FAS-associated factor 1 (FAF1)
The protein contains 650 amino acids for an estimated molecular weight of 73954 Da.
Ubiquitin-binding protein (PubMed:19722279). Required for the progression of DNA replication forks by targeting DNA replication licensing factor CDT1 for degradation (PubMed:26842564). Potentiates but cannot initiate FAS-induced apoptosis (By similarity). (updated: May 23, 2018)
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.
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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Biological Process
Apoptotic process
Cell death
Cytoplasmic sequestering of NF-kappaB
Positive regulation of apoptotic process
Positive regulation of cell death
Positive regulation of cellular protein catabolic process
Positive regulation of DNA replication
Positive regulation of extrinsic apoptotic signaling pathway via death domain receptors
Positive regulation of protein-containing complex assembly
Proteasome-mediated ubiquitin-dependent protein catabolic process
Regulation of cell adhesion
Regulation of protein catabolic process
Regulation of protein kinase activity
The reference OMIM entry for this protein is 604460
Fas-associated factor 1; faf1
Hfaf1
CLONING
Interaction of Fas ligand (TNFSF6; 134638) with FAS antigen (TNFRSF6; 134637) mediates programmed cell death, also called apoptosis, in a number of organ systems, notably the immune and nervous systems. Although these molecules are in the same family as TNF-alpha (191160) and TNFR (191190), the latter function to activate not only apoptosis but also NFKB1 (164011), a key transcription factor in chronic inflammatory diseases. By screening tumor-related proteins derived from a HeLa cDNA library in a yeast 2-hybrid assay, Ryu et al. (1999) isolated a truncated version of FAF1, which could enhance but not initiate apoptosis. Using PCR as well as sequence information from an EST database to screen HeLa as well as brain and kidney cDNA libraries, they derived a product corresponding to the expected size of the complete coding region of 1,970 bp. The deduced 650-amino acid protein has 2 ubiquitin homology domains (UB1 and UB2) near the N terminus, followed by a nuclear localization signal, a region of homology with chromatin assembly factor p150 (CHAF1A; 601246), and a C-terminal domain showing homology with proteins involved in ubiquitination. The human protein is 96% and 85% homologous to mouse and quail Faf1, respectively. Northern blot analysis revealed a single FAF1 mRNA transcript of 2.8 kb that was most abundant in testis, slightly less abundant in skeletal muscle and heart, followed by prostate, thymus, ovary, small intestine, and colon. Expression was detected in all other tissues tested with the exception of peripheral blood leukocytes. By immunoblotting with a mouse polyclonal antibody to FAF1, a 74-kD protein was detected in 6 of 8 tumor cell lines. A 40-kD protein was detected in 1 of the 2 remaining cell lines. Using whole-mount in-situ hybridization in zebrafish embryos, Ghassibe-Sabbagh et al. (2011) detected faf1 transcripts at 24 and 30 hours postfertilization (hpf) in the pharyngeal arch primordia. At 56 hpf, when the pharyngeal cartilages were forming, faf1 was strongly expressed in all arches, with the most prominent expression in the first (mandibular) and second (hyoid) arch. Knockdown of zebrafish faf1 led to pharyngeal cartilage defects and jaw abnormalities as a result of a failure of the cranial neural crest to differentiate and to express cartilage-specific markers, such as sox9a (see 608160) and col2a1 (see 120140). Administration of faf1 mRNA rescued the phenotype.GENE FUNCTION
Ryu et al. (1999) showed that FAF1 and FAS interacted in both yeast 2-hybrid and GST pull-down assay systems. The N-terminal 201 amino acids of FAF1, containing the UB1 domain, bound to the FAS death domain, but not to a death domain mutant, in the yeast 2-hybrid system. Using immunoprecipitation and protein pull-down assays, Sul et al. (2013) found that FAF1 interacted with the E3 ubiquitin ligase parkin (PARK2; 602544) in SH-SY5Y human neuroblastoma cells. Deletion analysis revealed that the UB1 domain of FAF1 and the N-terminal half of parkin, which includes a ubiquitin-like domain and a RING1 domain, were required for the interaction. Parkin overexpression significantly increased ubiquitination of FAF1. Parkin used UBCH7 (UBE2L3; 603721) as the E2 ubiquitin-conjugating enzyme for lys48-linked ubiquitination of FAF1, which targeted FAF1 for proteasomal degradation. Exposure of SH-SY5Y cells to Parkinson disease (PD; see 168600)-inducing neurotoxin 1-methyl-4-phenylpyridinium caused FAF1-dependent cell death ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
May 26, 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
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604460 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed