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Protein

Guanine nucleotide-binding protein subunit alpha-12

Gene

Gna12

Organism
Rattus norvegicus (Rat)
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:12176367, PubMed:21212405). 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: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. 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:12176367).By similarity2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi69MagnesiumBy similarity1
Metal bindingi206MagnesiumBy similarity1
Binding sitei351GTP; via amide nitrogenBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi65 – 70GTPBy similarity6
Nucleotide bindingi200 – 203GTPBy similarity4
Nucleotide bindingi294 – 297GTPBy similarity4

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-RNO-416482. G alpha (12/13) signalling events.
R-RNO-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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 12

Organism-specific databases

RGDi71018. Gna12.

Subcellular locationi

  • Cell membrane 1 Publication; Lipid-anchor 1 Publication
  • Lateral cell membrane By similarity; Lipid-anchor 1 Publication
  • Cytoplasm By similarity

  • Note: CDH1 enhances cell membrane localization.By similarity

GO - Cellular componenti

  • brush border membrane Source: RGD
  • focal adhesion Source: Ensembl
  • heterotrimeric G-protein complex Source: RGD

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi229Q → L: Constitutively active. Interacts with PPP5C, activates its phosphatase activity and translocates PPP5C to the plasma membrane. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002037721 – 379Guanine nucleotide-binding protein subunit alpha-12Add BLAST379

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi11S-palmitoyl cysteineBy similarity1

Keywords - PTMi

Lipoprotein, Palmitate

Proteomic databases

PaxDbiQ63210.
PRIDEiQ63210.

Expressioni

Gene expression databases

BgeeiENSRNOG00000001235.
ExpressionAtlasiQ63210. baseline and differential.
GenevisibleiQ63210. RN.

Interactioni

Subunit structurei

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

GO - Molecular functioni

  • D5 dopamine receptor binding Source: RGD
  • G-protein beta/gamma-subunit complex binding Source: GO_Central

Protein-protein interaction databases

MINTiMINT-132109.
STRINGi10116.ENSRNOP00000001654.

Structurei

3D structure databases

ProteinModelPortaliQ63210.
SMRiQ63210.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0082. Eukaryota.
ENOG410XNVQ. LUCA.
GeneTreeiENSGT00770000120503.
HOGENOMiHOG000038729.
HOVERGENiHBG063184.
InParanoidiQ63210.
KOiK04346.
OMAiGISEHIF.
OrthoDBiEOG091G0NV2.
PhylomeDBiQ63210.
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.

Q63210-1 [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 GKPLFHHFTT
360 370
AIDTENIRFV FHAVKDTILQ ENLKDIMLQ
Length:379
Mass (Da):44,065
Last modified:January 23, 2007 - v3
Checksum:iD178524AD7A0A9FF
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D85760 mRNA. Translation: BAA12867.1.
RefSeqiNP_112296.1. NM_031034.2.
UniGeneiRn.10497.

Genome annotation databases

EnsembliENSRNOT00000001654; ENSRNOP00000001654; ENSRNOG00000001235.
GeneIDi81663.
KEGGirno:81663.
UCSCiRGD:71018. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D85760 mRNA. Translation: BAA12867.1.
RefSeqiNP_112296.1. NM_031034.2.
UniGeneiRn.10497.

3D structure databases

ProteinModelPortaliQ63210.
SMRiQ63210.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-132109.
STRINGi10116.ENSRNOP00000001654.

Proteomic databases

PaxDbiQ63210.
PRIDEiQ63210.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000001654; ENSRNOP00000001654; ENSRNOG00000001235.
GeneIDi81663.
KEGGirno:81663.
UCSCiRGD:71018. rat.

Organism-specific databases

CTDi2768.
RGDi71018. Gna12.

Phylogenomic databases

eggNOGiKOG0082. Eukaryota.
ENOG410XNVQ. LUCA.
GeneTreeiENSGT00770000120503.
HOGENOMiHOG000038729.
HOVERGENiHBG063184.
InParanoidiQ63210.
KOiK04346.
OMAiGISEHIF.
OrthoDBiEOG091G0NV2.
PhylomeDBiQ63210.
TreeFamiTF300673.

Enzyme and pathway databases

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

Miscellaneous databases

PROiPR:Q63210.

Gene expression databases

BgeeiENSRNOG00000001235.
ExpressionAtlasiQ63210. baseline and differential.
GenevisibleiQ63210. RN.

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.
ProtoNetiSearch...

Entry informationi

Entry nameiGNA12_RAT
AccessioniPrimary (citable) accession number: Q63210
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 23, 2007
Last modified: May 10, 2017
This is version 133 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

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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.