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]
↑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. PMID11118629.
↑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. PMID18556652.
Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID8889548.
van Asseldonk M, Schepens M, de Bruijn D, et al. (2000). "Construction of a 350-kb sequence-ready 11q13 cosmid contig encompassing the markers D11S4933 and D11S546: mapping of 11 genes and 3 tumor-associated translocation breakpoints". Genomics. 66 (1): 35–42. doi:10.1006/geno.2000.6194. PMID10843802.
Liu SC, Lane WS, Lienhard GE (2001). "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. PMID11118629.
Kato M, Yano K, Morotomi-Yano K, et al. (2002). "Identification and characterization of the human protein kinase-like gene NTKL: mitosis-specific centrosomal localization of an alternatively spliced isoform". Genomics. 79 (6): 760–7. doi:10.1006/geno.2002.6774. PMID12036289.
Di Y, Li J, Fang J, et al. (2004). "Cloning and characterization of a novel gene which encodes a protein interacting with the mitosis-associated kinase-like protein NTKL". J. Hum. Genet. 48 (6): 315–21. doi:10.1007/s10038-003-0031-5. PMID12783284.
Bohlson SS, Zhang M, Ortiz CE, Tenner AJ (2005). "CD93 interacts with the PDZ domain-containing adaptor protein GIPC: implications in the modulation of phagocytosis". J. Leukoc. Biol. 77 (1): 80–9. doi:10.1189/jlb.0504305. PMID15459234.
Tang Z, Zhao Y, Mei F, et al. (2005). "Molecular cloning and characterization of a human gene involved in transcriptional regulation of hTERT". Biochem. Biophys. Res. Commun. 324 (4): 1324–32. doi:10.1016/j.bbrc.2004.09.201. PMID15504359.
Zhao Y, Zheng J, Ling Y, et al. (2005). "Transcriptional upregulation of DNA polymerase beta by TEIF". Biochem. Biophys. Res. Commun. 333 (3): 908–16. doi:10.1016/j.bbrc.2005.05.172. PMID15963946.
Mei F, Zhang B, Tang ZW, Hou L (2006). "Expression of a telomerase-associated gene in normal, atrophic, and tumorous testes". Chin. Med. Sci. J. 20 (3): 217–20. PMID16261899.
Lim J, Hao T, Shaw C, et al. (2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID16713569.
