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{{Infobox protein family
| Symbol = SWIB
| Name = SWIB
| image = PDB 1v31 EBI.jpg
| width =
| caption = 拟南芥假定蛋白AT5G14170的SWIB/MDM2结构域的解析结构
| Pfam = PF02201
| Pfam_clan =
| InterPro = IPR003121
| SMART = SWIB
| PROSITE =
| MEROPS =
| SCOP = 1ycr
| TCDB =
| OPM family =
| OPM protein =
| CAZy =
| CDD =
}}
在[[分子生物学]]领域，'''SWI/SNF'''（{{langx|en|SWItch/Sucrose NonFermentable}}）<ref name="pmid6392017">{{cite journal | author = Neigeborn L, Carlson M | title = Genes Affecting the Regulation of SUC2 Gene Expression by Glucose Repression in SACCHAROMYCES CEREVISIAE | journal = Genetics | volume = 108 | issue = 4 | pages = 845–58 | year = 1984 | pmid = 6392017 | doi = | url = http://www.genetics.org/cgi/content/abstract/108/4/845 | pmc = 1224269 | access-date = 2014-01-06 | archive-date = 2008-08-21 | archive-url = https://web.archive.org/web/20080821174131/http://www.genetics.org/cgi/content/abstract/108/4/845 | dead-url = no }}</ref><ref name="pmid6436497">{{cite journal | author = Stern M, Jensen R, Herskowitz I | title = Five SWI genes are required for expression of the HO gene in yeast | journal = J. Mol. Biol. | volume = 178 | issue = 4 | pages = 853–68 | year = 1984 | pmid = 6436497 | doi = 10.1016/0022-2836(84)90315-2 }}</ref>是同时存在于[[真核生物]]及[[原核生物]]中的一种[[核小体]]重塑复合物。简而言之，它们是一群与重塑DNA包装方式有关的[[蛋白质]]。SWI/SNF由多种蛋白构成，这些蛋白往往是SWI及SNF基因（{{Yeast Gene|SWI1}}、{{Yeast Gene|SWI2}}/{{Yeast Gene|SNF2}}、{{Yeast Gene|SWI3}}、{{Yeast Gene|SWI5}}、{{Yeast Gene|SWI6}}）的产物以及一些其它[[多肽]]<ref name="pmid9118215">{{cite journal | author = Pazin MJ, Kadonaga JT | title = SWI2/SNF2 and related proteins: ATP-driven motors that disrupt protein-DNA interactions? | journal = Cell | volume = 88 | issue = 6 | pages = 737–40 | year = 1997 | pmid = 9118215 | doi = 10.1016/S0092-8674(00)81918-2 }}</ref>。SWI/SNF受DNA刺激后表现出[[ATP酶]]活性，利用[[三磷酸腺苷|ATP]]破坏并重塑核小体的[[组蛋白]]和[[DNA]]之间相互作用的稳定性，不过这种结构改变的精确性质仍未明确。

人体中与SWI/SNF相似的蛋白是BAF（与SWI/SNF-A相似）和PBAF（与SWI/SNF-B相似）。BAF表示“{{link-en|SMARCA4|SMARCA4|BRG1}}或{{link-en|SMARCA2|SMARCA2|HRBM}}相关因子”，PBAF则表示“聚溴相关的BAF”<ref name="pmid12665591">{{cite journal | author = Nie Z, Yan Z, Chen EH, Sechi S, Ling C, Zhou S, Xue Y, Yang D, Murray D, Kanakubo E, Cleary ML, Wang W | title = Novel SWI/SNF chromatin-remodeling complexes contain a mixed-lineage leukemia chromosomal translocation partner | url = https://archive.org/details/sim_molecular-and-cellular-biology_2003-04_23_8/page/2942 | journal = Mol. Cell. Biol. | volume = 23 | issue = 8 | pages = 2942–52 |date=April 2003 | pmid = 12665591 | pmc = 152562 | doi = 10.1128/MCB.23.8.2942-2952.2003 }}</ref>。

== 作用机理 ==
人们发现酵母中的SWI/SNF复合物能使[[DNA]]在不同的位置与[[组蛋白]]结合成[[核小体]]<ref name="pmid10466730">{{cite journal | author = Whitehouse I, Flaus A, Cairns BR, White MF, Workman JL, Owen-Hughes T | title = Nucleosome mobilization catalysed by the yeast SWI/SNF complex | journal = Nature | volume = 400 | issue = 6746 | pages = 784–7 |date=August 1999 | pmid = 10466730 | doi = 10.1038/23506 | url =https://archive.org/details/sim_nature-uk_1999-08-19_400_6746/page/784}}</ref>。目前已提出两种SWI/SNF重塑核小体的机制<ref name="pmid12897850">{{cite journal | author = van Holde K, Yager T | title = Models for chromatin remodeling: a critical comparison | url = https://archive.org/details/sim_biochemistry-and-cell-biology_2003-06_81_3/page/169 | journal = Biochem. Cell Biol. | volume = 81 | issue = 3 | pages = 169–72 | year = 2003 | pmid = 12897850 | doi = 10.1139/o03-038 }}</ref>。一种机制叫做“扭转扩散”，认为核小体DNA中的扭转缺陷发生单向扩散，使DNA从进入核小体的地方开始贴着组蛋白八聚体的表面螺旋状地传播。另一种机制叫做“突起”或“环再捕获”，意即DNA在核小体边缘与之分离，形成一环状突起。环状突起在组蛋白八聚体表面像波浪般传播，最后在核小体内部重新与之结合。这样DNA就在和组蛋白接触点数量不变的情况下完成位移<ref name="pmid12666181">{{cite journal | author = Flaus A, Owen-Hughes T | title = Mechanisms for nucleosome mobilization | journal = Biopolymers | volume = 68 | issue = 4 | pages = 563–78 | year = 2003 | pmid = 12666181 | doi = 10.1002/bip.10323 }}</ref>。最新研究提出了与“扭转扩散”机制相抵触的有力证据，使“环再捕获”模型更有说服力<ref name="pmid16518397">{{cite journal | author = Zofall M, Persinger J, Kassabov SR, Bartholomew B | title = Chromatin remodeling by ISW2 and SWI/SNF requires DNA translocation inside the nucleosome | journal = Nat. Struct. Mol. Biol. | volume = 13 | issue = 4 | pages = 339–46 | year = 2006 | pmid = 16518397 | doi = 10.1038/nsmb1071 }}</ref>。

