MultifacetedProtDB - Bologna Biocomputing Group

Structure

PDB	Resolution (Å)	PDB name
1DEV	2.2	CRYSTAL STRUCTURE OF SMAD2 MH2 DOMAIN BOUND TO THE SMAD-BINDING DOMAIN OF SARA
1KHX	1.8	Crystal structure of a phosphorylated Smad2
1U7V	2.7	Crystal Structure of the phosphorylated Smad2/Smad4 heterotrimeric complex
2LB3		Structure of the WW domain of PIN1 in complex with a human phosphorylated Smad3 derived peptide
5XOD	1.851	Crystal structure of human Smad2-Ski complex
5ZOJ	2.794	Crystal structure of human SMAD2-MAN1 complex
6M64	1.45	Crystal structure of SMAD2 in complex with CBP
6YIA	1.3	14-3-3 sigma in complex with SMAD2 pS465 peptide
6ZVQ	2.03	Complex between SMAD2 MH2 domain and peptide from Ski corepressor
7CO1	3.3	Crystal structure of SMAD2 in complex with wild-type CBP

GO term

GO ontology	GO term	GO description
Biological Process	GO:0006351	DNA-templated transcription
Biological Process	GO:0007183	SMAD protein complex assembly
Biological Process	GO:0060395	SMAD protein signal transduction
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:0009952	anterior/posterior pattern specification
Biological Process	GO:0003180	aortic valve morphogenesis
Biological Process	GO:0030154	cell differentiation
Biological Process	GO:0045165	cell fate commitment
Biological Process	GO:0007182	common-partner SMAD protein phosphorylation
Biological Process	GO:0048701	embryonic cranial skeleton morphogenesis
Biological Process	GO:0048617	embryonic foregut morphogenesis
Biological Process	GO:0003203	endocardial cushion morphogenesis
Biological Process	GO:0001706	endoderm formation
Biological Process	GO:0007369	gastrulation
Biological Process	GO:0001701	in utero embryonic development
Biological Process	GO:0030073	insulin secretion
Biological Process	GO:0035556	intracellular signal transduction
Biological Process	GO:0030324	lung development
Biological Process	GO:0001707	mesoderm formation
Biological Process	GO:0045892	negative regulation of DNA-templated transcription
Biological Process	GO:0008285	negative regulation of cell population proliferation
Biological Process	GO:0038092	nodal signaling pathway
Biological Process	GO:0035265	organ growth
Biological Process	GO:0031016	pancreas development
Biological Process	GO:0048340	paraxial mesoderm morphogenesis
Biological Process	GO:0060039	pericardium development
Biological Process	GO:0030513	positive regulation of BMP signaling pathway
Biological Process	GO:0045893	positive regulation of DNA-templated transcription
Biological Process	GO:0010718	positive regulation of epithelial to mesenchymal transition
Biological Process	GO:0010628	positive regulation of gene expression
Biological Process	GO:1900224	positive regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry
Biological Process	GO:0045944	positive regulation of transcription by RNA polymerase II
Biological Process	GO:0009791	post-embryonic development
Biological Process	GO:0031053	primary miRNA processing
Biological Process	GO:0003184	pulmonary valve morphogenesis
Biological Process	GO:0051098	regulation of binding
Biological Process	GO:0017015	regulation of transforming growth factor beta receptor signaling pathway
Biological Process	GO:0070723	response to cholesterol
Biological Process	GO:0009749	response to glucose
Biological Process	GO:0062009	secondary palate development
Biological Process	GO:0023019	signal transduction involved in regulation of gene expression
Biological Process	GO:0007179	transforming growth factor beta receptor signaling pathway
Biological Process	GO:0001657	ureteric bud development
Biological Process	GO:0042060	wound healing
Biological Process	GO:0007352	zygotic specification of dorsal/ventral axis
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: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:0046332	SMAD binding
Molecular Function	GO:0003682	chromatin binding
Molecular Function	GO:0000987	cis-regulatory region sequence-specific DNA binding
Molecular Function	GO:0070410	co-SMAD binding
Molecular Function	GO:0097718	disordered domain specific binding
Molecular Function	GO:0003690	double-stranded DNA binding
Molecular Function	GO:0042802	identical protein binding
Molecular Function	GO:0046872	metal ion binding
Molecular Function	GO:0019902	phosphatase binding
Molecular Function	GO:0048156	tau protein binding
Molecular Function	GO:0005160	transforming growth factor beta receptor binding
Molecular Function	GO:0034713	type I transforming growth factor beta receptor binding
Molecular Function	GO:0031625	ubiquitin protein ligase binding
Cellular Component	GO:0071141	SMAD protein complex
Cellular Component	GO:0032444	activin responsive factor 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:0071142	homomeric SMAD protein complex
Cellular Component	GO:0005654	nucleoplasm
Cellular Component	GO:0005634	nucleus
Cellular Component	GO:0032991	protein-containing 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-452723	Transcriptional regulation of pluripotent stem cells	Internal node	R-HSA-1266738	Developmental Biology
R-HSA-5689880	Ub-specific processing proteases	Leaf	R-HSA-392499	Metabolism of proteins
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-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:16751101
Cytoplasm	ECO:0000269	PubMed:19289081
Cytoplasm	ECO:0000269	PubMed:21145499
Cytoplasm	ECO:0000269	PubMed:9865696
Nucleus	ECO:0000269	PubMed:16751101
Nucleus	ECO:0000269	PubMed:19289081
Nucleus	ECO:0000269	PubMed:21145499
Nucleus	ECO:0000269	PubMed:21599657
Nucleus	ECO:0000269	PubMed:22781750
Nucleus	ECO:0000269	PubMed:9865696

Interactor | Variant | Drug

Phenotype

HPO ID	HPO name
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000098	Tall stature
HP:0000218	High palate
HP:0000276	Long face
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000337	Broad forehead
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000525	Abnormality iris morphology
HP:0000766	Abnormal sternum morphology
HP:0000822	Hypertension
HP:0000965	Cutis marmorata
HP:0000978	Bruising susceptibility
HP:0001065	Striae distensae
HP:0001166	Arachnodactyly
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001297	Stroke
HP:0001519	Disproportionate tall stature
HP:0001601	Laryngomalacia
HP:0001607	Subglottic stenosis
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001640	Cardiomegaly
HP:0001642	Pulmonic stenosis
HP:0001643	Patent ductus arteriosus
HP:0001647	Bicuspid aortic valve
HP:0001651	Dextrocardia
HP:0001659	Aortic regurgitation
HP:0001677	Coronary artery atherosclerosis
HP:0001714	Ventricular hypertrophy
HP:0001719	Double outlet right ventricle
HP:0001746	Asplenia
HP:0001763	Pes planus
HP:0001770	Toe syndactyly
HP:0002105	Hemoptysis
HP:0002107	Pneumothorax
HP:0002138	Subarachnoid hemorrhage
HP:0002140	Ischemic stroke
HP:0002326	Transient ischemic attack
HP:0002566	Intestinal malrotation
HP:0002616	Aortic root aneurysm
HP:0002619	Varicose veins
HP:0002647	Aortic dissection
HP:0002650	Scoliosis
HP:0002705	High, narrow palate
HP:0002829	Arthralgia
HP:0002875	Exertional dyspnea
HP:0003549	Abnormality of connective tissue
HP:0003577	Congenital onset
HP:0003581	Adult onset
HP:0004322	Short stature
HP:0004933	Ascending aortic dissection
HP:0004944	Dilatation of the cerebral artery
HP:0004950	Peripheral arterial stenosis
HP:0004959	Descending thoracic aorta aneurysm
HP:0005086	Knee osteoarthritis
HP:0005112	Abdominal aortic aneurysm
HP:0005162	Abnormal left ventricular function
HP:0006315	Solitary median maxillary central incisor
HP:0007598	Bilateral single transverse palmar creases
HP:0008419	Intervertebral disc degeneration
HP:0008843	Hip osteoarthritis
HP:0010772	Anomalous pulmonary venous return
HP:0010773	Partial anomalous pulmonary venous return
HP:0011106	Hypovolemia
HP:0011579	Unbalanced atrioventricular canal defect
HP:0011669	Left superior vena cava draining directly to the left atrium
HP:0011800	Midface retrusion
HP:0012158	Carotid artery dissection
HP:0012163	Carotid artery dilatation
HP:0012432	Chronic fatigue
HP:0012499	Descending aortic dissection
HP:0012727	Thoracic aortic aneurysm
HP:0012763	Paroxysmal dyspnea
HP:0031348	Dextrotransposition of the great arteries
HP:0031853	Isomerism
HP:0034179	Vertebral artery aneurysm
HP:0100749	Chest pain
HP:0100775	Dural ectasia
HP:0200146	Mucoid extracellular matrix accumulation

Tissue and cell type

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

Disease

Disease name	MONDO ID	ICD10	ICD10 chapter	OMIM	Orphanet
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 Q15796

Gene: SMAD2, MADH2, MADR2
Protein: Mothers against decapentaplegic homolog 2

Structure

GO term

InterPro / Pfam

Reactome

Subcellular location

Interactor | Variant | Drug

Phenotype

Tissue and cell type

Disease

Summary of Q15796

Gene: SMAD2, MADH2, MADR2 Protein: Mothers against decapentaplegic homolog 2

Structure

GO term

InterPro / Pfam

Reactome

Subcellular location

Interactor | Variant | Drug

Phenotype

Tissue and cell type

Disease

Gene: SMAD2, MADH2, MADR2
Protein: Mothers against decapentaplegic homolog 2