SMAD4

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
موقعیت ژن (موش) کروموزوم کروموزوم ۱۸ (موش)[۱] نوار 18 E2|18 49.51 cM شروع 73,772,080 bp[۱] پایان 73,836,851 bp[۱]
الگوی گسترش RNA More reference expression data
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 • GO:0001131، GO:0001151، GO:0001130، GO:0001204 DNA-binding transcription factor activity • sequence-specific DNA binding • GO:0001158 cis-regulatory region sequence-specific DNA binding • GO:0001077، GO:0001212، GO:0001213، GO:0001211، GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific • I-SMAD binding • collagen binding • GO:0001948، GO:0016582 پیوند پروتئینی • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • R-SMAD binding • identical protein binding • sulfate binding • GO:0001200، GO:0001133، GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific • GO:0001104 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 • GO:0007329 positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus • 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 • branching involved in ureteric bud morphogenesis • GO:0009373 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 • GO:0045996 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 • GO:0007243 intracellular signal transduction • developmental growth • endoderm development • cellular iron ion homeostasis • kidney development • GO:0007364، GO:0007361، GO:0007358 formation of anatomical boundary • positive regulation of histone H3-K9 acetylation • regulation of transforming growth factor beta2 production • interleukin-6-mediated signaling pathway • GO:1901227 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 • GO:0060469، GO:0009371 positive regulation of transcription, DNA-templated • BMP signaling pathway • tissue morphogenesis • GO:0003257، GO:0010735، GO:1901228، GO:1900622، GO:1904488 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
گونه‌ها	انسان	موش
Entrez	4089	17128
آنسامبل	ENSG00000141646	ENSMUSG00000024515
یونی‌پروت	Q13485	P97471
RefSeq (mRNA)	NM_005359	XM_006525701، XM_011246855، NM_001364967، NM_001364968، NR_157374 NM_008540، XM_006525701، XM_011246855، NM_001364967، NM_001364968، NR_157374
RefSeq (پروتئین)	NP_005350	XP_006525764، XP_011245157، NP_001351896، NP_001351897 NP_032566، XP_006525764، XP_011245157، NP_001351896، NP_001351897
موقعیت (UCSC)	ن/م	Chr : 73.77 – 73.84 Mb
جستجوی PubMed	[۲]	[۳]
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.^[۴] 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.^[۵][۶]

پروتئین SMAD4 یک سوبسترا برای پروتئین کیناز فعال‌شده با میتوژن^[۷] و GSK-3^[۸] است.

اهمیت بالینی

اختلال در عملکرد این پروتئین موجب افزایش احتمال سرطان روده بزرگ و سرطان لوزالمعده^[۹] می‌گردد.^[۱۰]

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.^[۱۱][۱۲] این سندرم نخستین بار در سال ۱۹۸۱ توسط پزشک آمریکایی «سِـلما اِی. می‌یر» کشف و توصیف شد.

جستارهای وابسته

• مادران مخالف دکپنتاپلجیک

منابع

1. GRCm38: Ensembl release 89: ENSMUSG00000024515 - Ensembl, May 2017
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9. 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}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
10. 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}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
11. "Growth-Mental Deficiency Syndrome of Myhre". National Organization for rare disorders. Archived from the original on 2 April 2015. Retrieved 15 March 2020.
12. 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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