Mutation-Structure-Function Relationship Based Integrated Strategy Reveals the Potential Impact of Deleterious Missense Mutations in Autophagy Related Proteins on Hepatocellular Carcinoma (HCC): A Comprehensive Informatics Approach
Abstract
:1. Introduction
2. Results
2.1. Missense SNP Datasets
2.2. Missense SNP Analysis
2.3. Conservation Profile of High-Risk Missense SNPs
2.4. HCC Related Mutations by PinSnps and SNPEffect4.0 Tool
2.5. Prediction of Functional Binding Sites
2.6. Phosphorylation and Kinase-Specific Phosphorylation Sites in LC3A, LC3B, BECN1 and SCD1
2.7. Normal Mode Analysis of Highly Deleterious HCC-Associated SNPs
2.8. Ubiquitylation Sites in LC3A, LC3B, BECN1 and SCD1
2.9. Palmitoylation and Methylation Sites in LC3A, LC3B, BECN1 and SCD1
2.10. Prediction of Acetylating Sites in LC3A, LC3B, BECN1 and SCD1
2.11. Sumoylation Sites in LC3A, LC3B, BECN1 and SCD1
2.12. Analysis of Overlap between High Risk SNPs and Potential PTM Sites
3. Discussion
4. Materials and Methods
4.1. Protein Sequence Datasets
4.2. Retrieval of Missense SNP Datasets
4.3. Analysis of Functional Consequences of Missense SNPs
4.4. Analysis of Protein Stability Changes Due to High Risk Missense SNPs
4.5. Analysis of Structural Specificity of Functional SNPs
4.6. Prediction of Phenotypic Consequence for Deleterious Missense SNPs
4.7. Prediction of Ligand Binding Sites in LC3A, LC3B, BECN1 and SCD1 Proteins
4.8. Normal Mode Analysis
4.9. Prediction of Post-Translational Modification Sites
4.9.1. Prediction of Potential Phosphorylation and Kinase-Specific Phosphorylation Sites in LC3A, LC3B, BECN1 and SCD1
4.9.2. Prediction of Ubiquitylation Sites in LC3A, LC3B, BECN1 and SCD1
4.9.3. Prediction of Palmitoylation and Methylation Sites
4.9.4. Prediction of Acetylating Sites
4.9.5. Prediction of Sumoylation Sites in LC3A, LC3B, BECN1 and SCD1
4.10. PPI Analysis for LC3A, LC3B, BECN1 and SCD1
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Protein | Mutation | Deleterious SNPs | Destabilizing SNPs | |||||
---|---|---|---|---|---|---|---|---|
nsSNP Analyzer | PROVEAN | PMUT | SNPs & GO. | I-Mutant2.0 | DUET | STRUM | ||
LC3A | R24C | √ | √ | √ | √ | √ | √ | √ |
S29R | √ | – | √ | √ | √ | √ | √ | |
P55A | √ | √ | √ | √ | √ | √ | ||
P55L | √ | √ | √ | √ | √ | √ | √ | |
R70C | √ | √ | √ | √ | √ | √ | √ | |
P75R | – | √ | √ | √ | √ | – | – | |
F79V | √ | √ | √ | √ | √ | √ | √ | |
F79S | √ | √ | √ | √ | √ | √ | √ | |
N84K | – | √ | √ | √ | √ | – | √ | |
A96P | – | √ | √ | √ | √ | √ | √ | |
D104N | √ | √ | – | √ | √ | √ | √ | |
E105K | – | √ | √ | √ | √ | – | √ | |
