UniProtKB - P27600 (GNA12_MOUSE)
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Protein
Guanine nucleotide-binding protein subunit alpha-12
Gene
Gna12
Organism
Mus musculus (Mouse)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Metal bindingi | 69 | Magnesium1 Publication | 1 | |
| Metal bindingi | 206 | Magnesium1 Publication | 1 | |
| Binding sitei | 351 | GTP; via amide nitrogenCombined sources1 Publication | 1 |
Regions
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Nucleotide bindingi | 65 – 70 | GTPCombined sources1 Publication | 6 | |
| Nucleotide bindingi | 200 – 203 | GTPCombined sources1 Publication | 4 | |
| Nucleotide bindingi | 294 – 297 | GTPCombined sources1 Publication | 4 |
GO - Molecular functioni
- D5 dopamine receptor binding Source: GO_Central
- G-protein beta/gamma-subunit complex binding Source: GO_Central
- GTPase activity Source: MGI
- GTP binding Source: UniProtKB-KW
- metal ion binding Source: UniProtKB-KW
- signal transducer activity Source: GO_Central
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 function | Transducer |
| Ligand | GTP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
| Reactomei | R-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-12Short name: G alpha-12 Short name: G-protein subunit alpha-12 |
| Gene namesi | Name:Gna12 Synonyms:Gna-12 |
| Organismi | Mus musculus (Mouse) |
| Taxonomic identifieri | 10090 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
| Proteomesi |
|
Organism-specific databases
| MGIi | MGI: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
- brush border membrane Source: GO_Central
- cytoplasm Source: UniProtKB-SubCell
- focal adhesion Source: MGI
- heterotrimeric G-protein complex Source: MGI
- lateral plasma membrane Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cell membrane, Cytoplasm, MembranePathology & Biotechi
Mutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Mutagenesisi | 2 | S → G: Results in myristoylation of G-2, which restores the transformation activity; when associated with S-6. 1 Publication | 1 | |
| Mutagenesisi | 6 | R → S: Results in myristoylation of G-2, which restores the transformation activity; when associated with G-2. 1 Publication | 1 | |
| Mutagenesisi | 11 | C → S: Abolishes palmitoylation and transformation activity. 1 Publication | 1 |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| ChainiPRO_0000203771 | 1 – 379 | Guanine nucleotide-binding protein subunit alpha-12Add BLAST | 379 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Lipidationi | 11 | S-palmitoyl cysteine1 Publication | 1 |
Post-translational modificationi
Myristoylation of mutated N-terminus in place of original palmitoylation restores the transformation activity.1 Publication
Keywords - PTMi
Lipoprotein, PalmitateProteomic databases
| MaxQBi | P27600. |
| PaxDbi | P27600. |
| PeptideAtlasi | P27600. |
| PRIDEi | P27600. |
PTM databases
| iPTMneti | P27600. |
| PhosphoSitePlusi | P27600. |
| SwissPalmi | P27600. |
Expressioni
Gene expression databases
| Bgeei | ENSMUSG00000000149. |
| CleanExi | MM_GNA12. |
| ExpressionAtlasi | P27600. baseline and differential. |
| Genevisiblei | P27600. 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
- D5 dopamine receptor binding Source: GO_Central
- G-protein beta/gamma-subunit complex binding Source: GO_Central
Protein-protein interaction databases
| IntActi | P27600. 3 interactors. |
| MINTi | MINT-4096224. |
| STRINGi | 10090.ENSMUSP00000000153. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Beta strandi | 56 – 67 | Combined sources | 12 | |
| Helixi | 68 – 79 | Combined sources | 12 | |
| Helixi | 85 – 112 | Combined sources | 28 | |
| Helixi | 120 – 122 | Combined sources | 3 | |
| Helixi | 123 – 130 | Combined sources | 8 | |
| Helixi | 142 – 157 | Combined sources | 16 | |
| Helixi | 159 – 166 | Combined sources | 8 | |
| Helixi | 168 – 170 | Combined sources | 3 | |
| Helixi | 176 – 182 | Combined sources | 7 | |
| Helixi | 184 – 187 | Combined sources | 4 | |
| Helixi | 196 – 201 | Combined sources | 6 | |
| Beta strandi | 208 – 216 | Combined sources | 9 | |
| Beta strandi | 219 – 226 | Combined sources | 8 | |
| Helixi | 230 – 233 | Combined sources | 4 | |
| Helixi | 234 – 238 | Combined sources | 5 | |
| Turni | 239 – 242 | Combined sources | 4 | |
| Beta strandi | 244 – 251 | Combined sources | 8 | |
| Beta strandi | 260 – 266 | Combined sources | 7 | |
| Helixi | 267 – 279 | Combined sources | 13 | |
| Helixi | 282 – 284 | Combined sources | 3 | |
| Beta strandi | 287 – 294 | Combined sources | 8 | |
| Helixi | 296 – 305 | Combined sources | 10 | |
| Turni | 309 – 311 | Combined sources | 3 | |
| Helixi | 322 – 335 | Combined sources | 14 | |
| Beta strandi | 346 – 348 | Combined sources | 3 | |
| Helixi | 354 – 370 | Combined sources | 17 |
3D structure databases
| Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
| 1ZCA | X-ray | 2.90 | A/B | 48-379 | [»] | |
| ProteinModelPortali | P27600. | |||||
| SMRi | P27600. | |||||
| ModBasei | Search... | |||||
| MobiDBi | Search... | |||||
Miscellaneous databases
| EvolutionaryTracei | P27600. |
Family & Domainsi
Sequence similaritiesi
Phylogenomic databases
| eggNOGi | KOG0082. Eukaryota. ENOG410XNVQ. LUCA. |
| GeneTreei | ENSGT00770000120503. |
| HOGENOMi | HOG000038729. |
| HOVERGENi | HBG063184. |
| InParanoidi | P27600. |
| KOi | K04346. |
| OMAi | KEYQHVI. |
| OrthoDBi | EOG091G0NV2. |
| PhylomeDBi | P27600. |
| TreeFami | TF300673. |
Family and domain databases
| CDDi | cd00066. G-alpha. 1 hit. |
| Gene3Di | 1.10.400.10. 1 hit. |
| InterProi | View protein in InterPro IPR000469. Gprotein_alpha_12/13. IPR001019. Gprotein_alpha_su. IPR011025. GproteinA_insert. IPR027417. P-loop_NTPase. |
| PANTHERi | PTHR10218. PTHR10218. 1 hit. |
| Pfami | View protein in Pfam PF00503. G-alpha. 1 hit. |
| PRINTSi | PR00318. GPROTEINA. PR00440. GPROTEINA12. |
| SMARTi | View protein in SMART SM00275. G_alpha. 1 hit. |
| SUPFAMi | SSF47895. SSF47895. 1 hit. SSF52540. SSF52540. 2 hits. |
Sequencei
Sequence statusi: Complete.
P27600-1 [UniParc]FASTAAdd to basket
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
Sequence databases
| Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M63659 mRNA. Translation: AAA37648.1. M57618 mRNA. Translation: AAA63302.1. |
| CCDSi | CCDS19825.1. |
| PIRi | A41095. C33833. |
| RefSeqi | NP_034432.1. NM_010302.2. |
| UniGenei | Mm.370185. |
Genome annotation databases
| Ensembli | ENSMUST00000000153; ENSMUSP00000000153; ENSMUSG00000000149. |
| GeneIDi | 14673. |
| KEGGi | mmu:14673. |
| UCSCi | uc009aih.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 namei | GNA12_MOUSE | |
| Accessioni | P27600Primary (citable) accession number: P27600 | |
| Entry historyi | Integrated 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 statusi | Reviewed (UniProtKB/Swiss-Prot) | |
| Annotation program | Chordata Protein Annotation Program | |
Miscellaneousi
Keywords - Technical termi
3D-structure, Complete proteome, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families
