[cite journal | author = 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 | year = 2000 | month = December | pmid = 11118629 | doi = 10.1016/S0167-4781(00)00234-7 | url = | issn = ] ] 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-legnth (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 a 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.
The cytosolic pool of Scyl1 localizes to the cis-Golgi and ER-Golgi Intermediated 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.[cite journal | author = 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 | year = 2008 | month = August | pmid = 18556652 | doi = 10.1074/jbc.M801869200 | url = | issn = ] Furthermore, Scyl1 localization in rat hippocampal neurons also demonstrates a similar relationship to COPI. [cite web | url = http://www.jbc.org/content/vol283/issue33/cover.shtml | title = Hippocampal neurons stained for Scyl1 and clathrin adaptor protein-1 | author = Burman JL, Bourbonniere L, Philie J, Stroh T, Dejgaard SY, Presley JF, McPherson PS | authorlink = | coauthors = | date = 2008-08-15 | format = | work = JBC -- About the Cover | publisher = Journal of Biological Chemistry | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = 2008-09-23] ] Clinical significance
Mutations in Scyl1 are the genetic defect resulting in the phenotype of muscle deficient mice (mdf mice) that suffer from a progressive neuropathy of the cerebellum and lower motor neurons. Mdf mice model human spinocerebellar ataxia type disorders.[cite journal | author = 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 | year = 2007 | month = July | pmid = 17571074 | pmc = 1905899 | doi = 10.1038/sj.embor.7401001 | url = | issn = ] ]References
Further reading
PBB_Further_reading
citations =
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*cite journal | author=van Asseldonk M, Schepens M, de Bruijn D, "et al." |title=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. |journal=Genomics |volume=66 |issue= 1 |pages= 35–42 |year= 2000 |pmid= 10843802 |doi= 10.1006/geno.2000.6194
*cite journal | author=Carninci P, Shibata Y, Hayatsu N, "et al." |title=Normalization and subtraction of cap-trapper-selected cDNAs to prepare full-length cDNA libraries for rapid discovery of new genes. |journal=Genome Res. |volume=10 |issue= 10 |pages= 1617–30 |year= 2001 |pmid= 11042159 |doi=
*cite journal | author=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 |year= 2001 |pmid= 11118629 |doi=
*cite journal | author=Kato M, Yano K, Morotomi-Yano K, "et al." |title=Identification and characterization of the human protein kinase-like gene NTKL: mitosis-specific centrosomal localization of an alternatively spliced isoform. |journal=Genomics |volume=79 |issue= 6 |pages= 760–7 |year= 2002 |pmid= 12036289 |doi= 10.1006/geno.2002.6774
*cite journal | author=Strausberg RL, Feingold EA, Grouse LH, "et al." |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899
*cite journal | author=Di Y, Li J, Fang J, "et al." |title=Cloning and characterization of a novel gene which encodes a protein interacting with the mitosis-associated kinase-like protein NTKL. |journal=J. Hum. Genet. |volume=48 |issue= 6 |pages= 315–21 |year= 2004 |pmid= 12783284 |doi= 10.1007/s10038-003-0031-5
*cite journal | author=Suzuki Y, Yamashita R, Shirota M, "et al." |title=Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions. |journal=Genome Res. |volume=14 |issue= 9 |pages= 1711–8 |year= 2004 |pmid= 15342556 |doi= 10.1101/gr.2435604
*cite journal | author=Bohlson SS, Zhang M, Ortiz CE, Tenner AJ |title=CD93 interacts with the PDZ domain-containing adaptor protein GIPC: implications in the modulation of phagocytosis. |journal=J. Leukoc. Biol. |volume=77 |issue= 1 |pages= 80–9 |year= 2005 |pmid= 15459234 |doi= 10.1189/jlb.0504305
*cite journal | author=Gerhard DS, Wagner L, Feingold EA, "et al." |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504
*cite journal | author=Tang Z, Zhao Y, Mei F, "et al." |title=Molecular cloning and characterization of a human gene involved in transcriptional regulation of hTERT. |journal=Biochem. Biophys. Res. Commun. |volume=324 |issue= 4 |pages= 1324–32 |year= 2005 |pmid= 15504359 |doi= 10.1016/j.bbrc.2004.09.201
*cite journal | author=Zhao Y, Zheng J, Ling Y, "et al." |title=Transcriptional upregulation of DNA polymerase beta by TEIF. |journal=Biochem. Biophys. Res. Commun. |volume=333 |issue= 3 |pages= 908–16 |year= 2005 |pmid= 15963946 |doi= 10.1016/j.bbrc.2005.05.172
*cite journal | author=Mei F, Zhang B, Tang ZW, Hou L |title=Expression of a telomerase-associated gene in normal, atrophic, and tumorous testes. |journal=Chin. Med. Sci. J. |volume=20 |issue= 3 |pages= 217–20 |year= 2006 |pmid= 16261899 |doi=
*cite journal | author=Lim J, Hao T, Shaw C, "et al." |title=A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. |journal=Cell |volume=125 |issue= 4 |pages= 801–14 |year= 2006 |pmid= 16713569 |doi= 10.1016/j.cell.2006.03.032
*cite journal | author=Schmid EM, Ford MG, Burtey A, "et al." |title=Role of the AP2 beta-appendage hub in recruiting partners for clathrin-coated vesicle assembly. |journal=PLoS Biol. |volume=4 |issue= 9 |pages= e262 |year= 2007 |pmid= 16903783 |doi= 10.1371/journal.pbio.0040262
*cite journal | author=Olsen JV, Blagoev B, Gnad F, "et al." |title=Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. |journal=Cell |volume=127 |issue= 3 |pages= 635–48 |year= 2006 |pmid= 17081983 |doi= 10.1016/j.cell.2006.09.026
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