SOX9

SOX9
已知的結構
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	4EUW
識別號
别名	SOX9；, CMD1, CMPD1, SRA1, SRXX2, SRXY10, SRY-box 9, SRY-box transcription factor 9
外部ID	OMIM：608160 MGI：98371 HomoloGene：294 GeneCards：SOX9
基因位置（人类）
染色体	17號染色體
终止	72,126,416 bp
基因位置（小鼠）
染色体	小鼠11号染色体
终止	112,678,586 bp
RNA表达模式
	; ;
	查阅更多表达数据
基因本體
分子功能	• DNA结合转录因子活性; • DNA-binding transcription activator activity, RNA polymerase II-specific; • core promoter sequence-specific DNA binding; • 蛋白激酶活性; • protein kinase A catalytic subunit binding; • beta-catenin binding; • pre-mRNA intronic binding; • chromatin binding; • 血浆蛋白结合; • DNA结合; • sequence-specific DNA binding; • transcription cis-regulatory region binding; • bHLH transcription factor binding; • 核心启动子近端区域序列特异性DNA结合; • protein heterodimerization activity; • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding; • DNA-binding transcription factor activity, RNA polymerase II-specific; • RNA polymerase II cis-regulatory region sequence-specific DNA binding;
細胞組分	• 细胞核; • 轉錄調節複合物; • 核质; • 大分子复合体;
生物學過程	• 骨骼系统的发生; • cellular response to retinoic acid; • bronchus cartilage development; • positive regulation of protein phosphorylation; • heart valve development; • limb bud formation; • positive regulation of protein catabolic process; • regulation of transcription by RNA polymerase II; • ureter morphogenesis; • negative regulation of immune system process; • chondrocyte development; • positive regulation of cell proliferation involved in heart morphogenesis; • oligodendrocyte differentiation; • chondrocyte hypertrophy; • prostate gland development; • lung smooth muscle development; • 乳腺发育; • negative regulation of ossification; • negative regulation of photoreceptor cell differentiation; • cellular response to mechanical stimulus; • intrahepatic bile duct development; • regulation of cell adhesion; • negative regulation of chondrocyte differentiation; • positive regulation of mesenchymal cell proliferation; • astrocyte fate commitment; • positive regulation of chondrocyte differentiation; • 精子发生; • prostate gland morphogenesis; • negative regulation of epithelial cell proliferation; • lung epithelial cell differentiation; • chondrocyte differentiation involved in endochondral bone morphogenesis; • negative regulation of canonical Wnt signaling pathway; • endocrine pancreas development; • negative regulation of cell population proliferation; • regulation of apoptotic process; • cellular response to transforming growth factor beta stimulus; • negative regulation of mesenchymal cell apoptotic process; • 染色体重建; • negative regulation of myoblast differentiation; • positive regulation of branching involved in ureteric bud morphogenesis; • cell fate commitment; • regulation of transcription, DNA-templated; • epidermal growth factor receptor signaling pathway; • 成骨作用; • regulation of cell proliferation involved in tissue homeostasis; • ureter smooth muscle cell differentiation; • ERK1 and ERK2 cascade; • notochord development; • positive regulation of epithelial cell migration; • Sertoli cell differentiation; • male sex determination; • negative regulation of gene expression; • transcription, DNA-templated; • metanephric nephron tubule formation; • positive regulation of transcription, DNA-templated; • 心脏发育; • regulation of branching involved in lung morphogenesis; • ureter urothelium development; • branching involved in ureteric bud morphogenesis; • 軟骨生成; • Harderian gland development; • positive regulation of kidney development; • central nervous system development; • heart valve formation; • positive regulation of cartilage development; • tissue homeostasis; • metanephric tubule development; • negative regulation of biomineral tissue development; • endochondral bone morphogenesis; • trachea cartilage development; • male germ-line sex determination; • 泪腺的发生; • Notch信号通路; • hair follicle development; • 细胞分化; • 输尿管的发生; • regulation of cell cycle process; • male gonad development; • positive regulation of epithelial cell proliferation; • cell fate specification; • intestinal epithelial structure maintenance; • positive regulation of extracellular matrix assembly; • extracellular matrix organization; • negative regulation of apoptotic process; • negative regulation of transcription by RNA polymerase II; • Sertoli cell development; • positive regulation of mesenchymal stem cell differentiation; • retina development in camera-type eye; • cellular response to interleukin-1; • 上皮-間充質轉換; • homeostasis of number of cells within a tissue; • negative regulation of transcription, DNA-templated; • cAMP-mediated signaling; • cartilage condensation; • positive regulation of male gonad development; • nucleosome assembly; • negative regulation of bone mineralization; • morphogenesis of a branching epithelium; • neural crest cell development; • Akt/PKB信号通路; • somatic stem cell population maintenance; • otic vesicle formation; • otic vesicle development; • endocardial cushion morphogenesis; • cellular response to epidermal growth factor stimulus; • positive regulation of epithelial cell differentiation; • renal vesicle induction; • positive regulation of gene expression; • regulation of epithelial cell proliferation involved in lung morphogenesis; • regulation of cell population proliferation; • heart valve morphogenesis; • 细胞骨架组织; • cochlea morphogenesis; • positive regulation of cell population proliferation; • epithelial cell proliferation involved in prostatic bud elongation; • retinal rod cell differentiation; • protein localization to nucleus; • regulation of cell differentiation; • positive regulation of phosphatidylinositol 3-kinase signaling; • cellular response to heparin; • negative regulation of epithelial cell differentiation; • epithelial tube branching involved in lung morphogenesis; • 訊息傳遞; • positive regulation of transcription by RNA polymerase II; • negative regulation of pri-miRNA transcription by RNA polymerase II; • chondrocyte differentiation; • neural crest cell fate specification; • cellular response to BMP stimulus; • cell-cell adhesion; • transcription initiation from RNA polymerase II promoter; • protein-containing complex assembly; • anterior head development; • morphogenesis of an epithelium; • aortic valve morphogenesis; • 基因調節;
	Sources:Amigo / QuickGO
直系同源
	6662
	20682
	ENSG00000125398
	ENSMUSG00000000567
	P48436
	Q04887
	NM_000346
	NM_011448
	NP_000337
	NP_035578
	維基數據
檢視/編輯人類	檢視/編輯小鼠

