Synembryn-A (RIC8A)
The protein contains 531 amino acids for an estimated molecular weight of 59710 Da.
Guanine nucleotide exchange factor (GEF), which can activate some, but not all, G-alpha proteins. Able to activate GNAI1, GNAO1 and GNAQ, but not GNAS by exchanging bound GDP for free GTP. Involved in regulation of microtubule pulling forces during mitotic movement of chromosomes by stimulating G(i)-alpha protein, possibly leading to release G(i)-alpha-GTP and NuMA proteins from the NuMA-GPSM2-G(i)-alpha-GDP complex (By similarity). Also acts as an activator for G(q)-alpha (GNAQ) protein by enhancing the G(q)-coupled receptor-mediated ERK activation. (updated: March 4, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- 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.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- 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.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
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.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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Biological Process
Adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
Basement membrane organization
Cell migration involved in gastrulation
Cell-cell adhesion involved in gastrulation
G protein-coupled receptor signaling pathway
In utero embryonic development
Positive regulation of GTPase activity
Vasculature development
Visual learning
The reference OMIM entry for this protein is 609146
Ric8, c. elegans, homolog of, a; ric8a
Synembryn, c. elegans, homolog of, a
CLONING
Using G-alpha proteins (see GNAS; 139320) as bait in a yeast 2-hybrid screen of a rat brain cDNA library, Tall et al. (2003) cloned Ric8a, a homolog of C. elegans Ric8/synembryn. Database analysis identified 3 splice variants of human RIC8A that encode deduced proteins of 531, 537, and 401 amino acids. The 531-amino acid RIC8A isoform shares 87% identity with rat Ric8a. The 537-amino acid protein is identical to the 531-amino acid protein except for a 6-amino acid insertion, including a polyproline sequence, at codon 355. The variant encoding the 401-amino acid protein is derived from a 1-bp insertion at codon 395 of the transcript encoding the 531-amino acid protein. The resultant frameshift leads to a protein with 5 different C-terminal amino acids and a new stop codon that forms a consensus CAAX box for geranylgeranyl modification.GENE FUNCTION
By yeast 2-hybrid analysis, Tall et al. (2003) found that rat Ric8a interacted with GNAI1 (139310), GNAO (139311), GNAQ (600998), and weakly with GNA13 (604406). No interaction was observed with GNAS. Ric8a interacted preferentially with wildtype GNAI1 compared with its GTPase-defective counterpart. In detergent extracts of rat brain membranes, Ric8a interacted with GNAI1, GNAI2 (139360), GNAI3 (139370), GNAQ, and GNA13, but not with GNAS or G protein beta subunits (see GNB1; 139380). Tall et al. (2003) found that Ric8a preferentially interacted with nucleotide-free GNAI1. Ric8a stimulated the rate of binding between a nonhydrolyzable GTP analog and GNAQ, and it stimulated the steady-state GTPase activity of GNAQ. However, Ric8a did not interact with preformed G protein heterotrimers or facilitate their nucleotide exchange. Beta-gamma dimers appeared to compete with Ric8a for binding to G-alpha proteins. Afshar et al. (2004) determined that C. elegans Ric8 is required for proper asymmetric division of 1-cell-stage embryos. Spindle severing experiments demonstrated that Ric8 was required for the generation of substantial pulling forces on astral microtubules. Ric8 physically interacted with 2 nematode G-alpha subunits that act in a partially redundant manner in 1-cell-stage embryos. Ric8 behaved as a guanine nucleotide exchange factor for the G-alpha protein Goa1.GENE STRUCTURE
Tall et al. (2003) determined that the RIC8A gene contains at least 7 exons.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the RIC8A gene to chromosome 11 (TMAP WI-19967). ... More on the omim web site
Dec. 10, 2018: Protein entry updated
Automatic update: model status changed
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 609146 was added.