5m9t
From Proteopedia
Human angiogenin ALS variant H114R
Structural highlights
Disease[ANGI_HUMAN] Defects in ANG are the cause of susceptibility to amyotrophic lateral sclerosis type 9 (ALS9) [MIM:611895]. ALS is a degenerative disorder of motor neurons in the cortex, brain stem and spinal cord. ALS is characterized by muscular weakness and atrophy.[1] [2] [3] [4] [5] [6] Function[ANGI_HUMAN] May function as a tRNA-specific ribonuclease that abolishes protein synthesis by specifically hydrolyzing cellular tRNAs. Binds to actin on the surface of endothelial cells; once bound, angiogenin is endocytosed and translocated to the nucleus. Angiogenin induces vascularization of normal and malignant tissues. Angiogenic activity is regulated by interaction with RNH1 in vivo.[7] [8] Publication Abstract from PubMedMutations in Angiogenin (ANG), a member of the Ribonuclease A superfamily (also known as RNase 5) are known to be associated with Amyotrophic Lateral Sclerosis (ALS, motor neurone disease) (sporadic and familial) and Parkinson's Disease (PD). In our previous studies we have shown that ANG is expressed in neurons during neuro-ectodermal differentiation, and that it has both neurotrophic and neuroprotective functions. In addition, in an extensive study on selective ANG-ALS variants we correlated the structural changes to the effects on neuronal survival and the ability to induce stress granules in neuronal cell lines. Furthermore, we have established that ANG-ALS variants which affect the structure of the catalytic site and either decrease or increase the RNase activity affect neuronal survival. Neuronal cell lines expressing the ANG-ALS variants also lack the ability to form stress granules. Here, we report a detailed experimental structural study on eleven new ANG-PD/ALS variants which will have implications in understanding the molecular basis underlying their role in PD and ALS. Structural insights into human angiogenin variants implicated in Parkinson's disease and Amyotrophic Lateral Sclerosis.,Bradshaw WJ, Rehman S, Pham TT, Thiyagarajan N, Lee RL, Subramanian V, Acharya KR Sci Rep. 2017 Feb 8;7:41996. doi: 10.1038/srep41996. PMID:28176817[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Acharya, K R | Bradshaw, W J | Lee, R L | Pham, T T.K | Rehman, S | Subramanian, V | Thiyagarajan, N | Al | Angiogenesis | Hydrolase | Rnase
