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Sterol regulatory element-binding protein 2
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<h2 id="function">Function</h2> <p>This gene encodes a ubiquitously expressed <a href="/facts/Transcription_factor/wro0DPHe">transcription factor</a> that controls <a href="/facts/Cholesterol/TnfPlYc1">cholesterol</a> <a href="/facts/Homeostasis/rloTGAHa">homeostasis</a> by stimulating transcription of sterol-regulated genes. The encoded protein contains a basic helix-loop-helix leucine zipper (<a href="/facts/Basic_helix-loop-helix_leucine_zipper_transcription_factors/CjgJIGLq">bHLH-Zip</a>) domain.<a class="footnote-ref" id="fnref:2" href="#fn:2"><sup>2</sup></a> Various <a href="/facts/Single_nucleotide_polymorphism/Qy5Y2wom">single nucleotide polymorphisms</a> (SNPs) of the SREBF2 have been identified and some of them are found to be associated with higher risk of knee <a href="/facts/Osteoarthritis/Iy1wDA1B">osteoarthritis</a>. <a class="footnote-ref" id="fnref:3" href="#fn:3"><sup>3</sup></a> </p> <h2 id="interactions">Interactions</h2> <p>SREBF2 has been shown to <a href="/facts/Protein-protein_interaction/etvm9Wmg">interact</a> with <a href="/facts/INSIG1/HSDywQPh">INSIG1</a><a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a><a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a> and the <a href="/facts/CREB-binding_protein/F4p9VIV7">CREB-binding protein</a>.<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> </p> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/Sterol_regulatory_element-binding_protein/NNagad8S">Sterol regulatory element-binding protein</a></li></ul> <h2 id="further-reading">Further reading</h2> <ul><li>Osborne TF (Aug 2001). <a href="https://doi.org/10.1101%2Fgad.916601">"CREating a SCAP-less liver keeps SREBPs pinned in the ER membrane and prevents increased lipid synthesis in response to low cholesterol and high insulin"</a>. <i>Genes & Development</i>. 15 (15): 1873–8. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1101%2Fgad.916601">10.1101/gad.916601</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11485982">11485982</a>.</li> <li>Szolkiewicz M, Chmielewski M, Nogalska A, Stelmanska E, Swierczynski J, Rutkowski B (Jan 2007). "The potential role of sterol regulatory element binding protein transcription factors in renal injury". <i>Journal of Renal Nutrition</i>. 17 (1): 62–5. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1053%2Fj.jrn.2006.10.009">10.1053/j.jrn.2006.10.009</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/17198935">17198935</a>.</li> <li>Hua X, Wu J, Goldstein JL, Brown MS, Hobbs HH (Feb 1995). "Structure of the human gene encoding sterol regulatory element binding protein-1 (SREBF1) and localization of SREBF1 and SREBF2 to chromosomes 17p11.2 and 22q13". <i>Genomics</i>. 25 (3): 667–73. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2F0888-7543%2895%2980009-B">10.1016/0888-7543(95)80009-B</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/7759101">7759101</a>.</li> <li>Yokoyama C, Wang X, Briggs MR, Admon A, Wu J, Hua X, Goldstein JL, Brown MS (Oct 1993). "SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene". <i>Cell</i>. 75 (1): 187–97. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS0092-8674%2805%2980095-9">10.1016/S0092-8674(05)80095-9</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8402897">8402897</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:2784016">2784016</a>.</li> <li>Wang X, Zelenski NG, Yang J, Sakai J, Brown MS, Goldstein JL (Mar 1996). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC449996">"Cleavage of sterol regulatory element binding proteins (SREBPs) by CPP32 during apoptosis"</a>. <i>The EMBO Journal</i>. 15 (5): 1012–20. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1002%2Fj.1460-2075.1996.tb00438.x">10.1002/j.1460-2075.1996.tb00438.x</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC449996">449996</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8605870">8605870</a>.</li> <li>Hua X, Sakai J, Brown MS, Goldstein JL (Apr 1996). <a href="https://doi.org/10.1074%2Fjbc.271.17.10379">"Regulated cleavage of sterol regulatory element binding proteins requires sequences on both sides of the endoplasmic reticulum membrane"</a>. <i>The Journal of Biological Chemistry</i>. 271 (17): 10379–84. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1074%2Fjbc.271.17.10379">10.1074/jbc.271.17.10379</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8626610">8626610</a>.</li> <li>Pai JT, Brown MS, Goldstein JL (May 1996). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC39264">"Purification and cDNA cloning of a second apoptosis-related cysteine protease that cleaves and activates sterol regulatory element binding proteins"</a>. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 93 (11): 5437–42. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/1996PNAS...93.5437P">1996PNAS...93.5437P</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1073%2Fpnas.93.11.5437">10.1073/pnas.93.11.5437</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC39264">39264</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8643593">8643593</a>.</li> <li>Sato R, Inoue J, Kawabe Y, Kodama T, Takano T, Maeda M (Oct 1996). <a href="https://doi.org/10.1074%2Fjbc.271.43.26461">"Sterol-dependent transcriptional regulation of sterol regulatory element-binding protein-2"</a>. <i>The Journal of Biological Chemistry</i>. 271 (43): 26461–4. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1074%2Fjbc.271.43.26461">10.1074/jbc.271.43.26461</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8900111">8900111</a>.</li> <li>Oliner JD, Andresen JM, Hansen SK, Zhou S, Tjian R (Nov 1996). <a href="https://doi.org/10.1101%2Fgad.10.22.2903">"SREBP transcriptional activity is mediated through an interaction with the CREB-binding protein"</a>. <i>Genes & Development</i>. 10 (22): 2903–11. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1101%2Fgad.10.22.2903">10.1101/gad.10.22.2903</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8918891">8918891</a>.</li> <li>Miserez AR, Cao G, Probst LC, Hobbs HH (Feb 1997). "Structure of the human gene encoding sterol regulatory element binding protein 2 (SREBF2)". <i>Genomics</i>. 40 (1): 31–40. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1006%2Fgeno.1996.4525">10.1006/geno.1996.4525</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9070916">9070916</a>.</li> <li>Duncan EA, Brown MS, Goldstein JL, Sakai J (May 1997). <a href="https://doi.org/10.1074%2Fjbc.272.19.12778">"Cleavage site for sterol-regulated protease localized to a leu-Ser bond in the lumenal loop of sterol regulatory element-binding protein-2"</a>. <i>The Journal of Biological Chemistry</i>. 272 (19): 12778–85. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1074%2Fjbc.272.19.12778">10.1074/jbc.272.19.12778</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9139737">9139737</a>.</li> <li>Harris IR, Farrell AM, Holleran WM, Jackson S, Grunfeld C, Elias PM, Feingold KR (Feb 1998). <a href="https://doi.org/10.1016%2FS0022-2275%2820%2933902-X">"Parallel regulation of sterol regulatory element binding protein-2 and the enzymes of cholesterol and fatty acid synthesis but not ceramide synthesis in cultured human keratinocytes and murine epidermis"</a>. <i>Journal of Lipid Research</i>. 39 (2): 412–22. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS0022-2275%2820%2933902-X">10.1016/S0022-2275(20)33902-X</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9508001">9508001</a>.</li> <li>Kan HY, Pissios P, Chambaz J, Zannis VI (Feb 1999). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC148292">"DNA binding specificity and transactivation properties of SREBP-2 bound to multiple sites on the human apoA-II promoter"</a>. <i>Nucleic Acids Research</i>. 27 (4): 1104–17. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1093%2Fnar%2F27.4.1104">10.1093/nar/27.4.1104</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC148292">148292</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9927745">9927745</a>.</li> <li>Seidah NG, Mowla SJ, Hamelin J, Mamarbachi AM, Benjannet S, Touré BB, Basak A, Munzer JS, Marcinkiewicz J, Zhong M, Barale JC, Lazure C, Murphy RA, Chrétien M, Marcinkiewicz M (Feb 1999). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC15461">"Mammalian subtilisin/kexin isozyme SKI-1: A widely expressed proprotein convertase with a unique cleavage specificity and cellular localization"</a>. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 96 (4): 1321–6. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/1999PNAS...96.1321S">1999PNAS...96.1321S</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1073%2Fpnas.96.4.1321">10.1073/pnas.96.4.1321</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC15461">15461</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9990022">9990022</a>.</li> <li>Nagoshi E, Imamoto N, Sato R, Yoneda Y (Jul 1999). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC25438">"Nuclear import of sterol regulatory element-binding protein-2, a basic helix-loop-helix-leucine zipper (bHLH-Zip)-containing transcription factor, occurs through the direct interaction of importin beta with HLH-Zip"</a>. <i>Molecular Biology of the Cell</i>. 10 (7): 2221–33. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1091%2Fmbc.10.7.2221">10.1091/mbc.10.7.2221</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC25438">25438</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10397761">10397761</a>.</li> <li>Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP (Dec 1999). <a href="https://doi.org/10.1038%2F990031">"The DNA sequence of human chromosome 22"</a>. <i>Nature</i>. 402 (6761): 489–95. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/1999Natur.402..489D">1999Natur.402..489D</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1038%2F990031">10.1038/990031</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10591208">10591208</a>.</li> <li>DeBose-Boyd RA, Brown MS, Li WP, Nohturfft A, Goldstein JL, Espenshade PJ (Dec 1999). <a href="https://doi.org/10.1016%2FS0092-8674%2800%2981668-2">"Transport-dependent proteolysis of SREBP: relocation of site-1 protease from Golgi to ER obviates the need for SREBP transport to Golgi"</a>. <i>Cell</i>. 99 (7): 703–12. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS0092-8674%2800%2981668-2">10.1016/S0092-8674(00)81668-2</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10619424">10619424</a>.</li> <li>Kotzka J, Müller-Wieland D, Roth G, Kremer L, Munck M, Schürmann S, Knebel B, Krone W (Jan 2000). <a href="https://doi.org/10.1016%2FS0022-2275%2820%2932079-4">"Sterol regulatory element binding proteins (SREBP)-1a and SREBP-2 are linked to the MAP-kinase cascade"</a>. <i>Journal of Lipid Research</i>. 41 (1): 99–108. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS0022-2275%2820%2932079-4">10.1016/S0022-2275(20)32079-4</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10627507">10627507</a>.</li> <li>Yang T, Goldstein JL, Brown MS (Sep 2000). <a href="https://doi.org/10.1074%2Fjbc.M005439200">"Overexpression of membrane domain of SCAP prevents sterols from inhibiting SCAP.SREBP exit from endoplasmic reticulum"</a>. <i>The Journal of Biological Chemistry</i>. 275 (38): 29881–6. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1074%2Fjbc.M005439200">10.1074/jbc.M005439200</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10896675">10896675</a>.</li></ul> <h2 id="external-links">External links</h2> <ul><li><a href="https://meshb.nlm.nih.gov/record/ui?name=SREBF2+protein%2C+human">SREBF2+protein,+human</a> at the U.S. National Library of Medicine <a href="/facts/Medical_Subject_Headings/C57g2JuF">Medical Subject Headings</a> (MeSH)</li> <li><a href="/facts/ENCODE/X7hhKpsg">FactorBook</a> <a href="http://www.factorbook.org/mediawiki/index.php/SREBP2">SREBP2</a></li></ul> <p><i>This article incorporates text from the <a href="/facts/United_States_National_Library_of_Medicine/Hzty0MCX">United States National Library of Medicine</a>, which is in the <a href="/facts/Public_domain/YWKMDKw4">public domain</a>.</i> </p> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Hua X, Yokoyama C, Wu J, Briggs MR, Brown MS, Goldstein JL, Wang X (Dec 1993). "SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element". Proceedings of the National Academy of Sciences of the United States of America. 90 (24): 11603–7. Bibcode:1993PNAS...9011603H. doi:10.1073/pnas.90.24.11603. PMC 48032. PMID 7903453. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC48032" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC48032</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>"Entrez Gene: SREBF2 sterol regulatory element binding transcription factor 2". <a href="https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6721" target="_blank">https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6721</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Qiu XM, Jin CT, Wang W (Apr 2014). "Association between single nucleotide polymorphisms of sterol regulatory element binding protein-2 gene and risk of knee osteoarthritis in a Chinese Han population". The Journal of International Medical Research. 42 (2): 320–8. doi:10.1177/0300060513507392. PMID 24496149. <a href="https://doi.org/10.1177%2F0300060513507392" target="_blank">https://doi.org/10.1177%2F0300060513507392</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Dobrosotskaya IY, Goldstein JL, Brown MS, Rawson RB (Sep 2003). "Reconstitution of sterol-regulated endoplasmic reticulum-to-Golgi transport of SREBP-2 in insect cells by co-expression of mammalian SCAP and Insigs". The Journal of Biological Chemistry. 278 (37): 35837–43. doi:10.1074/jbc.M306476200. PMID 12842885. <a href="https://doi.org/10.1074%2Fjbc.M306476200" target="_blank">https://doi.org/10.1074%2Fjbc.M306476200</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Yang T, Espenshade PJ, Wright ME, Yabe D, Gong Y, Aebersold R, Goldstein JL, Brown MS (Aug 2002). "Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER". Cell. 110 (4): 489–500. doi:10.1016/S0092-8674(02)00872-3. PMID 12202038. S2CID 15052132. <a href="https://doi.org/10.1016%2FS0092-8674%2802%2900872-3" target="_blank">https://doi.org/10.1016%2FS0092-8674%2802%2900872-3</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Oliner JD, Andresen JM, Hansen SK, Zhou S, Tjian R (Nov 1996). "SREBP transcriptional activity is mediated through an interaction with the CREB-binding protein". Genes & Development. 10 (22): 2903–11. doi:10.1101/gad.10.22.2903. PMID 8918891. <a href="https://doi.org/10.1101%2Fgad.10.22.2903" target="_blank">https://doi.org/10.1101%2Fgad.10.22.2903</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> </ol>