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At least 37 records · Page 2Linked to original sources
PubMed1998

Hereditary cystatin C amyloid angiopathy: monitoring the presence of the Leu-68-->Gln cystatin C variant in cerebrospinal fluids and monocyte cultures by MS.

Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant condition in which the patients suffer at an early age from repeated cerebral haemorrhages. The development of HCCAA is directly linked to a Leu-68-->Gln (L68Q) mutation in the cystatin C protein sequence. The concentration of cystatin C in cerebrospinal fluid (CSF) of HCCAA patients is markedly diminished and cultivated monocytes from affected individuals accumulate cystatin C. The goal of this work was to characterize cystatin C isolated from CSF and monocyte cultures originating from healthy persons and HCCAA patients with respect to the L68Q mutation. Cystatin C was isolated by carboxymethylpapain affinity chromatography. Proteins from CSF and monocyte cultures that bound specifically to the carboxymethylated papain column were resolved by reverse-phase HPLC chromatography and tryptic peptides were subsequently analysed by matrix-assisted laser desorption ionization MS. No evidence for mutated cystatin C protein was found in CSF samples from healthy subjects or HCCAA patients, but approx. 60% of the protein was found to be hydroxylated on Pro-3. No evidence was found for secretion of mutated cystatin C from HCCAA monocytes. However, we obtained evidence for the presence of mutated cystatin C in HCCAA monocytes. These results support the conclusion that the mutated cystatin C is retained in association with the monocytes and not secreted. An increased intracellular concentration would presumably promote the aggregation and denaturation of the mutated cystatin C, leading to the formation of amyloid fibrils and cell death.

Amino Acid Sequence↗
PubMed2003

Cystatin E1 and E2, new members of male reproductive tract subgroup within cystatin type 2 family.

The family of type 2 cystatin proteins is a class of cysteine proteinase inhibitors that function as potent inhibitors of papain-like cysteine proteinases. Recent studies have suggested that cystatins in the male reproductive tract subgroup may perform functions distinct from those of typical cystatins. The objective of the present study was to identify and characterize the expression of new gene members of the cystatin family 2 in mouse male reproductive tissues. Two new members of cystatin family 2, named mouse Cystatin E1 and mouse Cystatin E2 (mCST E1 and mCST E2, respectively), were identified in mice by searching the National Center for Biotechnology Information database for proteins containing homology to known type 2 cystatins. Human CST E1 has recently been reported independently under the name CST 11. The deduced amino acid sequences of these genes have significant homology with the family 2 cystatins, including four conserved cysteine residues at the C-terminus. Similar to other male reproductive subgroup cystatins, the inhibitory motifs are not well conserved in these genes. Northern blot analyses showed that both genes were highly expressed only in the epididymis. In situ hybridization demonstrated that both genes were restricted in their expression to the epithelial cells of the caput and that the highest expression was localized to the initial segment of caput epididymis. Northern blot analyses and in situ hybridization showed that both mCST E1 and E2 mRNA decreased after castration, and treatment with testosterone propionate (T) did not maintain expression of these genes. In fact, T treatment further repressed the expression of these genes in the epididymis following castration. Efferent ductule ligation resulted in a dramatic decrease of epididymal expression of mCST E1 and E2. The expression of mCST E1 mRNA was up-regulated by 17 beta-estradiol (E) administration for 7 days postcastration, whereas no recovery of mCST E1 mRNA level was detected after 14 days of E treatment. Combined E and T (E+T) treatment for 1 and 2 wk reduced the mCST E1 transcripts. The expression of mCST E2 mRNA was maintained by E administration for both 7 and 14 days after castration, whereas treatment of both T and E repressed the expression of mCST E2. Although both mCST E1 and E2 share significant homology with family 2 cystatins, including similar distribution in tissues and localization in epididymis, these genes may have different functions, because their regulation involves different hormones and, probably, other testicular factors.

Amino Acid Sequence↗
PubMed1996

Inhibition of the growth and cysteine proteinase activity of Porphyromonas gingivalis by human salivary cystatin S and chicken cystatin.

The mutual effects of P. gingivalis and several cystatin species has been investigated. After incubation with P. gingivalis culture supernatant, cystatin S, cystatin C and chicken cystatin were truncated from a 14 kDa protein into a polypeptide of approximately 13 kDa. Amino acid sequence analysis of the truncated cystatin S polypeptide revealed that cystatin S was cleaved after Arg-8. All three types of truncated cystatins fully retained their inhibitory activity toward papain. Cystatin S and chicken cystatin partially inhibited proteolytic activity in the culture supernatant of P. gingivalis. Furthermore, cystatin S and chicken cystatin inhibited the growth of P. gingivalis in culture to 50% at approximately 1 microM.

Amino Acid Sequence↗
PubMed2004

Prevention of domain swapping inhibits dimerization and amyloid fibril formation of cystatin C: use of engineered disulfide bridges, antibodies, and carboxymethylpapain to stabilize the monomeric form of cystatin C.

Amyloidogenic proteins like cystatin C and prion proteins have been shown to form dimers by exchange of subdomains of the monomeric proteins. This process, called "three-dimensional domain swapping," has also been suggested to play a part in the generation of amyloid fibrils. One variant of cystatin C, L68Q cystatin C, is highly amyloidogenic, and persons carrying the corresponding gene suffer from massive cerebral amyloidosis leading to brain hemorrhage and death in early adult life. The present work describes the production of two variants of wild type and L68Q cystatin C with disulfide bridges at positions selected to inhibit domain swapping without affecting the biological function of the four cystatin C variants as cysteine protease inhibitors. The capacity of the four variant proteins to form dimers was tested and compared with that of wild type and L68Q cystatin C. In contrast to the latter two proteins, all four protein variants stabilized by disulfide bridges were resistant toward the formation of dimers. The capacity of the two stabilized variants of wild type cystatin C to form amyloid fibrils was investigated and found to be reduced by 80% compared with that of wild type cystatin C. In an effort to investigate whether exogenous agents could also suppress the formation of dimers of wild type and L68Q cystatin C, a monoclonal antibody or carboxymethylpapain, an inactivated form of a cysteine protease, was added to systems inducing dimerization of wild type and L68Q cystatin C. It was observed that catalytic amounts of both the monoclonal antibody and carboxymethylpapain could suppress dimerization.

Amyloid↗
PubMed1990

The amino terminal portion of cerebrospinal fluid cystatin C in hereditary cystatin C amyloid angiopathy is not truncated: direct sequence analysis from agarose gel electropherograms.

The isolated amyloid substance in hereditary cystatin C amyloid angiopathy (HCCAA) is mainly composed of a cystatin C variant devoid of the 10 amino terminal amino acid residues of extracellular cystatin C from healthy individuals. We have developed a procedure for protein sequencing directly from agarose gel electropherograms and used this in conjunction with isoelectric focusing to investigate the amino terminal sequence of cerebrospinal fluid (CSF) cystatin C in HCCAA patients. The amino-terminal sequence determined for cystatin C from a HCCAA patient CSF sample, Xaa-Ser-Pro-Gly-Lys-Pro-Pro-Xaa-Leu-Val-Gly-Gly-Pro-Met-Xaa-Ala-Xaa-Val, showed that the protein was not amino-terminally truncated. CSF cystatin C from all nine HCCAA patients investigated was found to have an isoelectric point identical to that of native cystatin C, and the truncated form of cystatin C isolated from amyloid deposits was shown to contribute to less than 1% of the total amount of cystatin C in CSF. The total cysteine proteinase inhibitory capacity of CSF from HCCAA patients was lower than that of CSF from other patients. This decreased CSF inhibitory capacity in HCCAA patients was caused by decreased levels of cystatin C, since the levels of the other two cysteine proteinase inhibitors found in CSF, alpha 2-macroglobulin and kininogen, were significantly higher than in CSF from non-HCCAA patients.

Amino Acid Sequence↗
PubMed1994

Linkage between phosphorylated cystatin alpha and filaggrin by epidermal transglutaminase as a model of cornified envelope and inhibition of cathepsin L activity by cornified envelope and the conjugated cystatin alpha.

