Annotations: 1G88

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
B	d1g88b_	All beta proteins	SMAD/FHA domain	SMAD/FHA domain	SMAD domain	Smad4 tumor suppressor C-terminal domain	(Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d1g88c_	All beta proteins	SMAD/FHA domain	SMAD/FHA domain	SMAD domain	Smad4 tumor suppressor C-terminal domain	(Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d1g88a_	All beta proteins	SMAD/FHA domain	SMAD/FHA domain	SMAD domain	Smad4 tumor suppressor C-terminal domain	(Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
B	SCOP2B Superfamily	SMAD/FHA domain-like	8041255	3000137	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	SMAD/FHA domain-like	8041255	3000137	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	SMAD/FHA domain-like	8041255	3000137	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
B	MH2	e1g88B2	A: beta sandwiches	X: SMAD/FHA domain (From Topology)	H: SMAD/FHA domain (From Topology)	T: SMAD/FHA domain	F: MH2	ECOD (1.6)
C	MH2	e1g88C2	A: beta sandwiches	X: SMAD/FHA domain (From Topology)	H: SMAD/FHA domain (From Topology)	T: SMAD/FHA domain	F: MH2	ECOD (1.6)
A	MH2	e1g88A1	A: beta sandwiches	X: SMAD/FHA domain (From Topology)	H: SMAD/FHA domain (From Topology)	T: SMAD/FHA domain	F: MH2	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
B	2.60.200.10	Mainly Beta	Sandwich	Tumour Suppressor Smad4		CATH (4.3.0)
C	2.60.200.10	Mainly Beta	Sandwich	Tumour Suppressor Smad4		CATH (4.3.0)
A	2.60.200.10	Mainly Beta	Sandwich	Tumour Suppressor Smad4		CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C	PF03166	MH2 domain (MH2)	MH2 domain	-	Family

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C	SMAD4	cytoskeletal protein binding protein binding binding filamin binding sequence-specific DNA binding DNA binding organic cyclic compound binding nucleic acid binding DNA-binding transcription factor activity, RNA polymerase II-specific transcription regulator activity DNA-binding transcription factor activity DNA-binding transcription activator activity, RNA polymerase II-specific DNA-binding transcription activator activity cation binding cytoskeletal protein binding protein binding binding filamin binding sequence-specific DNA binding DNA binding organic cyclic compound binding nucleic acid binding DNA-binding transcription factor activity, RNA polymerase II-specific transcription regulator activity DNA-binding transcription factor activity DNA-binding transcription activator activity, RNA polymerase II-specific DNA-binding transcription activator activity cation binding ion binding metal ion binding small molecule binding transcription factor binding transcription coregulator binding transcription corepressor binding collagen binding protein-containing complex binding identical protein binding protein homodimerization activity protein dimerization activity transcription coactivator binding SMAD binding R-SMAD binding sequence-specific double-stranded DNA binding transcription cis-regulatory region binding double-stranded DNA binding transcription regulatory region nucleic acid binding sulfate binding anion binding sulfur compound binding I-SMAD binding RNA polymerase II-specific DNA-binding transcription factor binding DNA-binding transcription factor binding RNA polymerase II transcription regulatory region sequence-specific DNA binding cis-regulatory region sequence-specific DNA binding RNA polymerase II cis-regulatory region sequence-specific DNA binding chromatin binding	cellular response to stimulus positive regulation of cell communication cell surface receptor protein serine/threonine kinase signaling pathway regulation of cellular process positive regulation of signal transduction response to stimulus signaling regulation of transmembrane receptor protein serine/threonine kinase signaling pathway positive regulation of biological process regulation of signal transduction intracellular signal transduction cell communication positive regulation of response to stimulus regulation of intracellular signal transduction intracellular signaling cassette cellular response to stimulus positive regulation of cell communication cell surface receptor protein serine/threonine kinase signaling pathway regulation of cellular process positive regulation of signal transduction response to stimulus signaling regulation of transmembrane receptor protein serine/threonine kinase signaling pathway positive regulation of biological process regulation of signal transduction intracellular signal transduction cell communication positive regulation of response to stimulus regulation of intracellular signal transduction intracellular signaling cassette signal transduction enzyme-linked receptor protein signaling pathway positive regulation of cellular process regulation of biological process regulation of signaling cell surface receptor signaling pathway biological regulation positive regulation of intracellular signal transduction positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway SMAD protein signal transduction regulation of response to stimulus regulation of cell communication cellular process regulation of SMAD protein signal