MultifacetedProtDB - Bologna Biocomputing Group

EC number	EC number description
2.7.11.30	Transferases; Transferring phosphorus-containing groups; Protein-serine/threonine kinases; receptor protein serine/threonine kinase

Structure

PDB	Resolution (Å)	PDB name
1B6C	2.6	CRYSTAL STRUCTURE OF THE CYTOPLASMIC DOMAIN OF THE TYPE I TGF-BETA RECEPTOR IN COMPLEX WITH FKBP12
1IAS	2.9	CYTOPLASMIC DOMAIN OF UNPHOSPHORYLATED TYPE I TGF-BETA RECEPTOR CRYSTALLIZED WITHOUT FKBP12
1PY5	2.3	Crystal Structure of TGF-beta receptor I kinase with inhibitor
1RW8	2.4	Crystal Structure of TGF-beta receptor I kinase with ATP site inhibitor
1VJY	2.0	Crystal Structure of a Naphthyridine Inhibitor of Human TGF-beta Type I Receptor
2L5S		Solution structure of the extracellular domain of the TGF-beta type I receptor
2PJY	3.0	Structural basis for cooperative assembly of the TGF-beta signaling complex
2WOT	1.85	ALK5 IN COMPLEX WITH 4-((5,6-dimethyl-2-(2-pyridyl)-3-pyridyl)oxy)-N-(3,4,5-trimethoxyphenyl)pyridin-2-amine
2WOU	2.3	ALK5 IN COMPLEX WITH 4-((4-((2,6-dimethyl-3-pyridyl)oxy)-2-pyridyl) amino)benzenesulfonamide
2X7O	3.7	Crystal structure of TGFbRI complexed with an indolinone inhibitor
3FAA	3.35	Crystal structure of TGFbRI complexed with a 2-aminoimidazole inhibitor
3GXL	1.8	ALK-5 kinase complex with GW857175
3HMM	1.7	Structure of Alk5 + GW855857
3KCF	2.8	Crystal structure of TGFbRI complexed with a pyrazolone inhibitor
3KFD	2.995	Ternary complex of TGF-b1 reveals isoform-specific ligand recognition and receptor recruitment in the superfamily
3TZM	1.7	TGF-beta Receptor type 1 in complex with SB431542
4X0M	1.68	Selection of fragments for kinase inhibitor design: decoration is key
4X2F	1.49	Selection of fragments for kinase inhibitor design: decoration is key
4X2G	1.51	Selection of fragments for kinase inhibitor design: decoration is key
4X2J	1.69	Selection of fragments for kinase inhibitor design: decoration is key
4X2K	1.69	Selection of fragments for kinase inhibitor design: decoration is key
4X2N	1.8	Selection of fragments for kinase inhibitor design: decoration is key
5E8S	1.45	TGF-BETA RECEPTOR TYPE 1 KINASE DOMAIN (WT)
5E8T	1.7	TGF-BETA RECEPTOR TYPE 1 KINASE DOMAIN (T204D)
5E8U	2.03	TGF-BETA RECEPTOR TYPE 1 KINASE DOMAIN (T204D,I211V,Y249F,S280T, Y282F,S287N,A350C,L352F)
5E8W	1.86	TGF-BETA RECEPTOR TYPE 1 KINASE DOMAIN (T204D) IN COMPLEX WITH STAUROSPORINE
5E8X	1.45	TGF-BETA RECEPTOR TYPE 1 KINASE DOMAIN (T204D,I211V,Y249F,S280T, Y282F,S287N,A350C,L352F) IN COMPLEX WITH STAUROSPORINE
5E8Z	1.51	TGF-BETA RECEPTOR TYPE 1 KINASE DOMAIN (T204D) IN COMPLEX WITH 3-AMINO-6-[4-(2-HYDROXYETHYL)PHENYL]-N-[4-(MORPHOLIN-4-YL)PYRIDIN-3-YL]PYRAZINE-2-CARBOXAMIDE
5E90	2.05	TGF-BETA RECEPTOR TYPE 1 KINASE DOMAIN (T204D,I211V,Y249F, S280T,Y282F,S287N,A350C,L352F) IN COMPLEX WITH 3-AMINO-6- [4-(2-HYDROXYETHYL)PHENYL]-N-[4-(MORPHOLIN-4-YL)PYRIDIN-3-YL]PYRAZINE-2-CARBOXAMIDE
5FRI	2.0	ALK5 in complex witha an N-(4-anilino-2-pyridyl)acetamide inhibitor.
5QIK	1.58	TGF-BETA RECEPTOR TYPE 1 KINASE DOMAIN (T204D) IN COMPLEX WITH N-{4-[3-(6-fluoropyridin-3-yl)-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}acetamide
5QIL	1.98	TGF-BETA RECEPTOR TYPE 1 KINASE DOMAIN (T204D) IN COMPLEX WITH N-{4-[3-(6-METHOXYPYRIDIN-3-YL)-1H-PYRROLO[3,2-B]PYRIDIN-2-YL]PYRIDIN-2-YL}ACETAMIDE
5QIM	1.75	TGF-BETA RECEPTOR TYPE 1 KINASE DOMAIN (T204D) IN COMPLEX WITH N-{4-[3-(5-METHOXYPYRIDIN-2-YL)-1H-PYRROLO[3,2-B] PYRIDIN-2-YL]PYRIDIN-2-YL}ACETAMIDE
5QTZ	1.83	TGF-BETA RECEPTOR TYPE 1 KINASE DOMAIN (T204D) IN COMPLEX WITH 6-[1-(2,2-DIFLUOROETHYL)-4-(6-METHYLPYRIDIN-2-YL)-1H-IMIDAZOL-5-YL]IMIDAZO[1,2-A]PYRIDINE
5QU0	1.67	TGF-BETA RECEPTOR TYPE 1 KINASE DOMAIN (T204D) IN COMPLEX WITH 6-[4-(3-CHLORO-4-FLUOROPHENYL)-1-(2-HYDROXYETHYL)-1H-IMIDAZOL-5-YL]IMIDAZO[1,2-B]PYRIDAZINE-3-CARBONITRILE
5USQ	2.55	ALK-5 kinase inhibitor complex
6B8Y	1.65	TGF-BETA RECEPTOR TYPE 1 KINASE DOMAIN (T204D) IN COMPLEX WITH N-(3-fluoropyridin-4-yl)-2-[6-(trifluoromethyl)pyridin-2-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine
6MAC	2.34	Ternary structure of GDF11 bound to ActRIIB-ECD and Alk5-ECD

