Annotations: 1MHD

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
C [auth A]	d1mhda_	Alpha and beta proteins (a+b)	SMAD MH1 domain	SMAD MH1 domain	SMAD MH1 domain	SMAD MH1 domain	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D [auth B]	d1mhdb_	Alpha and beta proteins (a+b)	SMAD MH1 domain	SMAD MH1 domain	SMAD MH1 domain	SMAD MH1 domain	human (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)
C [auth A]	SCOP2B Superfamily	SMAD MH1 domain	8038018	3001158	SCOP2B (2022-06-29)
D [auth B]	SCOP2B Superfamily	SMAD MH1 domain	8038018	3001158	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)
C [auth A]	MH1	e1mhdA1	A: few secondary structure elements	X: His-Me finger endonucleases (From Homology)	H: His-Me finger endonucleases	T: His-Me finger endonucleases	F: MH1	ECOD (1.6)
D [auth B]	MH1	e1mhdB1	A: few secondary structure elements	X: His-Me finger endonucleases (From Homology)	H: His-Me finger endonucleases	T: His-Me finger endonucleases	F: MH1	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
C [auth A]	3.90.520.10	Alpha Beta	Alpha-Beta Complex	Smad3	Chain A	CATH (4.3.0)
D [auth B]	3.90.520.10	Alpha Beta	Alpha-Beta Complex	Smad3	Chain A	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
C [auth A], D [auth B]	PF03165	MH1 domain (MH1)	MH1 domain	The MH1 (MAD homology 1) domain is found at the amino terminus of MAD related proteins such as Smads. This domain is separated from the MH2 domain by a non-conserved linker region. The crystal structure of the MH1 domain shows that a highly conserved ...	The MH1 (MAD homology 1) domain is found at the amino terminus of MAD related proteins such as Smads. This domain is separated from the MH2 domain by a non-conserved linker region. The crystal structure of the MH1 domain shows that a highly conserved 11 residue beta hairpin is used to bind the DNA consensus sequence GNCN in the major groove, shown to be vital for the transcriptional activation of target genes. Not all examples of MH1 can bind to DNA however. Smad2 cannot bind DNA and has a large insertion within the hairpin that presumably abolishes DNA binding. A basic helix (H2) in MH1 with the nuclear localisation signal KKLKK has been shown to be essential for Smad3 nuclear import. Smads also use the MH1 domain to interact with transcription factors such as Jun, TFE3, Sp1, and Runx [1,3].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A [auth C]	DNA	-	-	-
B [auth D]	DNA	-	-	-
C [auth A], D [auth B]	SMAD3	sequence-specific DNA binding DNA binding binding nucleic acid binding chromatin binding promoter-specific chromatin binding ubiquitin protein ligase binding protein binding ubiquitin-like protein ligase binding enzyme 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 sequence-specific DNA binding DNA binding binding nucleic acid binding chromatin binding promoter-specific chromatin binding ubiquitin protein ligase binding protein binding ubiquitin-like protein ligase binding enzyme 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 transcription factor binding transcription coregulator binding transcription corepressor binding ubiquitin binding ubiquitin-like protein binding collagen binding protein-containing complex binding identical protein binding protein homodimerization activity protein dimerization activity kinase binding protein kinase binding transcription coactivator binding chromatin DNA binding DNA-binding transcription factor binding RNA polymerase II-specific DNA-binding transcription factor binding nuclear receptor binding beta-catenin binding nuclear glucocorticoid receptor 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 co-SMAD binding DNA-binding transcription repressor activity transforming growth factor beta receptor binding signaling receptor binding cytokine receptor binding nuclear mineralocorticoid receptor binding cis-regulatory region sequence-specific DNA binding I-SMAD binding DEAD/H-box RNA helicase binding phosphatase binding bHLH transcription factor binding RNA polymerase II transcription regulatory region sequence-specific DNA binding RNA polymerase II cis-regulatory region sequence-specific DNA binding sterol response element binding cation binding transition metal ion binding zinc ion binding ion binding metal ion binding small molecule binding	regulation of biosynthetic process regulation of nitric oxide biosynthetic process regulation of biological process regulation of cellular process biological regulation positive regulation of biological process reactive nitrogen species metabolic process positive regulation of nitric oxide metabolic process nitric oxide metabolic process positive regulation of metabolic process nitric oxide biosynthetic process biosynthetic process positive regulation of biosynthetic process cellular process regulation of biosynthetic process regulation of nitric oxide biosynthetic process regulation of biological process regulation of cellular process biological regulation positive regulation of biological process reactive nitrogen species metabolic process positive regulation of nitric oxide metabolic process nitric oxide metabolic process positive regulation of metabolic process nitric oxide biosynthetic process biosynthetic process positive regulation of biosynthetic process cellular process metabolic process regulation of nitric oxide metabolic process positive regulation of nitric oxide biosynthetic process regulation of metabolic process positive regulation of cellular process cellular response to stimulus positive regulation of cell communication cell surface receptor protein serine/threonine kinase signaling pathway positive regulation of signal transduction response to stimulus signaling regulation of transmembrane receptor protein serine/threonine kinase signaling pathway 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 regulation of signaling cell surface receptor signaling pathway 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 regulation of SMAD protein signal transduction positive regulation of SMAD