transduction positive regulation of SMAD protein signal transduction positive regulation of signaling developmental process heart development multicellular organismal process cardiac chamber morphogenesis animal organ development heart morphogenesis ventricular septum development circulatory system development multicellular organism development anatomical structure morphogenesis cardiac septum development cardiac septum morphogenesis ventricular septum morphogenesis cardiac chamber development anatomical structure development animal organ morphogenesis cardiac ventricle development system development brainstem development atrioventricular canal development negative regulation of signaling negative regulation of intracellular signal transduction negative regulation of biological process negative regulation of cell communication negative regulation of cellular process negative regulation of response to stimulus regulation of MAPK cascade negative regulation of signal transduction negative regulation of ERK1 and ERK2 cascade MAPK cascade ERK1 and ERK2 cascade regulation of ERK1 and ERK2 cascade negative regulation of MAPK cascade sexual reproduction reproductive process fertilization single fertilization positive regulation of cell population proliferation positive regulation of cell proliferation involved in heart morphogenesis heart valve development cell proliferation involved in heart valve development cell population proliferation regulation of cell proliferation involved in heart valve morphogenesis cell proliferation involved in heart valve morphogenesis cell proliferation involved in heart morphogenesis positive regulation of cell proliferation involved in heart valve morphogenesis heart valve morphogenesis regulation of cell population proliferation regulation of cell proliferation involved in heart morphogenesis positive regulation of macromolecule biosynthetic process regulation of primary metabolic process nucleobase-containing compound metabolic process DNA-templated transcription positive regulation of metabolic process regulation of RNA metabolic process regulation of miRNA metabolic process organic substance biosynthetic process positive regulation of macromolecule metabolic process regulation of nucleobase-containing compound metabolic process miRNA metabolic process positive regulation of nucleobase-containing compound metabolic process cellular metabolic process primary metabolic process regulation of cellular metabolic process positive regulation of RNA metabolic process organic cyclic compound metabolic process regulation of gene expression biosynthetic process organic cyclic compound biosynthetic process metabolic process regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of DNA-templated transcription regulation of metabolic process cellular biosynthetic process positive regulation of DNA-templated transcription RNA metabolic process positive regulation of miRNA transcription positive regulation of cellular metabolic process positive regulation of miRNA metabolic process RNA biosynthetic process nucleic acid biosynthetic process miRNA transcription organic substance metabolic process positive regulation of biosynthetic process regulation of RNA biosynthetic process regulation of biosynthetic process regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of cellular biosynthetic process positive regulation of RNA biosynthetic process ncRNA metabolic process positive regulation of cellular biosynthetic process regulation of miRNA transcription outflow tract septum morphogenesis outflow tract morphogenesis skin development gland development sebaceous gland development gonad development reproductive system development sex differentiation female gonad development female sex differentiation development of primary female sexual characteristics developmental process involved in reproduction development of primary sexual characteristics reproductive structure development female gonad morphogenesis gonad morphogenesis negative regulation of cellular metabolic process negative regulation of RNA biosynthetic process transcription by RNA polymerase II negative regulation of nucleobase-containing compound metabolic process regulation of transcription by RNA polymerase II negative regulation of DNA-templated transcription negative regulation of transcription by RNA polymerase II negative regulation of metabolic process negative regulation of cellular biosynthetic process negative regulation of macromolecule biosynthetic process negative regulation of RNA metabolic process negative regulation of macromolecule metabolic process negative regulation of biosynthetic process cellular developmental process endocardial cushion morphogenesis mesenchyme development endocardial cushion development cell differentiation cardiac epithelial to mesenchymal transition epithelial to mesenchymal transition involved in endocardial cushion formation mesenchyme morphogenesis tissue development epithelial to mesenchymal transition endocardial cushion formation tissue morphogenesis anatomical structure formation involved in morphogenesis mesenchymal cell differentiation cellular response to growth factor