轉錄因子SOX9是一種蛋白質，在人類中由SOX9基因編碼，是塞特利氏細胞等细胞的标志物。^[5]^[6]

功能

SOX9識別序列CCTTGAG，與其他HMG-box類DNA結合蛋白一起發揮作用。它由增殖但非肥大軟骨細胞表達，對於前體細胞分化為軟骨細胞至關重要^[7]，並且與類固醇生成因子1一起調節抗苗勒氏激素（AMH）基因的轉錄。^[6]

SOX9也在雄性性發育中扮演著關鍵角色；通過與Sf1協同作用，SOX9可以在賽特利氏細胞中產生AMH，以抑制女性生殖系統的形成。^[8] 它還與其他幾個基因互作，以促進雄性生殖器官的發育。該過程始於轉錄因子睾丸決定因子（由Y染色體的性別決定區SRY編碼）通過結合在該基因上游的一段增強子序列，激活SOX9活性。^[9] 接著，SOX9活化FGF9並與FGF9形成前饋迴路^[10]和PGD2。^[9]

這些迴路對於產生SOX9十分重要；如果沒有這些迴路，SOX9將會耗盡，且幾乎可以確定會出現女性的發育。SOX9活化FGF9啟動男性發育中的重要過程，例如創建睪丸索以及塞特利氏細胞的增殖。^[10] SOX9與Dax1的結合實際上會產生塞爾托利細胞，這是雄性發育中另一個重要的過程。^[11] 在大腦發育中，其小鼠直系同源基因SOX9誘導Wwp1、Wwp2和miR-140的表達，以調節新生神經細胞進入皮質板，並調節皮質神經元的軸突分支和軸突形成。^[12]

Sox9，也被稱為SRY-Box轉錄因子9，是性別決定中一個重要的基因。SOX家族基因全都是Y染色體性別決定因子SRY的轉錄因子。SRY基因編碼SOX轉錄因子，同時它上調Sox9。Sox9之後啟動Fgf9，即成纖維細胞生長因子9，這也是雄性腺體形成過程中的另一個關鍵轉錄因子。Fgf9通過正向前饋級聯上調Sox9，這導致塞特利氏細胞分化，最終形成睪丸。^[13]

SOX9是Notch訊息傳遞途徑以及Hedgehog途徑的標靶，^[14]並在調節神經幹細胞命運中扮演角色。體內和體外研究顯示SOX9對神經元生成具有負調控作用，對膠質細胞生成和幹細胞存活具有正調控作用。^[15]

在成年關節軟骨細胞中，通過siRNA介導的SOX9或RTL3敲低會導致另一個基因的下調，以及II型膠原蛋白（COL2A1）mRNA和蛋白表達的降低。^[16]

在缺乏SRY的情況下，於XY性腺中過度表現SOX9可以進一步促進雄性性別決定和睾丸發育。^[17] 亦可發現，在XX性腺異位表現SOX9，即使在缺乏SRY的情況下亦會導致睾丸的發育。^[18] 這兩者皆證明，SOX9在缺乏SRY的情況下，無論在XX或XY性腺中，仍將持續於睾丸發育、睾丸分化和性別決定上發揮關鍵作用。亦有詳細說明SOX9可替代SRY的功能。^[19]^[20]

臨床意義

突變會導致骨骼畸形症候群彎骨發育不全，通常伴有常染色體性別反轉^[6]和裂顎。^[21]

SOX9位於人類17q24的基因沙漠中。SOX9兩側距轉錄單位超過1Mb的高度保守非編碼元件的缺失、被易位斷點干擾以及單點突變，都與皮埃爾·羅賓序列相關，且常伴有顎裂。^[21]^[22]

SOX9蛋白已被認為與多種實質固態瘤(solid tumors)的發生和進展有關。^[23] 其作為形態發生的主調節因子在人體發育過程中的角色，使其成為惡性組織中擾動的理想候選者。具體而言，SOX9似乎在前列腺、^[24]結直腸、^[25]乳腺^[26]和其他癌症中誘導侵襲性和治療抵抗性，從而促進致命的轉移。^[27]SOX9的許多這些致癌效應似乎是劑量依賴的。^[28]^[24]^[23]

SOX9 的定位和動態

SOX9 主要定位於細胞核中，且具有高度的流動性。對軟骨細胞系的研究顯示，近50%的 SOX9 與 DNA 結合，並且直接受到外部因素的調控。其在 DNA 上的駐留半衰期約為14秒。^[29]

