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Protein

Guanine nucleotide-binding protein subunit alpha-12

Gene

GNA12

Organism
Homo sapiens (Human)
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:22609986, PubMed:15525651, PubMed:15240885, PubMed:17565996, PubMed:12515866, PubMed:16787920, PubMed:16705036, PubMed:23762476, PubMed:27084452). Activates effector molecule RhoA by binding and activating RhoGEFs (ARHGEF12/LARG) (PubMed:15240885, PubMed:12515866, PubMed:16202387). GNA12-dependent Rho signaling subsequently regulates transcription factor AP-1 (activating protein-1) (By similarity). GNA12-dependent Rho signaling also regulates protein phosphatese 2A activation causing dephosphorylation of its target proteins (PubMed:15525651, PubMed:17565996). Promotes tumor cell invasion and metastasis by activating RhoA/ROCK signaling pathway and up-regulating proinflammatory cytokine production (PubMed:23762476, PubMed:16787920, PubMed:16705036, PubMed:27084452). Inhibits CDH1-mediated cell adhesion in process independent from Rho activation (PubMed:11976333, PubMed:16787920). Together with NAPA promotes CDH5 localization to plasma membrane (PubMed:15980433). May play a role in the control of cell migration through the TOR signaling cascade (PubMed:22609986).By similarity11 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi71MagnesiumBy similarity1
Metal bindingi208MagnesiumBy similarity1
Binding sitei353GTP; via amide nitrogenBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi67 – 72GTPBy similarity6
Nucleotide bindingi202 – 205GTPBy similarity4
Nucleotide bindingi296 – 299GTPBy similarity4

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-416482. G alpha (12/13) signalling events.
R-HSA-456926. Thrombin signalling through proteinase activated receptors (PARs).
SignaLinkiQ03113.
SIGNORiQ03113.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000146535.13.
HGNCiHGNC:4380. 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

Organism-specific databases

DisGeNETi2768.
OpenTargetsiENSG00000146535.
PharmGKBiPA28765.

Polymorphism and mutation databases

BioMutaiGNA12.
DMDMi38258934.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002037701 – 381Guanine nucleotide-binding protein subunit alpha-12Add BLAST381

Amino acid modifications

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

Keywords - PTMi

Lipoprotein, Palmitate

Proteomic databases

EPDiQ03113.
MaxQBiQ03113.
PaxDbiQ03113.
PeptideAtlasiQ03113.
PRIDEiQ03113.

PTM databases

iPTMnetiQ03113.
PhosphoSitePlusiQ03113.
SwissPalmiQ03113.

Expressioni

Gene expression databases

BgeeiENSG00000146535.
CleanExiHS_GNA12.
ExpressionAtlasiQ03113. baseline and differential.
GenevisibleiQ03113. HS.

Organism-specific databases

HPAiCAB010046.

Interactioni

Subunit structurei

G proteins are composed of 3 units; alpha, beta and gamma (PubMed:10026210). The alpha chain contains the guanine nucleotide binding site (By similarity). Interacts with UBXD5 (PubMed:16202387). Interacts (in GTP-bound form) with PPP5C (via TPR repeats); activates PPP5C phosphatase activity and translocates PPP5C to the cell membrane. Interacts with RGS22 (PubMed:18703424). Interacts (via N-terminus) with NAPA; the interaction promotes CDH5 localization to plasma membrane (PubMed:15980433). 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 (PubMed:15525651). Interacts (in GTP-bound form) with ARHGEF1 (By similarity). Interacts (in GTP-bound form) with ARHGEF11 (via RGS domain) (PubMed:10026210). Interacts (in GTP-bound form) with ARHGEF12 (via RGS domain) (PubMed:11094164).By similarity7 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109030. 29 interactors.
CORUMiQ03113.
IntActiQ03113. 4 interactors.
MINTiMINT-85969.
STRINGi9606.ENSP00000275364.

