
DR OrthoDB; 754573at2759; -.
DR PhylomeDB; Q63210; -.
DR TreeFam; TF300673; -.
DR Reactome; R-RNO-416482; G alpha (12/13) signalling events.
DR PRO; PR:Q63210; -.
DR Proteomes; UP000002494; Chromosome 12.
DR Bgee; ENSRNOG00000001235; Expressed in heart and 19 other tissues.
DR ExpressionAtlas; Q63210; baseline and differential.
DR Genevisible; Q63210; RN.
DR GO; GO:0031526; C:brush border membrane; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005834; C:heterotrimeric G-protein complex; IBA:GO_Central.
DR GO; GO:0016328; C:lateral plasma membrane; ISO:RGD.
DR GO; GO:0043005; C:neuron projection; ISO:RGD.
DR GO; GO:0043025; C:neuronal cell body; ISO:RGD.
DR GO; GO:0031752; F:D5 dopamine receptor binding; IPI:RGD.
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:0051721; F:protein phosphatase 2A binding; ISO:RGD.
DR GO; GO:0019888; F:protein phosphatase regulator activity; ISO:RGD.
DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; ISO:RGD.
DR GO; GO:0007212; P:dopamine receptor signaling pathway; TAS:RGD.
DR GO; GO:0042733; P:embryonic digit morphogenesis; ISO:RGD.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IMP:MGI.
DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:RGD.
DR GO; GO:0010259; P:multicellular organism aging; ISO:RGD.
DR GO; GO:1904753; P:negative regulation of vascular associated smooth muscle cell migration; IMP:MGI.
DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; IMP:MGI.
DR GO; GO:0032516; P:positive regulation of phosphoprotein phosphatase activity; ISO:RGD.
DR GO; GO:0008217; P:regulation of blood pressure; ISO:RGD.
DR GO; GO:0008360; P:regulation of cell shape; ISO:RGD.
DR GO; GO:0010762; P:regulation of fibroblast migration; ISS:UniProtKB.
DR GO; GO:0032434; P:regulation of proteasomal ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0032006; P:regulation of TOR signaling; ISS:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0007266; P:Rho protein signal transduction; ISO:RGD.
DR CDD; cd00066; G-alpha; 1.
DR Gene3D; 1.10.400.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR000469; Gprotein_alpha_12/13.
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; PR00440; GPROTEINA12.
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 membrane; Cytoplasm; GTP-binding; Lipoprotein; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Palmitate; Phosphoprotein;
KW Reference proteome; Transducer.
FT CHAIN 1..379
FT /note="Guanine nucleotide-binding protein subunit alpha-12"
FT /id="PRO_0000203772"
FT DOMAIN 54..379
FT /note="G-alpha"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 57..70
FT /note="G1 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 198..206
FT /note="G2 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 221..230
FT /note="G3 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 290..297
FT /note="G4 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 349..354
FT /note="G5 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT BINDING 65..70
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P27600"
FT BINDING 69
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P27600"
FT BINDING 200..203
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P27600"
FT BINDING 206
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P27600"
FT BINDING 294..297
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P27600"
FT BINDING 351
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P27600"
FT MOD_RES 206
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14344"
FT LIPID 11
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P27600"
FT MUTAGEN 229
FT /note="Q->L: Constitutively active. Interacts with PPP5C,
FT activates its phosphatase activity and translocates PPP5C
FT to the plasma membrane."
FT /evidence="ECO:0000269|PubMed:12176367"
SQ SEQUENCE 379 AA; 44065 MW; D178524AD7A0A9FF CRC64;
MSGVVRTLSR CLLPAEAGAR ERRAGAARDA EREARRRSRD IDALLARERR AVRRLVKILL
LGAGESGKST FLKQMRIIHG REFDQKALLE FRDTIFDNIL KGSRVLVDAR DKLGIPWQHS
ENEKHGMFLM AFENKAGLPV EPATFQLYVP ALSALWRDSG IREAFSRRSE FQLGESVKYF
LDNLDRIGQL NYFPSKQDIL LARKATKGIV EHDFVIKKIP FKMVDVGGQR SQRQKWFQCF
DGITSILFMV SSSEYDQVLM EDRRTNRLVE SMNIFETIVN NKLFFNVSII LFLNKMDLLV
EKVKSVSIKK HFPDFKGDPH RLEDVQRYLV QCFDRKRRNR GKPLFHHFTT AIDTENIRFV
FHAVKDTILQ ENLKDIMLQ
