Splicing factor 3B subunit 4 (SF3B4)
The protein contains 424 amino acids for an estimated molecular weight of 44386 Da.
Involved in pre-mRNA splicing as a component of the splicing factor SF3B complex (PubMed:27720643). SF3B complex is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence (BPS) in pre-mRNA. Sequence independent binding of SF3A/SF3B complex upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA (PubMed:12234937). May also be involved in the assembly of the 'E' complex. SF3B4 has been found in complex 'B' and 'C' as well (PubMed:10882114). Belongs also to the minor U12-dependent spliceosome, which is involved in the splicing of rare class of nuclear pre-mRNA intron (PubMed:15146077). (updated: Jan. 31, 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.
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
Gene expression
MRNA processing
MRNA splicing, via spliceosome
Positive regulation of mRNA splicing, via spliceosome
Regulation of RNA metabolic process
RNA splicing
RNA splicing, via transesterification reactions
The reference OMIM entry for this protein is 154400
Acrofacial dysostosis 1, nager type; afd1
Mandibulofacial dysostosis, treacher collins type, with limb anomalies
Nager acrofacial dysostosis
Afd, nager type
Nager syndrome
A number sign (#) is used with this entry because of evidence that the Nager type of acrofacial dysostosis (AFD1) is caused by heterozygous mutation in the SF3B4 gene (605593) on chromosome 1q21.
DESCRIPTION
Nager syndrome is the prototype for a group of disorders collectively referred to as the acrofacial dysostoses (AFDs), which are characterized by malformation of the craniofacial skeleton and the limbs. The major facial features of Nager syndrome include downslanted palpebral fissures, midface retrusion, and micrognathia, the latter of which often requires the placement of a tracheostomy in early childhood. Limb defects typically involve the anterior (radial) elements of the upper limbs and manifest as small or absent thumbs, triphalangeal thumbs, radial hypoplasia or aplasia, and radioulnar synostosis. Phocomelia of the upper limbs and, occasionally, lower-limb defects have also been reported. The presence of anterior upper-limb defects and the typical lack of lower-limb involvement distinguishes Nager syndrome from Miller syndrome (263750), another rare AFD; however, distinguishing Nager syndrome from other AFDs, including Miller syndrome, can be challenging (summary by Bernier et al., 2012).CLINICAL FEATURES
Nager acrofacial dysostosis was recognized as a specific entity by Nager and de Reynier (1948), but was probably first reported by Slingenberg (1908). The limb deformities in the Nager syndrome consist of absence of radius, radioulnar synostosis, and hypoplasia or absence of the thumbs. The mandibulofacial dysostosis is characterized mainly by severe micrognathia and malar hypoplasia. The disorder reported by Walker (1974) in sibs whose parents were normal may have been Nager syndrome. Weinbaum et al. (1981) described a kindred in which the proband had classic Nager syndrome and 5 other persons covering 4 generations showed lesser expression. They suggested that ptosis of the lower lids, hypoplasia of the lower lid eyelashes, and cartilaginous pegs between the antitragus and lobule are minimal expressions of the syndrome. Richieri-Costa et al. (1983) described 2 sisters, offspring of nonconsanguineous parents, who had facial and skeletal anomalies. One had mandibulofacial dysostosis with bilateral radial ray anomalies. The other had cleft lip and palate with hypoplastic thumbs. Halal et al. (1983) reported 4 patients and reviewed all previous cases. This led to an extended characterization of Nager acrofacial dysostosis, e.g., description of lower limb defects. The differentiation from AFD with postaxial defects (263750), the hemifacial microsomia/Goldenhar radial defect syndrome, and other syndromes was discussed. Opitz (1987) suggested that Nager acrofacial dysostosis represents an 'anomaly' rather than a syndrome because of its apparent causal heterogeneity. Aylsworth et al. (1987) described findings in a father and child consistent with the Nager syndrome and supporting autosomal dominant inheritance. In addition to cranial features, the child had a small left thumb and absence of the right thumb. The father had similar facial features, a nonfunctional, proximally placed right thumb, and the history of a rudimentary left thumb that was removed during childhood. Aylsworth and Lin (1990) described an affected father and 2 sons. One of the sons had Hirschsprung disease. Goldstein and Mirkin (1988) described an unusually severe form. Palomeque et al. (1990) also reported a severely affected patient. Bon ... More on the omim web site
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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 154400 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed