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Protein

Guanine nucleotide-binding protein subunit alpha-12

Gene

Gna12

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

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

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
Modified residuei206PhosphothreonineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

MaxQBiP27600
PaxDbiP27600
PeptideAtlasiP27600
PRIDEiP27600

PTM databases

iPTMnetiP27600
PhosphoSitePlusiP27600
SwissPalmiP27600

Expressioni

Gene expression databases

BgeeiENSMUSG00000000149 Expressed in 276 organ(s), highest expression level in cardiac ventricle
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
MINTiP27600
STRINGi10090.ENSMUSP00000000153

Structurei

Secondary structure

1379
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
GeneTreeiENSGT00760000118851
HOGENOMiHOG000038729
HOVERGENiHBG063184
InParanoidiP27600
KOiK04346
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, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0G2JG40A0A0G2JG40_MOUSE
Guanine nucleotide-binding protein ...
Gna12
316Annotation score:

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

Cross-referencesi

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

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...

Protein-protein interaction databases

IntActiP27600, 3 interactors
MINTiP27600
STRINGi10090.ENSMUSP00000000153

PTM databases

iPTMnetiP27600
PhosphoSitePlusiP27600
SwissPalmiP27600

Proteomic databases

MaxQBiP27600
PaxDbiP27600
PeptideAtlasiP27600
PRIDEiP27600

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi2768
MGIiMGI:95767 Gna12

Phylogenomic databases

eggNOGiKOG0082 Eukaryota
ENOG410XNVQ LUCA
GeneTreeiENSGT00760000118851
HOGENOMiHOG000038729
HOVERGENiHBG063184
InParanoidiP27600
KOiK04346
OrthoDBiEOG091G0NV2
PhylomeDBiP27600
TreeFamiTF300673

Enzyme and pathway databases

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

Miscellaneous databases

EvolutionaryTraceiP27600
PROiPR:P27600
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000000149 Expressed in 276 organ(s), highest expression level in cardiac ventricle
CleanExiMM_GNA12
ExpressionAtlasiP27600 baseline and differential
GenevisibleiP27600 MM

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, 1 hit
ProtoNetiSearch...

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: November 7, 2018
This is version 164 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. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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