The Roco protein family: a functional perspective

Abstract

In this review, we discuss the evolutionary, biochemical, and functional data available for members of the Roco protein family. They are characterized by having a conserved supradomain that contains a Ras-like GTPase domain, called Roc, and a characteristic COR (C-terminal of Roc) domain. A kinase domain and diverse regulatory and protein-protein interaction domains are also often found in Roco proteins. First detected in the slime mold Dictyostelium discoideum, they have a broad phylogenetic range, being present in both prokaryotes and eukaryotes. The functions of these proteins are diverse. The best understood are Dictyostelium Rocos, which are involved in cell division, chemotaxis, and development. However, this family has received extensive attention because mutations in one of the human Roco genes (LRRK2) cause familial Parkinson disease. Other human Rocos are involved in epilepsy and cancer. Biochemical data suggest that Roc domains are capable of activating kinase domains intramolecularly. Interestingly, some of the dominant, disease-causing mutations in both the GTPase and kinase domains of LRRK2 increase kinase activity. Thus, Roco proteins may act as stand-alone transduction units, performing roles that were thought so far to require multiple proteins, as occur in the Ras transduction pathway.

Human leucine-rich repeat proteins: a genome-wide bioinformatic categorization and functional analysis in innate immunity

“…Under similar experimental conditions, knockdown of CNOT6L did not alter LPS-and polyIC-mediated TLR activation. Apart from its LRR domain, MFHAS1 contains one other identifiable and recently described Roco (Ras-like GTPase and C-terminal of Roc) domain (26), which is also present in a group of LRR proteins in Dictyostelium and prokaryotes. Although there is currently no reported involvement of MFHAS1 in host defense processes, the strong induction of MFHAS1 expression observed following pathogen challenge (Fig.…”

The Ectocarpus genome and the independent evolution of multicellularity in brown algae

“…Interestingly, 75% of these target sequences occur in genes with leucine-rich repeat (LRR) domains (Supplementary Information 2.3.14). The LRR genes include many members of the ROCO (Roc GTPase plus COR (C-terminal of Roc) domain) family 27 that are predicted to have evolved since the split from the diatoms. Taken together, these observations indicate that a significant proportion of the microRNAs identified may regulate recently evolved processes.…”

Structural model of the dimeric Parkinson’s protein LRRK2 reveals a compact architecture involving distant interdomain contacts

“…LRRK2 is a multidomain, 286-kDa protein exhibiting both GTPase and kinase activities (5-7) that belongs to the recently identified Roco protein family of G proteins. Members of this family have a Ras of complex proteins (Roc) G-domain and an adjacent conserved C-terminal of Roc (COR) dimerization domain in common (8,9). Besides the enzymatic core region, LRRK2 contains four predicted solenoid domains commonly involved in proteinprotein interactions (10).…”