Small EDRK-rich factor 1A (SERF1A)

Small EDRK-rich factor 1A (SERF1A) is an evolutionarily conserved, small (~7.4 kDa), monomeric, intrinsically disordered protein with a high proportion of α-helical character[1][2]. It functions primarily as an amyloid-promoting factor: it accelerates the aggregation of various amyloidogenic proteins—including huntingtin with expanded polyglutamine tract (Htt-polyQ), α-synuclein, prion protein, and amyloid-β—by catalyzing conformational transitions in early amyloidogenesis and promoting “on-pathway” aggregate formation[1][2]. SERF1A interacts most strongly with the α-helical and C-terminal domains of its substrates and is distinct from classical chaperones in that it enhances, rather than inhibits, protein aggregation. Overexpression or increased levels of SERF1A have been observed in neurodegenerative settings such as Huntington’s disease, and its actions exacerbate cytotoxicity driven by toxic protein aggregates[1][2]. In addition to amyloid modulation, SERF1A may interact with RNA, forming complexes that further implicate it in cellular stress responses[1]. Currently, SERF1A is not an established therapeutic target, but it is of high interest due to its critical role in the pathogenesis of neurodegenerative proteinopathies.

Other names

Small EDRK-rich factor 1SERF1AFAM2ASERF1SMAM1Protein 4F5SMA modifier 1spinal muscular atrophy-related gene H4F5h4F5H4F54F5FAM2B