A Systematic Compilation of Human SH3 Domains: A Versatile Superfamily in Cellular Signaling

Mehrnaz Mehrabipour; Neda S Kazemein Jasemi; Radovan Dvorsky; Mohammad R Ahmadian

doi:10.3390/cells12162054

A Systematic Compilation of Human SH3 Domains: A Versatile Superfamily in Cellular Signaling

Cells. 2023 Aug 12;12(16):2054. doi: 10.3390/cells12162054.

Authors

Mehrnaz Mehrabipour¹, Neda S Kazemein Jasemi¹, Radovan Dvorsky^{1

2}, Mohammad R Ahmadian¹

Affiliations

¹ Institute of Biochemistry and Molecular Biology II, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
² Center for Interdisciplinary Biosciences, P. J. Šafárik University, 040 01 Košice, Slovakia.

Abstract

SRC homology 3 (SH3) domains are fundamental modules that enable the assembly of protein complexes through physical interactions with a pool of proline-rich/noncanonical motifs from partner proteins. They are widely studied modular building blocks across all five kingdoms of life and viruses, mediating various biological processes. The SH3 domains are also implicated in the development of human diseases, such as cancer, leukemia, osteoporosis, Alzheimer's disease, and various infections. A database search of the human proteome reveals the existence of 298 SH3 domains in 221 SH3 domain-containing proteins (SH3DCPs), ranging from 13 to 720 kilodaltons. A phylogenetic analysis of human SH3DCPs based on their multi-domain architecture seems to be the most practical way to classify them functionally, with regard to various physiological pathways. This review further summarizes the achievements made in the classification of SH3 domain functions, their binding specificity, and their significance for various diseases when exploiting SH3 protein modular interactions as drug targets.

Keywords: SH3 domain; SH3 domain-containing proteins; SRC homology 3; proline-rich motifs (PRM); protein interaction; signal transduction.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease*
Databases, Factual
Drug Delivery Systems
Humans
Phylogeny
src Homology Domains*

Grants and funding

This study was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft or DFG; AH 92/8-3) and the European Network on Noonan Syndrome and Related Disorders (NSEuroNet, 01GM1602B).