Eppin

experimental

Also known as: Cancer/testis antigen 71, Epididymal protease inhibitor, Protease inhibitor WAP7, Serine protease inhibitor-like with Kunitz and WAP domains 1, WAP four-disulfide core domain protein 7, EPPIN, O95925

**Mechanism of Action** Eppin (Epididymal protease inhibitor) is a serine protease inhibitor predominantly expressed in the male reproductive tract, particularly in the epididymis and testis. It contains both Kunitz-type and WAP (whey acidic protein) four-disulfide core domains, enabling it to inhibit serine proteases such as prostate-specific antigen (PSA) and acrosin. This inhibition is critical for regulating sperm motility, capacitation, and the acrosome reaction. Eppin also binds to the sperm surface via interactions with semenogelin and other seminal plasma proteins, contributing to the formation of a protective coating that modulates sperm function during transit through the female reproductive tract. **Key Research Findings** Preclinical studies demonstrate that Eppin is essential for male fertility; targeted disruption of the Eppin gene in animal models leads to impaired sperm motility, abnormal acrosome integrity, and reduced fertilization capacity. Immunocontraceptive approaches using Eppin as an antigen have shown promise in inducing reversible infertility in male primates without significant hormonal side effects. Additionally, Eppin expression has been detected in certain cancers (e.g., lung, breast, and ovarian tumors), where it may function as a cancer/testis antigen, though its role in oncogenesis remains under investigation. **Clinical Relevance** Eppin is primarily investigated as a target for non-hormonal male contraceptives, given its restricted expression in the reproductive tract and its critical role in sperm function. Its immunogenicity also positions it as a candidate for cancer vaccine development, particularly for tumors expressing this antigen. However, all applications remain at the experimental stage, with no approved therapies or diagnostics currently available. For research purposes only — not medical advice.

Key data

Category
Immune Modulation
Sequence
MGSSGLLSLLVLFVLLANVQGPGLTDWLFPRRCPKIREECEFQERDVCTKDRQCQDNKKCCVFSCGKKCLDLKQDVCEMPKETGPCLAYFLHWWYDKKDNTCSMFVYGGCQGNNNNFQSKANCLNTCKNKRFP
Molecular weight
15284 g/mol
Research status
experimental
References
76
Tags
uniprot, alternative-splicing, antimicrobial, disulfide-bond, protease-inhibitor, proteomics-identification, reference-proteome, secreted, serine-protease-inhibitor, signal

Mechanism of action

Serine protease inhibitor that plays an essential role in male reproduction and fertility. Modulates the hydrolysis of SEMG1 by KLK3/PSA (a serine protease), provides antimicrobial protection for spermatozoa in the ejaculate coagulum, and binds SEMG1 thereby inhibiting sperm motility

Research & studies

Interactions of the male contraceptive target EPPIN with semenogelin-1 and small organic ligands
Scientific reports · 2023 · PubMed

EPPIN model shows WFDC and Kunitz domains connected by a hinge region.; Binding pocket accommodates SEMG1 Glu229-Gln247, EP055, and EP012.; Hot spot residues for binding include Phe63, Lys68, Asp71, Asn113, Asn114, and Asn115.; Hydrophobic and hydrophilic residues in WFDC and Kunitz domains enable plasma membrane anchoring.

Dissecting EPPIN protease inhibitor domains in sperm motility and fertilizing ability: repercussions for male contraceptive development
Molecular human reproduction · 2021 · PubMed
Emerging approaches to male contraception
Fertility and sterility · 2021 · PubMed
Epididymal protease inhibitor (EPPIN) is a protein hub for seminal vesicle-secreted protein SVS2 binding in mouse spermatozoa
Molecular and cellular endocrinology · 2020 · PubMed
Binding interactions of epididymal protease inhibitor and semenogelin-1: a homology modeling, docking and molecular dynamics simulation study
PeerJ · 2019 · PubMed
Non-hormonal male contraception: A review and development of an Eppin based contraceptive
Pharmacology & therapeutics · 2016 · PubMed
Correlation of epididymal protease inhibitor and fibronectin in human semen
PloS one · 2013 · PubMed
Characterization of EPPIN's semenogelin I binding site: a contraceptive drug target
Biology of reproduction · 2012 · PubMed

Frequently asked questions

What is Eppin?

**Mechanism of Action** Eppin (Epididymal protease inhibitor) is a serine protease inhibitor predominantly expressed in the male reproductive tract, particularly in the epididymis and testis. It contains both Kunitz-type and WAP (whey acidic protein) four-disulfide core domains, enabling it to inhibit serine proteases

How does Eppin work?

Serine protease inhibitor that plays an essential role in male reproduction and fertility. Modulates the hydrolysis of SEMG1 by KLK3/PSA (a serine protease), provides antimicrobial protection for spermatozoa in the ejaculate coagulum, and binds SEMG1 thereby inhibiting sperm motility

What is the research status of Eppin?

Eppin is currently classified as experimental, with 76 research references on record. This is for research purposes only and is not medical advice.

What is the molecular weight of Eppin?

Eppin has a molecular weight of approximately 15284 g/mol.

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