Lysine-rich phosphorylated cystatin alpha (P-cystatin alpha) from newborn rat epidermis is a good substrate for epidermal transglutaminase (TGase) and also one of the component proteins of cornified envelope in the stratum corneum. Since the filaggrin linker segment peptide was efficiently conjugated with P-cystatin alpha and was mediated by epidermal TGase in the presence of Ca2+ ions, filaggrin is a candidate for the glutamine-rich linkage protein to conjugate with lysine-rich P-cystatin alpha. A conjugated protein was found by epidermal TGase in the activated condition with Ca2+ ions and dithiothreitol. In contrast, the conjugated protein was not formed under chelated conditions with EDTA. The conjugated protein reacted positively with anti-P-cystatin alpha polyclonal antibody (PoAb). The conjugated protein and purified cornified envelope showed an inhibitory effect against papain and cathepsin L, but cathepsin B and H were not inhibited by these P-cystatin alpha conjugates. Although the component protein, P-cystatin alpha itself, inhibited cathepsin H strongly, these conjugated proteins inhibited specifically the cathepsin L family. The amino acid composition of cornified envelope protein and the conjugated protein of P-cystatin alpha and filaggrin linker segment peptide was not completely the same. The conjugated protein of P-cystatin alpha and filaggrin linker segment peptide showed the same inhibitory properties against cysteine proteinases as the cornified envelope. These findings suggest that the linkage protein between P-cystatin alpha and filaggrin linker segment peptide may be considered a model of cornified envelope, although skin cornified envelope may be conjugated with some additional proteins.

Amino Acid Sequence↗
PubMed1992

Characterization of two members (CST4 and CST5) of the cystatin gene family and molecular evolution of cystatin genes.

Two members (CST4 and CST5) of the cystatin gene family have been characterized partially by DNA analysis. The CST4 clone contained the gene coding for the precursor form(141 amino acids) of cystatin S, and its exon-intron organization is the same as that of other members (the cystatin SN gene at the CST1 locus, the cystatin SA gene at the CST2 locus, the cystatin C gene at the CST3 locus and a cystatin pseudogene at the CSTP1 locus). The second cystatin pseudogene was elucidated in the clone, CST5, and it was assigned to the CSTP2 locus. Alignment of DNA sequences of cystatin genes with other genes suggested that the genes for cystatins, kininogens, and Bowman-Birk type inhibitors have evolved from an ancient ribonuclease-like gene.

Amino Acid Sequence↗
PubMed1994

Expressions of the genes for cysteine proteinase inhibitors cystatin C and cystatin S in rat submandibular salivary gland.

Rat cystatin S and rat cystatin C are members of family 2 (cystatin) of the cystatin superfamily. All members of the cystatin family inhibit cysteine proteinases to varying degree. The expression of these two inhibitors, which have a 48% similarity at the nucleotide level, was studied in the submandibular gland using reverse transcriptase-polymerase chain reaction (RT-PCR). Northern blot hybridization and in situ hybridization with digoxigenin-labelled DNA probes. Both inhibitors were expressed in the serous acinar cells of the submandibular gland. In accord with previous findings, cystatin S mRNA was induced by the beta-adrenergic agonist isoproterenol. The level of cystatin S mRNA, which was very low in the glands of untreated rats and was demonstrable by RT-PCR but not by Northern blot hybridization, was not altered by acute inflammation produced by turpentine. Neither the administration of isoproterenol nor acute inflammation had any effect on the level of cystatin C mRNA, indicating beta-adrenoreceptors are not involved in the regulation of the cystatin C gene(s) in the submandibular gland. The data indicate that these two closely related genes, expressed in the same cells, are differently regulated. The consequence of this difference in gene regulation on the physiological and pathological roles of these inhibitors remains to be established.

Animals↗
PubMed1989

Studies on the reactive site of the cystatin superfamily using recombinant cystatin A mutants. Evidence that the QVVAG region is not essential for cysteine proteinase inhibitory activities.

