MultifacetedProtDB - Bologna Biocomputing Group

Structure

PDB	Resolution (Å)	PDB name
1MHD	2.8	CRYSTAL STRUCTURE OF A SMAD MH1 DOMAIN BOUND TO DNA
1MJS	1.91	MH2 domain of transcriptional factor SMAD3
1MK2	2.74	SMAD3 SBD complex
1OZJ	2.4	Crystal structure of Smad3-MH1 bound to DNA at 2.4 A resolution
1U7F	2.6	Crystal Structure of the phosphorylated Smad3/Smad4 heterotrimeric complex
2LAJ		Third WW domain of human Nedd4L in complex with doubly phosphorylated human smad3 derived peptide
2LB2		Structure of the second domain of human Nedd4L in complex with a phosphorylated pTPY motif derived from human Smad3
5OD6	2.0	Crystal structure of Smad3-MH1 bound to the GGCGC site.
5ODG	2.12	Crystal structure of Smad3-MH1 bound to the GGCT site.
5XOC	2.4	Crystal structure of human Smad3-FoxH1 complex
6YIB	1.7	14-3-3 sigma in complex with SMAD3 pS423 peptide
6ZMN	2.333	Crystal structure of the Smad3-Smad5 MH1 domain chimera bound to the GGCGC site