K49A | √ | √ | √ | √ | √ | √ | √ | |
K51A | √ | √ | √ | √ | √ | √ | √ | |
L53A | √ | √ | √ | √ | √ | √ | ||
G120A | √ | √ | √ | √ | √ | √ | √ | |
LC3B | R11C | √ | √ | √ | √ | √ | √ | √ |
R24Q | √ | √ | √ | √ | √ | √ | ||
P32L | √ | √ | √ | √ | √ | √ | √ | |
V33A | √ | √ | √ | √ | √ | √ | ||
R37Q | √ | √ | √ | √ | √ | √ | √ | |
G40C | √ | √ | √ | √ | √ | √ | √ | |
R68A | √ | √ | √ | √ | √ | √ | √ | |
R70A | √ | √ | √ | √ | √ | √ | √ | |
R70H | √ | √ | √ | √ | √ | √ | √ | |
A78D | – | √ | √ | √ | √ | √ | √ | |
F79S | √ | √ | √ | √ | √ | √ | √ | |
S92C | – | √ | √ | √ | √ | √ | √ | |
D104N | – | √ | √ | √ | √ | √ | √ | |
D106G | √ | √ | √ | √ | √ | √ | √ | |
Y113S | √ | √ | √ | √ | √ | √ | √ | |
Y113C | √ | √ | √ | √ | – | √ | √ | |
E117V | – | √ | √ | √ | – | √ | √ | |
G120A | √ | √ | √ | √ | – | √ | √ | |
BECN1 | V14E | √ | √ | – | √ | √ | √ | √ |
A44P | – | √ | √ | √ | √ | – | ||
R74C | √ | – | √ | √ | √ | √ | √ | |
L112R | √ | √ | √ | √ | √ | – | √ | |
S113R | √ | √ | √ | √ | – | √ | √ | |
S127L | √ | √ | – | √ | √ | – | √ | |
L144F | √ | √ | √ | – | √ | √ | √ | |
E156V | – | √ | √ | √ | √ | – | √ | |
R164C | √ | √ | √ | √ | √ | √ | √ | |
L194P | √ | √ | √ | √ | √ | √ | √ | |
L198P | – | √ | √ | √ | √ | √ | √ | |
R205C | – | √ | √ | √ | √ | √ | √ | |
Q239P | – | √ | √ | √ | √ | – | √ | |
R255C | √ | √ | √ | √ | √ | √ | √ | |
N268S | √ | √ | – | √ | √ | – | √ | |
T284S | √ | √ | – | √ | √ | √ | √ | |
R292C | √ | √ | √ | √ | √ | √ | √ | |
R292H | √ | √ | √ | √ | √ | √ | √ | |
V298M | √ | √ | – | √ | √ | √ | √ | |
V298A | √ | √ | – | √ | √ | √ | √ | |
E302K | √ | √ | √ | √ | √ | √ | √ | |
L314H | √ | √ | √ | √ | √ | √ | √ | |
L323P | – | √ | √ | √ | √ | √ | √ | |
Y338C | √ | √ | √ | √ | √ | √ | √ | |
S346Y | √ | √ | √ | – | – | √ | √ | |
P350L | √ | √ | √ | – | √ | – | √ | |
Y352H | √ | √ | – | √ | √ | √ | √ | |
C353Y | √ | √ | √ | √ | √ | √ | √ | |
W361R | – | √ | √ | √ | √ | √ | √ | |
C375R | √ | √ | √ | √ | √ | √ | √ | |
I403S | √ | √ | √ | √ | √ | √ | √ | |
I403T | √ | √ | √ | √ | √ | √ | √ | |
G408R | √ | √ | √ | – | √ | √ | √ | |
W425C | √ | √ | √ | √ | √ | √ | √ | |
F431V | √ | √ | √ | √ | √ | √ | √ | |
F123A | √ | √ | √ | √ | √ | √ | √ | |
D133A | √ | √ | √ | √ | √ | – | √ | |
D149A | – | √ | √ | √ | √ | – | √ | |
Y352A | √ | √ | √ | √ | √ | √ | √ | |
W425A | √ | √ | √ | √ | √ | √ | √ | |
Y41C | √ | – | √ | √ | √ | √ | √ | |
SCD1 | P48R | √ | – | √ | √ | √ | √ | √ |
Y55D | √ | – | √ | √ | √ | √ | √ | |
E63G | √ | – | √ | √ | √ | √ | √ | |
Y88C | √ | √ | √ | √ | √ | √ | √ | |
G89R | √ | √ | √ | √ | √ | √ | – | |
G89A | √ | √ | – | √ | √ | √ | – | |
T100I | √ | √ | √ | √ | √ | – | – | |
