SCYL1

SCYL1
Identifiers
Aliases SCYL1, GKLP, NKTL, NTKL, P105, TAPK, TEIF, TRAP, HT019, SCAR21, SCY1 like pseudokinase 1
External IDs MGI: 1931787 HomoloGene: 6947 GeneCards: SCYL1
Orthologs
Species Human Mouse
Entrez

57410

78891

Ensembl

ENSG00000142186

ENSMUSG00000024941

UniProt

Q96KG9

Q9EQC5

RefSeq (mRNA)

NM_001048218
NM_020680

NM_023912

RefSeq (protein)

NP_001041683.1
NP_065731.3

NP_076401.1

Location (UCSC) Chr 11: 65.53 – 65.54 Mb Chr 19: 5.76 – 5.77 Mb
PubMed search [1] [2]
Wikidata
View/Edit HumanView/Edit Mouse

SCY1-like 1 (S. cerevisiae), also known as SCYL1, is a human gene which is highly conserved throughout evolution.[3][4]

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).[3]

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.[5] Furthermore, Scyl1 localization in rat hippocampal neurons also demonstrates a similar relationship to COPI.[6]

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.[7]

References

  1. "Human PubMed Reference:".
  2. "Mouse PubMed Reference:".
  3. 1 2 "Entrez Gene: SCYL1 SCY1-like 1 (S. cerevisiae)".
  4. Liu SC, Lane WS, Lienhard GE (December 2000). "Cloning and preliminary characterization of a 105 kDa protein with an N-terminal kinase-like domain". Biochim. Biophys. Acta. 1517 (1): 148–52. doi:10.1016/S0167-4781(00)00234-7. PMID 11118629.
  5. Burman JL, Bourbonniere L, Philie J, Stroh T, Dejgaard SY, Presley JF, McPherson PS (August 2008). "Scyl1, mutated in a recessive form of spinocerebellar neurodegeneration, regulates COPI-mediated retrograde traffic". J. Biol. Chem. 283 (33): 22774–86. doi:10.1074/jbc.M801869200. PMID 18556652.
  6. Burman JL, Bourbonniere L, Philie J, Stroh T, Dejgaard SY, Presley JF, McPherson PS (2008-08-15). "Hippocampal neurons stained for Scyl1 and clathrin adaptor protein-1". JBC -- About the Cover. Journal of Biological Chemistry. Archived from the original on October 10, 2008. Retrieved 2008-09-23.
  7. 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 (July 2007). "Mutation in the Scyl1 gene encoding amino-terminal kinase-like protein causes a recessive form of spinocerebellar neurodegeneration". EMBO Rep. 8 (7): 691–7. doi:10.1038/sj.embor.7401001. PMC 1905899Freely accessible. PMID 17571074.

Further reading


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