GO term

GO ontology	GO term	GO description
Biological Process	GO:0007254	JNK cascade
Biological Process	GO:0007183	SMAD protein complex assembly
Biological Process	GO:0060395	SMAD protein signal transduction
Biological Process	GO:0042110	T cell activation
Biological Process	GO:0006919	activation of cysteine-type endopeptidase activity involved in apoptotic process
Biological Process	GO:0097296	activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
Biological Process	GO:0032924	activin receptor signaling pathway
Biological Process	GO:0030325	adrenal gland development
Biological Process	GO:0009653	anatomical structure morphogenesis
Biological Process	GO:0030154	cell differentiation
Biological Process	GO:0045216	cell-cell junction organization
Biological Process	GO:0071560	cellular response to transforming growth factor beta stimulus
Biological Process	GO:0098586	cellular response to virus
Biological Process	GO:0048589	developmental growth
Biological Process	GO:0048701	embryonic cranial skeleton morphogenesis
Biological Process	GO:0048617	embryonic foregut morphogenesis
Biological Process	GO:0009880	embryonic pattern specification
Biological Process	GO:0007492	endoderm development
Biological Process	GO:0097191	extrinsic apoptotic signaling pathway
Biological Process	GO:0001947	heart looping
Biological Process	GO:0006955	immune response
Biological Process	GO:0002520	immune system development
Biological Process	GO:0001701	in utero embryonic development
Biological Process	GO:0070306	lens fiber cell differentiation
Biological Process	GO:0001889	liver development
Biological Process	GO:0001707	mesoderm formation
Biological Process	GO:0043066	negative regulation of apoptotic process
Biological Process	GO:1903243	negative regulation of cardiac muscle hypertrophy in response to stress
Biological Process	GO:0030308	negative regulation of cell growth
Biological Process	GO:0008285	negative regulation of cell population proliferation
Biological Process	GO:0051481	negative regulation of cytosolic calcium ion concentration
Biological Process	GO:0045599	negative regulation of fat cell differentiation
Biological Process	GO:0010629	negative regulation of gene expression
Biological Process	GO:0050728	negative regulation of inflammatory response
Biological Process	GO:0061767	negative regulation of lung blood pressure
Biological Process	GO:0045668	negative regulation of osteoblast differentiation
Biological Process	GO:0033689	negative regulation of osteoblast proliferation
Biological Process	GO:0042177	negative regulation of protein catabolic process
Biological Process	GO:0000122	negative regulation of transcription by RNA polymerase II
Biological Process	GO:0061045	negative regulation of wound healing
Biological Process	GO:0038092	nodal signaling pathway
Biological Process	GO:0002076	osteoblast development
Biological Process	GO:0048340	paraxial mesoderm morphogenesis
Biological Process	GO:0060039	pericardium development
Biological Process	GO:0051091	positive regulation of DNA-binding transcription factor activity
Biological Process	GO:0045893	positive regulation of DNA-templated transcription
Biological Process	GO:0010694	positive regulation of alkaline phosphatase activity
Biological Process	GO:0030501	positive regulation of bone mineralization
Biological Process	GO:0090263	positive regulation of canonical Wnt signaling pathway
Biological Process	GO:0030335	positive regulation of cell migration
Biological Process	GO:0032332	positive regulation of chondrocyte differentiation
Biological Process	GO:0010718	positive regulation of epithelial to mesenchymal transition
Biological Process	GO:1901203	positive regulation of extracellular matrix assembly
Biological Process	GO:0051894	positive regulation of focal adhesion assembly
Biological Process	GO:0010628	positive regulation of gene expression
Biological Process	GO:0032731	positive regulation of interleukin-1 beta production
Biological Process	GO:1902895	positive regulation of miRNA transcription
Biological Process	GO:0045429	positive regulation of nitric oxide biosynthetic process
Biological Process	GO:0050927	positive regulation of positive chemotaxis
Biological Process	GO:0042307	positive regulation of protein import into nucleus
Biological Process	GO:0051496	positive regulation of stress fiber assembly
Biological Process	GO:0045944	positive regulation of transcription by RNA polymerase II
Biological Process	GO:0032916	positive regulation of transforming growth factor beta3 production
Biological Process	GO:0031053	primary miRNA processing
Biological Process	GO:0050821	protein stabilization
Biological Process	GO:0006355	regulation of DNA-templated transcription
Biological Process	GO:0051098	regulation of binding
Biological Process	GO:0050678	regulation of epithelial cell proliferation
Biological Process	GO:0050776	regulation of immune response
Biological Process	GO:1902893	regulation of miRNA transcription
Biological Process	GO:0016202	regulation of striated muscle tissue development
Biological Process	GO:0006357	regulation of transcription by RNA polymerase II
Biological Process	GO:0017015	regulation of transforming growth factor beta receptor signaling pathway
Biological Process	GO:0032909	regulation of transforming growth factor beta2 production
Biological Process	GO:0001666	response to hypoxia
Biological Process	GO:0023019	signal transduction involved in regulation of gene expression
Biological Process	GO:0001756	somitogenesis
Biological Process	GO:0030878	thyroid gland development
Biological Process	GO:0060290	transdifferentiation
Biological Process	GO:0007179	transforming growth factor beta receptor signaling pathway
Biological Process	GO:0001657	ureteric bud development
Biological Process	GO:0042060	wound healing
Molecular Function	GO:0017151	DEAD/H-box RNA helicase binding
Molecular Function	GO:0003677	DNA binding
Molecular Function	GO:0001228	DNA-binding transcription activator activity, RNA polymerase II-specific
Molecular Function	GO:0003700	DNA-binding transcription factor activity
Molecular Function	GO:0000981	DNA-binding transcription factor activity, RNA polymerase II-specific
Molecular Function	GO:0140297	DNA-binding transcription factor binding
Molecular Function	GO:0001217	DNA-binding transcription repressor activity
Molecular Function	GO:0070411	I-SMAD binding
Molecular Function	GO:0070412	R-SMAD binding
Molecular Function	GO:0000978	RNA polymerase II cis-regulatory region sequence-specific DNA binding
Molecular Function	GO:0061629	RNA polymerase II-specific DNA-binding transcription factor binding
Molecular Function	GO:0043425	bHLH transcription factor binding
Molecular Function	GO:0008013	beta-catenin binding
Molecular Function	GO:0031490	chromatin DNA binding
Molecular Function	GO:0000987	cis-regulatory region sequence-specific DNA binding
Molecular Function	GO:0070410	co-SMAD binding
Molecular Function	GO:0005518	collagen binding
Molecular Function	GO:0042802	identical protein binding
Molecular Function	GO:0035259	nuclear glucocorticoid receptor binding
Molecular Function	GO:0031962	nuclear mineralocorticoid receptor binding
Molecular Function	GO:0016922	nuclear receptor binding
Molecular Function	GO:0019902	phosphatase binding
Molecular Function	GO:1990841	promoter-specific chromatin binding
Molecular Function	GO:0042803	protein homodimerization activity
Molecular Function	GO:0019901	protein kinase binding
Molecular Function	GO:0043565	sequence-specific DNA binding
Molecular Function	GO:0032810	sterol response element binding
Molecular Function	GO:0000976	transcription cis-regulatory region binding
Molecular Function	GO:0001223	transcription coactivator binding
Molecular Function	GO:0005160	transforming growth factor beta receptor binding
Molecular Function	GO:0043130	ubiquitin binding
Molecular Function	GO:0031625	ubiquitin protein ligase binding
Molecular Function	GO:0008270	zinc ion binding
Cellular Component	GO:0071141	SMAD protein complex
Cellular Component	GO:0000785	chromatin
Cellular Component	GO:0005737	cytoplasm
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0071144	heteromeric SMAD protein complex
Cellular Component	GO:0005637	nuclear inner membrane
Cellular Component	GO:0005654	nucleoplasm
Cellular Component	GO:0005634	nucleus
Cellular Component	GO:0005886	plasma membrane
Cellular Component	GO:0043235	receptor complex
Cellular Component	GO:0005667	transcription regulator complex

