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SMAD4
ساختارهای موجود
PDB	جستجوی هم‌ساخت‌شناسی: PDBe RCSB
فهرست شناسه‌های PDB
	1DD1, 1G88, 1MR1, 1U7F, 1U7V, 1YGS, 5MEY, 5MEZ, 5MF0
معین‌کننده‌ها
نام‌های دیگر	SMAD4, DPC4, JIP, MADH4, MYHRS, SMAD family member 4
شناسه‌های بیرونی	OMIM: 600993; MGI: 894293; HomoloGene: 31310; GeneCards: SMAD4; OMA:SMAD4 - orthologs
موقعیت ژن (انسان)
کروموزوم	کروموزوم ۱۸ (انسان)
پایان	51,085,045 bp
موقعیت ژن (موش)
کروموزوم	کروموزوم ۱۸ (موش)
پایان	73,836,851 bp
الگوی گسترش RNA
	بیشترین بیان در
	ventricular zone; ; ganglionic eminence; ; epithelium of colon; ; stromal cell of endometrium; ; left ovary; ; tibial arteries;
	بیشترین بیان در
	Rostral migratory stream; ; medullary collecting duct; ; conjunctival fornix; ; medial ganglionic eminence; ; retinal pigment epithelium;
	داده‌های بیشتر بیان
	; ;
	داده‌های بیشتر بیان
هستی‌شناسی ژن
عملکرد ملکولی	protein homodimerization activity; protein heterodimerization activity; RNA polymerase II transcription regulatory region sequence-specific DNA binding; metal ion binding; DNA binding; DNA-binding transcription factor activity; sequence-specific DNA binding; cis-regulatory region sequence-specific DNA binding; DNA-binding transcription activator activity, RNA polymerase II-specific; I-SMAD binding; collagen binding; پیوند پروتئینی; RNA polymerase II cis-regulatory region sequence-specific DNA binding; R-SMAD binding; identical protein binding; sulfate binding; DNA-binding transcription factor activity, RNA polymerase II-specific; transcription coregulator activity; molecular function regulator; chromatin binding;
ترکیبات سلولی	هسته یاخته; سیتوپلاسم; transcription regulator complex; activin responsive factor complex; intracellular anatomical structure; RNA polymerase II transcription regulator complex; نوکلئوپلاسم; میان‌تن; سیتوزول; SMAD protein complex;
فرایند زیستی	negative regulation of cell population proliferation; اسپرماتوژنز; positive regulation of pathway-restricted SMAD protein phosphorylation; positive regulation of luteinizing hormone secretion; regulation of cell population proliferation; cardiac septum development; negative regulation of cell death; regulation of hair follicle development; cellular response to BMP stimulus; epithelial to mesenchymal transition involved in endocardial cushion formation; brainstem development; تکثیر سلولی; regulation of binding; SMAD protein complex assembly; metanephric mesenchyme morphogenesis; positive regulation of epithelial to mesenchymal transition; positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus; regulation of transcription by RNA polymerase II; branching involved in ureteric bud morphogenesis; regulation of transcription, DNA-templated; embryonic digit morphogenesis; uterus development; هدایت آسه; somatic stem cell population maintenance; لایه‌زایی; positive regulation of histone H3-K4 methylation; negative regulation of transcription, DNA-templated; response to transforming growth factor beta; endothelial cell activation; positive regulation of transforming growth factor beta receptor signaling pathway; single fertilization; transforming growth factor beta receptor signaling pathway; anterior/posterior pattern specification; in utero embryonic development; positive regulation of cell proliferation involved in heart valve morphogenesis; atrioventricular valve formation; intracellular signal transduction; developmental growth; endoderm development; cellular iron ion homeostasis; kidney development; formation of anatomical boundary; positive regulation of histone H3-K9 acetylation; regulation of transforming growth factor beta2 production; interleukin-6-mediated signaling pathway; negative regulation of transcription by RNA polymerase II; male gonad development; ovarian follicle development; endocardial cell differentiation; nephrogenic mesenchyme morphogenesis; gastrulation with mouth forming second; female gonad development; SMAD protein signal transduction; response to hypoxia; atrioventricular canal development; mesoderm development; negative regulation of cell growth; positive regulation of transcription, DNA-templated; BMP signaling pathway; tissue morphogenesis; positive regulation of transcription by RNA polymerase II; positive regulation of SMAD protein signal transduction; somite rostral/caudal axis specification; sebaceous gland development; positive regulation of follicle-stimulating hormone secretion; positive regulation of BMP signaling pathway; neural crest cell differentiation; seminiferous tubule development; female gonad morphogenesis; regulation of transforming growth factor beta receptor signaling pathway; neuron fate commitment; transcription, DNA-templated; outflow tract septum morphogenesis; left ventricular cardiac muscle tissue morphogenesis; negative regulation of cardiac muscle hypertrophy; protein deubiquitination; ventricular septum morphogenesis; negative regulation of ERK1 and ERK2 cascade; negative regulation of cardiac myofibril assembly; protein homotrimerization; pri-miRNA transcription by RNA polymerase II; secondary palate development; anatomical structure morphogenesis; دگرگونی یاخته‌; mesendoderm development;
	منابع: آمیگو / کوئیک‌گو
هم‌ساخت‌شناسی
	4089
	17128
	ENSG00000141646
	ENSMUSG00000024515
	Q13485
	P97471
	NM_005359
	NM_008540; NM_001364967; NM_001364968
	NP_005350
	NP_032566; NP_001351896; NP_001351897
	ویکی‌داده
مشاهده/ویرایش انسان	مشاهده/ویرایش موش