stimulus cellular response to transforming growth factor beta stimulus response to endogenous stimulus cellular response to endogenous stimulus response to transforming growth factor beta transforming growth factor beta receptor signaling pathway response to growth factor transforming growth factor beta receptor superfamily signaling pathway tube development male gonad development male sex differentiation development of primary male sexual characteristics seminiferous tubule development negative regulation of cardiac myofibril assembly negative regulation of muscle cell differentiation regulation of cell differentiation regulation of cardiac muscle cell differentiation muscle cell differentiation regulation of cell development muscle structure development cellular component biogenesis cellular component assembly cellular anatomical entity morphogenesis negative regulation of cardiac muscle cell differentiation actin filament-based process negative regulation of supramolecular fiber organization muscle tissue development cardiac cell development regulation of cardiac myofibril assembly negative regulation of cardiocyte differentiation negative regulation of cellular component organization actomyosin structure organization negative regulation of striated muscle cell differentiation regulation of organelle organization myofibril assembly regulation of muscle cell differentiation regulation of organelle assembly regulation of supramolecular fiber organization regulation of cardiocyte differentiation striated muscle cell differentiation supramolecular fiber organization negative regulation of multicellular organismal process regulation of cytoskeleton organization regulation of cellular component organization regulation of actin filament-based process regulation of developmental process cardiac muscle cell development cellular component assembly involved in morphogenesis non-membrane-bounded organelle assembly negative regulation of organelle assembly cell development regulation of striated muscle cell differentiation striated muscle tissue development cellular component organization striated muscle cell development muscle cell development negative regulation of cell differentiation regulation of multicellular organismal process cellular component organization or biogenesis organelle assembly actin cytoskeleton organization cardiac muscle tissue development negative regulation of cytoskeleton organization negative regulation of developmental process cardiac muscle cell differentiation regulation of cellular component biogenesis cardiocyte differentiation organelle organization negative regulation of organelle organization cardiac myofibril assembly regulation of actomyosin structure organization regulation of actin cytoskeleton organization cytoskeleton organization gastrulation with mouth forming second embryonic morphogenesis embryo development gastrulation formation of anatomical boundary regulation of epithelial to mesenchymal transition positive regulation of epithelial to mesenchymal transition positive regulation of developmental process positive regulation of cell differentiation positive regulation of multicellular organismal process response to organic substance homeostatic process response to monosaccharide response to carbohydrate carbohydrate homeostasis cellular response to hexose stimulus intracellular chemical homeostasis cellular response to monosaccharide stimulus cellular response to organic substance response to oxygen-containing compound cellular response to glucose stimulus intracellular glucose homeostasis cellular response to oxygen-containing compound response to hexose cellular response to carbohydrate stimulus cellular response to chemical stimulus cellular homeostasis chemical homeostasis response to glucose response to chemical glucose homeostasis positive regulation of cellular component organization positive regulation of cellular component biogenesis positive regulation of extracellular matrix organization extracellular matrix organization regulation of extracellular matrix assembly positive regulation of extracellular matrix assembly regulation of extracellular matrix organization extracellular matrix assembly extracellular structure organization external encapsulating structure organization ventricular cardiac muscle tissue morphogenesis left ventricular cardiac muscle tissue morphogenesis ventricular cardiac muscle tissue development muscle organ development muscle tissue morphogenesis cardiac ventricle morphogenesis cardiac muscle tissue morphogenesis cardiac left ventricle morphogenesis muscle organ morphogenesis activin receptor signaling pathway positive regulation of cardiac muscle cell apoptotic process positive regulation of programmed cell death muscle cell apoptotic process positive regulation of striated muscle cell apoptotic process regulation of apoptotic process regulation of cardiac muscle cell apoptotic process regulation of muscle cell apoptotic process regulation of programmed cell death cell death positive regulation of apoptotic process cardiac muscle cell apoptotic process positive regulation of muscle cell apoptotic process regulation of striated