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Protein

Guanine nucleotide-binding protein subunit alpha-12

Gene

Gna12

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems (PubMed:19151758, PubMed:21212405, PubMed:22609986). Activates effector molecule RhoA by binding and activating RhoGEFs (ARHGEF12/LARG) (By similarity). GNA12-dependent Rho signaling subsequently regulates transcription factor AP-1 (activating protein-1) (PubMed:19151758, PubMed:21212405). GNA12-dependent Rho signaling also regulates protein phosphatese 2A activation causing dephosphorylation of its target proteins (By similarity). Promotes tumor cell invasion and metastasis by activating RhoA/ROCK signaling pathway and up-regulating proinflammatory cytokine production (By similarity). Inhibits CDH1-mediated cell adhesion in process independent from Rho activation (By similarity). Together with NAPA promotes CDH5 localization to plasma membrane (By similarity). May play a role in the control of cell migration through the TOR signaling cascade (PubMed:22609986).By similarity3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi69Magnesium1 Publication1
Metal bindingi206Magnesium1 Publication1
Binding sitei351GTP; via amide nitrogenCombined sources1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi65 – 70GTPCombined sources1 Publication6
Nucleotide bindingi200 – 203GTPCombined sources1 Publication4
Nucleotide bindingi294 – 297GTPCombined sources1 Publication4

GO - Molecular functioni

GO - Biological processi

  • adenylate cyclase-modulating G-protein coupled receptor signaling pathway Source: GO_Central
  • cell differentiation Source: MGI
  • embryonic digit morphogenesis Source: MGI
  • G-protein coupled receptor signaling pathway Source: MGI
  • intracellular signal transduction Source: MGI
  • in utero embryonic development Source: MGI
  • regulation of cell shape Source: MGI
  • regulation of fibroblast migration Source: UniProtKB
  • regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
  • regulation of TOR signaling Source: UniProtKB
  • response to drug Source: Ensembl
  • Rho protein signal transduction Source: MGI

Keywordsi

Molecular functionTransducer
LigandGTP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-416482. G alpha (12/13) signalling events.
R-MMU-456926. Thrombin signalling through proteinase activated receptors (PARs).

Names & Taxonomyi

Protein namesi
Recommended name:
Guanine nucleotide-binding protein subunit alpha-12
Short name:
G alpha-12
Short name:
G-protein subunit alpha-12
Gene namesi
Name:Gna12
Synonyms:Gna-12
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:95767. Gna12.

Subcellular locationi

  • Cell membrane By similarity; Lipid-anchor By similarity
  • Lateral cell membrane By similarity; Lipid-anchor By similarity
  • Cytoplasm By similarity

  • Note: CDH1 enhances cell membrane localization.By similarity

GO - Cellular componenti

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi2S → G: Results in myristoylation of G-2, which restores the transformation activity; when associated with S-6. 1 Publication1
Mutagenesisi6R → S: Results in myristoylation of G-2, which restores the transformation activity; when associated with G-2. 1 Publication1
Mutagenesisi11C → S: Abolishes palmitoylation and transformation activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002037711 – 379Guanine nucleotide-binding protein subunit alpha-12Add BLAST379

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi11S-palmitoyl cysteine1 Publication1

Post-translational modificationi

Myristoylation of mutated N-terminus in place of original palmitoylation restores the transformation activity.1 Publication

Keywords - PTMi

Lipoprotein, Palmitate

Proteomic databases

MaxQBiP27600.
PaxDbiP27600.
PeptideAtlasiP27600.
PRIDEiP27600.

PTM databases

iPTMnetiP27600.
PhosphoSitePlusiP27600.
SwissPalmiP27600.

Expressioni

Gene expression databases

BgeeiENSMUSG00000000149.
CleanExiMM_GNA12.
ExpressionAtlasiP27600. baseline and differential.
GenevisibleiP27600. MM.

Interactioni

Subunit structurei

G proteins are composed of 3 units; alpha, beta and gamma (PubMed:16388592). The alpha chain contains the guanine nucleotide binding site (PubMed:16388592). Interacts with UBXD5 (By similarity). Interacts (in GTP-bound form) with PPP5C (via TPR repeats); activates PPP5C phosphatase activity and translocates PPP5C to the cell membrane (By similarity). Interacts with RGS22 (By similarity). Interacts (via N-terminus) with NAPA; the interaction promotes CDH5 localization to plasma membrane (By similarity). Interacts with CTNND1 (via N-terminus); the interaction regulates CDH1-mediated cell-cell adhesion (PubMed:15240885). Interacts with PPP2R1A; the interaction promotes protein phosphatase 2A activation causing dephosphorylation of MAPT (By similarity). Interacts (in GTP-bound form) with ARHGEF1 (PubMed:16388592). Interacts (in GTP-bound form) with ARHGEF11 (via RGS domain) (By similarity). Interacts (in GTP-bound form) with ARHGEF12 (via RGS domain) (PubMed:16388592).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

IntActiP27600. 3 interactors.
MINTiMINT-4096224.
STRINGi10090.ENSMUSP00000000153.