protein signal transduction positive regulation of signaling regulation of protein stability regulation of biological quality protein stabilization developmental process multicellular organismal process digestive system development foregut morphogenesis tube development embryonic morphogenesis embryo development digestive tract development multicellular organism development anatomical structure morphogenesis tube morphogenesis embryonic foregut morphogenesis digestive tract morphogenesis anatomical structure development system development mesoderm morphogenesis mesenchyme morphogenesis animal organ development mesenchyme development tissue development tissue morphogenesis paraxial mesoderm development animal organ morphogenesis paraxial mesoderm morphogenesis mesoderm development positive regulation of DNA-binding transcription factor activity RNA metabolic process regulation of primary metabolic process nucleobase-containing compound metabolic process RNA biosynthetic process positive regulation of molecular function nucleic acid biosynthetic process DNA-templated transcription regulation of RNA metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process primary metabolic process regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of molecular function regulation of gene expression regulation of DNA-binding transcription factor activity regulation of macromolecule biosynthetic process regulation of DNA-templated transcription macromolecule metabolic process immune response immune system process regulation of immune response regulation of immune system process wound healing regulation of response to external stimulus negative regulation of response to stimulus negative regulation of wound healing negative regulation of biological process response to external stimulus negative regulation of response to wounding regulation of response to wounding response to stress regulation of response to stress negative regulation of response to external stimulus regulation of wound healing response to wounding regulation of developmental process regulation of biomineral tissue development regulation of bone mineralization positive regulation of ossification positive regulation of developmental process positive regulation of biomineral tissue development ossification biomineral tissue development regulation of multicellular organismal process regulation of multicellular organismal development bone mineralization positive regulation of bone mineralization positive regulation of multicellular organismal process regulation of ossification regulation of cellular component organization positive regulation of cellular component organization cell-substrate junction assembly positive regulation of cell-substrate junction organization cellular component organization cellular component biogenesis cell adhesion cellular component assembly cell junction assembly positive regulation of cell-substrate adhesion regulation of cell-substrate junction organization cellular component organization or biogenesis focal adhesion assembly positive regulation of focal adhesion assembly positive regulation of cellular component biogenesis regulation of cell-substrate adhesion positive regulation of cell adhesion regulation of cell adhesion cell-substrate adhesion positive regulation of cell-matrix adhesion regulation of cellular component biogenesis regulation of cell junction assembly positive regulation of cell junction assembly cell junction organization cell-matrix adhesion regulation of cell-matrix adhesion cell-substrate junction organization regulation of focal adhesion assembly regulation of cell-substrate junction assembly positive regulation of DNA-templated transcription positive regulation of miRNA transcription positive regulation of miRNA metabolic process positive regulation of macromolecule biosynthetic process miRNA transcription regulation of miRNA metabolic process positive regulation of macromolecule metabolic process miRNA metabolic process positive regulation of nucleobase-containing compound metabolic process positive regulation of RNA metabolic process positive regulation of RNA biosynthetic process regulation of miRNA transcription JNK cascade MAPK cascade signal transduction involved in regulation of gene expression negative regulation of cytosolic calcium ion concentration negative regulation of RNA biosynthetic process transcription by RNA polymerase II negative regulation of cellular process negative regulation of nucleobase-containing compound metabolic process negative regulation of macromolecule 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 biosynthetic process negative regulation of macromolecule biosynthetic process negative regulation of RNA metabolic process 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 fat cell differentiation cellular developmental process negative regulation of developmental process regulation of cell differentiation negative regulation of fat cell differentiation cell differentiation negative regulation of cell differentiation regulation of fat cell differentiation heart development epithelium development circulatory system development pericardium development thyroid gland development endocrine system development gland development somitogenesis chordate embryonic development segmentation anterior/posterior pattern specification pattern specification process regionalization embryo development ending in birth or egg hatching somite development anatomical structure formation involved in morphogenesis negative regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death cell death negative regulation of apoptotic process apoptotic process programmed cell death regulation of epithelial to mesenchymal transition positive regulation of epithelial to mesenchymal transition positive regulation of cell differentiation epithelial to mesenchymal transition mesenchymal cell differentiation homeostatic process 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 response to monosaccharide