在性別分化中的角色

SOX9幫助引導SRY在性別分化中的激活。SOX9或任何相關基因的突變可能導致性別逆轉。如果SOX9激活的FGF9不存在，具有X和Y染色體的胎兒將成為女性。^[9] 如果DAX1不存在，情況也是如此。^[11] 相關現象可能由於SRY在XX男性綜合症中的不尋常活動引起，通常是當它轉位到X染色體上並且其活動僅在某些細胞中被激活時。^[30] SOX9的突變或缺失可能導致XY胎兒成為女性，因為SOX9是一個關鍵的效應基因，通過SRY基因作用來分化支持細胞並推動男性睾丸的形成。^[13]

相互作用

已顯示SOX9與類固醇生成因子1^[8]、MED12^[31]、MAF^[32]、SWI/SNF、MLL3和MLL4發生相互作用。^[33]

基因剔除模型

SOX9的功能喪失突變可能導致彎曲肢體發育不全症（CD），這是由於影響蛋白質功能的突變和破壞基因表達的易位。已經有SOX9基因剔除小鼠顯示出中風恢復的改善，特別是在抑制如NOGO和硫酸軟骨素蛋白聚糖（CSPGs）等軸突萌芽抑制劑時。SOX9的去除導致CSPG水平降低，這增加了組織保護並改善了中風後的神經恢復。這些SOX9基因剔除小鼠促進修復性軸突萌芽、神經保護和中風後的恢復。^[34]

參見

SOX基因家族

進一步閱讀

Ninomiya S, Narahara K, Tsuji K, Yokoyama Y, Ito S, Seino Y. Acampomelic campomelic syndrome and sex reversal associated with de novo t(12;17) translocation. American Journal of Medical Genetics. March 1995, 56 (1): 31–34. PMID 7747782. doi:10.1002/ajmg.1320560109.
Lefebvre V, de Crombrugghe B. Toward understanding SOX9 function in chondrocyte differentiation. Matrix Biology. March 1998, 16 (9): 529–540. PMID 9569122. doi:10.1016/S0945-053X(98)90065-8.
Harley VR. The Molecular Action of Testis-Determining Factors SRY and SOX9. The Genetics and Biology of Sex Determination. Novartis Foundation Symposia 244. 2002: 57–66; discussion 66–7, 79–85, 253–7. ISBN 9780470843468. PMID 11990798. doi:10.1002/0470868732.ch6.
Kwok C, Weller PA, Guioli S, Foster JW, Mansour S, Zuffardi O, Punnett HH, Dominguez-Steglich MA, Brook JD, Young ID. Mutations in SOX9, the gene responsible for Campomelic dysplasia and autosomal sex reversal. American Journal of Human Genetics. November 1995, 57 (5): 1028–1036. PMC 1801368 . PMID 7485151.
Foster JW, Dominguez-Steglich MA, Guioli S, Kwok C, Weller PA, Stevanović M, Weissenbach J, Mansour S, Young ID, Goodfellow PN. Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene. Nature. December 1994, 372 (6506): 525–530. Bibcode:1994Natur.372..525F. PMID 7990924. S2CID 1472426. doi:10.1038/372525a0.
Wagner T, Wirth J, Meyer J, Zabel B, Held M, Zimmer J, Pasantes J, Bricarelli FD, Keutel J, Hustert E, Wolf U, Tommerup N, Schempp W, Scherer G. Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9. Cell. December 1994, 79 (6): 1111–1120. PMID 8001137. S2CID 24982682. doi:10.1016/0092-8674(94)90041-8.
Südbeck P, Schmitz ML, Baeuerle PA, Scherer G. Sex reversal by loss of the C-terminal transactivation domain of human SOX9. Nature Genetics. June 1996, 13 (2): 230–232. PMID 8640233. S2CID 22617889. doi:10.1038/ng0696-230.
Cameron FJ, Hageman RM, Cooke-Yarborough C, Kwok C, Goodwin LL, Sillence DO, Sinclair AH. A novel germ line mutation in SOX9 causes familial campomelic dysplasia and sex reversal. Human Molecular Genetics. October 1996, 5 (10): 1625–1630. PMID 8894698. doi:10.1093/hmg/5.10.1625 .
Meyer J, Südbeck P, Held M, Wagner T, Schmitz ML, Bricarelli FD, Eggermont E, Friedrich U, Haas OA, Kobelt A, Leroy JG, Van Maldergem L, Michel E, Mitulla B, Pfeiffer RA, Schinzel A, Schmidt H, Scherer G. Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations. Human Molecular Genetics. January 1997, 6 (1): 91–98. PMID 9002675. doi:10.1093/hmg/6.1.91 .
Cameron FJ, Sinclair AH. Mutations in SRY and SOX9: testis-determining genes. Human Mutation. 1997, 9 (5): 388–395. PMID 9143916. S2CID 45387678. doi:10.1002/(SICI)1098-1004(1997)9:5<388::AID-HUMU2>3.0.CO;2-0.
Wunderle VM, Critcher R, Hastie N, Goodfellow PN, Schedl A. Deletion of long-range regulatory elements upstream of SOX9 causes campomelic dysplasia. Proceedings of the National Academy of Sciences of the United States of America. September 1998, 95 (18): 10649–10654. Bibcode:1998PNAS...9510649W. PMC 27949 . PMID 9724758. doi:10.1073/pnas.95.18.10649 .
De Santa Barbara P, Bonneaud N, Boizet B, Desclozeaux M, Moniot B, Sudbeck P, Scherer G, Poulat F, Berta P. Direct interaction of SRY-related protein SOX9 and steroidogenic factor 1 regulates transcription of the human anti-Müllerian hormone gene. Molecular and Cellular Biology. November 1998, 18 (11): 6653–6665. PMC 109250 . PMID 9774680. doi:10.1128/mcb.18.11.6653.
McDowall S, Argentaro A, Ranganathan S, Weller P, Mertin S, Mansour S, Tolmie J, Harley V. Functional and structural studies of wild type SOX9 and mutations causing campomelic dysplasia. The Journal of Biological Chemistry. August 1999, 274 (34): 24023–24030. PMID 10446171. doi:10.1074/jbc.274.34.24023 .
Huang W, Zhou X, Lefebvre V, de Crombrugghe B. Phosphorylation of SOX9 by cyclic AMP-dependent protein kinase A enhances SOX9's ability to transactivate a Col2a1 chondrocyte-specific enhancer. Molecular and Cellular Biology. June 2000, 20 (11): 4149–4158. PMC 85784 . PMID 10805756. doi:10.1128/MCB.20.11.4149-4158.2000.
Thong MK, Scherer G, Kozlowski K, Haan E, Morris L. Acampomelic campomelic dysplasia with SOX9 mutation. American Journal of Medical Genetics. August 2000, 93 (5): 421–425. PMID 10951468. doi:10.1002/1096-8628(20000828)93:5<421::AID-AJMG14>3.0.CO;2-5.
Ninomiya S, Yokoyama Y, Teraoka M, Mori R, Inoue C, Yamashita S, Tamai H, Funato M, Seino Y. A novel mutation (296 del G) of the SOX90 gene in a patient with campomelic syndrome and sex reversal. Clinical Genetics. September 2000, 58 (3): 224–227. PMID 11076045. S2CID 28618271. doi:10.1034/j.1399-0004.2000.580310.x.
Preiss S, Argentaro A, Clayton A, John A, Jans DA, Ogata T, Nagai T, Barroso I, Schafer AJ, Harley VR. Compound effects of point mutations causing campomelic dysplasia/autosomal sex reversal upon SOX9 structure, nuclear transport, DNA binding, and transcriptional activation. The Journal of Biological Chemistry. July 2001, 276 (30): 27864–27872. PMID 11323423. doi:10.1074/jbc.M101278200 .

参考文献

^ ^1.0 ^1.1 ^1.2 GRCh38: Ensembl release 89: ENSG00000125398 - Ensembl, May 2017
^ ^2.0 ^2.1 ^2.2 GRCm38: Ensembl release 89: ENSMUSG00000000567 - Ensembl, May 2017
^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Tommerup N, Schempp W, Meinecke P, Pedersen S, Bolund L, Brandt C, Goodpasture C, Guldberg P, Held KR, Reinwein H. Assignment of an autosomal sex reversal locus (SRA1) and campomelic dysplasia (CMPD1) to 17q24.3-q25.1. Nature Genetics. June 1993, 4 (2): 170–174. PMID 8348155. S2CID 12263655. doi:10.1038/ng0693-170.
^ ^6.0 ^6.1 ^6.2 Entrez Gene: SOX9 SRY (sex determining region Y)-box 9 (campomelic dysplasia, autosomal sex-reversal).
^ Kumar V, Abbas AK, Aster JC. Robbins and Cotran pathologic basis of disease Ninth. Elsevier/Saunders. 2015: 1182. ISBN 9780808924500.
^ ^8.0 ^8.1 De Santa Barbara P, Bonneaud N, Boizet B, Desclozeaux M, Moniot B, Sudbeck P, Scherer G, Poulat F, Berta P. Direct interaction of SRY-related protein SOX9 and steroidogenic factor 1 regulates transcription of the human anti-Müllerian hormone gene. Molecular and Cellular Biology. November 1998, 18 (11): 6653–6665. PMC 109250 . PMID 9774680. doi:10.1128/mcb.18.11.6653.
^ ^9.0 ^9.1 ^9.2 Moniot B, Declosmenil F, Barrionuevo F, Scherer G, Aritake K, Malki S, Marzi L, Cohen-Solal A, Georg I, Klattig J, Englert C, Kim Y, Capel B, Eguchi N, Urade Y, Boizet-Bonhoure B, Poulat F. The PGD2 pathway, independently of FGF9, amplifies SOX9 activity in Sertoli cells during male sexual differentiation. Development. June 2009, 136 (11): 1813–1821. PMC 4075598 . PMID 19429785. doi:10.1242/dev.032631.
^ ^10.0 ^10.1 Kim Y, Kobayashi A, Sekido R, DiNapoli L, Brennan J, Chaboissier MC, Poulat F, Behringer RR, Lovell-Badge R, Capel B. Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination. PLOS Biology. June 2006, 4 (6): e187. PMC 1463023 . PMID 16700629. doi:10.1371/journal.pbio.0040187 .
^ ^11.0 ^11.1 Bouma GJ, Albrecht KH, Washburn LL, Recknagel AK, Churchill GA, Eicher EM. Gonadal sex reversal in mutant Dax1 XY mice: a failure to upregulate Sox9 in pre-Sertoli cells. Development. July 2005, 132 (13): 3045–3054. PMID 15944188. doi:10.1242/dev.01890 .
^ Ambrozkiewicz MC, Schwark M, Kishimoto-Suga M, Borisova E, Hori K, Salazar-Lázaro A, Rusanova A, Altas B, Piepkorn L, Bessa P, Schaub T, Zhang X, Rabe T, Ripamonti S, Rosário M, Akiyama H, Jahn O, Kobayashi T, Hoshino M, Tarabykin V, Kawabe H. Polarity Acquisition in Cortical Neurons Is Driven by Synergistic Action of Sox9-Regulated Wwp1 and Wwp2 E3 Ubiquitin Ligases and Intronic miR-140. Neuron. December 2018, 100 (5): 1097–1115.e15. PMID 30392800. doi:10.1016/j.neuron.2018.10.008 .
^ ^13.0 ^13.1 Gonen N, Quinn A, O'Neill HC, Koopman P, Lovell-Badge R. Normal Levels of Sox9 Expression in the Developing Mouse Testis Depend on the TES/TESCO Enhancer, but This Does Not Act Alone. PLOS Genetics. January 2017, 13 (1): e1006520. PMC 5207396 . PMID 28045957. doi:10.1371/journal.pgen.1006520 .
^ Place E, Manning E, Kim DW, Kinjo A, Nakamura G and Ohyama K (2022) SHH and Notch regulate SOX9+ progenitors to govern arcuate POMC neurogenesis. Front. Neurosci. 16:855288. doi: 10.3389/fnins.2022.855288
^ Vogel, Julia K.; Wegner, Michael PhD,*. Sox9 in the developing central nervous system: a jack of all trades?. Neural Regeneration Research 16(4):p 676-677, April 2021. | DOI: 10.4103/1673-5374.295327
^ Ball HC, Ansari MY, Ahmad N, Novak K, Haqqi TM. A retrotransposon gag-like-3 gene RTL3 and SOX-9 co-regulate the expression of COL2A1 in chondrocytes. Connective Tissue Research. November 2021, 62 (6): 615–628. PMC 8404968 . PMID 33043724. doi:10.1080/03008207.2020.1828380.
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^ Vidal, Valerie P.I., et al. “Sox9 induces testis development in XX transgenic mice.” Nature Genetics, vol. 28, July 2001, pp. 216–217, https://doi.org/10.1038/90046.
^ Ortega, Egle A., et al. “Sry-Independent Overexpression of Sox9 Supports Spermatogenesis and Fertility in the Mouse.” Biology of Reproduction, vol. 93, no. 6, 1 Dec. 2015, pp. 1–12, https://doi.org/10.1095/biolreprod.115.135400.
^ Vidal, Valerie P.I., et al. “Sox9 induces testis development in XX transgenic mice.” Nature Genetics, vol. 28, July 2001, pp. 216–217, https://doi.org/10.1038/90046.
^ ^21.0 ^21.1 Dixon MJ, Marazita ML, Beaty TH, Murray JC. Cleft lip and palate: understanding genetic and environmental influences. Nature Reviews. Genetics. March 2011, 12 (3): 167–178. PMC 3086810 . PMID 21331089. doi:10.1038/nrg2933.
^ Benko S, Fantes JA, Amiel J, Kleinjan DJ, Thomas S, Ramsay J, Jamshidi N, Essafi A, Heaney S, Gordon CT, McBride D, Golzio C, Fisher M, Perry P, Abadie V, Ayuso C, Holder-Espinasse M, Kilpatrick N, Lees MM, Picard A, Temple IK, Thomas P, Vazquez MP, Vekemans M, Roest Crollius H, Hastie ND, Munnich A, Etchevers HC, Pelet A, Farlie PG, Fitzpatrick DR, Lyonnet S. Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence. Nature Genetics. March 2009, 41 (3): 359–364. PMID 19234473. S2CID 29933548. doi:10.1038/ng.329.
^ ^23.0 ^23.1 Jo A, Denduluri S, Zhang B, Wang Z, Yin L, Yan Z, Kang R, Shi LL, Mok J, Lee MJ, Haydon RC. The versatile functions of Sox9 in development, stem cells, and human diseases. Genes & Diseases. December 2014, 1 (2): 149–161. PMC 4326072 . PMID 25685828. doi:10.1016/j.gendis.2014.09.004.
^ ^24.0 ^24.1 Nouri M, Massah S, Caradec J, Lubik AA, Li N, Truong S, Lee AR, Fazli L, Ramnarine VR, Lovnicki JM, Moore J, Wang M, Foo J, Gleave ME, Hollier BG, Nelson C, Collins C, Dong X, Buttyan R. Transient Sox9 Expression Facilitates Resistance to Androgen-Targeted Therapy in Prostate Cancer. Clinical Cancer Research. April 2020, 26 (7): 1678–1689. PMID 31919137. doi:10.1158/1078-0432.CCR-19-0098 .
^ Prévostel C, Blache P. The dose-dependent effect of SOX9 and its incidence in colorectal cancer. European Journal of Cancer. November 2017, 86: 150–157. PMID 28988015. doi:10.1016/j.ejca.2017.08.037.
^ Grimm D, Bauer J, Wise P, Krüger M, Simonsen U, Wehland M, Infanger M, Corydon TJ. The role of SOX family members in solid tumours and metastasis. Seminars in Cancer Biology. December 2020, 67 (Pt 1): 122–153. PMID 30914279. doi:10.1016/j.semcancer.2019.03.004 . hdl:21.11116/0000-0007-D3EE-F .
^ Aguilar-Medina M, Avendaño-Félix M, Lizárraga-Verdugo E, Bermúdez M, Romero-Quintana JG, Ramos-Payan R, Ruíz-García E, López-Camarillo C. SOX9 Stem-Cell Factor: Clinical and Functional Relevance in Cancer. Journal of Oncology. 2019, 2019: 6754040. PMC 6463569 . PMID 31057614. doi:10.1155/2019/6754040 .
^ Yang X, Liang R, Liu C, Liu JA, Cheung MP, Liu X, Man OY, Guan XY, Lung HL, Cheung M. SOX9 is a dose-dependent metastatic fate determinant in melanoma. Journal of Experimental & Clinical Cancer Research. January 2019, 38 (1): 17. PMC 6330758 . PMID 30642390. doi:10.1186/s13046-018-0998-6 .
^ Govindaraj K, Hendriks J, Lidke DS, Karperien M, Post JN. Changes in Fluorescence Recovery After Photobleaching (FRAP) as an indicator of SOX9 transcription factor activity. Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. January 2019, 1862 (1): 107–117. PMID 30465885. doi:10.1016/j.bbagrm.2018.11.001 .
^ Margarit E, Coll MD, Oliva R, Gómez D, Soler A, Ballesta F. SRY gene transferred to the long arm of the X chromosome in a Y-positive XX true hermaphrodite. American Journal of Medical Genetics. January 2000, 90 (1): 25–28. PMID 10602113. doi:10.1002/(SICI)1096-8628(20000103)90:1<25::AID-AJMG5>3.0.CO;2-5.
^ Zhou R, Bonneaud N, Yuan CX, de Santa Barbara P, Boizet B, Schomber T, Scherer G, Roeder RG, Poulat F, Berta P. SOX9 interacts with a component of the human thyroid hormone receptor-associated protein complex. Nucleic Acids Research. July 2002, 30 (14): 3245–3252. PMC 135763 . PMID 12136106. doi:10.1093/nar/gkf443.
^ Huang W, Lu N, Eberspaecher H, De Crombrugghe B. A new long form of c-Maf cooperates with Sox9 to activate the type II collagen gene. The Journal of Biological Chemistry. December 2002, 277 (52): 50668–50675. PMID 12381733. doi:10.1074/jbc.M206544200 .
^ Yang Y, Gomez N, Infarinato N, Adam RC, Sribour M, Baek I, Laurin M, Fuchs E. The pioneer factor SOX9 competes for epigenetic factors to switch stem cell fates. Nature Cell Biology. August 2023, 25 (8): 1185–1195. PMC 10415178 . PMID 37488435. doi:10.1038/s41556-023-01184-y .
^ Xu X, Bass B, McKillop WM, Mailloux J, Liu T, Geremia NM, Hryciw T, Brown A. Sox9 knockout mice have improved recovery following stroke. Experimental Neurology. May 2018, 303: 59–71. PMID 29425963. doi:10.1016/j.expneurol.2018.02.001.

外部链接

醫學主題詞表（MeSH）：SOX9+protein,+human
Template:UCSC genome browser
Template:UCSC gene details
PDB中UniProt可用的所有結構信息之概述：P48436 (Human Transcription factor SOX-9) 在PDBe-KB（英语：PDBe-KB）。
PDB中UniProt可用的所有結構信息之概述：Q04887 (Mouse Transcription factor SOX-9) 在PDBe-KB（英语：PDBe-KB）。

SOX9引用了美国国家医学图书馆提供的資料，这些資料属于公共领域。

[refGRCh38Ensembl-1] 1.0 ^1.1 ^1.2 GRCh38: Ensembl release 89: ENSG00000125398 - Ensembl, May 2017

[refGRCm38Ensembl-2] 2.0 ^2.1 ^2.2 GRCm38: Ensembl release 89: ENSMUSG00000000567 - Ensembl, May 2017

[3] Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid8348155-5] Tommerup N, Schempp W, Meinecke P, Pedersen S, Bolund L, Brandt C, Goodpasture C, Guldberg P, Held KR, Reinwein H. Assignment of an autosomal sex reversal locus (SRA1) and campomelic dysplasia (CMPD1) to 17q24.3-q25.1. Nature Genetics. June 1993, 4 (2): 170–174. PMID 8348155. S2CID 12263655. doi:10.1038/ng0693-170.

[entrez-6] 6.0 ^6.1 ^6.2 Entrez Gene: SOX9 SRY (sex determining region Y)-box 9 (campomelic dysplasia, autosomal sex-reversal).

[7] Kumar V, Abbas AK, Aster JC. Robbins and Cotran pathologic basis of disease Ninth. Elsevier/Saunders. 2015: 1182. ISBN 9780808924500.

[pmid9774680-8] 8.0 ^8.1 De Santa Barbara P, Bonneaud N, Boizet B, Desclozeaux M, Moniot B, Sudbeck P, Scherer G, Poulat F, Berta P. Direct interaction of SRY-related protein SOX9 and steroidogenic factor 1 regulates transcription of the human anti-Müllerian hormone gene. Molecular and Cellular Biology. November 1998, 18 (11): 6653–6665. PMC 109250 . PMID 9774680. doi:10.1128/mcb.18.11.6653.

[Moniot-9] 9.0 ^9.1 ^9.2 Moniot B, Declosmenil F, Barrionuevo F, Scherer G, Aritake K, Malki S, Marzi L, Cohen-Solal A, Georg I, Klattig J, Englert C, Kim Y, Capel B, Eguchi N, Urade Y, Boizet-Bonhoure B, Poulat F. The PGD2 pathway, independently of FGF9, amplifies SOX9 activity in Sertoli cells during male sexual differentiation. Development. June 2009, 136 (11): 1813–1821. PMC 4075598 . PMID 19429785. doi:10.1242/dev.032631.

[pmid16700629-10] 10.0 ^10.1 Kim Y, Kobayashi A, Sekido R, DiNapoli L, Brennan J, Chaboissier MC, Poulat F, Behringer RR, Lovell-Badge R, Capel B. Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination. PLOS Biology. June 2006, 4 (6): e187. PMC 1463023 . PMID 16700629. doi:10.1371/journal.pbio.0040187 .

[pmid15944188-11] 11.0 ^11.1 Bouma GJ, Albrecht KH, Washburn LL, Recknagel AK, Churchill GA, Eicher EM. Gonadal sex reversal in mutant Dax1 XY mice: a failure to upregulate Sox9 in pre-Sertoli cells. Development. July 2005, 132 (13): 3045–3054. PMID 15944188. doi:10.1242/dev.01890 .

[12] Ambrozkiewicz MC, Schwark M, Kishimoto-Suga M, Borisova E, Hori K, Salazar-Lázaro A, Rusanova A, Altas B, Piepkorn L, Bessa P, Schaub T, Zhang X, Rabe T, Ripamonti S, Rosário M, Akiyama H, Jahn O, Kobayashi T, Hoshino M, Tarabykin V, Kawabe H. Polarity Acquisition in Cortical Neurons Is Driven by Synergistic Action of Sox9-Regulated Wwp1 and Wwp2 E3 Ubiquitin Ligases and Intronic miR-140. Neuron. December 2018, 100 (5): 1097–1115.e15. PMID 30392800. doi:10.1016/j.neuron.2018.10.008 .

[Normal_Levels_of_Sox9_Expression_in-13] 13.0 ^13.1 Gonen N, Quinn A, O'Neill HC, Koopman P, Lovell-Badge R. Normal Levels of Sox9 Expression in the Developing Mouse Testis Depend on the TES/TESCO Enhancer, but This Does Not Act Alone. PLOS Genetics. January 2017, 13 (1): e1006520. PMC 5207396 . PMID 28045957. doi:10.1371/journal.pgen.1006520 .

[14] Place E, Manning E, Kim DW, Kinjo A, Nakamura G and Ohyama K (2022) SHH and Notch regulate SOX9+ progenitors to govern arcuate POMC neurogenesis. Front. Neurosci. 16:855288. doi: 10.3389/fnins.2022.855288

[15] Vogel, Julia K.; Wegner, Michael PhD,*. Sox9 in the developing central nervous system: a jack of all trades?. Neural Regeneration Research 16(4):p 676-677, April 2021. | DOI: 10.4103/1673-5374.295327

[16] Ball HC, Ansari MY, Ahmad N, Novak K, Haqqi TM. A retrotransposon gag-like-3 gene RTL3 and SOX-9 co-regulate the expression of COL2A1 in chondrocytes. Connective Tissue Research. November 2021, 62 (6): 615–628. PMC 8404968 . PMID 33043724. doi:10.1080/03008207.2020.1828380.

[17] Ortega, Egle A., et al. “Sry-Independent Overexpression of Sox9 Supports Spermatogenesis and Fertility in the Mouse.” Biology of Reproduction, vol. 93, no. 6, 1 Dec. 2015, pp. 1–12, https://doi.org/10.1095/biolreprod.115.135400.

[18] Vidal, Valerie P.I., et al. “Sox9 induces testis development in XX transgenic mice.” Nature Genetics, vol. 28, July 2001, pp. 216–217, https://doi.org/10.1038/90046.

[19] Ortega, Egle A., et al. “Sry-Independent Overexpression of Sox9 Supports Spermatogenesis and Fertility in the Mouse.” Biology of Reproduction, vol. 93, no. 6, 1 Dec. 2015, pp. 1–12, https://doi.org/10.1095/biolreprod.115.135400.

[20] Vidal, Valerie P.I., et al. “Sox9 induces testis development in XX transgenic mice.” Nature Genetics, vol. 28, July 2001, pp. 216–217, https://doi.org/10.1038/90046.

[Dixon_2011-21] 21.0 ^21.1 Dixon MJ, Marazita ML, Beaty TH, Murray JC. Cleft lip and palate: understanding genetic and environmental influences. Nature Reviews. Genetics. March 2011, 12 (3): 167–178. PMC 3086810 . PMID 21331089. doi:10.1038/nrg2933.

[pmid19234473-22] Benko S, Fantes JA, Amiel J, Kleinjan DJ, Thomas S, Ramsay J, Jamshidi N, Essafi A, Heaney S, Gordon CT, McBride D, Golzio C, Fisher M, Perry P, Abadie V, Ayuso C, Holder-Espinasse M, Kilpatrick N, Lees MM, Picard A, Temple IK, Thomas P, Vazquez MP, Vekemans M, Roest Crollius H, Hastie ND, Munnich A, Etchevers HC, Pelet A, Farlie PG, Fitzpatrick DR, Lyonnet S. Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence. Nature Genetics. March 2009, 41 (3): 359–364. PMID 19234473. S2CID 29933548. doi:10.1038/ng.329.

[The_versatile_functions_of_Sox9_in-23] 23.0 ^23.1 Jo A, Denduluri S, Zhang B, Wang Z, Yin L, Yan Z, Kang R, Shi LL, Mok J, Lee MJ, Haydon RC. The versatile functions of Sox9 in development, stem cells, and human diseases. Genes & Diseases. December 2014, 1 (2): 149–161. PMC 4326072 . PMID 25685828. doi:10.1016/j.gendis.2014.09.004.

[Transient_Sox9_Expression_Facilitat-24] 24.0 ^24.1 Nouri M, Massah S, Caradec J, Lubik AA, Li N, Truong S, Lee AR, Fazli L, Ramnarine VR, Lovnicki JM, Moore J, Wang M, Foo J, Gleave ME, Hollier BG, Nelson C, Collins C, Dong X, Buttyan R. Transient Sox9 Expression Facilitates Resistance to Androgen-Targeted Therapy in Prostate Cancer. Clinical Cancer Research. April 2020, 26 (7): 1678–1689. PMID 31919137. doi:10.1158/1078-0432.CCR-19-0098 .

[25] Prévostel C, Blache P. The dose-dependent effect of SOX9 and its incidence in colorectal cancer. European Journal of Cancer. November 2017, 86: 150–157. PMID 28988015. doi:10.1016/j.ejca.2017.08.037.

[26] Grimm D, Bauer J, Wise P, Krüger M, Simonsen U, Wehland M, Infanger M, Corydon TJ. The role of SOX family members in solid tumours and metastasis. Seminars in Cancer Biology. December 2020, 67 (Pt 1): 122–153. PMID 30914279. doi:10.1016/j.semcancer.2019.03.004 . hdl:21.11116/0000-0007-D3EE-F .

[27] Aguilar-Medina M, Avendaño-Félix M, Lizárraga-Verdugo E, Bermúdez M, Romero-Quintana JG, Ramos-Payan R, Ruíz-García E, López-Camarillo C. SOX9 Stem-Cell Factor: Clinical and Functional Relevance in Cancer. Journal of Oncology. 2019, 2019: 6754040. PMC 6463569 . PMID 31057614. doi:10.1155/2019/6754040 .

[28] Yang X, Liang R, Liu C, Liu JA, Cheung MP, Liu X, Man OY, Guan XY, Lung HL, Cheung M. SOX9 is a dose-dependent metastatic fate determinant in melanoma. Journal of Experimental & Clinical Cancer Research. January 2019, 38 (1): 17. PMC 6330758 . PMID 30642390. doi:10.1186/s13046-018-0998-6 .

[pmid30465885-29] Govindaraj K, Hendriks J, Lidke DS, Karperien M, Post JN. Changes in Fluorescence Recovery After Photobleaching (FRAP) as an indicator of SOX9 transcription factor activity. Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. January 2019, 1862 (1): 107–117. PMID 30465885. doi:10.1016/j.bbagrm.2018.11.001 .

[pmid10602113-30] Margarit E, Coll MD, Oliva R, Gómez D, Soler A, Ballesta F. SRY gene transferred to the long arm of the X chromosome in a Y-positive XX true hermaphrodite. American Journal of Medical Genetics. January 2000, 90 (1): 25–28. PMID 10602113. doi:10.1002/(SICI)1096-8628(20000103)90:1<25::AID-AJMG5>3.0.CO;2-5.

[pmid12136106-31] Zhou R, Bonneaud N, Yuan CX, de Santa Barbara P, Boizet B, Schomber T, Scherer G, Roeder RG, Poulat F, Berta P. SOX9 interacts with a component of the human thyroid hormone receptor-associated protein complex. Nucleic Acids Research. July 2002, 30 (14): 3245–3252. PMC 135763 . PMID 12136106. doi:10.1093/nar/gkf443.

[pmid12381733-32] Huang W, Lu N, Eberspaecher H, De Crombrugghe B. A new long form of c-Maf cooperates with Sox9 to activate the type II collagen gene. The Journal of Biological Chemistry. December 2002, 277 (52): 50668–50675. PMID 12381733. doi:10.1074/jbc.M206544200 .

[33] Yang Y, Gomez N, Infarinato N, Adam RC, Sribour M, Baek I, Laurin M, Fuchs E. The pioneer factor SOX9 competes for epigenetic factors to switch stem cell fates. Nature Cell Biology. August 2023, 25 (8): 1185–1195. PMC 10415178 . PMID 37488435. doi:10.1038/s41556-023-01184-y .

[34] Xu X, Bass B, McKillop WM, Mailloux J, Liu T, Geremia NM, Hryciw T, Brown A. Sox9 knockout mice have improved recovery following stroke. Experimental Neurology. May 2018, 303: 59–71. PMID 29425963. doi:10.1016/j.expneurol.2018.02.001.

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