GNA12_MOUSE
ID GNA12_MOUSE Reviewed; 379 AA.
AC P27600;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 184.
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; Synonyms=Gna-12;
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 [MRNA].
RC TISSUE=Brain;
RX PubMed=1905812; DOI=10.1073/pnas.88.13.5582;
RA Strathmann M.P., Simon M.I.;
RT "G alpha 12 and G alpha 13 subunits define a fourth class of G protein
RT alpha subunits.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:5582-5586(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 232-292.
RX PubMed=2508088; DOI=10.1073/pnas.86.19.7407;
RA Strathmann M., Wilkie T.M., Simon M.I.;
RT "Diversity of the G-protein family: sequences from five additional alpha
RT subunits in the mouse.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:7407-7409(1989).
RN [3]
RP PALMITOYLATION AT CYS-11, AND MUTAGENESIS OF SER-2; ARG-6 AND CYS-11.
RX PubMed=9485474; DOI=10.1021/bi972253j;
RA Jones T.L., Gutkind J.S.;
RT "Galpha12 requires acylation for its transforming activity.";
RL Biochemistry 37:3196-3202(1998).
RN [4]
RP INTERACTION WITH CTNND1, AND SUBCELLULAR LOCATION.
RX PubMed=15240885; DOI=10.1073/pnas.0401366101;
RA Krakstad B.F., Ardawatia V.V., Aragay A.M.;
RT "A role for Galpha12/Galpha13 in p120ctn regulation.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:10314-10319(2004).
RN [5]
RP FUNCTION.
RX PubMed=19151758; DOI=10.1038/onc.2008.488;
RA Lee S.J., Yang J.W., Cho I.J., Kim W.D., Cho M.K., Lee C.H., Kim S.G.;
RT "The gep oncogenes, Galpha(12) and Galpha(13), upregulate the transforming
RT growth factor-beta1 gene.";
RL Oncogene 28:1230-1240(2009).
RN [6]
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).
RN [7]
RP FUNCTION IN TOR SIGNALING.
RX PubMed=22609986; DOI=10.1038/ncb2507;
RA Gan X., Wang J., Wang C., Sommer E., Kozasa T., Srinivasula S., Alessi D.,
RA Offermanns S., Simon M.I., Wu D.;
RT "PRR5L degradation promotes mTORC2-mediated PKC-delta phosphorylation and
RT cell migration downstream of Galpha12.";
RL Nat. Cell Biol. 14:686-696(2012).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 48-379 IN COMPLEX WITH MAGNESIUM
RP AND GTP ANALOG, AND INTERACTION WITH ARHGEF1 AND ARHGEF12.
RX PubMed=16388592; DOI=10.1021/bi051729t;
RA Kreutz B., Yau D.M., Nance M.R., Tanabe S., Tesmer J.J., Kozasa T.;
RT "A new approach to producing functional G alpha subunits yields the
RT activated and deactivated structures of G alpha(12/13) proteins.";
RL Biochemistry 45:167-174(2006).
CC -!- FUNCTION: Guanine nucleotide-binding proteins (G proteins) are involved
CC as modulators or transducers in various transmembrane signaling systems
CC (PubMed:19151758, PubMed:21212405, PubMed:22609986). Activates effector
CC molecule RhoA by binding and activating RhoGEFs (ARHGEF12/LARG) (By
CC similarity). GNA12-dependent Rho signaling subsequently regulates
CC transcription factor AP-1 (activating protein-1) (PubMed:19151758,
CC PubMed:21212405). GNA12-dependent Rho signaling also regulates protein
CC phosphatese 2A activation causing dephosphorylation of its target
CC proteins (By similarity). Promotes tumor cell invasion and metastasis
CC by activating RhoA/ROCK signaling pathway and up-regulating pro-
CC inflammatory cytokine production (By similarity). Inhibits CDH1-
CC mediated cell adhesion in process independent from Rho activation (By
CC similarity). Together with NAPA promotes CDH5 localization to plasma
CC membrane (By similarity). May play a role in the control of cell
CC migration through the TOR signaling cascade (PubMed:22609986).
CC {ECO:0000250|UniProtKB:Q03113, ECO:0000269|PubMed:19151758,
CC ECO:0000269|PubMed:21212405, ECO:0000269|PubMed:22609986}.
CC -!- SUBUNIT: G proteins are composed of 3 units; alpha, beta and gamma
CC (PubMed:16388592). The alpha chain contains the guanine nucleotide
CC binding site (PubMed:16388592). Interacts with UBXD5 (By similarity).
