Dataset Information

Evolutionary journey of the Gc protein (vitamin D-binding protein) across vertebrates.

ABSTRACT: With so many diverse functions such as transporter of vitamin D metabolites and fatty acids, actin scavenger and macrophage activating factor, Gc must have been one of the most conserved proteins in animal kingdom. Our objective was to investigate the evolution of Gc by analyzing its differences at protein level. Using BLAST (Basic Local Alignment Search Tool) searches, Gc amino acid sequences were analyzed for homology. Clustal W2 and Jalview were used for multiple sequence alignment analysis, phylogenetic tree by PhyML 3.0 while Batch Web CD-Search Tool was used for identification for conserved domains within protein sequences. Gc protein percent identity between human and rabbit was 83%, which decreased to 81% with cow, 78% with mouse, 76% with rat, 51% with chicken, 41% with frog and 28% with zebrafish. Phylogram showed that rat Gc was the most diverged, while chicken Gc was the most conserved protein. Analysis also indicated high homology among mammals (human, rabbit, cow, rat, and mouse). Gc is a highly conserved protein in chicken and zebrafish. However, the distance from ancestral protein gradually increased in amphibian (frog) and mammals (human, rabbit, cow, rat, and mouse). Human Gc and rabbit Gc appear to be recently evolved proteins. There appears to be an interesting evolutionary pattern- chicken Gc has the least distance from the ancestral protein, while rat Gc is the most diverged. There is no vertebrate devoid of Gc which is suggestive of its important role in vitamin D metabolism in vertebrates.

SUBMITTER: Anwar S

PROVIDER: S-EPMC5424798 | biostudies-literature | 2013 Jan-Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Evolutionary journey of the Gc protein (vitamin D-binding protein) across vertebrates.

Anwar Shaheena S Iqbal Mohammed Perwaiz MP Zarina Shamshad S Bhutta Zulfiqar A ZA

Intrinsically disordered proteins 20130101 1

With so many diverse functions such as transporter of vitamin D metabolites and fatty acids, actin scavenger and macrophage activating factor, Gc must have been one of the most conserved proteins in animal kingdom. Our objective was to investigate the evolution of Gc by analyzing its differences at protein level. Using BLAST (Basic Local Alignment Search Tool) searches, Gc amino acid sequences were analyzed for homology. Clustal W2 and Jalview were used for multiple sequence alignment analysis, ...[more]

PMID: 28516027

Similar Datasets

Project description:BackgroundThe vitamins are important cofactors in various enzymatic-reactions. In past, many inhibitors have been designed against vitamin binding pockets in order to inhibit vitamin-protein interactions. Thus, it is important to identify vitamin interacting residues in a protein. It is possible to detect vitamin-binding pockets on a protein, if its tertiary structure is known. Unfortunately tertiary structures of limited proteins are available. Therefore, it is important to develop in-silico models for predicting vitamin interacting residues in protein from its primary structure.ResultsIn this study, first we compared protein-interacting residues of vitamins with other ligands using Two Sample Logo (TSL). It was observed that ATP, GTP, NAD, FAD and mannose preferred {G,R,K,S,H}, {G,K,T,S,D,N}, {T,G,Y}, {G,Y,W} and {Y,D,W,N,E} residues respectively, whereas vitamins preferred {Y,F,S,W,T,G,H} residues for the interaction with proteins. Furthermore, compositional information of preferred and non-preferred residues along with patterns-specificity was also observed within different vitamin-classes. Vitamins A, B and B6 preferred {F,I,W,Y,L,V}, {S,Y,G,T,H,W,N,E} and {S,T,G,H,Y,N} interacting residues respectively. It suggested that protein-binding patterns of vitamins are different from other ligands, and motivated us to develop separate predictor for vitamins and their sub-classes. The four different prediction modules, (i) vitamin interacting residues (VIRs), (ii) vitamin-A interacting residues (VAIRs), (iii) vitamin-B interacting residues (VBIRs) and (iv) pyridoxal-5-phosphate (vitamin B6) interacting residues (PLPIRs) have been developed. We applied various classifiers of SVM, BayesNet, NaiveBayes, ComplementNaiveBayes, NaiveBayesMultinomial, RandomForest and IBk etc., as machine learning techniques, using binary and Position-Specific Scoring Matrix (PSSM) features of protein sequences. Finally, we selected best performing SVM modules and obtained highest MCC of 0.53, 0.48, 0.61, 0.81 for VIRs, VAIRs, VBIRs, PLPIRs respectively, using PSSM-based evolutionary information. All the modules developed in this study have been trained and tested on non-redundant datasets and evaluated using five-fold cross-validation technique. The performances were also evaluated on the balanced and different independent datasets.ConclusionsThis study demonstrates that it is possible to predict VIRs, VAIRs, VBIRs and PLPIRs from evolutionary information of protein sequence. In order to provide service to the scientific community, we have developed web-server and standalone software VitaPred (http://crdd.osdd.net/raghava/vitapred/).

Project description:The vertebrate genome is a result of two rapid and successive rounds of whole genome duplication, referred to as 1R and 2R. Furthermore, teleost fish have undergone a third whole genome duplication (3R) specific to their lineage, resulting in the retention of multiple gene paralogs. The more recent 3R event in teleosts provides a unique opportunity to gain insight into how genes evolve through specific evolutionary processes. In this study we compare molecular activities of vitamin D receptors (VDR) from basal species that diverged at key points in vertebrate evolution in order to infer derived and ancestral VDR functions of teleost paralogs. Species include the sea lamprey (Petromyzon marinus), a 1R jawless fish; the little skate (Leucoraja erinacea), a cartilaginous fish that diverged after the 2R event; and the Senegal bichir (Polypterus senegalus), a primitive 2R ray-finned fish. Saturation binding assays and gel mobility shift assays demonstrate high affinity ligand binding and classic DNA binding characteristics of VDR has been conserved across vertebrate evolution. Concentration response curves in transient transfection assays reveal EC50 values in the low nanomolar range, however maximum transactivational efficacy varies significantly between receptor orthologs. Protein-protein interactions were investigated using co-transfection, mammalian 2-hybrid assays, and mutations of coregulator activation domains. We then combined these results with our previous study of VDR paralogs from 3R teleosts into a bioinformatics analysis. Our results suggest that 1, 25D3 acts as a partial agonist in basal species. Furthermore, our bioinformatics analysis suggests that functional differences between VDR orthologs and paralogs are influenced by differential protein interactions with essential coregulator proteins. We speculate that we may be observing a change in the pharmacodynamics relationship between VDR and 1, 25D3 throughout vertebrate evolution that may have been driven by changes in protein-protein interactions between VDR and essential coregulators.

Dataset Information

Evolutionary journey of the Gc protein (vitamin D-binding protein) across vertebrates.

Publications

Evolutionary journey of the Gc protein (vitamin D-binding protein) across vertebrates.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets