Ask about this productRelated genes to: UNC45B antibody
- Gene:
- UNC45B NIH gene
- Name:
- unc-45 myosin chaperone B
- Previous symbol:
- CMYA4
- Synonyms:
- UNC45
- Chromosome:
- 17q12
- Locus Type:
- gene with protein product
- Date approved:
- 2002-04-03
- Date modifiied:
- 2015-06-19
Related products to: UNC45B antibody
Related articles to: UNC45B antibody
- Skeletal muscle mass and force decline with age, and the loss of muscle force precedes muscle atrophy. However, the underlying mechanisms remain unclear. Here, we investigated the role of the myosin co-chaperone, uncoordinated mutant number-45 myosin chaperone B (UNC45B), in regulating muscle mass and force. UNC45B expression decreased in mouse gastrocnemius muscle with age, particularly at 24 months old, and adeno-associated virus vector-mediated knockdown of Unc45b in 3-month-old mouse triceps surae muscle first reduced plantar flexor torque and then decreased gastrocnemius muscle mass. In addition, Unc45b knockdown in the triceps surae muscle resulted in lower bone mineral density. While maximum Ca-activated force in mechanically skinned fibers was not affected by Unc45b knockdown, Unc45b knockdown decreased the ratio of depolarization-induced force to the maximum Ca-activated force. We established tamoxifen-inducible skeletal muscle-specific Unc45b knockout (Unc45b imKO) mice to investigate whether the muscle atrophy and weakness due to the loss of Unc45b impacts metabolism and behavior. We found that Unc45b imKO reduced muscle mass and force at a whole-body level, but did not influence systemic glucose tolerance, insulin sensitivity, or the respiratory exchange ratio. However, Unc45b imKO mice reduced the amount of deeper non-rapid eye movement sleep, locomotor activity, and body temperature during the sleep phase. We conclude that UNC45B is essential for maintaining fast-twitch muscle mass and muscle force. In addition, Unc45b deficiency-mediated muscle loss is also associated with bone fragility, decreased body temperature, and impaired sleep quality. - Source: PubMed
Mishima TaigaNagamune TaigaTada SaoriWatanabe DaikiTokuda NaoYamada TakashiHashimoto-Hachiya AkikoHigo-Yamamoto SayakaKido KoheiNagaoka NoriyukiIkedo AoiImai YuukiFujita RyoMizuno SeiyaTakahashi SatoruOishi KatsutakaAto SatoruOgasawara Riki - Uncoordinated-45 (UNC45) is a conserved protein required for myosin accumulation during muscle development. Invertebrates have one unc-45 gene whereas vertebrates have two paralogs, UNC45A and UNC45B, which exhibit different expression patterns. We used the Drosophila model to investigate the ability of the vertebrate proteins to function in an invertebrate system, as well as the potential evolutionary redundancy of its human paralogs. Transgenic expression of either human UNC45 paralog early in indirect flight muscle development resulted in impaired flight, disordered muscle organization and unique sub-sarcomere localizations. We then generated chimeric proteins that replaced each of three Drosophila Unc-45 domains with their human cognates. We found that a chimera containing the myosin-binding UCS domain of human UNC45A impaired muscle function, whereas none of the UNC45B domain chimeras significantly impacted flight ability. Overall, our study shows that there is significant evolutionary divergence between vertebrate and invertebrate paralogs and that the human proteins differentially disrupt Drosophila myofibril assembly and function, suggesting that they are functionally unique. - Source: PubMed
Publication date: 2025/11/17
Smith Daniel AMullens Morgan IRamos RaulMelkani Girish CBernstein Sanford I - The SMYD family comprises a distinct class of lysine methyltransferases (KMTases) that methylate both histone and non-histone proteins. Among its five members (SMYD1-5), SMYD1 has been identified as a cardiac and skeletal muscle-specific KMTase that interacts with Myosin, in coordination with Unc45b and Hsp90a, to regulate thick filament assembly. However, the precise mechanism by which SMYD1 orchestrates Myosin assembly remains largely unknown. Here, we demonstrate that SMYD1 physically associates with the N-terminal region of several myosin heavy chain (MyHC) isoforms and specifically catalyzes the mono-methylation of MyHC at lysine 35 (K35). Methylated MyHC is correctly incorporated into sarcomeres, whereas unmethylated MyHC in Smyd1-deficient zebrafish undergoes degradation via the ubiquitin-proteasome system (UPS), leading to defective thick filament assembly. Although UPS inhibition with MG132 restores Myosin levels in Smyd1-deficient zebrafish embryos, proper thick filament assembly remains impaired due to the absence of K35 MyHC mono-methylation. Similar to zebrafish striated muscle cells, SMYD1-mediated MyHC methylation is essential for thick filament assembly but also homeostasis in human cardiomyocytes, indicating a conserved cross-species mechanism of Myosin regulation, first described nearly 40 years ago. Further research is now required to explore the therapeutic potential of targeting this pathway in cardiomyopathies and skeletal muscle disorders. - Source: PubMed
Publication date: 2025/09/17
Diofano FedericaAmadi ChidinmaHartmann LarissaGahr Bernd MWeinmann-Emhardt KarolinaRottbauer WolfgangJust Steffen - The exquisitely organized sarcomere, the unit of contraction of striated muscle, is a stable structure with slow turnover of its components. The myosin chaperone UNC-45 and its binding partners, Hsp90 and Hsp70, are required for the initial folding of the myosin head domain and the assembly of myosin into thick filaments. There is increasing evidence that the UNC-45 system has an important role during aging to preserve sarcomere organization. Its decline may be a key factor in sarcopenia. Unlike skeletal muscle, the UNC-45 system in cardiac muscle in aging heart has not been examined extensively. Here we show that Unc45b and Hsp70 are localized to sarcomeric Z-discs in the mouse heart. We further show that during aging, there is a decline in the levels of myosin heavy chain, Unc-45b and Hsp70, but not Hsp90. While the decrease in Unc45b appears to be at the mRNA level, the decrease in the levels of myosin and Hsp70 were not at the mRNA but at the protein level. We have reported that in skeletal muscle, there is a decline in both Unc45b and Hsp90, and here we show that there is no such decline of Hsp70 in skeletal muscle. Hsp70 levels also did not decline with age in the brain or the liver. This heart-specific decrease of Hsp70 through its function as an Unc45b/Hsp70 complex might account for the age-dependent worsening of cardiomyopathies, and through Hsp70's multiple Unc-45b-independent functions, affect the folding and assembly of many other proteins in the aging heart. - Source: PubMed
Publication date: 2025/08/27
Bhat Purnima DevakiNalli AswanShoemaker LukeKwong Jennifer QQadota HiroshiKrishnamurthy PrasannaBenian Guy M - Flavobacterium oreochromis has been associated with elevated mortality rates during the early stages of tambaqui (Colossoma macropomum) aquaculture. This study investigated genetic responses to bacterial infection in juvenile fish by comparing gene expression profiles between symptomatic (IS) and asymptomatic (IA) individuals. - Source: PubMed
Publication date: 2025/06/18
de Souza Pereira CarolinaMastrochirico-Filho Vito AntonioPereira Elcimara CardosoButzge Arno Julianode Souza Borges Carolina HeloisaCáceres PabloPorto-Foresti FabioYáñez José ManuelGallani Silvia UmedaHashimoto Diogo Teruo