Guanine nucleotide-binding protein subunit alpha-13 (GNA13)

The protein contains 377 amino acids for an estimated molecular weight of 44050 Da.

 

Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems (PubMed:15240885, PubMed:16787920, PubMed:16705036, PubMed:27084452). Activates effector molecule RhoA by binding and activating RhoGEFs (ARHGEF1/p115RhoGEF, ARHGEF11/PDZ-RhoGEF and ARHGEF12/LARG) (PubMed:15240885, PubMed:12515866). GNA13-dependent Rho signaling subsequently regulates transcription factor AP-1 (activating protein-1) (By similarity). Promotes tumor cell invasion and metastasis by activating RhoA/ROCK signaling pathway (PubMed:16787920, PubMed:16705036, PubMed:27084452). Inhibits CDH1-mediated cell adhesion in process independent from Rho activation (PubMed:11976333). (updated: Dec. 20, 2017)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 96%
Model score: 184
MODL_MODELLER-9.18

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VariantDescription
dbSNP:rs1062597

The reference OMIM entry for this protein is 604406

Guanine nucleotide-binding protein, alpha-13; gna13
G-alpha-13

For background information on G proteins, see 600874.

CLONING

Kabouridis et al. (1995) cloned human thymocyte cDNAs corresponding to the full-length coding sequence of G-alpha-13. The GNA13 cDNA encodes a deduced 377-amino acid protein that is 97% homologous to the mouse Gna13 protein. It contains the highly conserved motifs found in all G protein alpha subunits that are thought to be directly involved in the interaction with the guanine nucleotide. Northern blot analysis revealed that GNA13 is expressed as a major 4.8-kb and a minor 5.3-kb transcript in Jurkat and HPB-ALL leukemic T-cell lines.

GENE FUNCTION

Moers et al. (2003) showed that lack of G-alpha-13, but not G-alpha-12 (604394), severely reduced the potency of thrombin (176930), thromboxane A2, and collagen to induce platelet shape changes and aggregation in vitro. These defects were accompanied by a reduced activation of RhoA (165390) and inability to form stable platelet thrombi under high shear stress ex vivo. G-alpha-13 deficiency in platelets resulted in a severe defect of primary hemostasis and complete protection against arterial thrombosis in vivo. Moers et al. (2003) concluded that G13-mediated signaling processes are required for normal hemostasis and thrombosis. Radhika et al. (2004) presented evidence that mammalian Gna13 associates with intracellular Hax1 (605998), a cortactin (164765)-interacting protein, and that Hax1 promotes Gna13-mediated cell migration. Gna13 and Hax1 existed in a complex with Rac (see 602048) and cortactin in transfected cells, and coexpression of Hax1 enhanced Gna13-mediated Rac activity while inhibiting Rho activity, both of which can promote cell movement. Shan et al. (2006) showed that Gna13 was essential for receptor tyrosine kinase-induced migration of mouse fibroblasts and endothelial cells. Gna13 activity in cell migration was retained in a C-terminal mutant that was defective in coupling to G protein-coupled receptors, suggesting that the migration function is independent of receptor signaling. G-alpha-q (GNAQ; 600998)-coupled receptors, such as alpha-1-adrenergic (see ADRA1A; 104221), angiotensin (106165), and endothelin (see ENDRA; 131243) receptors, play key roles in cardiac physiology. These receptors also interact with G-alpha-12 and G-alpha-13. Using photoaffinity labeling and immunoprecipitation, Kilts et al. (2007) showed that these receptors differentially activated cardiac G-alpha-12 and G-alpha-13 in membranes of human right atrial appendages. Endothelin receptors activated only G-alpha-12, whereas angiotensin receptors activated only G-alpha-13. Alpha-1-adrenergic receptors activated neither G-alpha-12 nor G-alpha-13. Using mice lacking G-alpha subunits specifically in smooth muscle cells, Wirth et al. (2008) found that G-alpha-q and G-alpha-11 (GNA11; 139313) were required for maintenance of basal blood pressure and for development of salt-induced hypertension. In contrast, lack of G-alpha-12 and G-alpha-13 and their effector, Larg (ARHGEF12; 604763), did not alter normal blood pressure regulation, but blocked development of salt-induced hypertension. Using small interfering RNAs and pharmacologic inhibitors with mouse embryonic fibroblasts and NIH3T3 mouse fibroblasts, Goulimari et al. (2008) defined a signal transduction pathway that regulated microtubule-based cell polarity and migration. This pathway included heterotrimeric Gna12 and Gna13 proteins, Larg, and actin-nucleating Dia1 (DIAPH1; 602 ... More on the omim web site

Subscribe to this protein entry history

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604406 was added.