# Functional Motif Prediction in ADAMTS-TSL proteins Based on Module(s) and Phenotype(s) Co-appearance

Olivier Dennler, Samuel Blanquart, François Coste, Catherine Belleannée,
Nathalie Théret

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## To cite this version:

Olivier Dennler, Samuel Blanquart, François Coste, Catherine Belleannée, Nathalie Théret. Functional Motif Prediction in ADAMTS-TSL proteins Based on Module(s) and Phenotype(s) Co-appearance. ALPHY/AIEM 2022 - Rencontres Génomique évolutive, Bioinformatique, Alignement et Phylogénie, Mar 2022, Rennes, France. hal-03870590

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Submitted on 24 Nov 2022

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Distributed under a Creative Commons Attribution 4.0 International License
# Functional Motif Prediction in ADAMTS-TSL proteins Based on Module(s) and Phenotype(s) Co-appearance

Olivier Dennler¹,², Samuel Blanquart², François Coste², Catherine Belleannee² and Nathalie Theret¹,²

¹ Univ Rennes, Inserm, EHESP, Irset - UMR S1085, F-35043 Rennes

² Univ Rennes, Inria, CNRS, IRISA, UMR 6074, Rennes, France

olivier.dennler@inria.fr

## Introduction and Objective

* Multi-genes (26 *H. sapiens* paralogs)

* Multi-domains

* Partial knowledge / experimental data [1]

=> A new method to identify functional motif

<figure><img src="image_3.png" /></figure>

**Hypothesis:**
During evolution, modules gained at the same time than a phenotype, are involved in this phenotype

## Association of Multiple Evolutionary Histories

<figure><img src="image_4.png" /></figure>

* Ortholog and paralog sequences

* Protein-Protein Interaction (PPI) and module evolutions on a common gene phylogeny

* Module(s) and Phenotype(s) Co-appearance(s)

## The Hyalectanase Spacer: Validation, Prediction and Diversity

<figure><img src="image_5.png" /></figure>

* 173 ADAMTS-TSL in 9 species

* 1700 modules, 119 PPIs

* 36 Co-appearances

<footnote>[1] Suneel S. Apte. ADAMTS Proteins: Concepts, Challenges, and Prospects. Methods in Molecular Biology (Clifton, N.J.), 2043:112, 2020.</footnote>

<footnote>[2] Lei Li and Mukul Bansal. Simultaneous Multi-Domain-Multi-Gene Reconciliation Under the Domain-Gene- Species Reconciliation Model. pages 73(86. January 2019. [3] Sohta A Ishikawa, Anna Zhukova, Wataru Iwasaki, and Olivier Gascuel. A Fast Likelihood Method to Reconstruct and Visualize Ancestral Scenarios. Molecular Biology and Evolution, 36(9):2069(2085, September 2019. [4] Chuan-Ju Liu, Wei Kong, Kiril Ilalov, Shuang Yu, Ke Xu, Lisa Prazak, Marc Fajardo, Bantoo Sehgal and Paul E. Di Cesare. ADAMTS-7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein. FASEB journal: official publication of the Federation of American</footnote>

<footnote>Societies for Experimental Biology, 20(7):988(990, May 2006.</footnote>

<footnote>Module(s) gained early in ADAMTS-TSL evolution
Module(s) gained at the Hyalectanases ancestor (G96)
Module(s) gained at ADAMTS-5 orthologs ancestor (G65)
Module(s) gained at ADAMTS-8 orthologs ancestor (G37)
Module(s) gained at ADAMTS-4 orthologs ancestor (G19)</footnote>

<footnote>Hypervariable loops in ADAMTS-4, -5 (from left to right : β1-β2, β3-β4, β9-β10 as described in Santamaria et al, 2019)
Sequences without any detected conservation</footnote>