SCY1-like 1, also known as SCYL1, is a human gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

 which is highly conserved throughout evolution.

Function

This gene encodes a transcriptional regulator belonging to the SCY1-like family of kinase

Kinase

In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...

-like proteins. The protein has a divergent N-terminal kinase domain

Protein domain

A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...

 that is thought to be catalytically inactive, and can bind specific DNA sequences through its C-terminal domain. It activates transcription of the telomerase reverse transcriptase

Telomerase reverse transcriptase

Telomerase reverse transcriptase is a catalytic subunit of the enzyme telomerase. Its absence is associated with the disorder Cri du chat....

 and DNA polymerase beta

DNA polymerase beta

[edit]Polymerase , beta, also known as POLB, is an enzyme that, in humans, is encoded by the POLB gene.- Function :...

 genes. The protein has been localized to the nucleus, and also to the cytoplasm and centrosome

Centrosome

In cell biology, the centrosome is an organelle that serves as the main microtubule organizing center of the animal cell as well as a regulator of cell-cycle progression. It was discovered by Edouard Van Beneden in 1883...

s during mitosis

Mitosis

Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...

. Multiple transcript variants encoding different isoforms have been found for this gene. At least three of the transcripts code for a protein containing all exon

Exon

An exon is a nucleic acid sequence that is represented in the mature form of an RNA molecule either after portions of a precursor RNA have been removed by cis-splicing or when two or more precursor RNA molecules have been ligated by trans-splicing. The mature RNA molecule can be a messenger RNA...

s, referred to as full-length (FL).

The mouse homolog of FL-Scyl1 is 90% identical and 93% similar in amino acid content to human FL-Scyl1. In Mus Musculus FL-Scyl1 encodes an 806-amino acid polypeptide. The FL protein contains HEAT repeats

Heat repeat domain

The HEAT repeat domain is a protein domain found in a number of cytoplasmic proteins including the four that the give rise to the acronym HEAT . HEAT repeats form a rod-like helical structures which are involved in intracellular transport....

 and a C-terminal coiled coil

Coiled coil

A coiled coil is a structural motif in proteins, in which 2-7 alpha-helices are coiled together like the strands of a rope . Many coiled coil type proteins are involved in important biological functions such as the regulation of gene expression e.g. transcription factors...

 domain that also contains multiple dibasic motifs, and ends in the dibasic motif RKLD-COOH.

Scyl1 localizes to the cis

Cisterna

A cisterna comprises a flattened membrane disk that makes up the Golgi apparatus. A typical Golgi has anywhere from 3 to 7 cisternae stacked upon each other like a stack of dinner plates, but there are usually around 6...

-Golgi

Golgi apparatus

The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....

 and ER

Endoplasmic reticulum

The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...

-Golgi Intermediate Compartment (ERGIC). Scyl1 binds to Coatomer I (COPI

COPI

COPI is a protein complex that coats vesicles transporting proteins from the cis end of the Golgi complex back to the rough endoplasmic reticulum , where they were originally synthesized and between golgi compartments. This type of transport is termed as retrograde transport...

) and colocalizes with beta-COPI and ERGIC53

LMAN1

Protein ERGIC-53 also known as ER-Golgi intermediate compartment 53 kDa protein or lectin mannose-binding 1 is a protein that in humans is encoded by the LMAN1 gene.- Function :...

. siRNA

Sírna

Sírna Sáeglach , son of Dian mac Demal, son of Demal mac Rothechtaid, son of Rothechtaid mac Main, was, according to medieval Irish legend and historical tradition, a High King of Ireland...

 mediated knockdown of the protein disrupted retrograde flow of the KDEL receptor

KDELR1

KDEL endoplasmic reticulum protein retention receptor 1, also known as KDELR1, is a protein which in humans is encoded by the KDELR1 gene.- Function :...

 from the Golgi to the ER. Furthermore, Scyl1 localization in rat hippocampal neurons also demonstrates a similar relationship to COPI.

Clinical significance

Mutations in Scyl1 are the genetic defect resulting in the phenotype of muscle deficient mice (mdf mice) that suffer from a progressive neurodegeneration of the cerebellum and lower motor neurons. Mdf mice model human spinocerebellar ataxia

Spinocerebellar ataxia

Spinocerebellar ataxia is a progressive, degenerative, genetic disease with multiple types, each of which could be considered a disease in its own right.-Classification:...

type disorders.

Further reading