muscle cell apoptotic process striated muscle cell apoptotic process apoptotic process programmed cell death regulation of localization system process regulation of system process localization regulation of luteinizing hormone secretion luteinizing hormone secretion regulation of biological quality regulation of hormone levels establishment of localization positive regulation of luteinizing hormone secretion regulation of secretion endocrine hormone secretion regulation of endocrine process regulation of hormone secretion gonadotropin secretion transport positive regulation of secretion by cell hormone secretion secretion by cell positive regulation of hormone secretion regulation of secretion by cell positive regulation of secretion signal release positive regulation of gonadotropin secretion secretion regulation of transport regulation of gonadotropin secretion cell-cell signaling export from cell endocrine process positive regulation of transport hormone transport metanephric mesenchyme development renal system development kidney mesenchyme development metanephros development metanephric mesenchyme morphogenesis kidney mesenchyme morphogenesis kidney development uterus development interleukin-6-mediated signaling pathway response to interleukin-6 cellular response to interleukin-6 response to cytokine cytokine-mediated signaling pathway cellular response to cytokine stimulus follicle-stimulating hormone secretion positive regulation of follicle-stimulating hormone secretion regulation of follicle-stimulating hormone secretion adrenal gland development endocrine system development axonogenesis cell projection organization plasma membrane bounded cell projection morphogenesis neuron projection development cell morphogenesis neurogenesis cell projection morphogenesis neuron differentiation neuron projection morphogenesis plasma membrane bounded cell projection organization axon guidance nervous system development axon development cell morphogenesis involved in neuron differentiation generation of neurons neuron projection guidance neuron development endoderm development mesendoderm development mesoderm development epithelium development endothelial cell differentiation endothelium development cardiac endothelial cell differentiation endocardium development epithelial cell differentiation endocardial cell differentiation limb development appendage development embryonic limb morphogenesis embryonic appendage morphogenesis appendage morphogenesis embryonic digit morphogenesis limb morphogenesis cellular response to BMP stimulus response to BMP somitogenesis embryonic pattern specification chordate embryonic development somite rostral/caudal axis specification anterior/posterior pattern specification segmentation pattern specification process regionalization embryonic axis specification anterior/posterior axis specification embryo development ending in birth or egg hatching somite development axis specification intracellular iron ion homeostasis inorganic ion homeostasis intracellular monoatomic cation homeostasis monoatomic ion homeostasis monoatomic cation homeostasis intracellular monoatomic ion homeostasis spermatogenesis multicellular organismal reproductive process male gamete generation gamete generation neural crest cell differentiation stem cell differentiation positive regulation of gene expression regulation of canonical Wnt signaling pathway canonical Wnt signaling pathway negative regulation of Wnt signaling pathway Wnt signaling pathway regulation of Wnt signaling pathway negative regulation of canonical Wnt signaling pathway regulation of growth growth negative regulation of cell growth regulation of cell growth cell growth negative regulation of growth nephrogenic mesenchyme development nephrogenic mesenchyme morphogenesis nephron development extrinsic apoptotic signaling pathway apoptotic signaling pathway in utero embryonic development ovarian follicle development secondary palate development roof of mouth development response to decreased oxygen levels response to hypoxia response to stress response to oxygen levels response to abiotic stimulus regulation of transforming growth factor beta production regulation of transforming growth factor beta2 production cytokine production regulation of cytokine production transforming growth factor beta production transforming growth factor beta2 production catabolic process macromolecule catabolic process negative regulation of protein catabolic process protein metabolic process negative regulation of protein metabolic process organonitrogen compound catabolic process negative regulation of catabolic process organonitrogen compound metabolic process regulation of protein metabolic process protein catabolic process regulation of catabolic process organic substance catabolic process regulation of protein catabolic process muscle hypertrophy regulation of muscle adaptation negative regulation of muscle hypertrophy striated muscle hypertrophy regulation of muscle system process muscle system process regulation of muscle hypertrophy regulation of cardiac muscle hypertrophy muscle adaptation cardiac muscle hypertrophy negative regulation