Structurei

3D structure databases

ProteinModelPortaliQ03113.
SMRiQ03113.
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.
InParanoidiQ03113.
KOiK04346.
OMAiKEYQHVI.
OrthoDBiEOG091G0NV2.
PhylomeDBiQ03113.
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.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative initiation. AlignAdd to basket

Isoform 1 (identifier: Q03113-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSGVVRTLSR CLLPAEAGGA RERRAGSGAR DAEREARRRS RDIDALLARE
60 70 80 90 100
RRAVRRLVKI LLLGAGESGK STFLKQMRII HGREFDQKAL LEFRDTIFDN
110 120 130 140 150
ILKGSRVLVD ARDKLGIPWQ YSENEKHGMF LMAFENKAGL PVEPATFQLY
160 170 180 190 200
VPALSALWRD SGIREAFSRR SEFQLGESVK YFLDNLDRIG QLNYFPSKQD
210 220 230 240 250
ILLARKATKG IVEHDFVIKK IPFKMVDVGG QRSQRQKWFQ CFDGITSILF
260 270 280 290 300
MVSSSEYDQV LMEDRRTNRL VESMNIFETI VNNKLFFNVS IILFLNKMDL
310 320 330 340 350
LVEKVKTVSI KKHFPDFRGD PHRLEDVQRY LVQCFDRKRR NRSKPLFHHF
360 370 380
TTAIDTENVR FVFHAVKDTI LQENLKDIML Q
Length:381
Mass (Da):44,279
Last modified:January 23, 2007 - v4
Checksum:i04C3F12B29255F89
GO
Isoform 2 (identifier: Q03113-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-103: MSGVVRTLSR...RDTIFDNILK → MKRRMFPRPC...HLLIAHPGSR

Show »
Length:322
Mass (Da):37,601
Checksum:iAB035356C0AACD6F
GO
Isoform 3 (identifier: Q03113-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-76: Missing.
     174-190: Missing.

Note: No experimental confirmation available.
Show »
Length:288
Mass (Da):34,002
Checksum:i72CABE32D6FC5D6C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti126K → E in AAM12615 (Ref. 2) Curated1
Sequence conflicti323R → Q in AAA35867 (PubMed:8423800).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07104468S → G1 PublicationCorresponds to variant dbSNP:rs11552939Ensembl.1
Natural variantiVAR_049359242F → L. Corresponds to variant dbSNP:rs45606633Ensembl.1
Natural variantiVAR_049360330Y → H. Corresponds to variant dbSNP:rs45583847Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0551711 – 103MSGVV…DNILK → MKRRMFPRPCLARMPGSRGS GSTPDGNRKCCRFEHLLIAH PGSR in isoform 2. 1 PublicationAdd BLAST103
Alternative sequenceiVSP_0552301 – 76Missing in isoform 3. 1 PublicationAdd BLAST76
Alternative sequenceiVSP_055231174 – 190Missing in isoform 3. 1 PublicationAdd BLAST17

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L01694 mRNA. Translation: AAA35867.1.
AF493901 mRNA. Translation: AAM12615.1.
AK127842 mRNA. Translation: BAG54584.1.
AK295830 mRNA. Translation: BAH12193.1.
AC006028 Genomic DNA. Translation: AAP21870.1.
AC004933 Genomic DNA. Translation: AAD05026.1.
CH236953 Genomic DNA. Translation: EAL23961.1.
BC087537 mRNA. Translation: AAH87537.1.
BC111464 mRNA. Translation: AAI11465.1.
CCDSiCCDS5335.1. [Q03113-1]
CCDS64584.1. [Q03113-2]
PIRiA48071.
RefSeqiNP_001269370.1. NM_001282441.1. [Q03113-2]
NP_001280021.1. NM_001293092.1.
NP_031379.2. NM_007353.2. [Q03113-1]
UniGeneiHs.487341.

Genome annotation databases

EnsembliENST00000275364; ENSP00000275364; ENSG00000146535. [Q03113-1]
ENST00000407904; ENSP00000385935; ENSG00000146535. [Q03113-2]
GeneIDi2768.
KEGGihsa:2768.
UCSCiuc003smt.5. human. [Q03113-1]

Keywords - Coding sequence diversityi

Alternative initiation, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGNA12_HUMAN
AccessioniPrimary (citable) accession number: Q03113
Secondary accession number(s): A4D204
, B3KXS2, B7Z3F7, Q2T9L1, Q5PPR5, Q86UM8, Q8TD71, Q9UDU9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: January 23, 2007
Last modified: September 27, 2017
This is version 167 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families