L102P | √ | √ | – | √ | √ | √ | √ | |
G104E | √ | – | √ | √ | √ | √ | √ | |
R121C | √ | √ | √ | √ | √ | √ | √ | |
H125P | √ | √ | √ | √ | – | √ | – | |
R126C | √ | √ | – | √ | √ | √ | √ | |
R126S | √ | √ | √ | √ | √ | √ | √ | |
R131W | √ | √ | √ | √ | √ | √ | √ | |
R135W | √ | √ | √ | √ | √ | √ | √ | |
R135Q | – | √ | √ | √ | √ | √ | √ | |
M144T | √ | √ | √ | √ | √ | √ | √ | |
Y151C | √ | √ | √ | √ | – | √ | √ | |
R188C | √ | √ | – | √ | √ | √ | √ | |
H190Y | √ | √ | – | √ | – | – | √ | |
F213L | √ | √ | – | √ | √ | √ | √ | |
Q214R | √ | √ | – | √ | √ | √ | √ | |
Y218H | √ | √ | – | √ | √ | √ | √ | |
Y218C | √ | √ | √ | √ | √ | √ | √ | |
M225T | √ | √ | – | √ | √ | √ | √ | |
T231M | √ | √ | – | √ | √ | √ | √ | |
W238G | √ | √ | √ | √ | √ | √ | √ | |
W238R | √ | √ | √ | √ | √ | √ | √ | |
A249D | – | √ | √ | √ | √ | √ | √ | |
G272R | √ | √ | √ | √ | √ | √ | – | |
Y273C | √ | – | √ | √ | √ | √ | √ | |
N279I | – | √ | √ | √ | – | – | √ | |
R283W | √ | √ | √ | √ | √ | √ | √ | |
L290P | √ | √ | – | √ | √ | √ | √ | |
F323V | √ | √ | √ | √ | √ | √ | √ | |
C326G | √ | √ | √ | √ | √ | √ | √ | |
C326F | √ | – | √ | √ | √ | √ | √ | |
M327V | – | √ | √ | √ | √ | √ | √ | |
G331S | √ | √ | √ | √ | √ | √ | √ | |
A333T | – | √ | √ | √ | √ | √ | – | |
R336Q | √ | – | √ | √ | √ | √ | √ | |
R336L | √ | – | √ | √ | √ | – | – |
© 2017 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
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Awan, F.M.; Obaid, A.; Ikram, A.; Janjua, H.A. Mutation-Structure-Function Relationship Based Integrated Strategy Reveals the Potential Impact of Deleterious Missense Mutations in Autophagy Related Proteins on Hepatocellular Carcinoma (HCC): A Comprehensive Informatics Approach. Int. J. Mol. Sci. 2017, 18, 139. https://doi.org/10.3390/ijms18010139
Awan FM, Obaid A, Ikram A, Janjua HA. Mutation-Structure-Function Relationship Based Integrated Strategy Reveals the Potential Impact of Deleterious Missense Mutations in Autophagy Related Proteins on Hepatocellular Carcinoma (HCC): A Comprehensive Informatics Approach. International Journal of Molecular Sciences. 2017; 18(1):139. https://doi.org/10.3390/ijms18010139
Chicago/Turabian StyleAwan, Faryal Mehwish, Ayesha Obaid, Aqsa Ikram, and Hussnain Ahmed Janjua. 2017. "Mutation-Structure-Function Relationship Based Integrated Strategy Reveals the Potential Impact of Deleterious Missense Mutations in Autophagy Related Proteins on Hepatocellular Carcinoma (HCC): A Comprehensive Informatics Approach" International Journal of Molecular Sciences 18, no. 1: 139. https://doi.org/10.3390/ijms18010139