RIOK1


Serine/threonine-protein kinase RIO1 is an enzyme that in humans is encode by the RIOK1 gene.
RIOK1 is an atypical protein, which exists in most archaea and eukaryotes. It belongs to the serine/threonine-specific protein kinase family.
It has been intensely studied to understand the maturation they promote on small ribosomal subunits. It is suggested that over-expression or mutations of the RIOK 1 gene may cause mis-regulation of its network. This was observed in primary cancer cells and may contribute to cancer initiation and progression.

Characteristics

RIOK 1 has a molecular weight of 65,583 Da, a basal isoelectric point of 5.84, and a chromosomal location of human orthodox 6p24.3.
PTM Effects
Effects on modified protein - protein degradation, triggered by ; protein stabilization, triggered by ; ubiquitination, triggered by K411-m1.
Effects on biological progress - cell growth, inhibited, triggered by K411-m1.
[Mutagenesis]
The effect of the experimental mutation of one or more amino acid on the biological properties of the protein. When amino acid residues are altered, we report the change, the name of the mutant, and the effects of the mutation on the protein, the cell or the complete organism. Examples: , , .
When the mutation is associated with several point mutations, we add the exact combination of mutations. Examples: , .
The mutation in RIOK1 abolishes autophosphorylation activity, enhances association with pre-40S ribosomal subunits and inhibits processing of 18S-E pre-rRNA to the mature 18S rRNA.
Conservation
Looking at the multiple sequence alignment it is possible to compare the modified residues, in the red boxes, from three different RIOK 1: human, mouse and rat.

Function

Inmunne Repressor

Despite the fact that RIOK1 functions remain unclear, it's been discovered that the lack of this protein grants resistance to a certain type of bacteria called Aeromonas, which shows its function as an inmune repressor.
The feedback loop is the model which RIOK1 allows the inhibition of our immune system against bacteria among p38 MAPK and SKN-1. Microorganism presence active the p38 MAPK pathway increasing the concentration of SKN-1, which will end up producing the necessary amount of RIOK1 to stop this pathway.

RNA Maturation

In addition, RIOK1 has also a potential role with the metabolism of the 40S ribosomal subunit, precisely, we know it's involved in the maturation of the 40S ribosomal subunit and needed for the recycling of PNO1 and NOB1, which are both RNA-binding proteins from 40S precursors.

Protein Binding

Furthermore, RIOK1 protein binding function stands out among other proteins involved in the same activity. For instance, in the binding of PRMT5 in which RIOK1 and PICln are involved, suggest that RIOK1 is a more general adapter than PICln. RIOK1 also interacts with NCL via its C-terminus, which targets NCL for PRMT5 methylation..

lists of the major functions and processes of RIOK1:

Functions
RIOK1 is the only component of the PRMT5 complex located exclusively in the cytoplasm.

Tissue expression

The protein Kinase RIO1 highest expression is in testicles, in addition the RNA that encodes this protein has low tissue especifity, as it is detected in every kind of tissue, but mostly in the pituitary gland, testicles, skeletal muscle, thymus and NK-cells

Sequence and primary structure">Protein primary structure">primary structure

RIOK1 gene has 5 different transcripts but only transcript variant 1 contains an ORF, whose origin sequence is formed of 17 coding exons :

RIOK1 transcript variant 1 encodes the protein kinase RIO1 which contains 568 aminoacids . As the result of posttranslational modifications the protein Kinase RIO1 has 2 phosphoserines in positions 21 and 22

Secondary Structure

Its secondary structure consist of 9 alpha helix and 7 beta strands


Native State

RIOK1 belongs to the serine/threonine-specific protein kinase family and therefore has the protein kinase domain in positions 180-479
It is an holoenzyme that uses Mg as its cofactor

Sites

This enzyme has 3 binding sites in positions 208, 278 and 280 ; 2 metal binding sites in positions 329 and 349 and 2 active sites in positions 324 and 341