Structural highlights6nas is a 3 chain structure with sequence from [1] and Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , , |
| NonStd Res: | , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease[PROF1_HUMAN] Defects in PFN1 are the cause of amyotrophic lateral sclerosis 18 (ALS18) [MIM:614808]. A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.[1]
Function[ACTS_RABIT] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. [PROF1_HUMAN] Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR) and HTT aggregation and binding of G-actin is essential for its inhibition of AR.[2] [NAA80_HUMAN] N-alpha-acetyltransferase that specifically mediates the acetylation of the acidic amino terminus of processed forms of beta- and gamma-actin (ACTB and ACTG, respectively) (PubMed:30028079, PubMed:29581253). N-terminal acetylation of processed beta- and gamma-actin regulates actin filament depolymerization and elongation (PubMed:29581253). In vivo, preferentially displays N-terminal acetyltransferase activity towards acid N-terminal sequences starting with Asp-Asp-Asp and Glu-Glu-Glu (PubMed:30028079, PubMed:29581253). In vitro, shows high activity towards Met-Asp-Glu-Leu and Met-Asp-Asp-Asp (PubMed:10644992, PubMed:29581307). May act as a tumor suppressor (PubMed:10644992).[3] [4] [5] [6]
References
- ↑ Wu CH, Fallini C, Ticozzi N, Keagle PJ, Sapp PC, Piotrowska K, Lowe P, Koppers M, McKenna-Yasek D, Baron DM, Kost JE, Gonzalez-Perez P, Fox AD, Adams J, Taroni F, Tiloca C, Leclerc AL, Chafe SC, Mangroo D, Moore MJ, Zitzewitz JA, Xu ZS, van den Berg LH, Glass JD, Siciliano G, Cirulli ET, Goldstein DB, Salachas F, Meininger V, Rossoll W, Ratti A, Gellera C, Bosco DA, Bassell GJ, Silani V, Drory VE, Brown RH Jr, Landers JE. Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature. 2012 Aug 23;488(7412):499-503. doi: 10.1038/nature11280. PMID:22801503 doi:10.1038/nature11280
- ↑ Shao J, Welch WJ, Diprospero NA, Diamond MI. Phosphorylation of profilin by ROCK1 regulates polyglutamine aggregation. Mol Cell Biol. 2008 Sep;28(17):5196-208. doi: 10.1128/MCB.00079-08. Epub 2008 Jun, 23. PMID:18573880 doi:10.1128/MCB.00079-08
- ↑ Zegerman P, Bannister AJ, Kouzarides T. The putative tumour suppressor Fus-2 is an N-acetyltransferase. Oncogene. 2000 Jan 6;19(1):161-3. doi: 10.1038/sj.onc.1203234. PMID:10644992 doi:http://dx.doi.org/10.1038/sj.onc.1203234
- ↑ Drazic A, Aksnes H, Marie M, Boczkowska M, Varland S, Timmerman E, Foyn H, Glomnes N, Rebowski G, Impens F, Gevaert K, Dominguez R, Arnesen T. NAA80 is actin's N-terminal acetyltransferase and regulates cytoskeleton assembly and cell motility. Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):4399-4404. doi:, 10.1073/pnas.1718336115. Epub 2018 Mar 26. PMID:29581253 doi:http://dx.doi.org/10.1073/pnas.1718336115
- ↑ Goris M, Magin RS, Foyn H, Myklebust LM, Varland S, Ree R, Drazic A, Bhambra P, Stove SI, Baumann M, Haug BE, Marmorstein R, Arnesen T. Structural determinants and cellular environment define processed actin as the sole substrate of the N-terminal acetyltransferase NAA80. Proc Natl Acad Sci U S A. 2018 Mar 26. pii: 1719251115. doi:, 10.1073/pnas.1719251115. PMID:29581307 doi:http://dx.doi.org/10.1073/pnas.1719251115
- ↑ Wiame E, Tahay G, Tyteca D, Vertommen D, Stroobant V, Bommer GT, Van Schaftingen E. NAT6 acetylates the N-terminus of different forms of actin. FEBS J. 2018 Sep;285(17):3299-3316. doi: 10.1111/febs.14605. Epub 2018 Aug 13. PMID:30028079 doi:http://dx.doi.org/10.1111/febs.14605
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