For study of the inhibition mechanism of the cystatin superfamily, cystatin A artificial mutants were obtained in which a well-conserved QVVAG region in the cystatin superfamily was changed to KVVAG or QVTAG and these mutants were then expressed in E. coli. For this, genes with these sequences were synthesized enzymatically from 11 oligodeoxynucleotides and expressed under the tac promoter gene of the E. coli plasmids. The products expressed were then purified on Sephadex G-50 and HPLC DEAE-5PW columns. The substitutions in cystatin A were confirmed by the amino acid compositions, N-terminal amino acid sequences and elution positions on ion-exchange chromatography of the products. The Ki values of these products for the cysteine proteinases, papain and cathepsins B, H and L, were determined in comparison with those of wild type recombinant cystatin A. Results showed that the cystatin A mutants had similar inhibitory activities to those of wild type recombinant cystatin A. Namely replacement of amino acids in the QVVAG sequence of cystatin A did not significantly affect the inhibitory activities on these proteinases. The results suggest that the QVVAG region is less important than the N-terminal region of cystatin for inhibitory activities on cysteine proteinases.

Amino Acid Sequence↗
PubMed2000

The N-terminal region of cystatin A (stefin A) binds to papain subsequent to the two hairpin loops of the inhibitor. Demonstration of two-step binding by rapid-kinetic studies of cystatin A labeled at the N-terminus with a fluorescent reporter group.

The three-dimensional structures of cystatins, and other evidence, suggest that the flexible N-terminal region of these inhibitors may bind to target proteinases independent of the two rigid hairpin loops forming the remainder of the inhibitory surface. In an attempt to demonstrate such two-step binding, which could not be identified in previous kinetics studies, we introduced a cysteine residue before the N-terminus of cystatin A and labeled this residue with fluorescent probes. Binding of AANS- and AEDANS-labeled cystatin A to papain resulted in approximately 4-fold and 1.2-fold increases of probe fluorescence, respectively, reflecting the interaction of the N-terminal region with the enzyme. Observed pseudo-first-order rate constants, measured by the loss of papain activity in the presence of a fluorogenic substrate, for the reaction of the enzyme with excess AANS-cystatin A increased linearly with the concentration of the latter. In contrast, pseudo-first-order rate constants, obtained from measurements of the change of probe fluorescence with either excess enzyme or labeled inhibitor, showed an identical hyperbolic dependence on the concentration of the reactant in excess. This dependence demonstrates that the binding occurs in two steps, and implies that the labeled N-terminal region of cystatin A interacts with the proteinase in the second step, subsequent to the hairpin loops. The comparable affinities and dissociation rate constants for the binding of labeled and unlabeled cystatin A to papain indicate that the label did not appreciably perturb the interaction, and that unlabeled cystatin therefore also binds in a similar two-step manner. Such independent binding of the N-terminal regions of cystatins to target proteinases after the hairpin loops may be characteristic of most cystatin-proteinase reactions.

Animals↗
PubMed1989

The human cystatin C gene (CST3) is a member of the cystatin gene family which is localized on chromosome 20.

The fourth gene from the human cystatin gene family of salivary-type cysteine-proteinase inhibitors has been isolated and partially characterized by DNA analysis. The gene, which we name CST3, codes for human cystatin C, and has the same organization as the CST1 gene for cystatin SN and the CST2 gene for cystatin SA. Southern analysis of EcoR I digested DNAs from 32 independent somatic cell hybrid clones hybridized to a probe from CST1 demonstrated that all members of the cystatin gene family segregate with human chromosome 20. These results indicate that the genes for salivary-type cystatins and cystatin C are members of a multigene family--the cystatin gene family.

Amino Acid Sequence↗
PubMed2005

Cystatin C levels are decreased in acute myocardial infarction: effect of cystatin C G73A gene polymorphism on plasma levels.