== 肿瘤抑制作用 ==
人类的SWI/SNF复合物（mSWI/SNF）对很多人类恶性肿瘤有抑制作用。1998年首先发现它能抑制横纹肌样瘤（一种罕见的儿童恶性肿瘤）<ref name="pmid9671307">{{cite journal | author = Versteege I, Sévenet N, Lange J, Rousseau-Merck MF, Ambros P, Handgretinger R, Aurias A, Delattre O | title = Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer | url = https://archive.org/details/sim_nature-uk_1998-07-09_394_6689/page/202 | journal = Nature | volume = 394 | issue = 6689 | pages = 203–6 |date=July 1998 | pmid = 9671307 | doi = 10.1038/28212 }}</ref>。随着[[DNA测序]]成本逐渐降低，2010年左右许多肿瘤首次得到测序。其中数项研究表明SWI/SNF对多种恶性肿瘤有抑制作用<ref name="pmid20942669">{{cite journal | author = Wiegand KC, Shah SP, Al-Agha OM, Zhao Y, Tse K, Zeng T, Senz J, McConechy MK, Anglesio MS, Kalloger SE, Yang W, Heravi-Moussavi A, Giuliany R, Chow C, Fee J, Zayed A, Prentice L, Melnyk N, Turashvili G, Delaney AD, Madore J, Yip S, McPherson AW, Ha G, Bell L, Fereday S, Tam A, Galletta L, Tonin PN, Provencher D, Miller D, Jones SJ, Moore RA, Morin GB, Oloumi A, Boyd N, Aparicio SA, Shih IeM, Mes-Masson AM, Bowtell DD, Hirst M, Gilks B, Marra MA, Huntsman DG | title = ARID1A mutations in endometriosis-associated ovarian carcinomas | journal = N. Engl. J. Med. | volume = 363 | issue = 16 | pages = 1532–43 |date=October 2010 | pmid = 20942669 | pmc = 2976679 | doi = 10.1056/NEJMoa1008433 }}</ref><ref name="pmid21822264">{{cite journal | author = Li M, Zhao H, Zhang X, Wood LD, Anders RA, Choti MA, Pawlik TM, Daniel HD, Kannangai R, Offerhaus GJ, Velculescu VE, Wang L, Zhou S, Vogelstein B, Hruban RH, Papadopoulos N, Cai J, Torbenson MS, Kinzler KW | title = Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma | journal = Nat. Genet. | volume = 43 | issue = 9 | pages = 828–9 |date=September 2011 | pmid = 21822264 | pmc = 3163746 | doi = 10.1038/ng.903 }}</ref><ref name="pmid22233809">{{cite journal | author = Shain AH, Giacomini CP, Matsukuma K, Karikari CA, Bashyam MD, Hidalgo M, Maitra A, Pollack JR | title = Convergent structural alterations define SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeler as a central tumor suppressive complex in pancreatic cancer | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 109 | issue = 5 | pages = E252–9 |date=January 2012 | pmid = 22233809 | pmc = 3277150 | doi = 10.1073/pnas.1114817109 }}</ref><ref name="pmid21248752">{{cite journal | author = Varela I, Tarpey P, Raine K, Huang D, Ong CK, Stephens P, Davies H, Jones D, Lin ML, Teague J, Bignell G, Butler A, Cho J, Dalgliesh GL, Galappaththige D, Greenman C, Hardy C, Jia M, Latimer C, Lau KW, Marshall J, McLaren S, Menzies A, Mudie L, Stebbings L, Largaespada DA, Wessels LF, Richard S, Kahnoski RJ, Anema J, Tuveson DA, Perez-Mancera PA, Mustonen V, Fischer A, Adams DJ, Rust A, Chan-on W, Subimerb C, Dykema K, Furge K, Campbell PJ, Teh BT, Stratton MR, Futreal PA | title = Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma | url = https://archive.org/details/sim_nature-uk_2011-01-27_469_7331/page/538 | journal = Nature | volume = 469 | issue = 7331 | pages = 539–42 |date=January 2011 | pmid = 21248752 | pmc = 3030920 | doi = 10.1038/nature09639 }}</ref>。对多个测序研究结果的荟萃分析表明，大约20%的人类恶性肿瘤中SWI/SNF存在变异<ref name="pmid23355908">{{cite journal | author = Shain AH, Pollack JR | title = The spectrum of SWI/SNF mutations, ubiquitous in human cancers | journal = PLoS ONE | volume = 8 | issue = 1 | pages = e55119 | year = 2013 | pmid = 23355908 | pmc = 3552954 | doi = 10.1371/journal.pone.0055119 }}</ref>。

== SWIB/MDM2蛋白结构域 ==
SWIB/MDM2蛋白[[结构域]]，全称是SWI/SNF复合物B/{{link-en|MDM2|MDM2}}蛋白结构域是相当重要的蛋白结构域。这个蛋白结构域在SWI/SNF复合物B和[[p53]]肿瘤抑制蛋白的负向调节蛋白MDM2中均存在。已证明MDM2与SWIB复合物[[同源]]<ref name="pmid12016060">{{cite journal| author=Bennett-Lovsey R, Hart SE, Shirai H, Mizuguchi K| title=The SWIB and the MDM2 domains are homologous and share a common fold. | journal=Bioinformatics | year= 2002 | volume= 18 | issue= 4 | pages= 626–30 | pmid=12016060 | doi= 10.1093/bioinformatics/18.4.626| pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12016060}}</ref>。