InterPro / Pfam

InterPro	InterPro name
IPR001132	SMAD domain, Dwarfin-type
IPR003619	MAD homology 1, Dwarfin-type
IPR008984	SMAD/FHA domain superfamily
IPR013019	MAD homology, MH1
IPR013790	Dwarfin
IPR017855	SMAD-like domain superfamily
IPR036578	SMAD MH1 domain superfamily

Pfam	Pfam name
PF03165	MH1 domain
PF03166	MH2 domain

Reactome

Reactome	Reactome Name	Node type	Reactome Root	Reactome Root Name
R-HSA-1181150	Signaling by NODAL	Internal node	R-HSA-1266738	Developmental Biology
R-HSA-1502540	Signaling by Activin	Internal node	R-HSA-162582	Signal Transduction
R-HSA-2173788	Downregulation of TGF-beta receptor signaling	Leaf	R-HSA-162582	Signal Transduction
R-HSA-2173789	TGF-beta receptor signaling activates SMADs	Internal node	R-HSA-162582	Signal Transduction
R-HSA-2173795	Downregulation of SMAD2/3:SMAD4 transcriptional activity	Leaf	R-HSA-74160	Gene expression (Transcription)
R-HSA-2173796	SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription	Leaf	R-HSA-74160	Gene expression (Transcription)
R-HSA-3304356	SMAD2/3 Phosphorylation Motif Mutants in Cancer	Leaf	R-HSA-1643685	Disease
R-HSA-3311021	SMAD4 MH2 Domain Mutants in Cancer	Leaf	R-HSA-1643685	Disease
R-HSA-3315487	SMAD2/3 MH2 Domain Mutants in Cancer	Leaf	R-HSA-1643685	Disease
R-HSA-3656532	TGFBR1 KD Mutants in Cancer	Leaf	R-HSA-1643685	Disease
R-HSA-5689880	Ub-specific processing proteases	Leaf	R-HSA-392499	Metabolism of proteins
R-HSA-8941855	RUNX3 regulates CDKN1A transcription	Leaf	R-HSA-74160	Gene expression (Transcription)
R-HSA-8952158	RUNX3 regulates BCL2L11 (BIM) transcription	Leaf	R-HSA-74160	Gene expression (Transcription)
R-HSA-9008059	Interleukin-37 signaling	Leaf	R-HSA-168256	Immune System
R-HSA-9013695	NOTCH4 Intracellular Domain Regulates Transcription	Leaf	R-HSA-162582	Signal Transduction
R-HSA-9615017	FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes	Leaf	R-HSA-74160	Gene expression (Transcription)
R-HSA-9617828	FOXO-mediated transcription of cell cycle genes	Leaf	R-HSA-74160	Gene expression (Transcription)
R-HSA-9735871	SARS-CoV-1 targets host intracellular signalling and regulatory pathways	Leaf	R-HSA-1643685	Disease
R-HSA-9754189	Germ layer formation at gastrulation	Leaf	R-HSA-1266738	Developmental Biology
R-HSA-9796292	Formation of axial mesoderm	Leaf	R-HSA-1266738	Developmental Biology

Subcellular location

Location	ECO term	Pubmed
Cytoplasm	ECO:0000269	PubMed:15799969
Cytoplasm	ECO:0000269	PubMed:16156666
Cytoplasm	ECO:0000269	PubMed:16751101
Cytoplasm	ECO:0000269	PubMed:17327236
Cytoplasm	ECO:0000269	PubMed:19218245
Cytoplasm	ECO:0000269	PubMed:19289081
Cytoplasm	ECO:0000269	PubMed:21145499
Cytoplasm	ECO:0000269	PubMed:22781750
Nucleus	ECO:0000269	PubMed:15601644
Nucleus	ECO:0000269	PubMed:15799969
Nucleus	ECO:0000269	PubMed:16156666
Nucleus	ECO:0000269	PubMed:16751101
Nucleus	ECO:0000269	PubMed:19218245
Nucleus	ECO:0000269	PubMed:19289081
Nucleus	ECO:0000269	PubMed:21145499
Nucleus	ECO:0000269	PubMed:22781750