BACKGROUND: Cystatin C is the most abundant protease inhibitor in the plasma. Low plasma levels have been found in patients with aortic aneurysms and they seem correlated with the extension of the aortic lesions in early aneurysms detected by ultrasonography. METHODS: In this study, plasma levels of cystatin C have been investigated in patients with acute myocardial infarction (AMI), unstable angina and controls. The effect on plasma levels of the G73A polymorphism of the CST3 gene has been also evaluated. RESULTS: Patients with acute myocardial infarction showed significantly lower levels of cystatin C compared to unstable angina and controls, but levels were nearly normal in a week after the acute event. The genotype distribution of the G73A polymorphism was not different among the groups. Nevertheless, cystatin C levels decreased proportionally with the number of A alleles. Cystatin C levels were positively correlated with age, triglyceride/HDL cholesterol ratio and creatinine, and negatively with HDL cholesterol and the number of A alleles. All variables, but not HDL cholesterol, were independently correlated in a multivariate analysis. CONCLUSIONS: Cystatin C is decreased in acute myocardial infarction. It is still not clear whether lower cystatin C levels are causally linked to the acute event or just represent a negative acute phase response. The CST3 gene G73A polymorphism functionally affects cystatin C plasma levels.

Aged↗
PubMed2003

Salivary cystatin activity and cystatin C in experimental gingivitis in non-smokers.

BACKGROUND: Subjects with natural gingivitis and periodontitis have elevated levels of salivary cystatins compared to periodontally healthy individuals. Experimental gingivitis studies, however, have yielded conflicting results. AIM: The present study investigated whether experimentally induced gingivitis is associated with changes in salivary cystatin levels. MATERIAL & METHODS: Plaque scores, bleeding indexes and whole saliva samples of 35 non-smoking young adults were collected at the start and at the end of an experimental gingivitis trial, and 3 weeks after resuming oral hygiene. The saliva samples were assayed for protein concentrations, cystatin activity and cystatin C concentration. RESULTS: During experimental gingivitis, plaque and bleeding scores increased significantly in all subjects and subsequently decreased significantly after reinstalment of oral hygiene procedures. No significant changes were observed for the protein concentration, cystatin activity and cystatin C concentration. No significant relation could be established between these salivary parameters and bleeding on marginal probing. CONCLUSION: The present study confirms earlier results from Lie et al. (2001) that no significant changes occur in salivary cystatin activity and cystatin C concentration during and after experimental gingivitis.

Adolescent↗
PubMed2006

Cystatin M/E is a high affinity inhibitor of cathepsin V and cathepsin L by a reactive site that is distinct from the legumain-binding site. A novel clue for the role of cystatin M/E in epidermal cornification.

Cystatin M/E is a high affinity inhibitor of the asparaginyl endopeptidase legumain, and we have previously reported that both proteins are likely to be involved in the regulation of stratum corneum formation in skin. Although cystatin M/E contains a predicted binding site for papain-like cysteine proteases, no high affinity binding for any member of this family has been demonstrated so far. We report that human cathepsin V (CTSV) and human cathepsin L (CTSL) are strongly inhibited by human cystatin M/E. Kinetic studies show that Ki values of cystatin M/E for the interaction with CTSV and CTSL are 0.47 and 1.78 nM, respectively. On the basis of the analogous sites in cystatin C, we used site-directed mutagenesis to identify the binding sites of these proteases in cystatin M/E. We found that the W135A mutant was rendered inactive against CTSV and CTSL but retained legumain-inhibiting activity. Conversely, the N64A mutant lost legumain-inhibiting activity but remained active against the papain-like cysteine proteases. We conclude that legumain and papain-like cysteine proteases are inhibited by two distinct non-overlapping sites. Using immunohistochemistry on normal human skin, we found that cystatin M/E co-localizes with CTSV and CTSL. In addition, we show that CTSL is the elusive enzyme that processes and activates epidermal transglutaminase 3. The identification of CTSV and CTSL as novel targets for cystatin M/E, their (co)-expression in the stratum granulosum of human skin, and the activity of CTSL toward transglutaminase 3 strongly imply an important role for these enzymes in the differentiation process of human epidermis.

Base Sequence↗
PubMed2005

Determination of the production rate and non-renal clearance of cystatin C and estimation of the glomerular filtration rate from the serum concentration of cystatin C in humans.

