Background: Protein C regulates blood coagulation and is composed of several domains like gamma-carboxyglutamic acid-rich (GLA) domain, epidermal growth factor (EGF) like domains, a short activation peptide, and serine protease domain (SP). Several mutations spreading throughout the PROC gene have been identified that may contribute to protein C deficiency. Alternative splicing of the human PROC gene may also generate multiple variants. Different exons encode the domains present in the protein C and alternative splicing may lead to the addition or removal of some of these crucial domains, thus altering the functioning of the protein.

Aims: Identification and characterization of alternatively spliced novel isoforms of human protein C (PROC) gene

Methods: Gene and exon finding tools were used to predict novel exons of the human PROC gene, and alternative splicing patterns were elucidated. RT-PCR and DNA sequencing were used to confirm predicted transcripts in the human liver, and their expression level was reported using real-time PCR. MD simulation studies were performed using GROMACS.

Results: Six novel exons were predicted in the PROC gene using bioinformatics and the expression of two novel isoforms was reported in the human liver. These isoforms were found to have exons with different promoter regions and splicing patterns. Some critical domains were reported to be missing in these novel isoforms suggesting an alteration in the activity of the encoded protein. The MD simulation study revealed the structural integrity of novel isoforms.

Conclusion(s): The novel protein C isoforms identified in our study may have physiological significance and contribute to protein C’s anticoagulant, anti-inflammatory, and anti-apoptotic properties.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/identification-and-functional-characterisation-of-alternatively-spliced-novel-isoforms-of-human-protein-c-proc-gene/