SCYL1

SCY1-like 1 (S. cerevisiae), also known as SCYL1, is a human gene which is highly conserved throughout evolution.[5][6]

SCYL1
Identifiers
Aliases	SCYL1, GKLP, NKTL, NTKL, P105, TAPK, TEIF, TRAP, HT019, SCAR21, SCY1 like pseudokinase 1
External IDs	OMIM: 607982 MGI: 1931787 HomoloGene: 6947 GeneCards: SCYL1
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11q13.1 Start 65,525,077 bp[1] End 65,538,704 bp[1]
Gene location (Mouse) Chr. Chromosome 19 (mouse)[2] Band 19 A|19 4.34 cM Start 5,758,351 bp[2] End 5,771,419 bp[2]
Gene ontology Molecular function • DNA binding • protein kinase activity • protein tyrosine kinase activity • ATP binding • cadherin binding Cellular component • microtubule organizing center • cis-Golgi network • Golgi apparatus • COPI vesicle coat • cytoskeleton • membrane • cell nucleus • endoplasmic reticulum-Golgi intermediate compartment • cytoplasm • cytosol Biological process • protein phosphorylation • regulation of transcription, DNA-templated • retrograde vesicle-mediated transport, Golgi to ER • vesicle-mediated transport • transcription, DNA-templated • peptidyl-tyrosine phosphorylation • transport Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	57410	78891
Ensembl	ENSG00000142186	ENSMUSG00000024941
UniProt	Q96KG9	Q9EQC5
RefSeq (mRNA)	NM_001048218 NM_020680	NM_023912 NM_001361921 NM_001361922
RefSeq (protein)	NP_001041683 NP_065731	NP_076401 NP_001348850 NP_001348851
Location (UCSC)	Chr 11: 65.53 – 65.54 Mb	Chr 19: 5.76 – 5.77 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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).[5]

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.[7] Furthermore, Scyl1 localization in rat hippocampal neurons also demonstrates a similar relationship to COPI.[8]

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.[9]

References

1. GRCh38: Ensembl release 89: ENSG00000142186 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000024941 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: SCYL1 SCY1-like 1 (S. cerevisiae)".
6. 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.
7. 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.
8. 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.
9. 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 1905899. PMID 17571074.

Further reading

• 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. PMID 8889548.
• 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. PMID 10843802.
• Carninci P, Shibata Y, Hayatsu N, et al. (2001). "Normalization and Subtraction of Cap-Trapper-Selected cDNAs to Prepare Full-Length cDNA Libraries for Rapid Discovery of New Genes". Genome Res. 10 (10): 1617–30. doi:10.1101/gr.145100. PMC 310980. PMID 11042159.
• 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. PMID 11118629.
• 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. PMID 12036289.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• 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. PMID 12783284.
• Suzuki Y, Yamashita R, Shirota M, et al. (2004). "Sequence Comparison of Human and Mouse Genes Reveals a Homologous Block Structure in the Promoter Regions". Genome Res. 14 (9): 1711–8. doi:10.1101/gr.2435604. PMC 515316. PMID 15342556.
• 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. PMID 15459234.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• 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. PMID 15504359.
• 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. PMID 15963946.
• 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. PMID 16261899.
• 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. PMID 16713569.
• Schmid EM, Ford MG, Burtey A, et al. (2007). "Role of the AP2 β-Appendage Hub in Recruiting Partners for Clathrin-Coated Vesicle Assembly". PLoS Biol. 4 (9): e262. doi:10.1371/journal.pbio.0040262. PMC 1540706. PMID 16903783.
• Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983.