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PMID:23139753

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Citation

Chhikara, N, Saraswat, M, Tomar, AK, Dey, S, Singh, S and Yadav, S (2012) Human Epididymis Protein-4 (HE-4): A Novel Cross-Class Protease Inhibitor. PLoS ONE 7:e47672

Abstract

Epididymal proteins represent the factors necessary for maturation of sperm and play a crucial role in sperm maturation. HE-4, an epididymal protein, is a member of whey acidic protein four-disulfide core (WFDC) family with no known function. A WFDC protein has a conserved WFDC domain of 50 amino acids with eight conserved cystine residue. HE-4 is a 124 amino acid long polypeptide with two WFDC domains. Here, we show that HE-4 is secreted in the human seminal fluid as a disulfide-bonded homo-trimer and is a cross-class protease inhibitor inhibits some of the serine, aspartyl and cysteine proteases tested using hemoglobin as a substrate. Using SPR we have also observed that HE-4 shows a significant binding with all these proteases. Disulfide linkages are essential for this activity. Moreover, HE-4 is N-glycosylated and highly stable on a wide range of pH and temperature. Taken together this suggests that HE-4 is a cross-class protease inhibitor which might confer protection against microbial virulence factors of proteolytic nature.

Links

PubMed PMC3489902 Online version:10.1371/journal.pone.0047672

Keywords


Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:WFDC2

GO:0004867: serine-type endopeptidase inhibitor activity

ECO:0000314:

F

Figure 4. A)Percentage inhibition of various proteases like: trypsin, chymottrypsin, PSA, proteinase K, pepsin and papain by HE-4. Graph shows a direct relationship with serine proteases.

complete
CACAO 5857

HUMAN:WFDC2

GO:0019828: aspartic-type endopeptidase inhibitor activity

ECO:0000314:

F

Figure 4. A)Percentage inhibition of various proteases like: trypsin, chymottrypsin, PSA, proteinase K, pepsin and papain by HE-4. Graph shows a direct relationship with aspartic proteases.

complete
CACAO 5858

HUMAN:WFDC2

enables

GO:0004867: serine-type endopeptidase inhibitor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:WFDC2

enables

GO:0019828: aspartic-type endopeptidase inhibitor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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