Interactor | Variant | Drug

Phenotype

HPO ID	HPO name
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000098	Tall stature
HP:0000139	Uterine prolapse
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000218	High palate
HP:0000268	Dolichocephaly
HP:0000272	Malar flattening
HP:0000276	Long face
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000348	High forehead
HP:0000518	Cataract
HP:0000520	Proptosis
HP:0000525	Abnormality iris morphology
HP:0000577	Exotropia
HP:0000689	Dental malocclusion
HP:0000766	Abnormal sternum morphology
HP:0000767	Pectus excavatum
HP:0000768	Pectus carinatum
HP:0000822	Hypertension
HP:0000939	Osteoporosis
HP:0000965	Cutis marmorata
HP:0000977	Soft skin
HP:0000978	Bruising susceptibility
HP:0000987	Atypical scarring of skin
HP:0001065	Striae distensae
HP:0001075	Atrophic scars
HP:0001083	Ectopia lentis
HP:0001166	Arachnodactyly
HP:0001297	Stroke
HP:0001363	Craniosynostosis
HP:0001388	Joint laxity
HP:0001519	Disproportionate tall stature
HP:0001537	Umbilical hernia
HP:0001627	Abnormal heart morphology
HP:0001631	Atrial septal defect
HP:0001634	Mitral valve prolapse
HP:0001640	Cardiomegaly
HP:0001642	Pulmonic stenosis
HP:0001643	Patent ductus arteriosus
HP:0001647	Bicuspid aortic valve
HP:0001653	Mitral regurgitation
HP:0001659	Aortic regurgitation
HP:0001677	Coronary artery atherosclerosis
HP:0001699	Sudden death
HP:0001712	Left ventricular hypertrophy
HP:0001714	Ventricular hypertrophy
HP:0001762	Talipes equinovarus
HP:0001763	Pes planus
HP:0002076	Migraine
HP:0002105	Hemoptysis
HP:0002107	Pneumothorax
HP:0002138	Subarachnoid hemorrhage
HP:0002140	Ischemic stroke
HP:0002315	Headache
HP:0002326	Transient ischemic attack
HP:0002616	Aortic root aneurysm
HP:0002617	Vascular dilatation
HP:0002619	Varicose veins
HP:0002647	Aortic dissection
HP:0002650	Scoliosis
HP:0002705	High, narrow palate
HP:0002758	Osteoarthritis
HP:0002875	Exertional dyspnea
HP:0003179	Protrusio acetabuli
HP:0003302	Spondylolisthesis
HP:0003549	Abnormality of connective tissue
HP:0004268	Osteoarthritis of the small joints of the hand
HP:0004933	Ascending aortic dissection
HP:0004938	Tortuous cerebral arteries
HP:0004942	Aortic aneurysm
HP:0004944	Dilatation of the cerebral artery
HP:0004950	Peripheral arterial stenosis
HP:0004959	Descending thoracic aorta aneurysm
HP:0005086	Knee osteoarthritis
HP:0005110	Atrial fibrillation
HP:0005112	Abdominal aortic aneurysm
HP:0005116	Arterial tortuosity
HP:0005162	Abnormal left ventricular function
HP:0005294	Arterial dissection
HP:0006687	Aortic tortuosity
HP:0008419	Intervertebral disc degeneration
HP:0008843	Hip osteoarthritis
HP:0010646	Cervical spine instability
HP:0010648	Dermal translucency
HP:0010886	Osteochondritis dissecans
HP:0011106	Hypovolemia
HP:0011645	Dilatation of the sinus of Valsalva
HP:0012163	Carotid artery dilatation
HP:0012385	Camptodactyly
HP:0012432	Chronic fatigue
HP:0012499	Descending aortic dissection
HP:0012727	Thoracic aortic aneurysm
HP:0012763	Paroxysmal dyspnea
HP:0025487	Abnormality of bladder morphology
HP:0100490	Camptodactyly of finger
HP:0100645	Cystocele
HP:0100749	Chest pain
HP:0100775	Dural ectasia
HP:0200146	Mucoid extracellular matrix accumulation
HP:0410151	Eosinophilic infiltration of the esophagus

Tissue and cell type

Tissue	Cell type	Expression level	Reliability
adipose tissue	adipocytes	Low	Approved
adrenal gland	glandular cells	High	Approved
appendix	glandular cells	High	Approved
appendix	lymphoid tissue	Medium	Approved
bone marrow	hematopoietic cells	High	Approved
bronchus	respiratory epithelial cells	High	Approved
caudate	glial cells	Medium	Approved
caudate	neuronal cells	High	Approved
cerebellum	Purkinje cells	Medium	Approved
cerebellum	cells in granular layer	Medium	Approved
cerebellum	cells in molecular layer	High	Approved
cerebral cortex	endothelial cells	Medium	Approved
cerebral cortex	glial cells	Low	Approved
cerebral cortex	neuronal cells	High	Approved
cerebral cortex	neuropil	Medium	Approved
cervix	glandular cells	High	Approved
cervix	squamous epithelial cells	High	Approved
colon	endothelial cells	Low	Approved
colon	glandular cells	High	Approved
duodenum	glandular cells	High	Approved
endometrium 1	glandular cells	High	Approved
endometrium 2	glandular cells	Low	Approved
epididymis	glandular cells	Medium	Approved
esophagus	squamous epithelial cells	High	Approved
fallopian tube	glandular cells	High	Approved
gallbladder	glandular cells	High	Approved
heart muscle	cardiomyocytes	Medium	Approved
hippocampus	neuronal cells	Medium	Approved
kidney	cells in glomeruli	Low	Approved
kidney	cells in tubules	Medium	Approved
liver	hepatocytes	Low	Approved
lung	alveolar cells	Medium	Approved
lung	macrophages	High	Approved
lymph node	germinal center cells	High	Approved
lymph node	non-germinal center cells	High	Approved
pancreas	exocrine glandular cells	Medium	Approved
pancreas	pancreatic endocrine cells	High	Approved
placenta	decidual cells	Low	Approved
prostate	glandular cells	Medium	Approved
rectum	glandular cells	High	Approved
salivary gland	glandular cells	Medium	Approved
seminal vesicle	glandular cells	High	Approved
skeletal muscle	myocytes	Medium	Approved
skin 2	epidermal cells	High	Approved
small intestine	glandular cells	High	Approved
soft tissue 1	chondrocytes	High	Approved
soft tissue 2	fibroblasts	Low	Approved
soft tissue 2	peripheral nerve	Low	Approved
spleen	cells in red pulp	Medium	Approved
spleen	cells in white pulp	High	Approved
stomach 1	glandular cells	High	Approved
stomach 2	glandular cells	High	Approved
testis	Leydig cells	High	Approved
testis	cells in seminiferous ducts	High	Approved
thyroid gland	glandular cells	Medium	Approved
tonsil	germinal center cells	High	Approved
tonsil	non-germinal center cells	Low	Approved
tonsil	squamous epithelial cells	High	Approved
urinary bladder	urothelial cells	High	Approved
vagina	squamous epithelial cells	Medium	Approved

Disease name	MONDO ID	ICD10	ICD10 chapter	OMIM	Orphanet
colorectal cancer	MONDO:0005575	C18	chapter2, Neoplasms	OMIM:114500	Orphanet:466667
aneurysm-osteoarthritis syndrome	MONDO:0013426	Q87	chapter17, Congenital malformations, deformations and chromosomal abnormalities	OMIM:613795	Orphanet:284984
familial thoracic aortic aneurysm and aortic dissection	MONDO:0019625	I71	chapter9, Diseases of the circulatory system	OMIMPS:607086	Orphanet:91387
familial thoracic aortic aneurysm and aortic dissection	MONDO:0019625	Q87	chapter17, Congenital malformations, deformations and chromosomal abnormalities	OMIMPS:607086	Orphanet:91387

Summary of P84022

Gene: SMAD3, MADH3
Protein: Mothers against decapentaplegic homolog 3

Structure

GO term

InterPro / Pfam

Reactome

Subcellular location

Interactor | Variant | Drug

Phenotype

Tissue and cell type

Disease

Summary of P84022

Gene: SMAD3, MADH3 Protein: Mothers against decapentaplegic homolog 3

Structure

GO term

InterPro / Pfam

Reactome

Subcellular location

Interactor | Variant | Drug

Phenotype

Tissue and cell type

Disease

Gene: SMAD3, MADH3
Protein: Mothers against decapentaplegic homolog 3