Structurei

Secondary structure

1379
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi56 – 67Combined sources12
Helixi68 – 79Combined sources12
Helixi85 – 112Combined sources28
Helixi120 – 122Combined sources3
Helixi123 – 130Combined sources8
Helixi142 – 157Combined sources16
Helixi159 – 166Combined sources8
Helixi168 – 170Combined sources3
Helixi176 – 182Combined sources7
Helixi184 – 187Combined sources4
Helixi196 – 201Combined sources6
Beta strandi208 – 216Combined sources9
Beta strandi219 – 226Combined sources8
Helixi230 – 233Combined sources4
Helixi234 – 238Combined sources5
Turni239 – 242Combined sources4
Beta strandi244 – 251Combined sources8
Beta strandi260 – 266Combined sources7
Helixi267 – 279Combined sources13
Helixi282 – 284Combined sources3
Beta strandi287 – 294Combined sources8
Helixi296 – 305Combined sources10
Turni309 – 311Combined sources3
Helixi322 – 335Combined sources14
Beta strandi346 – 348Combined sources3
Helixi354 – 370Combined sources17

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ZCAX-ray2.90A/B48-379[»]
ProteinModelPortaliP27600.
SMRiP27600.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP27600.

Family & Domainsi

Sequence similaritiesi

Belongs to the G-alpha family. G(12) subfamily.Curated

Phylogenomic databases

eggNOGiKOG0082. Eukaryota.
ENOG410XNVQ. LUCA.
GeneTreeiENSGT00770000120503.
HOGENOMiHOG000038729.
HOVERGENiHBG063184.
InParanoidiP27600.
KOiK04346.
OMAiKEYQHVI.
OrthoDBiEOG091G0NV2.
PhylomeDBiP27600.
TreeFamiTF300673.

Family and domain databases

CDDicd00066. G-alpha. 1 hit.
Gene3Di1.10.400.10. 1 hit.
InterProiView protein in InterPro
IPR000469. Gprotein_alpha_12/13.
IPR001019. Gprotein_alpha_su.
IPR011025. GproteinA_insert.
IPR027417. P-loop_NTPase.
PANTHERiPTHR10218. PTHR10218. 1 hit.
PfamiView protein in Pfam
PF00503. G-alpha. 1 hit.
PRINTSiPR00318. GPROTEINA.
PR00440. GPROTEINA12.
SMARTiView protein in SMART
SM00275. G_alpha. 1 hit.
SUPFAMiSSF47895. SSF47895. 1 hit.
SSF52540. SSF52540. 2 hits.

Sequencei

Sequence statusi: Complete.

P27600-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSGVVRTLSR CLLPAEAGAR ERRAGAARDA EREARRRSRD IDALLARERR
60 70 80 90 100
AVRRLVKILL LGAGESGKST FLKQMRIIHG REFDQKALLE FRDTIFDNIL
110 120 130 140 150
KGSRVLVDAR DKLGIPWQHS ENEKHGMFLM AFENKAGLPV EPATFQLYVP
160 170 180 190 200
ALSALWRDSG IREAFSRRSE FQLGESVKYF LDNLDRIGQL NYFPSKQDIL
210 220 230 240 250
LARKATKGIV EHDFVIKKIP FKMVDVGGQR SQRQKWFQCF DGITSILFMV
260 270 280 290 300
SSSEYDQVLM EDRRTNRLVE SMNIFETIVN NKLFFNVSII LFLNKMDLLV
310 320 330 340 350
EKVKSVSIKK HFPDFKGDPH RLEDVQRYLV QCFDRKRRNR SKPLFHHFTT
360 370
AIDTENIRFV FHAVKDTILQ ENLKDIMLQ
Length:379
Mass (Da):44,095
Last modified:January 23, 2007 - v3
Checksum:i647C524AD7A0B5E2
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M63659 mRNA. Translation: AAA37648.1.
M57618 mRNA. Translation: AAA63302.1.
CCDSiCCDS19825.1.
PIRiA41095.
C33833.
RefSeqiNP_034432.1. NM_010302.2.
UniGeneiMm.370185.

Genome annotation databases

EnsembliENSMUST00000000153; ENSMUSP00000000153; ENSMUSG00000000149.
GeneIDi14673.
KEGGimmu:14673.
UCSCiuc009aih.1. mouse.

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiGNA12_MOUSE
AccessioniPrimary (citable) accession number: P27600
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: January 23, 2007
Last modified: June 7, 2017
This is version 160 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families