response to carbohydrate chemical homeostasis response to glucose response to chemical glucose homeostasis carbohydrate homeostasis cellular response to hexose stimulus intracellular chemical homeostasis cellular response to monosaccharide stimulus 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 regulation of defense response negative regulation of inflammatory response defense response regulation of inflammatory response negative regulation of defense response inflammatory response activin receptor signaling pathway negative regulation of miRNA transcription negative regulation of miRNA metabolic process adrenal gland development positive regulation of locomotion regulation of cell motility positive regulation of cell migration regulation of locomotion positive regulation of cell motility regulation of cell migration cell migration cell motility locomotion apoptotic signaling pathway regulation of canonical Wnt signaling pathway canonical Wnt signaling pathway positive regulation of Wnt signaling pathway Wnt signaling pathway positive regulation of canonical Wnt signaling pathway regulation of Wnt signaling pathway negative regulation of gene expression embryonic pattern specification negative regulation of multicellular organismal process negative regulation of ossification positive regulation of organelle organization regulation of cytoskeleton organization regulation of actin filament-based process regulation of actin filament bundle assembly positive regulation of actin filament bundle assembly actin filament bundle organization positive regulation of stress fiber assembly actin filament-based process stress fiber assembly regulation of actin filament organization actin cytoskeleton organization actomyosin structure organization positive regulation of cytoskeleton organization actin filament organization positive regulation of supramolecular fiber organization regulation of organelle organization regulation of stress fiber assembly organelle organization contractile actin filament bundle assembly regulation of actomyosin structure organization regulation of actin cytoskeleton organization actin filament bundle assembly regulation of supramolecular fiber organization supramolecular fiber organization cytoskeleton organization sensory organ development eye development visual system development epithelial cell differentiation camera-type eye development lens fiber cell differentiation sensory system development lens development in camera-type eye positive regulation of gene expression cell population proliferation response to angiotensin response to hormone response to peptide hormone response to nitrogen compound regulation of growth growth negative regulation of cell growth regulation of cell growth cell growth negative regulation of growth extrinsic apoptotic signaling pathway protein localization regulation of localization cellular localization establishment of protein localization nitrogen compound transport regulation of protein localization nucleocytoplasmic transport transport positive regulation of nucleocytoplasmic transport nuclear transport positive regulation of establishment of protein localization regulation of protein localization to nucleus positive regulation of protein transport localization import into nucleus regulation of protein import into nucleus cellular macromolecule localization establishment of localization in cell protein import into nucleus positive regulation of intracellular transport regulation of intracellular transport regulation of transport positive regulation of protein localization to nucleus regulation of establishment of protein localization positive regulation of protein import into nucleus intracellular transport regulation of nucleocytoplasmic transport protein localization to nucleus regulation of protein transport establishment of localization establishment of protein localization to organelle positive regulation of transport regulation of cellular localization protein transport macromolecule localization protein localization to organelle positive regulation of protein localization regulation of intracellular protein transport positive regulation of intracellular protein transport intracellular protein transport in utero embryonic development interleukin-1 production regulation of interleukin-1 beta production positive regulation of interleukin-1 beta production regulation of cytokine production cytokine production positive regulation of interleukin-1 production regulation of interleukin-1 production interleukin-1 beta production positive regulation of cytokine production negative regulation of cell population proliferation osteoblast proliferation regulation of cell population proliferation negative regulation of osteoblast proliferation regulation of osteoblast proliferation response to decreased oxygen levels response to hypoxia response to oxygen levels response to abiotic stimulus regulation of transforming growth factor beta production regulation of transforming growth factor beta2 production transforming growth factor beta2 production transforming growth factor beta production catabolic process macromolecule catabolic process negative regulation of protein catabolic process protein metabolic process negative regulation of protein metabolic process negative regulation of catabolic process regulation of protein metabolic process protein catabolic process regulation of catabolic process regulation of protein catabolic process positive regulation of transcription by RNA polymerase II heart morphogenesis embryonic heart tube development embryonic heart tube morphogenesis heart looping determination of bilateral symmetry epithelial tube morphogenesis embryonic organ development determination of left/right symmetry specification of symmetry embryonic organ morphogenesis morphogenesis of an epithelium determination of heart left/right asymmetry left/right pattern formation formation of primary germ layer gastrulation mesoderm formation hepaticobiliary system