Annotating single amino acid polymorphisms in the UniProt/Swiss-Prot knowledgebase

Yip, Yum Lina; Famiglietti, Maria Livia; Gos, Arnaud; Duek, Paula D.; David, Fabrice; Gateau, Alain; Bairoch, Amos Marc

doi:10.1002/humu.20671

Cited by 111 publications

(110 citation statements)

References 9 publications

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“…SAMUL stores amino acid sequence variants from the Homo sapiens genome annotation provided by the human variation database Ensemble, cancer somatic mutations from COSMIS, and UniProt human sequence variations (Yip et al, 2008). UniProt is a main store for protein sequences, which provides rich annotation on function and cross references.…”

Section: Variant Phenotype Interactionmentioning

confidence: 99%

Mini Review Identifying human disease genes: advances in molecular genetics and computational approaches

Bakhtiar¹,

Ali²,

Baig³

et al. 2014

Genet. Mol. Res.

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Section: Variant Phenotype Interactionmentioning

confidence: 99%

Mini Review Identifying human disease genes: advances in molecular genetics and computational approaches

Bakhtiar¹,

Ali²,

Baig³

et al. 2014

Genet. Mol. Res.

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“…The protein sequence and variants (single amino acid polymorphisms/missense mutations/point mutations/nsSNP) for ADD domain were obtained from the Swissprot database (Yip et al 2008) available at http://www.expasy. ch/sprot/ to find out the detrimental point mutants.…”

Section: Data Setsmentioning

confidence: 99%

In silico analysis of detrimental mutations in ADD domain of chromatin remodeling protein ATRX that cause ATR-X syndrome: X-linked disorder

Chandrasekaran

Doss

Nisha³

et al. 2013

Netw Model Anal Health Inform Bioinforma

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Many biological functions involve specific interactions of proteins. Mutations in ATRX gene can change the sequence and structure of a protein thereby impairing its function. Thus, the dysfunction of chromatin remodeling protein ATRX as a result of amino acid substitution in ADD domain often underlies the human disease, ATR-X syndrome. In general, it is mainly caused by amino acid substitution that interfered with the interactions of interest at the interface level. Hence, the study of protein-protein interactions and the interface that mediate the interactions stand important for understanding of biological function. In this work, we address the loss of function in chromatin remodeling protein ATRX due to loss of structural stability that affect the functional activity in mutant ADD domain by 17 missense mutations viz., G175E, N179S, P190A, P190L, P190S, L192F, V194I, C200S, Q219P, C220R, C220Y, W222S, C243F, R246C, R246L, G249C, and G249D. Furthermore, the loss of binding affinity of ADD domain with their interacting partner namely histone H3-peptide were investigated by (1) computing the RMSD (root mean square deviation) for the ADD domain of native with all the 17 mutants, (2) computing intra-molecular interactions in ADD domain of native with all the mutants, (3) computing binding affinity of native and mutant structures of ADD domain with histone H3-peptide through docking studies, and (4) cross validating the loss of function on binding affinity through inter-molecular interactions and normal mode analysis. Finally, as from our computational result, we concluded that all the parameters mentioned above used for studying ADD domain of mutant structures showed the decreased potential values compared to native structure that underlie ATR-X syndrome.

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“…The segments of every Swissprot entry imparted details on polymorphic variants, some of which were disease(s) -associated by causing defects in a given protein (Yip et al, 2004(Yip et al, , 2008Boeckmann et al, 2003). The 3D structure of angiogenin and their complexes were extracted from Protein Data Bank with PDB ID 2ANG (Berman et al, 2000) for mutant modeling and docking studies according to harmful point mutants.…”

Section: Datasetsmentioning

confidence: 99%

A computational approach to analyze the missense mutations in human angiogenin variants leading to amyotrophic lateral sclerosis

Sreevishnupriya

Rajasekaran

2013

Bangladesh J Pharmacol

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A computational approach to analyze the missense mutations in human angiogenin variants leading to amyotrophic lateral sclerosis BJP IntroductionAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by selective destruction of motor neurons, resulting paralysis in stages and death within a few years from onset (Bruijin et al., 2004). In the past decade, a small number of genes involved in the etiology of the disease have been identified. Angiogenin (ANG), which encodes an angiogenic protein, has been recently identified as a candidate susceptibility gene for ALS in the Irish and Scottish population by Greenway et al (Greenway et al., 2004).The ANG gene provides instructions for making a protein called angiogenin. This protein promotes the formation of new blood vessels from pre-existing blood vessels through a process called angiogenesis. The ANG gene is located on the long (q) arm of chromosome 14 between positions 11.1 and 11.2. More precisely, the ANG gene is located from base pair 21,152,335 to base pair 21,162,344 on chromosome 14.The protein aggregation, defective axonal transport, oxidative stress, dysfunctional growth factor signaling, mitochondrial dysfunction and excitotoxicity are some of the factors found to be combined to the inception of ALS.Around 10% of ALS cases are inherited genetically, but the other 90% have no clear genetic cause (Dion et al., 2009 AbstractThe most deleterious missense mutations of angiogenin forming amyotrophic lateral sclerosis were identified computationally and the substrate binding efficiencies of these mutations were also analyzed. Out of 12 variants, IMutant2.0, SIFT and PolyPhen programs identified 3 variants that were less stable, deleterious and damaging respectively. These 3 variants were modeled to find their conformational changes in concern with native angiogenin through RMSD calculation and Total energy. Docking of native and 3 mutants with ribonuclease inhibitor was performed to describe the binding efficiencies of those detrimental missense mutations. By computing the binding amino acids' flexibility of angiogenin and computing the binding free energy (ΔG)between native and mutant complexes, the loss in binding affinity with their interacting protein namely ribonuclease inhibitor was investigated. This work is licensed under a Creative Commons Attribution 3.0 License. You are free to copy, distribute and perform the work. You must attribute the work in the manner specified by the author or licensor. Article Info

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Annotating single amino acid polymorphisms in the UniProt/Swiss-Prot knowledgebase

Cited by 111 publications

References 9 publications

Mini Review Identifying human disease genes: advances in molecular genetics and computational approaches

Mini Review Identifying human disease genes: advances in molecular genetics and computational approaches

In silico analysis of detrimental mutations in ADD domain of chromatin remodeling protein ATRX that cause ATR-X syndrome: X-linked disorder

A computational approach to analyze the missense mutations in human angiogenin variants leading to amyotrophic lateral sclerosis

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