ARMC Subfamily: Structures, Functions, Evolutions, Interactions, and Diseases

Abstract

Armadillo repeat-containing proteins (ARMCs) are widely distributed in eukaryotes and have important influences on cell adhesion, signal transduction, mitochondrial function regulation, tumorigenesis, and other processes. These proteins share a similar domain consisting of tandem repeats approximately 42 amino acids in length, and this domain constitutes a substantial platform for the binding between ARMCs and other proteins. An ARMC subfamily, including ARMC1∼10, ARMC12, and ARMCX1∼6, has received increasing attention. These proteins may have many terminal regions and play a critical role in various diseases. On the one hand, based on their similar central domain of tandem repeats, this ARMC subfamily may function similarly to other ARMCs. On the other hand, the unique domains on their terminals may cause these proteins to have different functions. Here, we focus on the ARMC subfamily (ARMC1∼10, ARMC12, and ARMCX1∼6), which is relatively conserved in vertebrates and highly conserved in mammals, particularly primates. We review the structures, biological functions, evolutions, interactions, and related diseases of the ARMC subfamily, which involve more than 30 diseases and 40 bypasses, including interactions and relationships between more than 100 proteins and signaling molecules. We look forward to obtaining a clearer understanding of the ARMC subfamily to facilitate further in-depth research and treatment of related diseases.

Identification of nonhistone substrates of the lysine methyltransferase PRDM9

“…Furthermore, we have demonstrated that PRDM9 methylates CTNNBL1 at K394 both in vitro and in cells. Lysine 394 resides within an ARM repeat region of CTNNBL1; ARM repeats form an α-superhelix, providing a platform for protein interactions, including activation or degradation of the target protein ( 32 ). In the case of the related protein β-catenin, regulation of lysine methylation within an ARM repeat region was shown to regulate protein stability ( 24 ).…”

Substrate selectivity of the PRDM9 lysine methyltransferase domain

“…Furthermore, we have demonstrated that PRDM9 methylates recombinant CTNNBL1 protein at K394. Lysine 394 resides within an ARM repeat region of CTNNBL1; ARM repeats form an α-superhelix, providing a platform for protein interactions, including activation or degradation of the target protein (32). In the case of the related protein β-catenin, regulation of lysine methylation within an ARM repeat region was shown to regulate protein stability (24).…”

A genomic approach to analyze the cold adaptation of yeasts isolated from Italian Alps

“…Some α/β hydrolases have been involved in salt and cold tolerance in plants and microorganisms, including yeasts ( Brody et al, 2001 ; Takahashi et al, 2006 ; Liu et al, 2014 ; Wu et al, 2020 ). ARMCs form a large family of enzymes primarily characterized in multicellular organisms (e.g., in plants) and exhibiting very versatile and fundamental functions, including response to stress, such as osmotic ( Kojima et al, 2013 ; Sharma and Pandey, 2015 ; Huang et al, 2021 ). MFS is a ubiquitous transporter superfamily whose members have a broad spectrum of substrates, such as inorganic and amino acids, nucleosides, lipids, and short peptides ( Yan, 2015 ); some members of MFS are involved in resistance to oxidative stress and fungicides in fungal pathogen Alternaria alternata ( Chen et al, 2017 ).…”