{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSEPTIN14 is a recently identified member of the septin family of GTP-binding cytoskeletal proteins that participates in several key cellular processes. Initially discovered as an interacting partner of other septins such as SEPT9 in human testis tissue, SEPTIN14 contains a conserved GTPase domain and a predicted coiled-coil region. Its expression appears to be highly tissue specific, predominantly localized in the testis where it may function as a tumor suppressor given its absence in testicular cancer cell lines."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic studies have further implicated SEPTIN14 in neurodegenerative disease. Specific single-nucleotide polymorphisms within the SEPTIN14 gene locus, including those affecting its promoter, are associated with a reduced risk of Parkinson’s disease. In addition to its testicular expression, SEPTIN14 is also expressed in the brain, particularly in the substantia nigra, suggesting a protective role in the pathological mechanisms underlying Parkinson’s disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctional analyses in the context of male fertility have revealed that appropriate levels of SEPTIN14 are critical for normal spermatogenesis. Quantitative studies indicate that reduced expression of SEPTIN14 in testicular tissues correlates with impaired spermatogenesis in azoospermic men. Moreover, immunolocalization studies of spermatozoa show that SEPTIN14 is distributed along the head-to-tail axis with notable enrichment near the acrosome and neck regions, hinting at its potential role in sperm structure and function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOn a structural level, SEPTIN14 forms part of the septin heterocomplexes that are essential for proper cytoskeletal architecture. Recent structural studies have demonstrated that SEPTIN14 engages in heterodimerization with SEPT7 through its coiled-coil domain. This heterodimer exhibits unusual knobs-into-holes side-chain packing and a combination of heptad and hendecad repeats, which may facilitate specific septin recognition and contribute to the metastability needed for correct protofilament assembly."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Esther A Peterson, Linda M Kalikin, Jonathan D Steels, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of a SEPT9 interacting protein, SEPT14, a novel testis-specific septin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mamm Genome (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00335-007-9065-x"}], "href": "https://doi.org/10.1007/s00335-007-9065-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17922164"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17922164"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Liron Rozenkrantz, Ziv Gan-Or, Mali Gana-Weisz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SEPT14 Is Associated with a Reduced Risk for Parkinson's Disease and Expressed in Human Brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Neurosci (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12031-016-0738-3"}], "href": "https://doi.org/10.1007/s12031-016-0738-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27115672"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27115672"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Nastaran Vahabi Barzi, Kianoosh Kakavand, Niloofar Sodeifi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and localization of Septin 14 gene and protein in infertile men testis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Reprod Biol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.repbio.2020.03.007"}], "href": "https://doi.org/10.1016/j.repbio.2020.03.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32249155"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32249155"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Italo A Cavini, Ashley J Winter, Humberto D'Muniz Pereira, et al. "}, {"type": "b", "children": [{"type": "t", "text": "X-ray structure of the metastable SEPT14-SEPT7 coiled coil reveals a hendecad region crucial for heterodimerization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Crystallogr D Struct Biol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1107/S2059798323006514"}], "href": "https://doi.org/10.1107/S2059798323006514"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37712436"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37712436"}]}]}]}