Gene Symbol: UNC45A
Description: unc-45 myosin chaperone A
Alias: GC-UNC45, GCUNC-45, GCUNC45, IRO039700, SMAP-1, SMAP1, UNC-45A, protein unc-45 homolog A, general cell UNC45, smooth muscle cell associated protein-1, unc-45 homolog A
Species: human
Products:     UNC45A

Top Publications

  1. Eisa N, Jilani Y, Kainth K, Redd P, Lu S, Bougrine O, et al. The co-chaperone UNC45A is essential for the expression of mitotic kinase NEK7 and tumorigenesis. J Biol Chem. 2019;294:5246-5260 pubmed publisher
    Cumulative evidence suggests that the heat shock protein 90 (Hsp90) co-chaperone UNC-45 myosin chaperone A (UNC45A) contributes to tumorigenesis and that its expression in cancer cells correlates with proliferation and metastasis of solid ..
  2. Mooneyham A, Iizuka Y, Yang Q, Coombes C, McClellan M, Shridhar V, et al. UNC-45A Is a Novel Microtubule-Associated Protein and Regulator of Paclitaxel Sensitivity in Ovarian Cancer Cells. Mol Cancer Res. 2019;17:370-383 pubmed publisher
    UNC-45A, a highly conserved member of the UCS (UNC45A/CRO1/SHE4P) protein family of cochaperones, plays an important role in regulating cytoskeletal-associated functions in invertebrates and mammalian cells, including cytokinesis, ..
  3. Natsume W, Tanabe K, Kon S, Yoshida N, Watanabe T, Torii T, et al. SMAP2, a novel ARF GTPase-activating protein, interacts with clathrin and clathrin assembly protein and functions on the AP-1-positive early endosome/trans-Golgi network. Mol Biol Cell. 2006;17:2592-603 pubmed
    We recently reported that SMAP1, a GTPase-activating protein (GAP) for Arf6, directly interacts with clathrin and regulates the clathrin-dependent endocytosis of transferrin receptors from the plasma membrane...
  4. Tanabe K, Torii T, Natsume W, Braesch Andersen S, Watanabe T, Satake M. A novel GTPase-activating protein for ARF6 directly interacts with clathrin and regulates clathrin-dependent endocytosis. Mol Biol Cell. 2005;16:1617-28 pubmed
    ..Here, we identified a novel species of GAP denoted as SMAP1 that preferentially acts on Arf6...
  5. Märtens B, Bezerra G, Kreuter M, Grishkovskaya I, Manica A, Arkhipova V, et al. The Heptameric SmAP1 and SmAP2 Proteins of the Crenarchaeon Sulfolobus Solfataricus Bind to Common and Distinct RNA Targets. Life (Basel). 2015;5:1264-81 pubmed publisher
    ..The aim of this study was to shed light on the function of SmAP1 and SmAP2 of the crenarchaeon Sulfolobus solfataricus (Sso)...
  6. Yasuda Yamahara M, Rogg M, Yamahara K, Maier J, Huber T, Schell C. AIF1L regulates actomyosin contractility and filopodial extensions in human podocytes. PLoS ONE. 2018;13:e0200487 pubmed publisher
    ..podocyte specific AIF1L interactome and identify several components of the actomyosin machinery such as MYL9 and UNC45A as potential AIF1L interaction partners...
  7. Kobayashi N, Kon S, Henmi Y, Funaki T, Satake M, Tanabe K. The Arf GTPase-activating protein SMAP1 promotes transferrin receptor endocytosis and interacts with SMAP2. Biochem Biophys Res Commun. 2014;453:473-9 pubmed publisher
    ..The small Arf GTPase-activating protein (SMAP) subfamily of Arf GAPs has two members, SMAP1 and SMAP2, in mammals...
  8. Sumiyoshi M, Masuda N, Tanuma N, Ogoh H, Imai E, Otsuka M, et al. Mice doubly-deficient in the Arf GAPs SMAP1 and SMAP2 exhibit embryonic lethality. FEBS Lett. 2015;589:2754-62 pubmed publisher
    ..GTPase-activating protein (SMAP) subfamily of Arf GTPase-activating proteins consists of closely related members, SMAP1 and SMAP2...
  9. Esteve C, Francescatto L, Tan P, Bourchany A, De Leusse C, Marinier E, et al. Loss-of-Function Mutations in UNC45A Cause a Syndrome Associating Cholestasis, Diarrhea, Impaired Hearing, and Bone Fragility. Am J Hum Genet. 2018;102:364-374 pubmed publisher
    ..of all affected individuals and their parents identified biallelic mutations in Unc-45 Myosin Chaperone A (UNC45A) as a likely driver for this disorder...

