SMAD3

هم‌ساخت ۳ مادران مخالف دکپنتاپلجیک (انگلیسی: Mothers against decapentaplegic homolog 3) یک پروتئین است که در انسان توسط ژن «SMAD3» واقع بر بازوی بلند کروموزوم ۱۵ کُدگذاری می‌شود.^[4][5]

SMAD3
ساختارهای موجود PDB جستجوی هم‌ساخت‌شناسی: PDBe RCSB فهرست شناسه‌های PDB 2LB2, 1MHD, 1MJS, 1MK2, 1OZJ, 1U7F, 2LAJ, 5OD6, 5ODG
معین‌کننده‌ها
نام‌های دیگر	SMAD3, HSPC193, HsT17436, JV15-2, LDS1C, LDS3, MADH3, SMAD family member 3
شناسه‌های بیرونی	OMIM: 603109 MGI: 1201674 HomoloGene: 55937 GeneCards: SMAD3
موقعیت ژن (موش) کروموزوم کروموزوم ۹ (موش)[1] نوار 9|9 C شروع 63,554,049 bp[1] پایان 63,665,276 bp[1]
الگوی گسترش RNA More reference expression data
هستی‌شناسی ژن عملکرد ملکولی • phosphatase binding • GO:0001131، GO:0001151، GO:0001130، GO:0001204 DNA-binding transcription factor activity • R-SMAD binding • co-SMAD binding • RNA polymerase II transcription regulatory region sequence-specific DNA binding • transcription factor binding • metal ion binding • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • enzyme binding • transforming growth factor beta receptor binding • protein homodimerization activity • collagen binding • zinc ion binding • chromatin binding • GO:0001158 cis-regulatory region sequence-specific DNA binding • GO:0001948، GO:0016582 پیوند پروتئینی • double-stranded DNA binding • protein kinase binding • sequence-specific DNA binding • DNA binding • bHLH transcription factor binding • ubiquitin binding • identical protein binding • protein heterodimerization activity • chromatin DNA binding • ubiquitin protein ligase binding • beta-catenin binding • GO:0000983 RNA polymerase II general transcription initiation factor activity • DEAD/H-box RNA helicase binding • mineralocorticoid receptor binding • glucocorticoid receptor binding • primary miRNA binding • GO:0001200، GO:0001133، GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific • SMAD binding • GO:0001077، GO:0001212، GO:0001213، GO:0001211، GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific • GO:0001104 transcription coregulator activity ترکیبات سلولی • سیتوپلاسم • هسته یاخته • heteromeric SMAD protein complex • SMAD protein complex • transcription regulator complex • receptor complex • پوسته یاخته • intracellular anatomical structure • نوکلئوپلاسم • nuclear inner membrane • سیتوزول • GO:0009327 protein-containing complex فرایند زیستی • somitogenesis • skeletal system development • ureteric bud development • endoderm development • regulation of transforming growth factor beta2 production • embryonic pattern specification • GO:0044324، GO:0003256، GO:1901213، GO:0046019، GO:0046020، GO:1900094، GO:0061216، GO:0060994، GO:1902064، GO:0003258، GO:0072212 regulation of transcription by RNA polymerase II • negative regulation of osteoblast differentiation • heart looping • positive regulation of chondrocyte differentiation • positive regulation of alkaline phosphatase activity • positive regulation of interleukin-1 beta production • pericardium development • regulation of binding • negative regulation of wound healing • activation of cysteine-type endopeptidase activity involved in apoptotic process • transforming growth factor beta receptor signaling pathway • negative regulation of inflammatory response • positive regulation of positive chemotaxis • negative regulation of cell population proliferation • negative regulation of fat cell differentiation • cell-cell junction organization • GO:0009373 regulation of transcription, DNA-templated • extrinsic apoptotic signaling pathway • activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway • signal transduction involved in regulation of gene expression • in utero embryonic development • negative regulation of transforming growth factor beta receptor signaling pathway • nodal signaling pathway • GO:0060469، GO:0009371 positive regulation of transcription, DNA-templated • negative regulation of cell growth • regulation of immune response • positive regulation of transforming growth factor beta3 production • T cell activation • activin receptor signaling pathway • regulation of striated muscle tissue development • embryonic foregut morphogenesis • positive regulation of bone mineralization • بهبود زخم • negative regulation of apoptotic process • positive regulation of extracellular matrix assembly • GO:1901227 negative regulation of transcription by RNA polymerase II • positive regulation of epithelial to mesenchymal transition • GO:0019049، GO:0030683 mitigation of host defenses by virus • thyroid gland development • developmental growth • lens fiber cell differentiation • لایه‌زایی • GO:0046730، GO:0046737، GO:0046738، GO:0046736 پاسخ ایمنی • osteoblast differentiation • GO:1990744، GO:1990729 primary miRNA processing • negative regulation of osteoblast proliferation • osteoblast development • embryonic cranial skeleton morphogenesis • transdifferentiation • paraxial mesoderm morphogenesis • response to hypoxia • positive regulation of cell migration • mesoderm formation • regulation of transforming growth factor beta receptor signaling pathway • GO:1901313 positive regulation of gene expression • immune system development • positive regulation of focal adhesion assembly • liver development • regulation of epithelial cell proliferation • positive regulation of stress fiber assembly • GO:0003257، GO:0010735، GO:1901228، GO:1900622، GO:1904488 positive regulation of transcription by RNA polymerase II • negative regulation of mitotic cell cycle • negative regulation of cytosolic calcium ion concentration • canonical Wnt signaling pathway • protein stabilization • transcription, DNA-templated • GO:1903363 negative regulation of protein catabolic process • protein deubiquitination • positive regulation of nitric oxide biosynthetic process • negative regulation of lung blood pressure • positive regulation of pri-miRNA transcription by RNA polymerase II • negative regulation of cardiac muscle hypertrophy in response to stress • cellular response to transforming growth factor beta stimulus • cellular response to cytokine stimulus • positive regulation of protein import into nucleus • positive regulation of DNA-binding transcription factor activity • SMAD protein signal transduction • positive regulation of canonical Wnt signaling pathway • SMAD protein complex assembly • adrenal gland development منابع: آمیگو / کوئیک‌گو
هم‌ساخت‌شناسی
گونه‌ها	انسان	موش
Entrez	4088	17127
آنسامبل	ENSG00000166949	ENSMUSG00000032402
یونی‌پروت	P84022	Q8BUN5
RefSeq (mRNA)	NM_001145103، NM_001145104، NM_005902، XM_011521559 NM_001145102، NM_001145103، NM_001145104، NM_005902، XM_011521559	XM_006510819، XM_006510821 NM_016769، XM_006510819، XM_006510821
RefSeq (پروتئین)	NP_001138575، NP_001138576، NP_005893، XP_011519861، XP_011519862 NP_001138574، NP_001138575، NP_001138576، NP_005893، XP_011519861، XP_011519862	XP_006510882، XP_006510884 NP_058049، XP_006510882، XP_006510884
موقعیت (UCSC)	ن/م	Chr : 63.55 – 63.67 Mb
جستجوی PubMed	[2]	[3]
ویکی‌داده
مشاهده/ویرایش انسان مشاهده/ویرایش موش

این پروتئین عضوی از خانواده بزرگ SMAD است که این نیز به نوبهٔ خود، جزئی از اَبَرخانوادهٔ فاکتور رشد تغییردهنده بتا است.

نقش این پروتئین، تعدیل پیام‌هایی است که توسط فاکتور رشد تغییردهنده بتا آغاز می‌شود و در تزاید، تمایز و مرگ سلول نقش دارد.^[6][7]

اهمیت بالینی

افزایش فعالیت SMAD3 در بیماری‌زایی اسکلرودرمی نقش دارد. مولکول SMAD3 همچنین یک تنظیم‌کنندهٔ چندکاره در فیزیولوژی چربی است و با بروز چاقی و دیابت نوع ۲ مرتبط است.

این پروتئین همچنین در سرطان پروستات،^[8][9] سرطان روده بزرگ،^[10][11][12] سرطان پستان^[13] و فیبروز کلیه‌ها^[14] نقش دارد.

جستارهای وابسته

• مادران مخالف دکپنتاپلجیک

منابع

1. GRCm38: Ensembl release 89: ENSMUSG00000032402 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Entrez Gene: SMAD3 SMAD family member 3".
5. Zhang Y, Feng X, We R, Derynck R (September 1996). "Receptor-associated Mad homologues synergize as effectors of the TGF-beta response". Nature. 383 (6596): 168–72. doi:10.1038/383168a0. PMID 8774881.
6. Massagué J (1998). "TGF-beta signal transduction". Annual Review of Biochemistry. 67 (1): 753–91. doi:10.1146/annurev.biochem.67.1.753. PMID 9759503.
7. Moustakas A, Souchelnytskyi S, Heldin CH (December 2001). "Smad regulation in TGF-beta signal transduction". Journal of Cell Science. 114 (Pt 24): 4359–69. PMID 11792802.
8. Huang S, Liao Q, Li L, Xin D (July 2014). "PTTG1 inhibits SMAD3 in prostate cancer cells to promote their proliferation". Tumour Biology. 35 (7): 6265–70. doi:10.1007/s13277-014-1818-z. PMID 24627133.
9. Lu S, Lee J, Revelo M, Wang X, Lu S, Dong Z (October 2007). "Smad3 is overexpressed in advanced human prostate cancer and necessary for progressive growth of prostate cancer cells in nude mice". Clinical Cancer Research. 13 (19): 5692–702. doi:10.1158/1078-0432.CCR-07-1078. PMID 17908958.
10. Hachimine D, Uchida K, Asada M, Nishio A, Kawamata S, Sekimoto G, Murata M, Yamagata H, Yoshida K, Mori S, Tahashi Y, Matsuzaki K, Okazaki K (June 2008). "Involvement of Smad3 phosphoisoform-mediated signaling in the development of colonic cancer in IL-10-deficient mice". International Journal of Oncology. 32 (6): 1221–6. doi:10.3892/ijo.32.6.1221. PMID 18497983.
11. Seamons A, Treuting PM, Brabb T, Maggio-Price L (2013). "Characterization of dextran sodium sulfate-induced inflammation and colonic tumorigenesis in Smad3(-/-) mice with dysregulated TGFβ". PLOS ONE. 8 (11): e79182. doi:10.1371/journal.pone.0079182. PMC 3823566. PMID 24244446.
12. Kawamata S, Matsuzaki K, Murata M, Seki T, Matsuoka K, Iwao Y, Hibi T, Okazaki K (March 2011). "Oncogenic Smad3 signaling induced by chronic inflammation is an early event in ulcerative colitis-associated carcinogenesis". Inflammatory Bowel Diseases. 17 (3): 683–95. doi:10.1002/ibd.21395. PMID 20602465.
13. Petersen M, Pardali E, van der Horst G, Cheung H, van den Hoogen C, van der Pluijm G, Ten Dijke P (March 2010). "Smad2 and Smad3 have opposing roles in breast cancer bone metastasis by differentially affecting tumor angiogenesis". Oncogene. 29 (9): 1351–61. doi:10.1038/onc.2009.426. PMID 20010874.
14. Meng XM, Chung AC, Lan HY (February 2013). "Role of the TGF-β/BMP-7/Smad pathways in renal diseases". Clinical Science. 124 (4): 243–54. doi:10.1042/CS20120252. PMID 23126427.

• مشارکت‌کنندگان ویکی‌پدیا. «Mothers against decapentaplegic homolog 3». در دانشنامهٔ ویکی‌پدیای انگلیسی، بازبینی‌شده در ۱۵ مارس ۲۰۲۰.

برای مطالعهٔ بیشتر

• Tan CK, Chong HC, Tan EH, Tan NS (March 2012). "Getting 'Smad' about obesity and diabetes". Nutrition & Diabetes. 2 (3): e29. doi:10.1038/nutd.2012.1. PMC 3341711. PMID 23449528.
• Li H, Liu JP (October 2007). "Mechanisms of action of TGF-beta in cancer: evidence for Smad3 as a repressor of the hTERT gene". Annals of the New York Academy of Sciences. 1114: 56–68. doi:10.1196/annals.1396.016. PMID 17934056.
• Matsuzaki K (June 2006). "Smad3 phosphoisoform-mediated signaling during sporadic human colorectal carcinogenesis". Histology and Histopathology. 21 (6): 645–62. doi:10.14670/HH-21.645. PMID 16528675.
• Miyazono K (2000). "TGF-beta signaling by Smad proteins". Cytokine & Growth Factor Reviews. 11 (1–2): 15–22. doi:10.1016/S1359-6101(99)00025-8. PMID 10708949.
• Wrana JL, Attisano L (2000). "The Smad pathway". Cytokine & Growth Factor Reviews. 11 (1–2): 5–13. doi:10.1016/S1359-6101(99)00024-6. PMID 10708948.
• Verschueren K, Huylebroeck D (2000). "Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells". Cytokine & Growth Factor Reviews. 10 (3–4): 187–99. doi:10.1016/S1359-6101(99)00012-X. PMID 10647776.
• Massagué J (1998). "TGF-beta signal transduction". Annual Review of Biochemistry. 67: 753–91. doi:10.1146/annurev.biochem.67.1.753. PMID 9759503.
• Walker LC, Waddell N, Ten Haaf A, Grimmond S, Spurdle AB (November 2008). "Use of expression data and the CGEMS genome-wide breast cancer association study to identify genes that may modify risk in BRCA1/2 mutation carriers". Breast Cancer Research and Treatment. 112 (2): 229–36. doi:10.1007/s10549-007-9848-5. PMID 18095154.
• Lee KB, Jeon JH, Choi I, Kwon OY, Yu K, You KH (February 2008). "Clusterin, a novel modulator of TGF-beta signaling, is involved in Smad2/3 stability". Biochemical and Biophysical Research Communications. 366 (4): 905–9. doi:10.1016/j.bbrc.2007.12.033. PMID 18082619.
• Kim TD, Shin S, Janknecht R (February 2008). "Repression of Smad3 activity by histone demethylase SMCX/JARID1C". Biochemical and Biophysical Research Communications. 366 (2): 563–7. doi:10.1016/j.bbrc.2007.12.013. PMID 18078810.
• Zhao X, Nicholls JM, Chen YG (February 2008). "Severe acute respiratory syndrome-associated coronavirus nucleocapsid protein interacts with Smad3 and modulates transforming growth factor-beta signaling". The Journal of Biological Chemistry. 283 (6): 3272–80. doi:10.1074/jbc.M708033200. PMID 18055455.
• Li T, Chiang JY (November 2007). "A novel role of transforming growth factor beta1 in transcriptional repression of human cholesterol 7alpha-hydroxylase gene". Gastroenterology. 133 (5): 1660–9. doi:10.1053/j.gastro.2007.08.042. PMID 17920062.
• Lu S, Lee J, Revelo M, Wang X, Lu S, Dong Z (October 2007). "Smad3 is overexpressed in advanced human prostate cancer and necessary for progressive growth of prostate cancer cells in nude mice". Clinical Cancer Research. 13 (19): 5692–702. doi:10.1158/1078-0432.CCR-07-1078. PMID 17908958.
• Kalo E, Buganim Y, Shapira KE, Besserglick H, Goldfinger N, Weisz L, Stambolsky P, Henis YI, Rotter V (December 2007). "Mutant p53 attenuates the SMAD-dependent transforming growth factor beta1 (TGF-beta1) signaling pathway by repressing the expression of TGF-beta receptor type II". Molecular and Cellular Biology. 27 (23): 8228–42. doi:10.1128/MCB.00374-07. PMC 2169171. PMID 17875924.
• Weng HL, Ciuclan L, Liu Y, Hamzavi J, Godoy P, Gaitantzi H, Kanzler S, Heuchel R, Ueberham U, Gebhardt R, Breitkopf K, Dooley S (October 2007). "Profibrogenic transforming growth factor-beta/activin receptor-like kinase 5 signaling via connective tissue growth factor expression in hepatocytes". Hepatology. 46 (4): 1257–70. doi:10.1002/hep.21806. PMID 17657819.
• Dennler S, André J, Alexaki I, Li A, Magnaldo T, ten Dijke P, Wang XJ, Verrecchia F, Mauviel A (July 2007). "Induction of sonic hedgehog mediators by transforming growth factor-beta: Smad3-dependent activation of Gli2 and Gli1 expression in vitro and in vivo". Cancer Research. 67 (14): 6981–6. doi:10.1158/0008-5472.CAN-07-0491. PMID 17638910.
• Zhang M, Lee CH, Luo DD, Krupa A, Fraser D, Phillips A (September 2007). "Polarity of response to transforming growth factor-beta1 in proximal tubular epithelial cells is regulated by beta-catenin". The Journal of Biological Chemistry. 282 (39): 28639–47. doi:10.1074/jbc.M700594200. PMID 17623674.
• Martin MM, Buckenberger JA, Jiang J, Malana GE, Knoell DL, Feldman DS, Elton TS (September 2007). "TGF-beta1 stimulates human AT1 receptor expression in lung fibroblasts by cross talk between the Smad, p38 MAPK, JNK, and PI3K signaling pathways". American Journal of Physiology. Lung Cellular and Molecular Physiology. 293 (3): L790-9. doi:10.1152/ajplung.00099.2007. PMC 2413071. PMID 17601799.
• Dai F, Chang C, Lin X, Dai P, Mei L, Feng XH (September 2007). "Erbin inhibits transforming growth factor beta signaling through a novel Smad-interacting domain". Molecular and Cellular Biology. 27 (17): 6183–94. doi:10.1128/MCB.00132-07. PMC 1952163. PMID 17591701.
• Levy L, Howell M, Das D, Harkin S, Episkopou V, Hill CS (September 2007). "Arkadia activates Smad3/Smad4-dependent transcription by triggering signal-induced SnoN degradation". Molecular and Cellular Biology. 27 (17): 6068–83. doi:10.1128/MCB.00664-07. PMC 1952153. PMID 17591695.