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Gene Review

SPRR2A  -  small proline-rich protein 2A

Homo sapiens

Synonyms: 2-1, SPR-2A, Small proline-rich protein 2A
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Disease relevance of SPRR2A

  • This first report of expression of ESE-1, and of SPRR2A and ENDOA/CK8 (both related to terminal differentiation in different types of epithelia lining) in anal cancer excludes the hypothesis that these genes influenced carcinogenesis in our patients [1].
  • The metabolism of hydroxyproline was investigated in six healthy subjects and four patients with chronic renal insufficiency (creatinine clearances respectively 40, 10, 7, 2 1/2 ml/min) [2].

High impact information on SPRR2A

  • Interdependent transcription control elements regulate the expression of the SPRR2A gene during keratinocyte terminal differentiation [3].
  • Skn-1a and Skn-1d1 bound the SPRR2A octamer site with comparable affinity and functioned as transcriptional activators [4].
  • The strict AP-1 requirement in SPRR1A for calcium-induced differentiation is not found for SPRR2A, despite the presence of an identical AP-1 consensus binding site in this gene [5].
  • Interestingly, ELF3 suppressed basal keratin 4 promoter activity in both esophageal and cervical epithelial cancer cell lines, a novel result, while simultaneously activating the late-differentiation linked SPRR2A promoter [6].
  • Apparently, the association of the SPRR2A gene with the nuclear matrix results in a general, differentiation-independent enhancement of gene expression [7].

Biological context of SPRR2A

  • The single intron of SPRR2A enhanced the activity of the SPRR2A promoter in transient transfection assays [7].
  • The inhibitory effect is targeted to a 150-bp minimal promoter region, which is essential and sufficient for SPRR2A expression during keratinocyte terminal differentiation [8].
  • The conserved high mobility group (HMG) box domain found in the MAT1-2-1 protein was used as a starting point for cloning and sequencing the entire MAT1-2 idiomorph plus flanking regions [9].

Anatomical context of SPRR2A


Associations of SPRR2A with chemical compounds

  • Expression of the SPRR2A gene, a member of the small proline-rich family of cornified cell envelope precursor proteins, is strictly linked to keratinocyte terminal differentiation both in vivo and in vitro [3].

Regulatory relationships of SPRR2A

  • Epidermal growth factor (EGF) enhances the expression of the keratinocyte terminal differentiation marker SPRR2A, when added to monolayers of basal keratinocytes, induced to stratify by increasing the extracellular calcium concentration [8].

Other interactions of SPRR2A

  • This indicates that the Ras and PKC pathways, which both can be triggered by EGF, although at different time points, have opposite effects on SPRR2A gene expression [8].
  • SPR2B protein quantities were moderately increased while SPR2A was not significantly changed [11].

Analytical, diagnostic and therapeutic context of SPRR2A

  • Deletion mapping and site-directed mutagenesis of SPRR2A promoter-chloramphenicol acetyltransferase constructs indicate that four transcription control elements are essential and sufficient for promoter activity [3].
  • Expression of SPRR2A and ENDOA/CK8, two epithelium-specific ESE-1 target genes, were revealed by RT-PCR in all cases [1].


  1. Expression analysis and mutational screening of the epithelium-specific ets gene-1 (ESE-1) in patients with squamous anal cancer. Zucchini, C., Strippoli, P., Rosati, G., Del Governatore, M., Milano, E., Ugolini, G., Solmi, R., Mattei, G., Caira, A., Zanotti, S., Carinci, P., Valvassori, L. Int. J. Oncol. (2000) [Pubmed]
  2. The use of hydroxy-DL-proline-2-(14)C in the investigation of hydroxyproline metabolism in normal subjects and in patients with renal insufficiency. Hart, W., van den Hamer, C.J., van der Sluys Veer, J. Clin. Nephrol. (1976) [Pubmed]
  3. Interdependent transcription control elements regulate the expression of the SPRR2A gene during keratinocyte terminal differentiation. Fischer, D.F., Gibbs, S., van De Putte, P., Backendorf, C. Mol. Cell. Biol. (1996) [Pubmed]
  4. Distinct functional interactions of human Skn-1 isoforms with Ese-1 during keratinocyte terminal differentiation. Cabral, A., Fischer, D.F., Vermeij, W.P., Backendorf, C. J. Biol. Chem. (2003) [Pubmed]
  5. AP-1 and ets transcription factors regulate the expression of the human SPRR1A keratinocyte terminal differentiation marker. Sark, M.W., Fischer, D.F., de Meijer, E., van de Putte, P., Backendorf, C. J. Biol. Chem. (1998) [Pubmed]
  6. Dual function of the epithelial specific ets transcription factor, ELF3, in modulating differentiation. Brembeck, F.H., Opitz, O.G., Libermann, T.A., Rustgi, A.K. Oncogene (2000) [Pubmed]
  7. Involvement of a nuclear matrix association region in the regulation of the SPRR2A keratinocyte terminal differentiation marker. Fischer, D.F., van Drunen, C.M., Winkler, G.S., van de Putte, P., Backendorf, C. Nucleic Acids Res. (1998) [Pubmed]
  8. Opposite effects of Ras or PKC activation on the expression of the SPRR2A keratinocyte terminal differentiation marker. Sark, M.W., Borgstein, A.M., Medema, J.P., van de Putte, P., Backendorf, C. Exp. Cell Res. (1999) [Pubmed]
  9. Mating-type genes from asexual phytopathogenic ascomycetes Fusarium oxysporum and Alternaria alternata. Arie, T., Kaneko, I., Yoshida, T., Noguchi, M., Nomura, Y., Yamaguchi, I. Mol. Plant Microbe Interact. (2000) [Pubmed]
  10. Up-regulated gene expression in the conjunctival epithelium of patients with Sjögren's syndrome. Kawasaki, S., Kawamoto, S., Yokoi, N., Connon, C., Minesaki, Y., Kinoshita, S., Okubo, K. Exp. Eye Res. (2003) [Pubmed]
  11. Infection with Human Papillomavirus alters expression of the small proline rich proteins 2 and 3. Lehr, E., Hohl, D., Huber, M., Brown, D. J. Med. Virol. (2004) [Pubmed]
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