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词条 SEC16B
释义

  1. Discovery

  2. Gene

  3. Function

  4. Model organisms

  5. References

  6. Further reading

{{Infobox_gene}}Protein transport protein Sec16B also known as regucalcin gene promoter region-related protein p117 (RGPR-p117) and leucine zipper transcription regulator 2 (LZTR2) is a protein that in humans is encoded by the SEC16B gene.[1][2][3]

Discovery

RGPR-p117/SEC16B, which was named as a regucalcin gene promoter region-related protein, was originally discovered as a novel transcription factor that specifically binds to a nuclear factor I (NFI) consensus motif TTGGC(N)6CC that is located on the 5’-flanking region of the regucalcin gene (rgn) in 2001.[2][4] This gene is a highly conserved a leucine zipper motif, and it was also named as the leucine zipper transcription regulator 2 (LZTR2). In 2007, RGPR-p117 was also renamed as Sec16 homologue B (SEC16B), an endoplasmic reticulum export factor.[5]

Gene

The gene consists of 26 exons spanning approximately 4.1 kbp and is localized on human chromosome 1q25.2.[2] This gene expression is stimulated through various signaling factors in cells.[6][7] RGPR-p117 is present in the plasma membranes, cytoplasm, mitochondria, microsomes and nucleus of the cells.[7] Cytoplasm RGPR-p117 is translocated to nucleus.[6] Phosphorylated RGPR-p117 specifically binds to the TTGGC motif in the promoter region of various genes to enhance the gene expression of various proteins, and plays a crucial role as a transcription factor in the cells.[7][8][9]

Function

In the role in the regulation of cell regulation, RGPR-p117 possesses protective effects on apoptotic cell death induced by various signaling factors.[8] Overexpression of RGPR-p117 did not cause an alteration of cell proliferation and led to significant decreases in protein and DNA contents in cloned normal rat kidney proximal tubular epithelial NRK52E cells.[10] It also plays a role as an endoplasmic reticulum export factor to deliver to newly synthesized proteins and lipids to the Golgi.[5][11][12] RGPR-p117/SEC16B may be involved in human obesity to possess an association between single nucleotide polymorphisms and different measures of obesity.[13][14][15]

Model organisms

Model organisms have been used in the study of SEC16B function. A conditional knockout mouse line, called Sec16btm1a(KOMP)Wtsi[21][22] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[23][24][25]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[19][26] Twenty one tests were carried out on mutant mice and one significant abnormality was observed: homozygote mutants had decreased circulating cholesterol levels.[19]

