Serine/threonine-protein kinase A-Raf (ARAF)
The protein contains 606 amino acids for an estimated molecular weight of 67585 Da.
Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May also regulate the TOR signaling cascade.', 'Serves as a positive regulator of myogenic differentiation by inducing cell cycle arrest, the expression of myogenin and other muscle-specific proteins, and myotube formation. (updated: Dec. 11, 2019)
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.
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.
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| Variant | Description |
|---|---|
| dbSNP:rs56197559 | |
| a colorectal adenocarcinoma sample; somatic mutation | |
| dbSNP:rs55852926 |
Biological Process
Cell differentiation
Cellular protein modification process
MAPK cascade
Multicellular organism development
Negative regulation of apoptotic process
Negative regulation of signal transduction
Positive regulation of ERK1 and ERK2 cascade
Positive regulation of peptidyl-serine phosphorylation
Regulation of proteasomal ubiquitin-dependent protein catabolic process
Regulation of TOR signaling
Molecular Function
ATP binding
MAP kinase kinase kinase activity
Metal ion binding
Mitogen-activated protein kinase kinase binding
Obsolete signal transducer activity, downstream of receptor
Protein kinase activity
Protein serine kinase activity
Protein serine/threonine kinase activity
Protein threonine kinase activity
The reference OMIM entry for this protein is 311010
V-raf murine sarcoma 3611 viral oncogene homolog 1; araf1
Oncogene araf1
Rafa1
Oncogene pks2
CLONING
By screening a fetal liver cDNA library at reduced stringency for v-raf-related sequences, Mark et al. (1986) found a sequence in addition to the expected RAF1 (164760). This sequence, which they called PKS (presumably for 'protein kinase sequence'), showed 71% nucleotide homology to RAF1. The predicted amino acid sequence of the kinase domain was sufficiently like the sequence of v-raf to suggest that PKS may encode a polypeptide with serine/threonine kinase activity. Mark et al. (1986) found that expression of PKS mRNA (2.7 kb) was elevated in peripheral blood mononuclear cells isolated from 2 patients with angioimmunoblastic lymphadenopathy with dysproteinemia, a disease in which autoantibodies are produced following the lymphoproliferative activation of B cells. By screening a mouse cDNA library with a v-raf oncogene probe, Huebner et al. (1986) also isolated a transforming raf-related cDNA, A-raf, that represented a gene distinct from RAF1. As an initial step in the analysis of this RAF1-related cDNA, they isolated a human ARAF cDNA and used it to map the genes in mouse and man. Beck et al. (1987) deduced the complete 606-amino acid sequence of the human ARAF1 oncogene from the 2,453-nucleotide sequence of the cDNA. Yuryev et al. (2000) stated that ARAF contains an N-terminal regulatory domain and a C-terminal catalytic domain. The regulatory domain contains a RAS (HRAS; 190020)-binding domain and a cysteine-rich domain. Immunohistochemical analysis and immunoelectron microscopy of fractionated rat liver revealed that a portion of Araf localized to mitochondria.GENE FUNCTION
Because of an 80% homology to RAF1 in its kinase domain, Huebner et al. (1986) speculated that the ARAF1 gene product may have serine/threonine-specific kinase activity. The RAF protooncogenes encode cytoplasmic protein serine/threonine kinases that play a critical role in cell growth and development. Araf1 in the mouse is expressed predominantly in urogenital tissues (Lee et al., 1994). Pelkmans and Zerial (2005) explored the role of some kinases in caveolae dynamics. Using RNAi, they identified functions at distinct steps of the caveolar cycle. In the first step, the silencing of ARAF1, a serine/threonine kinase involved in mitogenic signaling, resulted in diffuse CAV1 (601047)-GFP staining that was laterally mobile, in addition to the characteristic spot-like pattern. The authors suggested that in the absence of ARAF1, the caveolar coat is less stable or inefficiently assembled. Their observations revealed new principles in caveolae trafficking and suggested that the dynamic properties of caveolae and their transport competence are regulated by different kinases operating at several levels. Using yeast 2-hybrid analysis of HeLa cells, Yuryev et al. (2000) showed that the N-terminal regulatory domain of ARAF interacted with the putative mitochondrial proteins TOM (PPRF6; 613979) and TIM44 (TIMM44; 605058).GENE STRUCTURE
Lee et al. (1994) demonstrated that the ARAF1 gene in the human comprises 16 exons encoded by a minimum of 10,776 nucleotides.MAPPING
Huebner et al. (1986) used a human ARAF cDNA to map the genes in mouse and man. The mouse gene cosegregated with the X chromosome in Chinese hamster-mouse hybrid cells. In humans, 2 independently segregating loci, designated ARAF1 and ARAF2, were mapped to chromosomes X and 7, respectively. (Huebner et al. (1986) had not conclusively shown that the ARAF2 loc ... More on the omim web site
Jan. 22, 2020: 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 311010 was added.
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed