“SCYL1”的意思、由来-开放百科全书

Function

This gene encodes a transcriptional regulator belonging to the SCY1-like family of 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 telomerase reverse transcriptase and DNA polymerase beta genes. The protein has been localized to the nucleus, and also to the cytoplasm and centrosomes during 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 exons, referred to as full-length (FL).^[1]

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 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 (ERGIC). Scyl1 binds to Coatomer I (COPI) and colocalizes with beta-COPI and ERGIC53. siRNA mediated knockdown of the protein disrupted retrograde flow of the KDEL receptor from the Golgi to the ER.^[3] Furthermore, Scyl1 localization in rat hippocampal neurons also demonstrates a similar relationship to COPI.^[4]

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 type disorders.^[5]

References

1. ^¹{{cite web | title = Entrez Gene: SCYL1 SCY1-like 1 (S. cerevisiae)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=57410| accessdate = }}
2. ^{{cite journal | vauthors = Liu SC, Lane WS, Lienhard GE | title = Cloning and preliminary characterization of a 105 kDa protein with an N-terminal kinase-like domain | journal = Biochim. Biophys. Acta | volume = 1517 | issue = 1 | pages = 148–52 |date=December 2000 | pmid = 11118629 | doi = 10.1016/S0167-4781(00)00234-7 | url = }}
3. ^{{cite journal | vauthors = Burman JL, Bourbonniere L, Philie J, Stroh T, Dejgaard SY, Presley JF, McPherson PS | title = Scyl1, mutated in a recessive form of spinocerebellar neurodegeneration, regulates COPI-mediated retrograde traffic | journal = J. Biol. Chem. | volume = 283 | issue = 33 | pages = 22774–86 |date=August 2008 | pmid = 18556652 | doi = 10.1074/jbc.M801869200 | url = }}
4. ^{{cite web|url=http://www.jbc.org/content/vol283/issue33/cover.shtml |title=Hippocampal neurons stained for Scyl1 and clathrin adaptor protein-1 |vauthors=Burman JL, Bourbonniere L, Philie J, Stroh T, Dejgaard SY, Presley JF, McPherson PS |authorlink= |date=2008-08-15 |work=JBC -- About the Cover |publisher=Journal of Biological Chemistry |pages= |archiveurl=https://web.archive.org/web/20081010191015/http://www.jbc.org/content/vol283/issue33/cover.shtml |archivedate=October 10, 2008 |accessdate=2008-09-23 |deadurl=yes }}
5. ^{{cite journal | vauthors = Schmidt WM, Kraus C, Höger H, Hochmeister S, Oberndorfer F, Branka M, Bingemann S, Lassmann H, Müller M, Macedo-Souza LI, Vainzof M, Zatz M, Reis A, Bittner RE | title = Mutation in the Scyl1 gene encoding amino-terminal kinase-like protein causes a recessive form of spinocerebellar neurodegeneration | journal = EMBO Rep. | volume = 8 | issue = 7 | pages = 691–7 |date=July 2007 | pmid = 17571074 | pmc = 1905899 | doi = 10.1038/sj.embor.7401001 | url = }}

Function

Clinical significance

References

Further reading