GO term

GO ontology	GO term	GO description
Biological Process	GO:0032924	activin receptor signaling pathway
Biological Process	GO:0060978	angiogenesis involved in coronary vascular morphogenesis
Biological Process	GO:0009952	anterior/posterior pattern specification
Biological Process	GO:0006915	apoptotic process
Biological Process	GO:0048844	artery morphogenesis
Biological Process	GO:0001824	blastocyst development
Biological Process	GO:0060317	cardiac epithelial to mesenchymal transition
Biological Process	GO:0048870	cell motility
Biological Process	GO:0071363	cellular response to growth factor stimulus
Biological Process	GO:0071560	cellular response to transforming growth factor beta stimulus
Biological Process	GO:0030199	collagen fibril organization
Biological Process	GO:0060982	coronary artery morphogenesis
Biological Process	GO:0048701	embryonic cranial skeleton morphogenesis
Biological Process	GO:0042118	endothelial cell activation
Biological Process	GO:0043542	endothelial cell migration
Biological Process	GO:0001935	endothelial cell proliferation
Biological Process	GO:1905223	epicardium morphogenesis
Biological Process	GO:0001837	epithelial to mesenchymal transition
Biological Process	GO:0043062	extracellular structure organization
Biological Process	GO:0046847	filopodium assembly
Biological Process	GO:0008354	germ cell migration
Biological Process	GO:0007507	heart development
Biological Process	GO:0001701	in utero embryonic development
Biological Process	GO:0035556	intracellular signal transduction
Biological Process	GO:0001822	kidney development
Biological Process	GO:0002088	lens development in camera-type eye
Biological Process	GO:0008584	male gonad development
Biological Process	GO:0048762	mesenchymal cell differentiation
Biological Process	GO:0032331	negative regulation of chondrocyte differentiation
Biological Process	GO:0001937	negative regulation of endothelial cell proliferation
Biological Process	GO:2001237	negative regulation of extrinsic apoptotic signaling pathway
Biological Process	GO:0007399	nervous system development
Biological Process	GO:0048663	neuron fate commitment
Biological Process	GO:0060017	parathyroid gland development
Biological Process	GO:0060389	pathway-restricted SMAD protein phosphorylation
Biological Process	GO:0018105	peptidyl-serine phosphorylation
Biological Process	GO:0018107	peptidyl-threonine phosphorylation
Biological Process	GO:0060037	pharyngeal system development
Biological Process	GO:0045893	positive regulation of DNA-templated transcription
Biological Process	GO:0043410	positive regulation of MAPK cascade
Biological Process	GO:0060391	positive regulation of SMAD protein signal transduction
Biological Process	GO:2001235	positive regulation of apoptotic signaling pathway
Biological Process	GO:0030307	positive regulation of cell growth
Biological Process	GO:0030335	positive regulation of cell migration
Biological Process	GO:0008284	positive regulation of cell population proliferation
Biological Process	GO:0001938	positive regulation of endothelial cell proliferation
Biological Process	GO:0010718	positive regulation of epithelial to mesenchymal transition
Biological Process	GO:1905007	positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation
Biological Process	GO:0051491	positive regulation of filopodium assembly
Biological Process	GO:0010628	positive regulation of gene expression
Biological Process	GO:0010862	positive regulation of pathway-restricted SMAD protein phosphorylation
