Parveen, A.; Kumar, R.; Tandon, R.; Khurana, S.; Goswami, C.; Kumar, A. Mutational Hotspots and Protein Interactome Analyses of Collagen-Specific Chaperone—HSP47. Preprints2018, 2018110280. https://doi.org/10.20944/preprints201811.0280.v1
APA Style
Parveen, A., Kumar, R., Tandon, R., Khurana, S., Goswami, C., & Kumar, A. (2018). Mutational Hotspots and Protein Interactome Analyses of Collagen-Specific Chaperone—HSP47. Preprints. https://doi.org/10.20944/preprints201811.0280.v1
Chicago/Turabian Style
Parveen, A., Chandan Goswami and Abhishek Kumar. 2018 "Mutational Hotspots and Protein Interactome Analyses of Collagen-Specific Chaperone—HSP47" Preprints. https://doi.org/10.20944/preprints201811.0280.v1
Abstract
Heat shock protein 47kDa (HSP47) serves as a client-specific chaperone, essential for collagen biosynthesis and its folding and structural assembly. To date, there is no comprehensive study on mutational hotspots and protein network for human HSP47. Using five different human mutational databases, we deduced a comprehensive list of human HSP47 mutations and we found 24 67, 50, 43 and 2 deleterious mutations from the 1000 genomes data, gnomAD, COSMICv86, cBioPortal, and CanVar. We identified thirteen top-ranked missense mutations of HSP47 with the stringent cut-off of CADD score (>25) and Grantham score (≥151) as Ser76Trp, Arg103Cys, Arg116Cys, Ser159Phe, Arg167Cys, Arg280Cys, Trp293Cys, Gly323Trp, Arg339Cys, Arg373Cys, Arg377Cys, Ser399Phe, and Arg405Cys with the arginine-cysteine change as the predominant mutation. We also found that HSP47 is up-regulated and down-regulated in 11 and 4 of cancers types. Upon constructing protein interactome map of human HSP47, we found that a set of molecular chaperones is interaction partners of HSP47, which included two copies each of CREB binding proteins, HSP27, HSP40, HSP70, HSP90, ubiquitin proteins and one copy each of cartilage associated protein (CRTAP), HSPH1, HSBP1, FK506-binding protein B (FKBP), kruppel-like factor (KLF13), peptidyl-prolyl isomerase PIPB and Prolyl 4-hydroxylase beta subunit (P4HB). This suggested a cocktail of different chaperones interact with HSP47. These findings will assist in the evaluation of roles of HSP47 in human disease including different types of cancers.
Keywords
HSP47; missense mutation; mutational hotspot; variant analysis; cancer database; chaperone
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