of cardiac muscle hypertrophy regulation of multicellular organismal development epidermis development molting cycle process hair cycle regulation of hair cycle skin epidermis development hair follicle development molting cycle regulation of hair follicle development hair cycle process mesonephric epithelium development kidney epithelium development nephron morphogenesis branching morphogenesis of an epithelial tube nephron tubule morphogenesis nephron epithelium morphogenesis nephron tubule development ureteric bud morphogenesis tube morphogenesis branching involved in ureteric bud morphogenesis renal tubule development epithelial tube morphogenesis nephron epithelium development ureteric bud development mesonephros development morphogenesis of an epithelium kidney morphogenesis morphogenesis of a branching structure mesonephric tubule morphogenesis mesonephric tubule development renal tubule morphogenesis morphogenesis of a branching epithelium positive regulation of transcription by RNA polymerase II neuron fate commitment cell fate specification neuron fate specification cell fate commitment ossification osteoblast differentiation BMP signaling pathway epithelium migration tissue migration ameboidal-type cell migration epithelial cell migration cell migration cell motility regulation of transforming growth factor beta receptor signaling pathway regulation of cellular response to transforming growth factor beta stimulus regulation of cellular response to growth factor stimulus positive regulation of transforming growth factor beta receptor signaling pathway positive regulation of cellular response to transforming growth factor beta stimulus developmental growth cardiac conduction system development negative regulation of cell population proliferation atrioventricular valve development atrioventricular valve formation heart valve formation atrioventricular valve morphogenesis striated muscle adaptation cardiac muscle adaptation cardiac muscle hypertrophy in response to stress muscle hypertrophy in response to stress endothelial cell activation cell activation	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol RNA polymerase II transcription regulator complex membrane-bounded organelle protein-containing complex nucleus nuclear protein-containing complex transcription regulator complex intracellular membrane-bounded organelle activin responsive factor complex intracellular organelle organelle intracellular anatomical structure cytoplasm cellular anatomical entity cytosol RNA polymerase II transcription regulator complex membrane-bounded organelle protein-containing complex nucleus nuclear protein-containing complex transcription regulator complex intracellular membrane-bounded organelle activin responsive factor complex intracellular organelle organelle SMAD protein complex protein-DNA complex intracellular non-membrane-bounded organelle chromatin chromosome non-membrane-bounded organelle heteromeric SMAD protein complex centrosome microtubule organizing center cytoskeleton microtubule cytoskeleton membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C	IPR013019	MAD homology, MH1	Domain
A, B, C	IPR013790	Dwarfin	Family
A, B, C	IPR003619	MAD homology 1, Dwarfin-type	Domain
A, B, C	IPR008984	SMAD/FHA domain superfamily	Homologous Superfamily
A, B, C	IPR036578	SMAD MH1 domain superfamily	Homologous Superfamily
A, B, C	IPR017855	SMAD-like domain superfamily	Homologous Superfamily
A, B, C	IPR001132	SMAD domain, Dwarfin-type	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C	Pharos: Q13485	hereditary hemorrhagic telangiectasia myopathy cholangiocarcinoma juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Myhre syndrome esophageal adenocarcinoma familial pancreatic carcinoma colorectal cancer generalized juvenile polyposis/juvenile polyposis coli brachydactyly juvenile polyposis syndrome Craniofacial Abnormalities exocrine pancreatic carcinoma gastric cancer intrahepatic cholangiocarcinoma hereditary hemorrhagic telangiectasia myopathy cholangiocarcinoma juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Myhre syndrome esophageal adenocarcinoma familial pancreatic carcinoma colorectal cancer generalized juvenile polyposis/juvenile polyposis coli brachydactyly juvenile polyposis syndrome Craniofacial Abnormalities exocrine pancreatic carcinoma gastric cancer intrahepatic cholangiocarcinoma cancer invasive ductal breast carcinoma malignant pancreatic neoplasm muscle tissue disease ovarian cancer pulmonary arterial hypertension allergic rhinitis hereditary diffuse gastric adenocarcinoma subependymal giant cell astrocytoma benign neoplasm of pancreas intellectual disability breast disease digestive system disease muscular disease oligodendroglioma pancreatic neoplasm arthrogryposis thoracic aortic aneurysm large cell medulloblastoma colorectal carcinoma malignant ependymoma medulloblastoma Ehlers-Danlos syndrome osteosarcoma gastric neoplasm small intestine neoplasm atrial fibrillation idiopathic pulmonary arterial hypertension bile duct cancer breast cancer cerebrovascular disorder colorectal adenocarcinoma malignant glioma

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.