CC Interacts (in GTP-bound form) with PPP5C (via TPR repeats); activates
CC PPP5C phosphatase activity and translocates PPP5C to the cell membrane
CC (By similarity). Interacts with RGS22 (By similarity). Interacts (via
CC N-terminus) with NAPA; the interaction promotes CDH5 localization to
CC plasma membrane (By similarity). Interacts with CTNND1 (via N-
CC terminus); the interaction regulates CDH1-mediated cell-cell adhesion
CC (PubMed:15240885). Interacts with PPP2R1A; the interaction promotes
CC protein phosphatase 2A activation causing dephosphorylation of MAPT (By
CC similarity). Interacts (in GTP-bound form) with ARHGEF1
CC (PubMed:16388592). Interacts (in GTP-bound form) with ARHGEF11 (via RGS
CC domain) (By similarity). Interacts (in GTP-bound form) with ARHGEF12
CC (via RGS domain) (PubMed:16388592). {ECO:0000250|UniProtKB:Q03113,
CC ECO:0000269|PubMed:15240885, ECO:0000269|PubMed:16388592}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q03113};
CC Lipid-anchor {ECO:0000250|UniProtKB:Q63210}. Lateral cell membrane
CC {ECO:0000250|UniProtKB:Q03113}; Lipid-anchor
CC {ECO:0000250|UniProtKB:Q63210}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q03113}. Note=CDH1 enhances cell membrane
CC localization. {ECO:0000250|UniProtKB:Q03113}.
CC -!- PTM: Myristoylation of mutated N-terminus in place of original
CC palmitoylation restores the transformation activity.
CC {ECO:0000269|PubMed:9485474}.
CC -!- SIMILARITY: Belongs to the G-alpha family. G(12) subfamily.
CC {ECO:0000305}.
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DR EMBL; M63659; AAA37648.1; -; mRNA.
DR EMBL; M57618; AAA63302.1; -; mRNA.
DR CCDS; CCDS19825.1; -.
DR PIR; A41095; A41095.
DR PIR; C33833; C33833.
DR RefSeq; NP_034432.1; NM_010302.2.
DR PDB; 1ZCA; X-ray; 2.90 A; A/B=48-379.
DR PDBsum; 1ZCA; -.
DR AlphaFoldDB; P27600; -.
DR SMR; P27600; -.
DR BioGRID; 199962; 1.
DR IntAct; P27600; 2.
DR MINT; P27600; -.
DR STRING; 10090.ENSMUSP00000000153; -.
DR iPTMnet; P27600; -.
DR PhosphoSitePlus; P27600; -.
DR SwissPalm; P27600; -.
DR EPD; P27600; -.
DR jPOST; P27600; -.
DR MaxQB; P27600; -.
DR PaxDb; P27600; -.
DR PeptideAtlas; P27600; -.
DR PRIDE; P27600; -.
DR ProteomicsDB; 271002; -.
DR Antibodypedia; 4103; 233 antibodies from 30 providers.
DR DNASU; 14673; -.
DR Ensembl; ENSMUST00000000153; ENSMUSP00000000153; ENSMUSG00000000149.
DR GeneID; 14673; -.
DR KEGG; mmu:14673; -.
DR UCSC; uc009aih.1; mouse.
DR CTD; 2768; -.
DR MGI; MGI:95767; Gna12.
DR VEuPathDB; HostDB:ENSMUSG00000000149; -.
DR eggNOG; KOG0082; Eukaryota.
DR GeneTree; ENSGT00940000157636; -.
DR InParanoid; P27600; -.
DR OMA; MVASNEY; -.
DR OrthoDB; 754573at2759; -.
DR PhylomeDB; P27600; -.
DR TreeFam; TF300673; -.
DR Reactome; R-MMU-416482; G alpha (12/13) signalling events.
DR Reactome; R-MMU-456926; Thrombin signalling through proteinase activated receptors (PARs).
DR BioGRID-ORCS; 14673; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Gna12; mouse.
DR EvolutionaryTrace; P27600; -.
DR PRO; PR:P27600; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; P27600; protein.
DR Bgee; ENSMUSG00000000149; Expressed in right kidney and 245 other tissues.
DR ExpressionAtlas; P27600; baseline and differential.
DR Genevisible; P27600; MM.
DR GO; GO:0031526; C:brush border membrane; ISO:MGI.
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:MGI.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0031752; F:D5 dopamine receptor binding; ISO:MGI.
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; ISA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051721; F:protein phosphatase 2A binding; ISO:MGI.
DR GO; GO:0019888; F:protein phosphatase regulator activity; ISO:MGI.
DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IDA:MGI.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IGI:MGI.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISA:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IGI:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:MGI.
DR GO; GO:0010259; P:multicellular organism aging; IMP:MGI.
DR GO; GO:1904753; P:negative regulation of vascular associated smooth muscle cell migration; ISO:MGI.
DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0032516; P:positive regulation of phosphoprotein phosphatase activity; ISO:MGI.
DR GO; GO:0008217; P:regulation of blood pressure; IGI:MGI.
DR GO; GO:0008360; P:regulation of cell shape; IDA:MGI.
DR GO; GO:0010762; P:regulation of fibroblast migration; IMP:UniProtKB.
DR GO; GO:0032434; P:regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0032006; P:regulation of TOR signaling; IMP:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0007266; P:Rho protein signal transduction; IDA:MGI.
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 3D-structure; Cell membrane; Cytoplasm; GTP-binding; Lipoprotein;
KW Magnesium; Membrane; Metal-binding; Nucleotide-binding; Palmitate;
KW Phosphoprotein; Reference proteome; Transducer.
FT CHAIN 1..379
FT /note="Guanine nucleotide-binding protein subunit alpha-12"
FT /id="PRO_0000203771"
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:0000269|PubMed:16388592,
FT ECO:0007744|PDB:1ZCA"
FT BINDING 69
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:16388592"
FT BINDING 200..203
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:16388592,
FT ECO:0007744|PDB:1ZCA"
FT BINDING 206
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:16388592"
FT BINDING 294..297
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:16388592,
FT ECO:0007744|PDB:1ZCA"
FT BINDING 351
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:16388592,
FT ECO:0007744|PDB:1ZCA"
FT MOD_RES 206
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14344"
FT LIPID 11
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:9485474"
FT MUTAGEN 2
FT /note="S->G: Results in myristoylation of G-2, which
FT restores the transformation activity; when associated with
FT S-6."
FT /evidence="ECO:0000269|PubMed:9485474"
FT MUTAGEN 6
FT /note="R->S: Results in myristoylation of G-2, which
FT restores the transformation activity; when associated with
FT G-2."
FT /evidence="ECO:0000269|PubMed:9485474"
FT MUTAGEN 11
FT /note="C->S: Abolishes palmitoylation and transformation
FT activity."
FT /evidence="ECO:0000269|PubMed:9485474"
FT STRAND 56..67
FT /evidence="ECO:0007829|PDB:1ZCA"
FT HELIX 68..79
FT /evidence="ECO:0007829|PDB:1ZCA"
FT HELIX 85..112
FT /evidence="ECO:0007829|PDB:1ZCA"
FT HELIX 120..122
FT /evidence="ECO:0007829|PDB:1ZCA"
FT HELIX 123..130
FT /evidence="ECO:0007829|PDB:1ZCA"
FT HELIX 142..157
FT /evidence="ECO:0007829|PDB:1ZCA"
FT HELIX 159..166
FT /evidence="ECO:0007829|PDB:1ZCA"
FT HELIX 168..170
FT /evidence="ECO:0007829|PDB:1ZCA"
FT HELIX 176..182
FT /evidence="ECO:0007829|PDB:1ZCA"
FT HELIX 184..187
FT /evidence="ECO:0007829|PDB:1ZCA"
FT HELIX 196..201
FT /evidence="ECO:0007829|PDB:1ZCA"
FT STRAND 208..216
FT /evidence="ECO:0007829|PDB:1ZCA"
FT STRAND 219..226
FT /evidence="ECO:0007829|PDB:1ZCA"
FT HELIX 230..233
FT /evidence="ECO:0007829|PDB:1ZCA"
FT HELIX 234..238
FT /evidence="ECO:0007829|PDB:1ZCA"
FT TURN 239..242
FT /evidence="ECO:0007829|PDB:1ZCA"
FT STRAND 244..251
FT /evidence="ECO:0007829|PDB:1ZCA"
FT STRAND 260..266
FT /evidence="ECO:0007829|PDB:1ZCA"
FT HELIX 267..279
FT /evidence="ECO:0007829|PDB:1ZCA"
FT HELIX 282..284
FT /evidence="ECO:0007829|PDB:1ZCA"
FT STRAND 287..294
FT /evidence="ECO:0007829|PDB:1ZCA"
FT HELIX 296..305
FT /evidence="ECO:0007829|PDB:1ZCA"
FT TURN 309..311
FT /evidence="ECO:0007829|PDB:1ZCA"
FT HELIX 322..335
FT /evidence="ECO:0007829|PDB:1ZCA"
FT STRAND 346..348
FT /evidence="ECO:0007829|PDB:1ZCA"
FT HELIX 354..370
FT /evidence="ECO:0007829|PDB:1ZCA"
SQ SEQUENCE 379 AA; 44095 MW; 647C524AD7A0B5E2 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 SKPLFHHFTT AIDTENIRFV
FHAVKDTILQ ENLKDIMLQ