هم‌ساخت ۴ مادران مخالف دکپنتاپلجیک (انگلیسی: Mothers against decapentaplegic homolog 4) یک پروتئین است که در انسان توسط ژن «SMAD4» کُدگذاری می‌شود.^[۵] این پروتئین در تمامی جانوران یافت می‌شود و 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 رشد رویان، هم‌ایستایی بافت‌ها، بازسازی بافتی و تنظیم دستگاه ایمنی دخیل است. نقش‌های دیگر این پروتئین شامل تمایز سلولی، آپوپتوز، لایه‌زایی، رویان‌زایی و دخالت در چرخه سلول است.

این مولکول، یک پپتید با ۵۲۲ اسید آمینه است که وزن مولکولی‌اش ۶۰٫۴۳۹ کیلو دالتون است. ژن «SMAD4» از ۵۴۸۲۹ جفت باز تشکیل شده که در ناحیهٔ ۲۱٫۱ از بازوی بلند کروموزوم ۱۸ قرار گرفته‌اند.^[۶]^[۷]

پروتئین SMAD4 یک سوبسترا برای پروتئین کیناز فعال‌شده با میتوژن^[۸] و GSK-3^[۹] است.

اهمیت بالینی

اختلال در عملکرد این پروتئین موجب افزایش احتمال سرطان روده بزرگ و سرطان لوزالمعده^[۱۰] می‌گردد.^[۱۱]

جهش در ژن «SMAD4» سبب بروز سندرم می‌یر می‌گردد که نوعی اختلال ژنتیکی نادر است و که مشخصه‌اش، ناتوانی‌های ذهنی، قد کوتاه، مشخصات غیرطبیعی چهره و چندین ناهنجاری استخوانی است.^[۱۲]^[۱۳] این سندرم نخستین بار در سال ۱۹۸۱ توسط پزشک آمریکایی «سِـلما اِی. می‌یر» کشف و توصیف شد.

جستارهای وابسته

مادران مخالف دکپنتاپلجیک

منابع

↑ ^۱٫۰ ^۱٫۱ ^۱٫۲ GRCh38: Ensembl release 89: ENSG00000141646 – Ensembl, May 2017
↑ ^۲٫۰ ^۲٫۱ ^۲٫۲ GRCm38: Ensembl release 89: ENSMUSG00000024515 – 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.
↑ Massagué, Joan (2012). "TGFβ signalling in context". Nature Reviews Molecular Cell Biology (in English). 13 (10): 616–630. doi:10.1038/nrm3434. ISSN 1471-0080. PMC 4027049. PMID 22992590.
↑ "SMAD4 SMAD family member 4". Entrez Gene.
↑ "SMAD 4". The Genetics Home Reference Website.
↑ Roelen BA, Cohen OS, Raychowdhury MK, Chadee DN, Zhang Y, Kyriakis JM, Alessandrini AA, Lin HY (Oct 2003). "Phosphorylation of threonine 276 in Smad4 is involved in transforming growth factor-beta-induced nuclear accumulation". American Journal of Physiology. Cell Physiology. 285 (4): C823–30. doi:10.1152/ajpcell.00053.2003. PMID 12801888.
↑ Demagny H, Araki T, De Robertis EM (Oct 2014). "The tumor suppressor Smad4/DPC4 is regulated by phosphorylations that integrate FGF, Wnt, and TGF-β signaling". Cell Reports. 9 (2): 688–700. doi:10.1016/j.celrep.2014.09.020. PMID 25373906.
↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. ISBN 0-7216-0187-1. {{cite book}}: از پارامتر ناشناخته |name-list-format= صرف نظر شد (|name-list-style= پیشنهاد می‌شود) (کمک)
↑ Demagny, Hadrien; De Robertis, Edward M. (2015). "Point Mutations in the Tumor Suppressor Smad4/DPC4 Enhance its Phosphorylation by GSK3 and Reversibly Inactivate TGF-β Signaling". Molecular & Cellular Oncology. 3 (1): e1025181. doi:10.1080/23723556.2015.1025181. PMC 4845174. PMID 27308538. {{cite journal}}: از پارامتر ناشناخته |name-list-format= صرف نظر شد (|name-list-style= پیشنهاد می‌شود) (کمک)نگهداری یادکرد:شماره مقاله به‌جای شماره صفحه (رده)
↑ "Growth-Mental Deficiency Syndrome of Myhre". National Organization for rare disorders. Archived from the original on 2 آوریل 2015. Retrieved 15 مارس 2020.
↑ Caputo V, Bocchinfuso G, Castori M, Traversa A, Pizzuti A, Stella L, Grammatico P, Tartaglia M (Jul 2014). "Novel SMAD4 mutation causing Myhre syndrome". American Journal of Medical Genetics Part A. 164A (7): 1835–40. doi:10.1002/ajmg.a.36544. PMID 24715504.

