SEC16B

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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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. ↑ Nagase T, Kikuno R, Ohara O (August 2001). "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". DNA Research. 8 (4): 179–87. doi:10.1093/dnares/8.4.179. PMID 11572484.
  2. ↑ 2.0 2.1 2.2 Misawa H, Yamaguchi M (November 2001). "Molecular cloning and sequencing of the cDNA coding for a novel regucalcin gene promoter region-related protein in rat, mouse and human liver". International Journal of Molecular Medicine. 8 (5): 513–20. doi:10.3892/ijmm.8.5.513. PMID 11605020.
  3. ↑ "Entrez Gene: LZTR2 leucine zipper transcription regulator 2".
  4. ↑ Misawa H, Yamaguchi M (2002). "Gene expression for a novel protein RGPR-p117 in various species: the stimulation by intracellular signaling factors". Journal of Cellular Biochemistry. 87 (2): 188–93. doi:10.1002/jcb.10289. PMID 12244571.
  5. ↑ 5.0 5.1 Bhattacharyya D, Glick BS (March 2007). "Two mammalian Sec16 homologues have nonredundant functions in endoplasmic reticulum (ER) export and transitional ER organization". Molecular Biology of the Cell. 18 (3): 839–49. doi:10.1091/mbc.E06-08-0707. PMC 1805085. PMID 17192411.
  6. ↑ 6.0 6.1 Sawada N, Nakagawa T, Murata T, Yamaguchi M (November 2005). "Nuclear localization of a novel protein, RGPR-p117, in cloned normal rat kidney proximal tubular epithelial cells". International Journal of Molecular Medicine. 16 (5): 809–14. doi:10.3892/ijmm.16.5.809. PMID 16211248.
  7. ↑ 7.0 7.1 7.2 Sawada N, Yamaguchi M (December 2005). "Overexpression of RGPR-p117 enhances regucalcin gene expression in cloned normal rat kidney proximal tubular epithelial cells". International Journal of Molecular Medicine. 16 (6): 1049–55. doi:10.3892/ijmm.16.6.1049. PMID 16273285.
  8. ↑ 8.0 8.1 Yamaguchi M, Tomono S, Nakagawa T (October 2007). "Overexpression of RGPR-p117 suppresses apoptotic cell death and its related gene expression in cloned normal rat kidney proximal tubular epithelial NRK52E cells". International Journal of Molecular Medicine. 20 (4): 565–71. doi:10.3892/ijmm.20.4.565. PMID 17786289.
  9. ↑ Yamaguchi M (July 2009). "Novel protein RGPR-p117: its role as the regucalcin gene transcription factor". Molecular and Cellular Biochemistry. 327 (1–2): 53–63. doi:10.1007/s11010-009-0042-4. PMID 19214710.
  10. ↑ Tomono S, Sawada N, Yamaguchi M (July 2007). "Overexpression of RGPR-p117 induces the decrease in protein and DNA contents in cloned normal rat kidney proximal tubular epithelial NRK52E cells". International Journal of Molecular Medicine. 20 (1): 79–83. doi:10.3892/ijmm.20.1.79. PMID 17549392.
  11. ↑ Budnik A, Heesom KJ, Stephens DJ (2011). "Characterization of human Sec16B: indications of specialized, non-redundant functions". Scientific Reports. 1: 77. doi:10.1038/srep00077. PMC 3216564. PMID 22355596.
  12. ↑ Yonekawa S, Furuno A, Baba T, Fujiki Y, Ogasawara Y, Yamamoto A, Tagaya M, Tani K (August 2011). "Sec16B is involved in the endoplasmic reticulum export of the peroxisomal membrane biogenesis factor peroxin 16 (Pex16) in mammalian cells". Proceedings of the National Academy of Sciences of the United States of America. 108 (31): 12746–51. doi:10.1073/pnas.1103283108. PMC 3150892. PMID 21768384.
  13. ↑ Albuquerque D, Nóbrega C, Rodríguez-López R, Manco L (June 2014). "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 of Human Genetics. 59 (6): 307–13. doi:10.1038/jhg.2014.23. PMID 24670271.
  14. ↑ 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 (April 2015). "Genetic variations in SEC16B, MC4R, MAP2K5 and KCTD15 were associated with childhood obesity and interacted with dietary behaviors in Chinese school-age population". Gene. 560 (2): 149–55. doi:10.1016/j.gene.2015.01.054. PMID 25637721.
  15. ↑ Yamasguchi M, Murata T (April 2017). "Involvement of regucalcin gene promoter region-related protein-117, a transcription factor, in human obesity (Review)". Biomedical Reports. 6 (4): 374–378. doi:10.3892/br.2017.874. PMC 5374946. PMID 28413634.
  16. ↑ "Clinical chemistry data for Sec16b". Wellcome Trust Sanger Institute.
  17. ↑ "Salmonella infection data for Sec16b". Wellcome Trust Sanger Institute.
  18. ↑ "Citrobacter infection data for Sec16b". Wellcome Trust Sanger Institute.
  19. ↑ 19.0 19.1 19.2 Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  20. ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  21. ↑ "International Knockout Mouse Consortium".
  22. ↑ "Mouse Genome Informatics".
  23. ↑ 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 (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  24. ↑ Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  25. ↑ Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  26. ↑ van der Weyden L, White JK, Adams DJ, Logan DW (June 2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading

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