SCAF1 (SR-related CTD-associated factor 1)

Written2010-03Christos Kontos, Andreas Scorilas
Department of Biochemistry, Molecular Biology, Faculty of Biology, University of Athens, 157 01, Panepistimiopolis, Athens, Greece

(Note : for Links provided by Atlas : click)

1. Identity

Alias_symbol (synonym)
General Information
Other aliasSCAF
LocusID (NCBI) 58506
Atlas_Id 46074
Location 19q13.33  [Link to chromosome band 19q13]
Location_base_pair Starts at 49642125 and ends at 49658649 bp from pter ( according to hg19-Feb_2009)  [Mapping SCAF1.png]
Local_order Telomere to centromere.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
EBF1 (5q33.3) / SCAF1 (19q13.33)LINC01547 (21q22.3) / SCAF1 (19q13.33)SCAF1 (19q13.33) / ADAMTSL4 (1q21.3)
SCAF1 (19q13.33) / FLT3LG (19q13.33)SCAF1 (19q13.33) / MAP4K1 (19q13.2)SCAF1 (19q13.33) / TRAPPC6A (19q13.32)
VAMP8 (2p11.2) / SCAF1 (19q13.33)
Note The first name of this gene, discovered and cloned by Scorilas et al. was SR-A1. After the establishment of the name "SRA1" for steroid receptor RNA activator 1, the official name of SR-A1 gene has changed into SCAF1, to avoid confusion.


  Schematic representation of the SCAF1 gene. Exons are shown as boxes and introns as connecting lines. Arrows show the positions of the start codon, stop codon, and polyadenylation signal. Roman numerals indicate intron phases. The intron phase refers to the location of the intron within the codon; I denotes that the intron occurs after the first nucleotide of the codon, II that the intron occurs after the second nucleotide, and 0 that the intron occurs between distinct codons. The numbers inside boxes indicate exon lengths and the vertical connecting lines show the intron lengths (in bp). Figure is not drawn to scale.
Description Spanning 16.5 kb of genomic DNA, the SCAF1 gene consists of 11 exons and 10 intervening introns (Scorilas et al., 2001).
Transcription The unique transcript of SCAF1 gene is 4313 bp. The human SCAF1 gene was shown to be expressed widely in many normal tissues, but its mRNA levels vary a lot. The highest levels of SCAF1 transcripts were detected in the fetal brain and fetal liver and the lowest in salivary gland, skin, heart, uterus and ovary. In the mammary and prostate gland, SCAF1 mRNA transcripts are constitutively present at relatively high levels.
The mRNA levels of SCAF1 appear to increase 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).
Pseudogene Not identified so far.

3. Protein

  Schematic representation of the amino acid sequence of the SCAF1 protein. The Arg/Ser-rich domain is shown in bold and underlined, and the CTD-binding domain is double-underlined. Additionally, the SCAF1 protein contains two areas with negatively charged polyglutamic acid (E) stretches, shown as underlined with dashes, and an Arg/Asp-rich motif, which is normally underlined. Various putative post-translational modification sites have also been identified, including numerous potential sites for either O- or N-glycosylation, and several possible sites of phosphorylation by cAMP-dependent protein kinase (PKA), protein kinase C (PKC), and casein kinase 2.
Description The SCAF1 protein is composed of 1312 amino acids, with a calculated molecular mass of 139.1 kDa and a theoretical isoelectric point of 9.31.
The SCAF1 protein contains an Arg/Ser-rich domain (SR) as well as a CTD-binding domain, 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, Arg/Ser-rich proteins have been shown to regulate alternative splicing. In addition, we identified two areas with negatively charged polyglutamic acid (E) stretches and an Arg/Asp-rich motif in the SCAF1 protein. This motif is also present in a number of other RNA-binding proteins such as the U1-70 K, the RD RNA-binding protein and the 68 kDa human pre-mRNA cleavage factor Im.
Examination of the hydrophobicity profile of the SCAF1 protein did not reveal regions with long stretches of hydrophobic residues. SCAF1 is predicted to be a nuclear protein with no transmembrane region. Various putative post-translational modification sites have been identified, including numerous potential sites for either O- or N-glycosylation, and several possible sites of phosphorylation by cAMP-dependent protein kinase (PKA), protein kinase C (PKC), and casein kinase 2 (Scorilas et al., 2001).
Expression Currently, there are no data concerning the in vivo expression of the human SCAF1 protein.
Localisation The SCAF1 protein is predicted to be localized to the nucleus.
Function SCAF1 interacts with the CTD domain of the RNA polymerase II polypeptide A (POLR2A) and may be involved in pre-mRNA splicing.
Homology 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 PHRF1 protein ("PHD and RING finger domain-containing protein 1", also known as "CTD-binding SR-like protein rA9"), and to a lesser extent with other Arg/Ser-rich splicing factors.

4. Mutations

Note No germinal or somatic mutations associated with cancer have been identified so far.

5. Implicated in

Entity Breast and ovarian cancer
Prognosis Expression analysis of the SCAF1 gene has showed that SCAF1 mRNA expression may be considered as a new unfavorable prognostic marker for breast and ovarian cancer. Expression of the SCAF1 gene in breast cancer tissues is influenced by the tumor size and the existence of lymph node metastases. Furthermore, high SCAF1 expression is a significant independent prognostic marker of disease-free survival (DFS), and low mRNA expression of the gene is associated with long DFS and overall survival (OS).

Regarding SCAF1 gene expression in ovarian cancer, it is positively related to the histological grade and stage of the disease, the size of the tumor, and the debulking success. Additionally, high SCAF1 expression is a significant independent prognostic marker of OS, and low mRNA expression of the gene is related to long DFS and OS.

Entity Colon cancer
Prognosis SCAF1 mRNA expression seems also to be associated with colon cancer progression, since its expression is higher at the initial stages of tumorigenesis and is reduced as cancer progresses.
Entity Leukemia
Prognosis Alterations of SCAF1 mRNA expression have been noticed in the human acute promyelocytic leukemia cell line HL-60, after treatment with cisplatin and bleomycin. mRNA levels of SCAF1 are modulated in both cases as a response to apoptosis induction by each drug, with up-regulation in bleomycin-induced apoptosis and down-regulation in cisplatin-induced apoptosis in HL-60 cells. This differential response of SCAF1 mRNA levels to apoptosis induced by each drug may be due to distinct apoptotic pathways and therefore to distinct cellular needs for the splice variants of specific genes.
Cytogenetics No cytogenetic abnormalities have been identified so far.
Hybrid/Mutated Gene Not identified so far.

6. Bibliography

Effect of bleomycin and cisplatin on the expression profile of SRA1, a novel member of pre-mRNA splicing factors, in HL-60 human promyelocytic leukemia cells.
Katsarou ME, Thomadaki H, Katsaros N, Scorilas A.
Biol Chem. 2007 Aug;388(8):773-8.
PMID 17655495
Prognostic significance of the expression of SR-A1, encoding a novel SR-related CTD-associated factor, in breast cancer.
Leoutsakou T, Talieri M, Scorilas A.
Biol Chem. 2006 Dec;387(12):1613-8.
PMID 17132108
SR-A1, a member of the human pre-mRNA splicing factor family, and its expression in colon cancer progression.
Mathioudaki K, Leotsakou T, Papadokostopoulou A, Paraskevas E, Ardavanis A, Talieri M, Scorilas A.
Biol Chem. 2004 Sep;385(9):785-90.
PMID 15493872
Cloning of a gene (SR-A1), encoding for a new member of the human Ser/Arg-rich family of pre-mRNA splicing factors: overexpression in aggressive ovarian cancer.
Scorilas A, Kyriakopoulou L, Katsaros D, Diamandis EP.
Br J Cancer. 2001 Jul 20;85(2):190-8.
PMID 11461075

7. Citation

This paper should be referenced as such :
Kontos, C ; Scorilas, A
SCAF1 (SR-related CTD-associated factor 1)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(12):1149-1151.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 4 ]
  t(2;19)(p11;q13) VAMP8/SCAF1
SCAF1/FLT3LG (19q13)
SCAF1/MAP4K1 (19q13)
SCAF1/TRAPPC6A (19q13)

8. External links

HGNC (Hugo)SCAF1   30403
Entrez_Gene (NCBI)SCAF1  58506  SR-related CTD associated factor 1
GeneCards (Weizmann)SCAF1
Ensembl hg19 (Hinxton)ENSG00000126461 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000126461 [Gene_View] &nbspENSG00000126461 [Sequence]  chr19:49642125-49658649 [Contig_View]  SCAF1 [Vega]
ICGC DataPortalENSG00000126461
TCGA cBioPortalSCAF1
Genatlas (Paris)SCAF1
SOURCE (Princeton)SCAF1
Genetics Home Reference (NIH)SCAF1
Genomic and cartography
GoldenPath hg38 (UCSC)SCAF1  -     chr19:49642125-49658649 +  19q13.33   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)SCAF1  -     19q13.33   [Description]    (hg19-Feb_2009)
EnsemblSCAF1 - 19q13.33 [CytoView hg19]  SCAF1 - 19q13.33 [CytoView hg38]
Mapping of homologs : NCBISCAF1 [Mapview hg19]  SCAF1 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AK024444 BC011662 BC018398 BC023628 BC053992
RefSeq transcript (Entrez)NM_021228
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)SCAF1
Cluster EST : UnigeneHs.103521 [ NCBI ]
CGAP (NCI)Hs.103521
Alternative Splicing GalleryENSG00000126461
Gene ExpressionSCAF1 [ NCBI-GEO ]   SCAF1 [ EBI - ARRAY_EXPRESS ]   SCAF1 [ SEEK ]   SCAF1 [ MEM ]
Gene Expression Viewer (FireBrowse)SCAF1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets] &nbsp [Normal Tissue Atlas] &nbsp[carcinoma Classsification] &nbsp[NCI60]
GenevestigatorExpression in : [tissues] &nbsp[cell-lines] &nbsp[cancer] &nbsp[perturbations] &nbsp
BioGPS (Tissue expression)58506
GTEX Portal (Tissue expression)SCAF1
Human Protein AtlasENSG00000126461-SCAF1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9H7N4   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9H7N4  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9H7N4
Splice isoforms : SwissVarQ9H7N4
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)SCAF1
DMDM Disease mutations58506
Blocks (Seattle)SCAF1
Human Protein Atlas [tissue]ENSG00000126461-SCAF1 [tissue]
Peptide AtlasQ9H7N4
IPIIPI00303343   IPI00412372   
Protein Interaction databases
IntAct (EBI)Q9H7N4
Ontologies - Pathways
Ontology : AmiGORNA binding  nucleus  transcription by RNA polymerase II  mRNA processing  RNA splicing  protein domain specific binding  RNA polymerase II C-terminal domain binding  
Ontology : EGO-EBIRNA binding  nucleus  transcription by RNA polymerase II  mRNA processing  RNA splicing  protein domain specific binding  RNA polymerase II C-terminal domain binding  
NDEx NetworkSCAF1
Atlas of Cancer Signalling NetworkSCAF1
Wikipedia pathwaysSCAF1
Orthology - Evolution
GeneTree (enSembl)ENSG00000126461
Phylogenetic Trees/Animal Genes : TreeFamSCAF1
Homologs : HomoloGeneSCAF1
Homology/Alignments : Family Browser (UCSC)SCAF1
Gene fusions - Rearrangements
Fusion : MitelmanSCAF1/FLT3LG [19q13.33/19q13.33] &nbsp
Fusion : MitelmanSCAF1/MAP4K1 [19q13.33/19q13.2] &nbsp[t(19;19)(q13;q13)]  
Fusion : MitelmanSCAF1/TRAPPC6A [19q13.33/19q13.32] &nbsp[t(19;19)(q13;q13)]  
Fusion : MitelmanVAMP8/SCAF1 [2p11.2/19q13.33] &nbsp[t(2;19)(p11;q13)]  
Fusion PortalSCAF1 19q13.33 FLT3LG 19q13.33 HNSC
Fusion PortalSCAF1 19q13.33 MAP4K1 19q13.2 BRCA
Fusion PortalSCAF1 19q13.33 TRAPPC6A 19q13.32 GBM
Fusion : QuiverSCAF1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSCAF1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SCAF1
Exome Variant ServerSCAF1
ExAC (Exome Aggregation Consortium)ENSG00000126461
GNOMAD BrowserENSG00000126461
Varsome BrowserSCAF1
Genetic variants : HAPMAP58506
Genomic Variants (DGV)SCAF1 [DGVbeta]
DECIPHERSCAF1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisSCAF1 
ICGC Data PortalSCAF1 
TCGA Data PortalSCAF1 
Broad Tumor PortalSCAF1
OASIS PortalSCAF1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICSCAF1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDSCAF1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch SCAF1
DgiDB (Drug Gene Interaction Database)SCAF1
DoCM (Curated mutations)SCAF1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)SCAF1 (select a term)
NCG5 (London)SCAF1
Cancer3DSCAF1(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry SCAF1
NextProtQ9H7N4 [Medical]
Target ValidationSCAF1
Huge Navigator SCAF1 [HugePedia]
snp3D : Map Gene to Disease58506
BioCentury BCIQSCAF1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD58506
Chemical/Pharm GKB GenePA162402459
Clinical trialSCAF1
canSAR (ICR)SCAF1 (select the gene name)
DataMed IndexSCAF1
PubMed24 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu Jan 17 19:07:43 CET 2019

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