Guanine nucleotide-binding protein subunit beta-4 (GNB4)
The protein contains 340 amino acids for an estimated molecular weight of 37567 Da.
Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. (updated: April 1, 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.
- 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.
Biological Process
Cellular response to glucagon stimulus
Energy reserve metabolic process
G protein-coupled receptor signaling pathway
Protein folding
Signal transduction
Small molecule metabolic process
Substantia nigra development
The reference OMIM entry for this protein is 610863
Guanine nucleotide-binding protein, beta-4; gnb4
G protein, beta-4 subunit; g beta-4
DESCRIPTION
Heterotrimeric G proteins, made up of an alpha subunit (see GNAS, 139320), a beta subunit, like GNB4, and a gamma subunit (see GNG2, 606981), relay signals from cell surface receptors to internal effectors. The alpha subunit is a GTPase that interacts in the GDP-bound state with beta-gamma dimers (Rosskopf et al., 2003).CLONING
By searching an EST database for G-protein beta-like sequences, followed by 5-prime RACE of a human brain cDNA library, Ruiz-Velasco et al. (2002) cloned GNB4. Like other beta subunits, the deduced GNB4 protein contains 340 amino acids with 7 WD repeat motifs forming a beta-propeller structure. GNB4 shares 91% identity with GNB1 (139380) and 96% identity with mouse Gnb4. PCR analysis detected high GNB4 expression in human lung, pancreas, and placenta, moderate expression in kidney and liver, and weak expression in brain and heart. By searching an EST database for sequences similar to mouse Gnb4, followed by PCR of human B lymphoblast and brain RNA, Rosskopf et al. (2003) cloned GNB4. PCR analysis of human, rat, and mouse tissues and cultured cells showed wide GNB4 expression. Soong et al. (2013) found that GNB4 colocalized with neurofilament heavy chain and S100 in peripheral human nerves, indicating that it is expressed in both axons and Schwann cells.GENE FUNCTION
By heterologous overexpression in rat sympathetic neurons, Ruiz-Velasco et al. (2002) found that human G-beta-4 coexpressed with G-gamma-2 (GNG2; 606981) or G-gamma-4 (GNG4; 604388) caused tonic modulation of N-type voltage-gated calcium currents and G protein-gated inwardly rectifying potassium currents. Coexpression of G-beta-4, G-gamma-2 and G-alpha-oA (GNAO1; 139311) resulted in heterotrimer formation. Using coprecipitation analysis, Rosskopf et al. (2003) showed that GNB4 formed dimers with all 11 gamma subunits analyzed. The strength of the interaction was variable and was strongest between GNB1 and GNG4, followed by GNG13 (607298) and GNG1 (GNGT1; 189970), and was weakest with GNG8C (GNGT2; 139391). Overexpression of most GNB4-GNG dimers resulted in significant, although sometimes modest, activation of phospholipase beta-2 (PLCB2; 604114), with highest activation by the GNB4-GNG4 dimer. Vertebrate retinas have distinct light-on (ON) and light-off (OFF) channels that originate at the level of the retinal bipolar cells. For the conversion from OFF to ON, ON bipolar cells use the GNAO1-coupled glutamate receptor-6 (GRIK2; 138244) such that binding of glutamate suppresses a cation current rather than activating it. Using immunohistochemical analysis and single-cell PCR, Huang et al. (2003) showed that the gamma subunit Gng13 (607298) was coexpressed with the beta subunits Gnb3 (139130) and Gnb4, but no other beta subunit, in dissociated mouse ON bipolar cells. Huang et al. (2003) hypothesized that these G protein subunits selectively participate in signal transduction in ON bipolar cells. Soong et al. (2013) found that Gnb4 expression in rats decreased in nerve tissue distal to sciatic nerve transection and increased in nerve tissue after conditioning, suggesting that the protein plays a role in peripheral nerve regeneration.GENE STRUCTURE
Rosskopf et al. (2003) determined that the GNB4 gene contains 10 exons. The first exon is noncoding.MAPPING
By genomic sequence analysis, Rosskopf et al. (2003) mapped the GNB4 gene to chromosome 3.MOLECULAR GENETICS
In affected me ... More on the omim web site
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 25, 2017: Additional information
No protein expression data in P. Mayeux work for GNB4
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 610863 was added.