Cystatin C has been proposed as an endogenous marker for measuring glomerular filtration rate (GFR) and is regarded as being equivalent to or better than creatinine. However, there are no published data on the production rate (Cys(pr)) or on the non-renal clearance of cystatin C (CL(nr)) in humans, which are essential parameters for GFR calculation. GFR was determined by measuring the plasma clearance of iohexol. Cystatin C, creatinine, urea and albumin were determined on the same serum samples as iohexol; 381 patients with a GFR range of 12-151 ml/min/1.73 m2, and 70 patients on haemodialysis were evaluated. Renal clearance of cystatin C (CLr) equals GFR * S (the sieving coefficient). Plasma clearance (CL) = CLr + CLnr. The relationship between Cys(pr) and the elimination rate (CL * serum-cystatin C) can be expressed as Cys(pr) = (S * GFR+CLnr) * serum-cystatin C. Assuming that the unknown values of Cys(pr) and CLnr are independent of GFR, the equation can be solved from GFR (iohexol clearance) and serum cystatin C (s-Cys) patient data. For S=1, we found Cys(pr) = 0.124 +/- 0.023 mg/min/1.73 m2 and Cl(nr)=22.3 ml/min/1.73 m2. For S = 0.94, found in rats, the values will be Cys(pr) = 0.117 mg/min/1.73 m2 and Cl(nr) = 21 ml/min/1.73 m2 and S-Cys in 70 patients on chronic haemodialysis was found to be 5.74 +/- 1.15 mg/l, in agreement with a calculated value of 5.56 mg/l (s-Cys=124/22.3) for GFR=zero. The mean value of the calculated Cl(nr) for the 70 patients was 22.7 +/- 6.6 ml/min/1.73 m2, which confirms the calculated level and indicates its biological variation. We thus propose the following formula for calculating GFR using the values found for CLnr and Cys(pr) in this study: GFR=124/s - Cys - 22.3 ml/min/1.73 m2, where serum cystatin C concentration is given as mg/l.

Adolescent↗
PubMed1987

Histidine-rich glycoprotein is evolutionarily related to the cystatin superfamily. Presence of two cystatin domains in the N-terminal region.

A new member of the cystatin superfamily is introduced. Human plasma histidine-rich glycoprotein (HRG) was found to contain 2 cystatin-like sequences in tandem in the N-terminal region. Domain 1 (residues 1-112) was most homologous to domain 1 of the heavy chain of human kininogen and domain 2 (residues 113-225) was most homologous to human cystatin S as well as other cystatins and domain 3 of the heavy chain of kininogen, suggesting that the cystatin domains of HRG may represent a hitherto unknown binary form (or intermediate molecule) composed of 2 cystatin domains, and evolutionarily intermediate between the cystatin and the kininogen families.

Amino Acid Sequence↗
PubMed2003

Grafting of features of cystatins C or B into the N-terminal region or second binding loop of cystatin A (stefin A) substantially enhances inhibition of cysteine proteinases.

Replacement of the three N-terminal residues preceding the conserved Gly of cystatin A by the corresponding 10-residue long segment of cystatin C increased the affinity of the inhibitor for the major lysosomal cysteine proteinase, cathepsin B, by approximately 15-fold. This tighter binding was predominantly due to a higher overall association rate constant. Characterization of the interaction with an inactive Cys29 to Ala variant of cathepsin B indicated that the higher rate constant was a result of an increased ability of the N-terminal region of the chimeric inhibitor to promote displacement of the cathepsin B occluding loop in the second binding step. The low dissociation rate constant for the binding of cystatin A to cathepsin B was retained by the chimeric inhibitor, which therefore had a higher affinity for this enzyme than any natural cystatin identified so far. In contrast, the N-terminal substitution negligibly affected the ability of cystatin A to inhibit papain. However, substitutions of Gly75 in the second binding loop of cystatin A by Trp or His, making the loop similar to those of cystatins C or B, respectively, increased the affinity for papain by approximately 10-fold. This enhanced affinity was due to both a higher association rate constant and a lower dissociation rate constant. Modeling of complexes between the two variants and papain indicated the possibility of favorable interactions being established between the substituting residues and the enzyme. The second-loop substitutions negligibly affected or moderately reduced the affinity for cathepsin B. Together, these results show that the inhibitory ability of cystatins can be substantially improved by protein engineering.

Amino Acid Sequence↗
PubMed2003

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

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.

Amino Acid Sequence↗