Serine/threonine-protein kinase RIO1 is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

that in humans is encode by the RIOK1

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. RIOK1 is an atypical

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

, which exists in most archaea and

eukaryote Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bact ...

s. 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 (SSU). It is suggested that over-expression or

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, m ...

s of the RIOK 1 gene may cause mis-regulation of its network (in metazoans - large signaling network at the protein and gene levels via which it stimulates or restricts growth and division in response to nutrient availability). This was observed in primary

cancer cell Cancer cells are cells that divide continually, forming solid tumors or flooding the blood with abnormal cells. Cell division is a normal process used by the body for growth and repair. A parent cell divides to form two daughter cells, and these ...

s 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 (predict pI for various

phosphorylation In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, ...

states; pI for unphosphorylated state = 5.84), and a chromosomal location of human orthodox 6p24.3.
6:7,389,496-7,418,037

PTM Effects

Effects on modified protein - protein degradation, triggered b
K411-m1
protein stabilization, triggered by
T410-p
ubiquitination, triggered by K411-m1. Effects on biological progress - cell growth, inhibited, triggered by K411-m1.

Mutagenesis Mutagenesis () is a process by which the genetic information of an organism is changed by the production of a mutation. It may occur spontaneously in nature, or as a result of exposure to mutagens. It can also be achieved experimentally using l ...

The effect of the experimental mutation of one or more

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...

(s) on the biological properties of the protein. When amino acid residues are altered, we report the change, the name of the mutant (if known), and the effects of the mutation on the protein, the

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...

or the complete

organism In biology, an organism () is any life, living system that functions as an individual entity. All organisms are composed of cells (cell theory). Organisms are classified by taxonomy (biology), taxonomy into groups such as Multicellular o ...

. Examples
Q1LCS4P04395Q38914
When the mutation is associated with several point mutations, we add the exact combination of mutations (positions and amino acid modifications). Examples
P62166O14776
The mutation (D324A) 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 (aligned using Clustal Omega) it is possible to compare the modified residues, in the red boxes, from three different RIOK 1: human,

mouse A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...

and

rat Rats are various medium-sized, long-tailed rodents. Species of rats are found throughout the order Rodentia, but stereotypical rats are found in the genus ''Rattus''. Other rat genera include '' Neotoma'' ( pack rats), '' Bandicota'' (bandico ...

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 ''Aeromonas'' is a genus of Gram-negative, facultative anaerobic, rod-shaped bacteria that morphologically resemble members of the family Enterobacteriaceae. Most of the 14 described species have been associated with human diseases. The most impo ...

'', 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 A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...

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. Immune repression by RIOK1

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 Protein arginine N-methyltransferase 5 is an enzyme that in humans is encoded by the ''PRMT5'' gene. PRMT5 symmetrically dimethylates H2AR3, H4R3, H3R2, and H3R8 in vivo, all of which are linked to a range of transcriptional regulatory events. PR ...

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

methylation. RioK1 binds to a shallow groove of the

TIM barrel The TIM barrel (triose-phosphate isomerase), also known as an alpha/beta barrel, is a conserved protein fold consisting of eight alpha helices (α-helices) and eight parallel beta strands (β-strands) that alternate along the peptide backbone. ...

domain of

via its N-terminal sequence VPGQFDDAD (residues 12-20). The binding amino acid sequence was used as a basis for synthesis of a

macrocyclic Macrocycles are often described as molecules and ions containing a ring of twelve or more atoms. Classical examples include the crown ethers, calixarenes, porphyrins, and cyclodextrins. Macrocycles describe a large, mature area of chemistry. ...

inhibitor of protein-protein interactions between

and its adaptor proteins.

lists of the major functions and processes of RIOK1:

Functions

* ATP binding *

Hydrolase Hydrolase is a class of enzyme that commonly perform as biochemical catalysts that use water to break a chemical bond, which typically results in dividing a larger molecule into smaller molecules. Some common examples of hydrolase enzymes are es ...

activity *Metal ion binding *Protein binding *Protein serine/kerotonine kinase activity

Processes it's involved

* Maturation of SSUU-rRNA *Positive regulation of rRNA processing *Protein

Phosphorylation In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, ...

*Ribosomal small subunit biogenesis

Location and structure

RIOK1 is the only component of the

complex located exclusively in the

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...

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
RIOK1 tissue expression

Sequence and
primary structure Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthes ...

RIOK1 gene has 5 different transcripts but only transcript variant 1 (

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein. mRNA is created during the ...

) (RIOK1-202) contains an

ORF ORF or Orf may refer to: * Norfolk International Airport, IATA airport code ORF * Observer Research Foundation, an Indian research institute * One Race Films, a film production company founded by Vin Diesel * Open reading frame, a portion of t ...

NCBI GenBank
, whose origin sequence is formed of 17 coding exons (represented in red): RIOK1 transcript variant 1 encodes the protein kinase RIO1 (

isoform A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some iso ...

1) which contains 568 aminoacids
NCBI GenPept
. As the result of

posttranslational modification Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribosome ...

s the protein Kinase RIO1 has 2

phosphoserine Phosphoserine (abbreviated as SEP or J) is an ester of serine and phosphoric acid. Phosphoserine is a component of many proteins as the result of posttranslational modifications. The phosphorylation of the alcohol functional group in serine to pro ...

s in positions 21 and 22

Secondary Structure

Its secondary structure consist of 9

alpha helix The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues earl ...

(red) and 7

beta strands Beta (, ; uppercase , lowercase , or cursive ; grc, βῆτα, bē̂ta or ell, βήτα, víta) is the second letter of the Greek alphabet. In the system of Greek numerals, it has a value of 2. In Modern Greek, it represents the voiced labiod ...

(blue)
Protein Data Bank in Europe

Native State

RIOK1 belongs to the serine/threonine-specific protein kinase family and therefore has the

protein kinase domain The protein kinase domain is a structurally conserved protein domain containing the catalytic function of protein kinases. Protein kinases are a group of enzymes that move a phosphate group onto proteins, in a process called phosphorylation. This ...

in positions 180-479 It is an holoenzyme that uses Mg(+2) as its cofactor

Sites

This enzyme has 3 binding sites in positions 208 (for ATP), 278 (for ATP via carbonyl oxygen) and 280 (for ATP via nitrogen amide); 2 metal binding sites g(+2)in positions 329 and 349 and 2 active sites in positions 324 (which is a proton acceptor) and 341 (4-aspartylphosphate intermediate)

References

External links

* {{PDBe-KB2, Q9BRS2, Serine/threonine-protein kinase RIO1