Cres2 and Cres3: new members of the cystatin-related epididymal spermatogenic subgroup of family 2 cystatins

Endocrinology. 2003 Mar;144(3):909-15. doi: 10.1210/en.2002-220890.


The cystatin-related epididymal spermatogenic (CRES) and recently identified testatin and cystatin T proteins define a new subgroup within the family 2 cystatins of cysteine protease inhibitors. Members of the CRES subgroup are predominantly expressed in reproductive tissues and lack critical cystatin active-site sequences implying divergent functions. To determine whether there are additional members of the subgroup, we searched nucleotide databases and identified two novel genes that we designated Cres2 and Cres3. These genes, like other subgroup members, encode proteins with four conserved cysteine residues and predicted molecular weights characteristic of family 2 cystatins but have divergent cystatin inhibitory sequences. Furthermore, the genes exhibited reproductive-specific expression with Cres2 exclusively expressed in the epithelial cells of the proximal and midcaput epididymal regions and Cres3 expressed in the proximal caput epididymal epithelium, Sertoli cells of the testis, and early follicles and corpora lutea in the ovary. Additional studies showed that, like Cres, both Cres2 and Cres3 genes are dependent on testicular factors for epididymal expression. Taken together, CRES2 and CRES3 represent new members of a subgroup of cystatin family 2 proteins that likely carry out tissue-specific functions distinct from that of typical cystatins.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Northern
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • Corpus Luteum / chemistry
  • Cystatins / analysis
  • Cystatins / chemistry
  • Cystatins / genetics*
  • DNA, Complementary / analysis
  • Epididymis / chemistry
  • Epithelium / chemistry
  • Female
  • Gene Expression Regulation
  • Gene Expression*
  • In Situ Hybridization
  • Male
  • Mice
  • Molecular Sequence Data
  • Orchiectomy
  • Ovarian Follicle / chemistry
  • Promoter Regions, Genetic
  • RNA, Messenger / analysis
  • Sertoli Cells / chemistry
  • Testis / chemistry
  • Tissue Distribution


  • CCAAT-Enhancer-Binding Protein-beta
  • Cst11 protein, mouse
  • Cst12 protein, mouse
  • Cystatins
  • DNA, Complementary
  • RNA, Messenger
  • Cst8 protein, mouse