{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSERPINB11 was first characterized in a chicken model of ovarian cancer, where it is induced by estrogen and highly expressed in the glandular epithelium of endometrioid adenocarcinoma, in contrast to its absence in normal ovarian tissue. Differential methylation of CpG sites in the gene’s promoter region appears to correlate with its aberrant expression in cancer, and similar cytoplasmic expression in human ovarian cancer cell lines supports its potential as a diagnostic biomarker and a candidate for monitoring therapy effects."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMolecular studies of human SERPINB11 have revealed that, although it belongs to the serpin superfamily, the protein does not function as a conventional protease inhibitor. Alternative splicing and single nucleotide polymorphisms in regions outside the reactive site loop result in amino acid substitutions within the protein scaffold that impair its ability to undergo the conformational changes required for inhibition of target peptidases. Notably, engineering experiments substituting parts of the mouse ortholog’s scaffold can partially restore inhibitory activity, underscoring how naturally occurring variants have led to a loss of classical serpin function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEvolutionary analyses further suggest that SERPINB11 has been subject to positive selection in humans, with specific codons under adaptive pressure potentially influencing its structural dynamics and functional repertoire. This evolutionary trajectory—whereby the gene appears to be “resurrected” from a pseudogene state—has been linked to adaptive responses in host-pathogen interactions, implying that SERPINB11 may have acquired a novel noninhibitory role that contributes to immune defense mechanisms."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Whasun Lim, Ji-Hye Kim, Suzie E Ahn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Avian SERPINB11 gene: a marker for ovarian endometrioid cancer in chickens."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Biol Med (Maywood) (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1258/ebm.2011.011250"}], "href": "https://doi.org/10.1258/ebm.2011.011250"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22289513"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22289513"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "David J Askew, Sule Cataltepe, Vasantha Kumar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SERPINB11 is a new noninhibitory intracellular serpin. Common single nucleotide polymorphisms in the scaffold impair conformational change."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M703182200"}], "href": "https://doi.org/10.1074/jbc.M703182200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17562709"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17562709"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Susana Seixas, Nevyana Ivanova, Zelia Ferreira, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss and gain of function in SERPINB11: an example of a gene under selection on standing variation, with implications for host-pathogen interactions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0032518"}], "href": "https://doi.org/10.1371/journal.pone.0032518"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22393410"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22393410"}]}]}]}