SCYL1

SCY1-like 1 (S. cerevisiae), also known as SCYL1, is a human is_associated_with::gene which is highly conserved throughout evolution.

Function
This gene encodes a transcriptional regulator belonging to the SCY1-like family of is_associated_with::kinase-like proteins. The protein has a divergent N-terminal kinase domain that is thought to be catalytically inactive, and can bind specific DNA sequences through its C-terminal domain. It activates transcription of the is_associated_with::telomerase reverse transcriptase and is_associated_with::DNA polymerase beta genes. The protein has been localized to the nucleus, and also to the cytoplasm and is_associated_with::centrosomes during is_associated_with::mitosis. Multiple transcript variants encoding different isoforms have been found for this gene. At least three of the transcripts code for a protein containing all is_associated_with::exons, 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 and a C-terminal is_associated_with::coiled coil domain that also contains multiple dibasic motifs, and ends in the dibasic motif RKLD-COOH.

Scyl1 localizes to the cis-Golgi and ER-Golgi Intermediate Compartment (is_associated_with::ERGIC). Scyl1 binds to Coatomer I (is_associated_with::COPI) and colocalizes with beta-COPI and ERGIC53. is_associated_with::siRNA mediated knockdown of the protein disrupted retrograde flow of the KDEL receptor 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 is_associated_with::spinocerebellar ataxia type disorders.