ARL6IP4
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ADP-ribosylation-like factor 6 interacting protein 4 (ARL6IP4), also called SRp25 is the product of the ARL6IP4 gene located on chromosome 12q24. 31. Its function is unknown.


Structure

It is 360
amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...
in length. It is expressed ubiquitously but only in G1/S phase of the
cell cycle The cell cycle, or cell-division cycle, is the sequential series of events that take place in a cell (biology), cell that causes it to divide into two daughter cells. These events include the growth of the cell, duplication of its DNA (DNA re ...
. The human and mouse
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 Protein biosynthesis, synthesizing a protein. mRNA is ...
s of this protein have 77% homology. Two types of
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
clusters have been observed, a
serine Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − ...
cluster and a basic cluster.


Function

Its function(s) are unknown. However, due to sequence homology of its protein with SR splicing factors, it is widely believed that the protein is nuclear and may have a role in splicing regulation. The protein is believed to be a mediator in the RAC1 signalling pathway.


RNA editing

The pre-mRNA of the ARL6IP4 gene product is subject to RNA Editing.


Type

A to I RNA editing is catalyzed by a family of adenosine deaminases acting on RNA (ADARs) that specifically recognize adenosines within double-stranded regions of pre- mRNAs and deaminate them to inosine. Inosines are recognised as
guanosine Guanosine (symbol G or Guo) is a purine nucleoside comprising guanine attached to a ribose ( ribofuranose) ring via a β-N9- glycosidic bond. Guanosine can be phosphorylated to become guanosine monophosphate (GMP), cyclic guanosine monophosp ...
by cellular translational machinery. ADAR 1 and ADAR 2 are the only enzymatically active members. ADAR3 is thought to have a regulatory role in the brain. ADAR1 and ADAR 2 are widely expressed in tissues while ADAR 3 is restricted to the brain. The double stranded regions of RNA are formed by base-pairing between residues in the region close to the editing site with residues usually in a neighboring
intron An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e., a region inside a gene."The notion of the cistron .e., gen ...
but can be an exonic sequence. The region that base pairs with the editing region is known as an Editing Complementary Sequence (ECS).


Location

Editing occurs at a K/R editing site within amino acid position 225 of the final protein. Using RT-PCR and sequencing of 100 individual clones, 7% of isoform 3 of the protein showed a G instead of an A at this position during sequencing. Other minor editing sites may be potentially present including some in the same exon as the major editing site. As is the case of
IGFBP7 Insulin-like growth factor-binding protein 7 is a protein that in humans is encoded by the ''IGFBP7'' gene. The major function of the protein is the regulation of availability of insulin-like growth factors (IGFs) in tissue as well as in modulat ...
, pre-mRNA, editing is unusual as the RNA fold back structure is made up off exonic sequence only.


Effects on protein structure

Editing at this site results in a codon changed from a
Lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. Lysine contains an α-amino group (which is in the protonated form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group ( ...
to an
Arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidinium, guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) a ...
. This occurs in a highly basic region of the protein.


Effects on protein function

The function of the unedited protein is largely uncharacterised. Therefore, the effect of editing on the pre-mRNA on the proteins function is also unknown. The amino acid change is conservative and is unlikely to massively alter protein function. However, the editing site may be important since the amino acid being altered is a
Lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. Lysine contains an α-amino group (which is in the protonated form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group ( ...
, which may be involved in the regulation of protein expression. Lysines can be sites of
post-translational modification In molecular biology, post-translational modification (PTM) is the covalent process of changing proteins following protein biosynthesis. PTMs may involve enzymes or occur spontaneously. Proteins are created by ribosomes, which translation (biolog ...
and the conversion of Lysine to an Arginine could affect post-translational modification.


References


External links

* * Human proteins