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J. Biol. Chem., Vol. 278, Issue 48, 47827-47833, November 28, 2003

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The Novel Murine Ca²⁺-binding Protein, Scarf, Is Differentially Expressed during Epidermal Differentiation^*

Meeyul Hwang and Maria I. Morasso

From the Developmental Skin Biology Unit, NIAMS, National Institutes of Health, Bethesda, Maryland 20892

Calcium (Ca²⁺) signaling-dependent systems, such as the epidermal differentiation process, must effectively respond to variations in Ca²⁺ concentration. Members of the Ca²⁺-binding proteins play a central function in the transduction of Ca²⁺ signals, exerting their roles through a Ca²⁺-dependent interaction with their target proteins, spatially and temporally. By performing a suppression subtractive hybridization screen we identified a novel mouse gene, Scarf (skin calmodulin-related factor), which has homology to calmodulin (CaM)-like Ca²⁺-binding protein genes and is exclusively expressed in differentiating keratinocytes in the epidermis. The Scarf open reading frame encodes a 148-amino acid protein that contains four conserved EF-hand motifs (predicted to be Ca²⁺-binding domains) and has homology to mouse CaM, human CaM-like protein, hClp, and human CaM-like skin protein, hClsp. The functionality of Scarf EF-hand domains was assayed with a radioactive Ca²⁺-binding method. By Southern blot and computational genome sequence analysis, a highly related gene, Scarf2, was found 15 kb downstream of Scarf on mouse chromosome 13. The functional Scarf Ca²⁺-binding domains suggest a role in the regulation of epidermal differentiation through the control of Ca²⁺-mediated signaling.

Received for publication, June 20, 2003 , and in revised form, August 5, 2003.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AY293058 and AY314008.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Developmental Skin Biology Unit, Bldg. 50, Rm. 1525, NIAMS, National Institutes of Health, Bethesda, MD 20892. Tel.: 301-435-7842; Fax: 301-435-7910; E-mail: morasso{at}nih.gov.

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