References

1. ^{{cite journal | vauthors = Nagase T, Kikuno R, Ohara O | title = Prediction of the coding sequences of unidentified human genes. XXI. The complete sequences of 60 new cDNA clones from brain which code for large proteins | journal = DNA Research | volume = 8 | issue = 4 | pages = 179–87 | date = August 2001 | pmid = 11572484 | pmc = | doi = 10.1093/dnares/8.4.179 }}
2. ^1 2 {{cite journal | vauthors = Misawa H, Yamaguchi M | title = Molecular cloning and sequencing of the cDNA coding for a novel regucalcin gene promoter region-related protein in rat, mouse and human liver | journal = International Journal of Molecular Medicine | volume = 8 | issue = 5 | pages = 513–20 | date = November 2001 | pmid = 11605020 | pmc = | doi = 10.3892/ijmm.8.5.513 }}
3. ^{{cite web | title = Entrez Gene: LZTR2 leucine zipper transcription regulator 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=89866| accessdate = }}
4. ^{{cite journal | vauthors = Misawa H, Yamaguchi M | title = Gene expression for a novel protein RGPR-p117 in various species: the stimulation by intracellular signaling factors | journal = Journal of Cellular Biochemistry | volume = 87 | issue = 2 | pages = 188–93 | year = 2002 | pmid = 12244571 | doi = 10.1002/jcb.10289 }}
5. ^1 {{cite journal | vauthors = Bhattacharyya D, Glick BS | title = Two mammalian Sec16 homologues have nonredundant functions in endoplasmic reticulum (ER) export and transitional ER organization | journal = Molecular Biology of the Cell | volume = 18 | issue = 3 | pages = 839–49 | date = March 2007 | pmid = 17192411 | pmc = 1805085 | doi = 10.1091/mbc.E06-08-0707 }}
6. ^1 {{cite journal | vauthors = Sawada N, Nakagawa T, Murata T, Yamaguchi M | title = Nuclear localization of a novel protein, RGPR-p117, in cloned normal rat kidney proximal tubular epithelial cells | journal = International Journal of Molecular Medicine | volume = 16 | issue = 5 | pages = 809–14 | date = November 2005 | pmid = 16211248 | doi = 10.3892/ijmm.16.5.809 }}
7. ^1 2 {{cite journal | vauthors = Sawada N, Yamaguchi M | title = Overexpression of RGPR-p117 enhances regucalcin gene expression in cloned normal rat kidney proximal tubular epithelial cells | journal = International Journal of Molecular Medicine | volume = 16 | issue = 6 | pages = 1049–55 | date = December 2005 | pmid = 16273285 | doi = 10.3892/ijmm.16.6.1049 }}
8. ^1 {{cite journal | vauthors = Yamaguchi M, Tomono S, Nakagawa T | title = Overexpression of RGPR-p117 suppresses apoptotic cell death and its related gene expression in cloned normal rat kidney proximal tubular epithelial NRK52E cells | journal = International Journal of Molecular Medicine | volume = 20 | issue = 4 | pages = 565–71 | date = October 2007 | pmid = 17786289 | doi = 10.3892/ijmm.20.4.565 }}
9. ^{{cite journal | vauthors = Yamaguchi M | title = Novel protein RGPR-p117: its role as the regucalcin gene transcription factor | journal = Molecular and Cellular Biochemistry | volume = 327 | issue = 1–2 | pages = 53–63 | date = July 2009 | pmid = 19214710 | doi = 10.1007/s11010-009-0042-4 }}
10. ^{{cite journal | vauthors = Tomono S, Sawada N, Yamaguchi M | title = Overexpression of RGPR-p117 induces the decrease in protein and DNA contents in cloned normal rat kidney proximal tubular epithelial NRK52E cells | journal = International Journal of Molecular Medicine | volume = 20 | issue = 1 | pages = 79–83 | date = July 2007 | pmid = 17549392 | doi = 10.3892/ijmm.20.1.79 }}
11. ^{{cite journal | vauthors = Budnik A, Heesom KJ, Stephens DJ | title = Characterization of human Sec16B: indications of specialized, non-redundant functions | journal = Scientific Reports | volume = 1 | issue = | pages = 77 | year = 2011 | pmid = 22355596 | pmc = 3216564 | doi = 10.1038/srep00077 }}
12. ^{{cite journal | vauthors = Yonekawa S, Furuno A, Baba T, Fujiki Y, Ogasawara Y, Yamamoto A, Tagaya M, Tani K | title = Sec16B is involved in the endoplasmic reticulum export of the peroxisomal membrane biogenesis factor peroxin 16 (Pex16) in mammalian cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 31 | pages = 12746–51 | date = August 2011 | pmid = 21768384 | pmc = 3150892 | doi = 10.1073/pnas.1103283108 }}
13. ^{{cite journal | vauthors = Albuquerque D, Nóbrega C, Rodríguez-López R, Manco L | title = Association study of common polymorphisms in MSRA, TFAP2B, MC4R, NRXN3, PPARGC1A, TMEM18, SEC16B, HOXB5 and OLFM4 genes with obesity-related traits among Portuguese children | journal = Journal of Human Genetics | volume = 59 | issue = 6 | pages = 307–13 | date = June 2014 | pmid = 24670271 | doi = 10.1038/jhg.2014.23 }}
14. ^{{cite journal | vauthors = Lv D, Zhang DD, Wang H, Zhang Y, Liang L, Fu JF, Xiong F, Liu GL, Gong CX, Luo FH, Chen SK, Li ZL, Zhu YM | title = Genetic variations in SEC16B, MC4R, MAP2K5 and KCTD15 were associated with childhood obesity and interacted with dietary behaviors in Chinese school-age population | journal = Gene | volume = 560 | issue = 2 | pages = 149–55 | date = April 2015 | pmid = 25637721 | doi = 10.1016/j.gene.2015.01.054 }}
15. ^{{cite journal | vauthors = Yamasguchi M, Murata T | title = Involvement of regucalcin gene promoter region-related protein-117, a transcription factor, in human obesity (Review) | journal = Biomedical Reports | volume = 6 | issue = 4 | pages = 374–378 | date = April 2017 | pmid = 28413634 | doi = 10.3892/br.2017.874 | pmc=5374946}}
16. ^{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBHT/plasma-chemistry/ |title=Clinical chemistry data for Sec16b |publisher=Wellcome Trust Sanger Institute}}
17. ^{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBHT/salmonella-challenge/ |title=Salmonella infection data for Sec16b |publisher=Wellcome Trust Sanger Institute}}
18. ^{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBHT/citrobacter-challenge/ |title=Citrobacter infection data for Sec16b |publisher=Wellcome Trust Sanger Institute}}
19. ^1 2 {{cite journal | doi = 10.1111/j.1755-3768.2010.4142.x | title = The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice | year = 2010 | author = Gerdin AK | journal = Acta Ophthalmologica | volume = 88 | pages = 925–7 }}
20. ^Mouse Resources Portal, Wellcome Trust Sanger Institute.
21. ^{{cite web |url=http://www.knockoutmouse.org/martsearch/search?query=Sec16b |title=International Knockout Mouse Consortium}}
22. ^{{cite web |url=http://www.informatics.jax.org/searchtool/Search.do?query=MGI:4365061 |title=Mouse Genome Informatics}}
23. ^{{cite journal | vauthors = Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A | title = A conditional knockout resource for the genome-wide study of mouse gene function | journal = Nature | volume = 474 | issue = 7351 | pages = 337–42 | date = June 2011 | pmid = 21677750 | pmc = 3572410 | doi = 10.1038/nature10163 }}
24. ^{{cite journal | vauthors = Dolgin E | title = Mouse library set to be knockout | journal = Nature | volume = 474 | issue = 7351 | pages = 262–3 | date = June 2011 | pmid = 21677718 | doi = 10.1038/474262a }}
25. ^{{cite journal | vauthors = Collins FS, Rossant J, Wurst W | title = A mouse for all reasons | journal = Cell | volume = 128 | issue = 1 | pages = 9–13 | date = January 2007 | pmid = 17218247 | doi = 10.1016/j.cell.2006.12.018 }}
26. ^{{cite journal | vauthors = van der Weyden L, White JK, Adams DJ, Logan DW | title = The mouse genetics toolkit: revealing function and mechanism | journal = Genome Biology | volume = 12 | issue = 6 | pages = 224 | date = June 2011 | pmid = 21722353 | pmc = 3218837 | doi = 10.1186/gb-2011-12-6-224 }}