More Information


  1. Rühle F, Witten A, Barysenka A, Huge A, Arning A, Heller C, et al. Rare genetic variants in SMAP1, B3GAT2, and RIMS1 contribute to pediatric venous thromboembolism. Blood. 2017;129:783-790 pubmed publisher
    ..These SNPs reside in a region on chromosome 6q13 comprising the genes small ARF GAP1 (SMAP1), an ARF6 guanosine triphosphatase-activating protein that functions in clathrin-dependent endocytosis, and ?-..
  2. Price M, Landsverk M, Barral J, Epstein H. Two mammalian UNC-45 isoforms are related to distinct cytoskeletal and muscle-specific functions. J Cell Sci. 2002;115:4013-23 pubmed
    ..These results suggest that the general cell UNC-45 isoform may have primarily cytoskeletal functions and that the striated muscle UNC-45 isoform may be restricted to roles in muscle-specific differentiation. ..
  3. Chadli A, Graham J, Abel M, Jackson T, Gordon D, Wood W, et al. GCUNC-45 is a novel regulator for the progesterone receptor/hsp90 chaperoning pathway. Mol Cell Biol. 2006;26:1722-30 pubmed
    ..These findings reveal a new cochaperone binding site near the N terminus of hsp90, add insight on the role of FKBP52, and identify GCUNC-45 as a novel regulator of the PR signaling pathway. ..
  4. Guo W, Chen D, Fan Z, Epstein H. Differential turnover of myosin chaperone UNC-45A isoforms increases in metastatic human breast cancer. J Mol Biol. 2011;412:365-78 pubmed publisher
    ..The differential accumulation was explained by cellular labeling experiments that showed that the 944 isoform is degraded at a 5-fold greater rate than the 929 isoform and that this degradation required the ubiquitin-proteasome system. ..
  5. Iizuka Y, Mooneyham A, Sieben A, Chen K, Maile M, Hellweg R, et al. UNC-45A is required for neurite extension via controlling NMII activation. Mol Biol Cell. 2017;28:1337-1346 pubmed publisher
    ..Collectively our results provide novel insights into the molecular mechanisms of neurite growth and define UNC-45A as a novel and master regulator of NMII-mediated cellular processes in neurons. ..
  6. Ni W, Odunuga O. UCS proteins: chaperones for myosin and co-chaperones for Hsp90. Subcell Biochem. 2015;78:133-52 pubmed publisher
    ..This chapter reviews the implications of the outcome of studies on these proteins in cellular processes such as muscle formation, and disease states such as myopathies and cancer. ..
  7. Hultquist J, Schumann K, Woo J, Manganaro L, McGregor M, DOUDNA J, et al. A Cas9 Ribonucleoprotein Platform for Functional Genetic Studies of HIV-Host Interactions in Primary Human T Cells. Cell Rep. 2016;17:1438-1452 pubmed publisher
    ..This technology should accelerate target validation for pharmaceutical and cell-based therapies to cure HIV infection. ..
  8. Iizuka Y, Cichocki F, Sieben A, Sforza F, Karim R, Coughlin K, et al. UNC-45A Is a Nonmuscle Myosin IIA Chaperone Required for NK Cell Cytotoxicity via Control of Lytic Granule Secretion. J Immunol. 2015;195:4760-70 pubmed publisher
    ..Lastly, loss of UNC-45A leads to reduced NMIIA binding to actin, suggesting that UNC-45A is a crucial component in regulating human NK cell cytoskeletal dynamics via promoting the formation of actomyosin complexes. ..
  9. Lehtimäki J, Fenix A, Kotila T, Balistreri G, Paavolainen L, Varjosalo M, et al. UNC-45a promotes myosin folding and stress fiber assembly. J Cell Biol. 2017;216:4053-4072 pubmed publisher
    ..Thus, UNC-45a promotes generation of contractile actomyosin bundles through synchronized NM-II folding and filament-assembly activities. ..
  10. Jilani Y, Lu S, Lei H, Karnitz L, Chadli A. UNC45A localizes to centrosomes and regulates cancer cell proliferation through ChK1 activation. Cancer Lett. 2015;357:114-20 pubmed publisher
    ..Here we show that one member of this family, UNC45A, is also a novel centrosomal protein...
  11. Takahashi M, Umetsu K, Oono Y, Higaki T, Blancaflor E, Rahman A. Small acidic protein 1 and SCFTIR1 ubiquitin proteasome pathway act in concert to induce 2,4-dichlorophenoxyacetic acid-mediated alteration of actin in Arabidopsis roots. Plant J. 2017;89:940-956 pubmed publisher
    ..Analysis of the 2,4-D-specific mutant aar1-1 revealed that small acidic protein 1 (SMAP1) functions positively to facilitate the 2,4-D-induced depolymerization of actin...
  12. Gomez Escalante S, Piper P, Millson S. Mutation of the Ser18 phosphorylation site on the sole Saccharomyces cerevisiae UCS protein, She4, can compromise high-temperature survival. Cell Stress Chaperones. 2017;22:135-141 pubmed publisher
  13. Bazzaro M, Santillan A, Lin Z, Tang T, Lee M, Bristow R, et al. Myosin II co-chaperone general cell UNC-45 overexpression is associated with ovarian cancer, rapid proliferation, and motility. Am J Pathol. 2007;171:1640-9 pubmed
    ..In sum, these findings implicate elevated GC UNC-45 protein expression in ovarian carcinoma proliferation and metastasis. ..
  14. Chadli A, Felts S, Toft D. GCUNC45 is the first Hsp90 co-chaperone to show alpha/beta isoform specificity. J Biol Chem. 2008;283:9509-12 pubmed publisher
    ..In this study, we show that the Hsp90 co-chaperone GCUNC45 bound preferentially to the beta isoform of Hsp90 in vitro...