development liver development immune system development nodal signaling pathway regulation of muscle tissue development regulation of striated muscle tissue development striated muscle tissue development muscle structure development regulation of muscle organ development muscle tissue development muscle organ development 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 regulation of osteoblast differentiation negative regulation of osteoblast differentiation osteoblast differentiation positive regulation of transforming growth factor beta3 production regulation of transforming growth factor beta3 production transforming growth factor beta3 production positive regulation of transforming growth factor beta production embryonic cranial skeleton morphogenesis skeletal system development cranial skeletal system development embryonic skeletal system development skeletal system morphogenesis embryonic skeletal system morphogenesis endoderm development regulation of cartilage development regulation of chondrocyte differentiation connective tissue development positive regulation of chondrocyte differentiation chondrocyte differentiation positive regulation of cartilage development cartilage development developmental growth system process negative regulation of lung blood pressure circulatory system process regulation of blood pressure regulation of lung blood pressure blood circulation osteoblast development cell development T cell activation cell activation lymphocyte activation leukocyte activation positive chemotaxis chemotaxis positive regulation of positive chemotaxis regulation of chemotaxis positive regulation of chemotaxis regulation of positive chemotaxis positive regulation of response to external stimulus taxis ureteric bud development mesonephric epithelium development kidney epithelium development mesonephros development renal system development kidney development mesonephric tubule development regulation of epithelial cell proliferation epithelial cell proliferation RNA processing regulatory ncRNA processing regulatory ncRNA-mediated gene silencing primary miRNA processing miRNA processing transdifferentiation negative regulation of muscle adaptation striated muscle adaptation negative regulation of muscle hypertrophy regulation of system process regulation of muscle hypertrophy regulation of cardiac muscle hypertrophy in response to stress muscle adaptation cardiac muscle adaptation cardiac muscle hypertrophy cardiac muscle hypertrophy in response to stress muscle hypertrophy regulation of muscle adaptation negative regulation of cardiac muscle hypertrophy in response to stress striated muscle hypertrophy regulation of muscle system process muscle system process regulation of cardiac muscle hypertrophy negative regulation of cardiac muscle adaptation regulation of cardiac muscle adaptation negative regulation of cardiac muscle hypertrophy muscle hypertrophy in response to stress cell-cell junction organization cellular response to virus biological process involved in interspecies interaction between organisms response to other organism response to external biotic stimulus response to virus response to biotic stimulus	cellular anatomical structure intracellular anatomical structure cytoplasm cytosol protein-containing complex receptor complex SMAD protein complex cell periphery plasma membrane membrane transcription regulator complex intracellular organelle organelle membraneless organelle cellular anatomical structure intracellular anatomical structure cytoplasm cytosol protein-containing complex receptor complex SMAD protein complex cell periphery plasma membrane membrane transcription regulator complex intracellular organelle organelle membraneless organelle intracellular membraneless organelle chromatin chromosome RNA polymerase II transcription regulator complex membrane-bounded organelle nucleus heteromeric SMAD protein complex nuclear protein-containing complex intracellular membrane-bounded organelle organelle inner membrane nuclear membrane endomembrane system organelle envelope nuclear inner membrane nuclear envelope organelle membrane membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen

InterPro: Protein Family Classification InterPro Database Homepage

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

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
C [auth A], D [auth B]	Pharos: P84022	Loeys-Dietz syndrome Crohn disease aortic aneurysm colorectal cancer Aneurysm, Dissecting osteoarthritis thoracic aortic aneurysm aneurysm-osteoarthritis syndrome alcoholic liver cirrhosis uterine cancer juvenile idiopathic arthritis cocaine abuse uterine corpus leiomyoma cocaine dependence cirrhosis of liver Loeys-Dietz syndrome Crohn disease aortic aneurysm colorectal cancer Aneurysm, Dissecting osteoarthritis thoracic aortic aneurysm aneurysm-osteoarthritis syndrome alcoholic liver cirrhosis uterine cancer juvenile idiopathic arthritis cocaine abuse uterine corpus leiomyoma cocaine dependence cirrhosis of liver leiomyoma osteoarthritis susceptibility 1 osteosarcoma pancreatic intraductal papillary-mucinous neoplasm psoriasis ileocolitis thyroid gland carcinoma interstitial cystitis asthma cancer kidney disease colorectal adenoma malignant mesothelioma myocardial infarction Crohn's colitis osteoarthritis, hip dermatomyositis ovarian cancer Ehlers-Danlos syndrome pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia glioblastoma allergic rhinitis inflammatory bowel disease tuberculosis interstitial lung disease atypical teratoid rhabdoid tumor cerebrovascular disorder Marfan syndrome pancreatic ductal adenocarcinoma familial thoracic aortic aneurysm and aortic dissection pilocytic astrocytoma heart disease intellectual disability ureteral obstruction arthrogryposis B-cell chronic lymphocytic leukemia lymphoplasmacytic lymphoma common variable immunodeficiency medulloblastoma

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), 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 R01GM157729.