Further reading

{{refbegin|33em}}
  • {{cite journal | vauthors = Bhattacharyya D, Glick BS | title = Two mammalian Sec16 homologues have nonredundant functions in endoplasmic reticulum (ER) export and transitional ER organization | journal = Molecular Biology of the Cell | volume = 18 | issue = 3 | pages = 839–49 | date = March 2007 | pmid = 17192411 | pmc = 1805085 | doi = 10.1091/mbc.E06-08-0707 }}
  • {{cite journal | vauthors = Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP | title = Large-scale characterization of HeLa cell nuclear phosphoproteins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 33 | pages = 12130–5 | date = August 2004 | pmid = 15302935 | pmc = 514446 | doi = 10.1073/pnas.0404720101 }}
  • {{cite journal | vauthors = Xu XR, Huang J, Xu ZG, Qian BZ, Zhu ZD, Yan Q, Cai T, Zhang X, Xiao HS, Qu J, Liu F, Huang QH, Cheng ZH, Li NG, Du JJ, Hu W, Shen KT, Lu G, Fu G, Zhong M, Xu SH, Gu WY, Huang W, Zhao XT, Hu GX, Gu JR, Chen Z, Han ZG | title = Insight into hepatocellular carcinogenesis at transcriptome level by comparing gene expression profiles of hepatocellular carcinoma with those of corresponding noncancerous liver | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 26 | pages = 15089–94 | date = December 2001 | pmid = 11752456 | pmc = 64988 | doi = 10.1073/pnas.241522398 }}
{{refend}}

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