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. 2017 Nov 2;7(1):14924.
doi: 10.1038/s41598-017-14617-0.

KIXBASE: A comprehensive web resource for identification and exploration of KIX domains

Archana Yadav  1 , Jitendra K Thakur  1 , Gitanjali Yadav  2
Affiliations

KIXBASE: A comprehensive web resource for identification and exploration of KIX domains

Archana Yadav et al. Sci Rep. .

Abstract

The KIX domain has emerged in the last two decades as a critical site of interaction for transcriptional assembly, regulation and gene expression. Discovered in 1994, this conserved, triple helical globular domain has been characterised in various coactivator proteins of yeast, mammals and plants, including the p300/CBP (a histone acetyl transferase), MED15 (a subunit of the mediator complex of RNA polymerase II), and RECQL5 helicases. In this work, we describe the first rigorous meta analysis of KIX domains across all forms of life, leading to the development of KIXBASE, a predictive web server and global repository for detection and analysis of KIX domains. To our knowledge, KIXBASE comprises the largest online collection of KIX sequences, enabling assessments at the level of both sequence and structure, incorporating PSIPRED and MUSTER at the backend for further annotation and quality assessment. In addition, KIXBASE provides useful information about critical aspects of KIX domains such as their intrinsic disorder, hydrophobicity profiles, functional classification and annotation based on domain architectures. KIXBASE represents a significant enrichment of the currently annotated KIX dataset, especially in the plant kingdom, thus highlighting potential targets for biochemical characterization. The KIX webserver and database are both freely available to the scientific community, at http://www.nipgr.res.in/kixbase/home.php .

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
KIXBASE Workflow. Flowchart depicts KIX prediction algorithm adopted by KIXBASE which is made stringent for false positives in the pre-processing step by use of filters at primary sequence level like the E-value cutoff of 0.05, KIX length >=70 and structure level through tertiary fold recognition match with any of the PDP KIX domain. After the prediction of KIX domains, post processing includes analysis of all KIX domains at various conservation, structural and functional level.
Figure 2
Figure 2
KIXBASE Screenshots. (A) Fasta with highlighted KIX domains, (B) Multi-feature plots depicting secondary structure of KIX mapped with internal disorder and hydrophobicity, (C) Secondary structure prediction of KIX, (D) Conservation of predicted KIX with characterised KIX domains, (E) Extracted KIX domains, (F) Domain alignment with HMM consensus, (G) Domains present in KIX proteins in domain organisation plots and tabular format.
Figure 3
Figure 3
KIXBASE Benchmarking. KIX records from KIXBASE were compared with the recent release of InterPro, Pfam and Prosite. KIXBASE currently have the highest number of KIX entries both in terms of number of proteins and number of species as compared to other three databases, owing to its power to identify more variable and unique domains.
Figure 4
Figure 4
KIX Domain Prediction for MED15 and RECQL5 containing proteins of metazoans. Here we have compared the number of KIX domain containing proteins that can be correctly assigned by four programs, namely KIXBASE, InterPro, Pfam and Prosite, from among the known MED15 (panel A) and RECQL5 (panel B) containing proteins. The lower panel shows the taxonomic classes of these proteins.
Figure 5
Figure 5
CREB-KID binding site analysis in CBP-KIX domain through multi-feature plot output in KIXBASE. (A) Domain arrangements in mouse CBP protein. KIX sequence highlighting residues that bind to CREB-KID. (B) Solution structure of CBP-KIX bound to CREB-KID, yellow region represents hydrophobic binding site. (C) KID binding residues marked as red arrows in hydrophobicity plots, mapped to their internal disorder and secondary structure.
Figure 6
Figure 6
Comparison of structural features among characterised KIX. domains. The common structural patterns in multi feature plots of Human (A) CBP, (B) RECQL5, (C) MED15, (D) Arabidopsis thaliana RECQL3 and (E) Arabidopsis thaliana HAC5 can be observed here.
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