مشارکت‌کنندگان ویکی‌پدیا. «Mothers against decapentaplegic homolog 4». در دانشنامهٔ ویکی‌پدیای انگلیسی، بازبینی‌شده در ۱۵ مارس ۲۰۲۰.

برای مطالعهٔ بیشتر

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[refGRCh38Ensembl-1] ۱٫۰ ^۱٫۱ ^۱٫۲ GRCh38: Ensembl release 89: ENSG00000141646 – Ensembl, May 2017

[refGRCm38Ensembl-2] ۲٫۰ ^۲٫۱ ^۲٫۲ GRCm38: Ensembl release 89: ENSMUSG00000024515 – 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.

[5] Massagué, Joan (2012). "TGFβ signalling in context". Nature Reviews Molecular Cell Biology (in English). 13 (10): 616–630. doi:10.1038/nrm3434. ISSN 1471-0080. PMC 4027049. PMID 22992590.

[entrez-6] "SMAD4 SMAD family member 4". Entrez Gene.

[gene_library-7] "SMAD 4". The Genetics Home Reference Website.

[8] Roelen BA, Cohen OS, Raychowdhury MK, Chadee DN, Zhang Y, Kyriakis JM, Alessandrini AA, Lin HY (Oct 2003). "Phosphorylation of threonine 276 in Smad4 is involved in transforming growth factor-beta-induced nuclear accumulation". American Journal of Physiology. Cell Physiology. 285 (4): C823–30. doi:10.1152/ajpcell.00053.2003. PMID 12801888.

[9] Demagny H, Araki T, De Robertis EM (Oct 2014). "The tumor suppressor Smad4/DPC4 is regulated by phosphorylations that integrate FGF, Wnt, and TGF-β signaling". Cell Reports. 9 (2): 688–700. doi:10.1016/j.celrep.2014.09.020. PMID 25373906.

[isbn0-7216-0187-1-10] Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. ISBN 0-7216-0187-1. {{cite book}}: از پارامتر ناشناخته |name-list-format= صرف نظر شد (|name-list-style= پیشنهاد می‌شود) (کمک)

[11] Demagny, Hadrien; De Robertis, Edward M. (2015). "Point Mutations in the Tumor Suppressor Smad4/DPC4 Enhance its Phosphorylation by GSK3 and Reversibly Inactivate TGF-β Signaling". Molecular & Cellular Oncology. 3 (1): e1025181. doi:10.1080/23723556.2015.1025181. PMC 4845174. PMID 27308538. {{cite journal}}: از پارامتر ناشناخته |name-list-format= صرف نظر شد (|name-list-style= پیشنهاد می‌شود) (کمک)نگهداری یادکرد:شماره مقاله به‌جای شماره صفحه (رده)

[12] "Growth-Mental Deficiency Syndrome of Myhre". National Organization for rare disorders. Archived from the original on 2 آوریل 2015. Retrieved 15 مارس 2020.

[13] Caputo V, Bocchinfuso G, Castori M, Traversa A, Pizzuti A, Stella L, Grammatico P, Tartaglia M (Jul 2014). "Novel SMAD4 mutation causing Myhre syndrome". American Journal of Medical Genetics Part A. 164A (7): 1835–40. doi:10.1002/ajmg.a.36544. PMID 24715504.

[۱]

[۲]

[۳]

[۴]

[۵]

[۶]

[۷]

[۸]

[۹]

[۱۰]

[۱۱]

[۱۲]

[۱۳]

SMAD4

اهمیت بالینی

جستارهای وابسته

منابع

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