=== 功能 ===
SWIB/MDM2蛋白结构域的主要功能是协助[[基因表达]]。在[[酵母]]中，它表达{{link-en|甜菜碱醛脱氢酶|betaine-aldehyde dehydrogenase|BADH2}}、GAL1、GAL4和SUC2等数个基因。该蛋白结构域作用是促进基因[[转录]]。它有[[ATP酶]]的活性，能分解细胞基本能量“货币”单位[[三磷酸腺苷|ATP]]，放出能量以破坏DNA和组蛋白结合的稳定性，从而干扰[[染色质]]，并开放可供转录因子结合的位点，这就促进了基因的转录<ref name="pmid11147808"/>。

== 系列成员 ==

以下列出酵母SWI/SNF系列基因成员以及人类相应的直系同源基因<ref name="pmid10601972">{{cite journal | author = Collingwood TN, Urnov FD, Wolffe AP | title = Nuclear receptors: coactivators, corepressors and chromatin remodeling in the control of transcription | journal = J. Mol. Endocrinol. | volume = 23 | issue = 3 | pages = 255–75 | year = 1999 | pmid = 10601972 | doi = 10.1677/jme.0.0230255 }}</ref>：
{| class="wikitable"
|-
! 酵母
! 人类
! 功能
|-
| {{Yeast Gene|SWI1}}
| {{link-en|ARID1A|ARID1A}}、{{link-en|ARID1B|ARID1B}}
| 含有LXXLL[[核受体]]结合基序
|-
| {{Yeast Gene|SWI2}}/{{Yeast Gene|SNF2}}
| {{link-en|SMARCA4|SMARCA4}}
| [[三磷酸腺苷|ATP]]依赖的染色质重塑
|-
| {{Yeast Gene|SWI3}}
| {{link-en|SMARCC1|SMARCC1}}、{{link-en|SMARCC2|SMARCC2}}
| 功能未知的相似序列
|-
| {{Yeast Gene|SWP73}}
| {{link-en|SMARCD1|SMARCD1}}、{{link-en|SMARCD2|SMARCD2}}、{{link-en|SMARCD3|SMARCD3}}
| 功能未知的相似序列
|-
| {{Yeast Gene|SWP61}}
| {{link-en|ACTL6A|ACTL6A}}、{{link-en|ACTL6B|ACTL6B}}
| [[肌动蛋白]]样蛋白
|}

== 历史 ==
SWI/SNF首先发现于[[釀酒酵母]]（{{lang|la|Saccharomyces cerevisiae}}）中，以交替（{{lang|en|switching}}，缩写SWI）型和不发酵蔗糖型（{{lang|en|sucrose nonfermenting}}，缩写SNF）型交配后所得的酵母命名<ref name="pmid11147808">{{cite journal| author=Decristofaro MF, Betz BL, Rorie CJ, Reisman DN, Wang W, Weissman BE| title=Characterization of SWI/SNF protein expression in human breast cancer cell lines and other malignancies. | journal=J Cell Physiol | year= 2001 | volume= 186 | issue= 1 | pages= 136–45 | pmid=11147808 | doi=10.1002/1097-4652(200101)186:1<136::AID-JCP1010>3.0.CO;2-4 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11147808}}</ref>。

== 另见 ==
*{{link-en|MDM2|MDM2}}
*{{link-en|染色质结构重塑复合物|Chromatin Structure Remodeling (RSC) Complex}}
*{{link-en|转录共调控物|Transcription coregulator}}

== 参考文献 s==
{{Reflist|2}}

== 外部链接 ==
*[http://www.nextbio.com/b/home/home.nb?q=SWI%2FSNF%20complex&id=39051&type=biogroup&name=SWI%2FSNF%20complex&synonym=#cid=39051&tab=lit Nextbio]{{Dead link}}

{{Transcription coregulators}}

{{DEFAULTSORT:SWI SNF}}
[[Category:酶]]
[[Category:转录共调控物]]

SWI/SNF - 版本历史

imported>InternetArchiveBot：​Add 3 books for verifiability (20251017sim)) #IABot (v2.0.9.5) (GreenC bot

imported>InternetArchiveBot：Add 3 books for verifiability (20251017sim)) #IABot (v2.0.9.5) (GreenC bot