Spanning 18.2 kb of genomic DNA, the SCAF1 gene consists of 13 exons and 12 intervening introns.

Twenty-three transcripts of the SCAF1 gene have been annotated. The primary transcript (SCAF1 v.1; GenBank accession number: NM_021228.3) has a length of 4222 bp and an open reading frame (ORF) (Scorilas et al., 2001). This transcript is widely present in many normal tissues, with its levels varying importantly. The highest levels of SCAF1 v.1 were detected in fetal brain and fetal liver and the lowest in salivary gland, skin, heart, uterus, and ovary. In the mammary and prostate gland, SCAF1 v.1 is constitutively present at relatively high levels. Additionally, SCAF1 v.1 levels are increased in cancer cell lines treated with various steroid hormones, including estrogens, androgens and glucocorticoids, and to a lesser extent with progestins (Scorilas et al., 2001).
Recently, members of our research group discovered fifteen new SCAF1 transcripts (SCAF1 v.2 - v.16; GenBank accession numbers: KY849380.1 - KY849394.1), resulting from alternative splicing of the SCAF1 pre-mRNAs (Adamopoulos et al., 2018). These splice variants are much shorter compared to main transcript, as all of them lack exon 9. They show a wide expression profile in several cancerous and normal cells. Seven out of these fifteen SCAF1 splice variants seem to have an ORF, whereas the remaining eight novel transcripts contain a premature termination codon and thus represent non-sense-mediated mRNA decay (NMD) candidates.
Bioinformatic analysis of expressed sequence tags (ETSs) revealed three additional splice variants (v.X1, X2, and X3), all of which are predicted to be protein-coding. These transcripts have different 5 untranslated regions (5 UTRs), compared to aforementioned transcripts. Moreover, four partial sequences have been deposited in the Ensembl (accession numbers: ENST00000601038.5 and ENST00000595242.3) or GenBank databases (accession numbers: BC011662.2 and BQ896877.1).

Not identified so far.

The full-length SCAF1 protein is composed of 1312 amino acid residues, with a calculated molecular mass of 139.3 kDa and a theoretical isoelectric point of 9.31 (Scorilas et al., 2001). It contains an Arg/Ser-rich domain as well as a CTD-binding domain, which is present only in a subset of Arg/Ser-rich splicing factors. Through interactions with the pre-mRNA and the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), Arg/Ser-rich proteins have been shown to regulate alternative splicing (Scorilas et al., 2001; Katsarou et al., 2005). Moreover, it has been observed that Arg/Ser-rich proteins may participate in tumorigenesis by regulating alternative splicing of several mRNAs. In addition, two areas with negatively charged polyglutamic acid (E) stretches and an Arg/Asp-rich motif are present in the full-length protein sequence. This motif is also present in a number of other RNA-binding proteins such as the small nuclear ribonucleoprotein U1 subunit 70 (SNRNP70), the negative elongation factor complex member E (NELFE), and the 68 kDa human pre-mRNA cleavage factor Im (CPSF6).
Examination of the hydrophobicity profile of the primary SCAF1 protein did not reveal regions with long stretches of hydrophobic residues (Scorilas et al., 2001). Various putative post-translational modification sites have been identified, including numerous potential sites for either O- or N-glycosylation, N-myristoylation, as well as phosphorylation by protein kinase A (PKA), protein kinase C (PKC), and casein kinase 2 (CSNK2).
Seven SCAF1 protein isoforms are likely to be encoded by splice variants of this gene. These protein isoforms are expected to have completely different secondary structures. Interestingly, they lack the Arg/Ser-rich domain and are hence unlikely to be involved in the regulation of alternative splicing (Adamopoulos et al., 2018).

Currently, there are no data concerning the in vivo expression of the human SCAF1 protein.

The SCAF1 protein is predicted to be localized to the nucleus (Scorilas et al., 2001).

SCAF1 interacts with the CTD domain of the RNA polymerase II polypeptide A (POLR2A) and is involved in pre-mRNA splicing (Katsarou et al., 2005).

Human SCAF1 shares 85% amino acid identity and 91% similarity with the mouse and rat Scaf1 protein. Moreover, it shows 25% identity and 48% similarity with the human PHD and ring finger domains 1 protein (PHRF1), and to a lesser extent with other Arg/Ser-rich splicing factors (Scorilas et al., 2001).

SCAF1 was mutated in some cases of patients with familial focal and segmental glomerulosclerosis, a histologically defined pattern of kidney injury (Wang et al., 2019).

A single nucleotide polymorphism (SNP), rs12104272, located within the first intron of the SCAF1 gene, is be associated with liver cirrhosis in patients with hepatitis C virus. Specifically, the majority of patients with hepatitis C that were carriers of this dominant allele, did not exhibit liver cirrhosis (Real et al., 2014). SCAF1 was also mutated in some cases of patients with pulmonary sarcomatoid carcinoma. Specifically, alterations either without predicted effect or with deleterious effect were observed (Liu et al., 2016). Moreover, SCAF1 was mutated in some cases of patients with sporadic focal and segmental glomerulosclerosis, a histologically defined pattern of kidney injury (Wang et al., 2019).