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Gene Review

SCAF1  -  SR-related CTD-associated factor 1

Homo sapiens

Synonyms: FLJ00034, SCAF, SFRS19, SR-A1, SR-related and CTD-associated factor 1, ...
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Disease relevance of SR-A1

  • 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 [1].
  • The CTD of human SR-A1 protein (aa 1187-1312), containing a conserved CTD-interaction domain and bearing a decahistidine (His10) tag was produced by DNA recombinant overexpression techniques in Escherichia coli from the vector pET16b and it was localized in the periplasmic space [2].
  • To the best of our knowledge, this is the first study examining the expression of the novel gene SR-A1 in colon cancer progression [3].
  • High SR-A1 expression was observed in 31/81 (38.3%) breast cancer tissues and was found to be more frequent in patients with tumors of large size (p=0.027), as well as in lymph node-positive patients (p=0.035) [4].
  • Chinese hamster ovary cells stably transfected with human SR-A bound Escherichia coli and Staphylococcus aureus but ingested few organisms [5].

High impact information on SR-A1

  • Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA activator (SRA) [6].
  • Because all nucleotide changes in the mutants that disrupted SRA function were silent mutations presumed not to alter deduced encoded amino acid sequence, our analysis provides strong evidence that SRA-mediated coactivation is executed by distinct RNA motifs and not by an encoded protein [6].
  • These findings support a role for mildly oxidized LDL in the redox regulation of macrophage differentiation and SR-A expression and suggest that increased vascular oxidative stress may contribute to the formation of both SMC and macrophage foam cells [7].
  • Here we show that coincubation of SMC with macrophages or oxidized low density lipoproteins (LDL) from macrophage-conditioned medium activates these same regulatory pathways and stimulates SR-A expression [7].
  • Oxidative stress caused by phorbol esters or reactive oxygen up-regulates the class A scavenger receptor (SR-A) in human smooth muscle cells (SMC), which normally do not express this receptor [7].

Chemical compound and disease context of SR-A1


Biological context of SR-A1


Anatomical context of SR-A1

  • Furthermore, the mRNA of the SR-A1 gene in these cell lines appears to increase by estrogens, androgens and glucocorticoids, and to a lesser extend by progestins [1].
  • Therefore, in the present study we examined the expression of the SR-A1 gene in colon cancer tissues by RT-PCR and found that it is overexpressed as compared to normal mucosa (p=0.01) [3].
  • Using these antisera we show that the expression of SR-A protein is induced during monocyte to macrophage differentiation and that SR-A mediates 80% of the uptake of acetylated low density lipoprotein by human monocyte-derived macrophages [9].
  • A specific and selective role for SR-A was shown, since bone marrow culture-derived Mphi from SR-A(-/-) mice ingested fewer E. coli organisms than did wild-type cells, while uptake of antibody-opsonized E. coli was unaffected [5].
  • In contrast, among a scavenger receptor family, IL-4 as well as histamine up-regulated U937 cells to express the LOX-1 gene but not the SR-A gene, which genes encode receptors that scavenge oxidized lipids [10].

Associations of SR-A1 with chemical compounds

  • Studies with the steroid hormone receptor-positive breast and prostate carcinoma cell lines ZR-75-1, BT-474 and LNCaP, respectively, suggest that SR-A1 is constitutively expressed [1].

Physical interactions of SR-A1

  • Performing a pull-down assay we proved that the novel SR-A1 [1187-1312 His10] protein interacts with the CTD domain of RNA polymerase II [2].

Other interactions of SR-A1

  • The SR-A1 protein contains an SR-rich domain as well as a CTD-binding domain present only in a subset of SR-proteins [1].
  • Expression of the C-terminal domain of novel human SR-A1 protein: interaction with the CTD domain of RNA polymerase II [2].

Analytical, diagnostic and therapeutic context of SR-A1

  • Follow-up analysis revealed that low SR-A1 expression increases the probability of both overall and disease-free survival of patients [4].
  • The antisera recognize both type I and II SR-A in a wide range of immunological techniques [9].
  • The fragment sequence of tie-1 promoter and human SR-A cDNA in plasmids pTie-1/hSR-A was correct and no ATG before the translation initiation sites of human SR-A was found by sequence analysis [11].


  1. 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, E.P. Br. J. Cancer (2001) [Pubmed]
  2. Expression of the C-terminal domain of novel human SR-A1 protein: interaction with the CTD domain of RNA polymerase II. Katsarou, M.E., Papakyriakou, A., Katsaros, N., Scorilas, A. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  3. 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) [Pubmed]
  4. 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) [Pubmed]
  5. Macrophage class A scavenger receptor-mediated phagocytosis of Escherichia coli: role of cell heterogeneity, microbial strain, and culture conditions in vitro. Peiser, L., Gough, P.J., Kodama, T., Gordon, S. Infect. Immun. (2000) [Pubmed]
  6. Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA activator (SRA). Lanz, R.B., Razani, B., Goldberg, A.D., O'Malley, B.W. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  7. Class A scavenger receptor up-regulation in smooth muscle cells by oxidized low density lipoprotein. Enhancement by calcium flux and concurrent cyclooxygenase-2 up-regulation. Mietus-Snyder, M., Gowri, M.S., Pitas, R.E. J. Biol. Chem. (2000) [Pubmed]
  8. Translocation breakpoints in three patients with campomelic dysplasia and autosomal sex reversal map more than 130 kb from SOX9. Wirth, J., Wagner, T., Meyer, J., Pfeiffer, R.A., Tietze, H.U., Schempp, W., Scherer, G. Hum. Genet. (1996) [Pubmed]
  9. Analysis of macrophage scavenger receptor (SR-A) expression in human aortic atherosclerotic lesions. Gough, P.J., Greaves, D.R., Suzuki, H., Hakkinen, T., Hiltunen, M.O., Turunen, M., Herttuala, S.Y., Kodama, T., Gordon, S. Arterioscler. Thromb. Vasc. Biol. (1999) [Pubmed]
  10. Effects of histamine and interleukin-4 synthesized in arterial intima on phagocytosis by monocytes/macrophages in relation to atherosclerosis. Higuchi, S., Tanimoto, A., Arima, N., Xu, H., Murata, Y., Hamada, T., Makishima, K., Sasaguri, Y. FEBS Lett. (2001) [Pubmed]
  11. Transgenic mice with overexpression of human scavenger receptor A on endothelial cells. Wan, L., Chung, S.K., Yang, Y., Chung, S.S., Cao, D., Ma, M., Wu, M., Wan, Z., Chen, X. Chin. Med. J. (2001) [Pubmed]
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