Biological Process	GO:0051897	positive regulation of protein kinase B signaling
Biological Process	GO:0051496	positive regulation of stress fiber assembly
Biological Process	GO:1905075	positive regulation of tight junction disassembly
Biological Process	GO:0009791	post-embryonic development
Biological Process	GO:0006468	protein phosphorylation
Biological Process	GO:0006355	regulation of DNA-templated transcription
Biological Process	GO:0060043	regulation of cardiac muscle cell proliferation
Biological Process	GO:0051726	regulation of cell cycle
Biological Process	GO:0010717	regulation of epithelial to mesenchymal transition
Biological Process	GO:0010468	regulation of gene expression
Biological Process	GO:0043393	regulation of protein binding
Biological Process	GO:0031396	regulation of protein ubiquitination
Biological Process	GO:0070723	response to cholesterol
Biological Process	GO:0060021	roof of mouth development
Biological Process	GO:0007165	signal transduction
Biological Process	GO:0001501	skeletal system development
Biological Process	GO:0048705	skeletal system morphogenesis
Biological Process	GO:0048538	thymus development
Biological Process	GO:0007179	transforming growth factor beta receptor signaling pathway
Biological Process	GO:0003223	ventricular compact myocardium morphogenesis
Biological Process	GO:0060412	ventricular septum morphogenesis
Biological Process	GO:0003222	ventricular trabecula myocardium morphogenesis
Biological Process	GO:0042060	wound healing
Molecular Function	GO:0005524	ATP binding
Molecular Function	GO:0070411	I-SMAD binding
Molecular Function	GO:0046332	SMAD binding
Molecular Function	GO:0048185	activin binding
Molecular Function	GO:0016361	activin receptor activity, type I
Molecular Function	GO:0046872	metal ion binding
Molecular Function	GO:0004672	protein kinase activity
Molecular Function	GO:0004674	protein serine/threonine kinase activity
Molecular Function	GO:0050431	transforming growth factor beta binding
Molecular Function	GO:0005024	transforming growth factor beta receptor activity
Molecular Function	GO:0005025	transforming growth factor beta receptor activity, type I
Molecular Function	GO:0005114	type II transforming growth factor beta receptor binding
Cellular Component	GO:0048179	activin receptor complex
Cellular Component	GO:0005923	bicellular tight junction
Cellular Component	GO:0009986	cell surface
Cellular Component	GO:0005768	endosome
Cellular Component	GO:0016020	membrane
Cellular Component	GO:0045121	membrane raft
Cellular Component	GO:0005634	nucleus
Cellular Component	GO:0005886	plasma membrane
Cellular Component	GO:0043235	receptor complex
Cellular Component	GO:0070021	transforming growth factor beta ligand-receptor complex

InterPro / Pfam

InterPro	InterPro name
IPR000333	Ser/Thr protein kinase, TGFB receptor
IPR000472	Activin types I and II receptor domain
IPR000719	Protein kinase domain
IPR003605	GS domain
IPR008271	Serine/threonine-protein kinase, active site
IPR011009	Protein kinase-like domain superfamily
IPR017441	Protein kinase, ATP binding site
IPR045860	Snake toxin-like superfamily

Pfam	Pfam name
PF00069	Protein kinase domain
PF01064	Activin types I and II receptor domain
PF08515	Transforming growth factor beta type I GS-motif

Reactome

Reactome	Reactome Name	Node type	Reactome Root	Reactome Root Name
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-2173791	TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)	Leaf	R-HSA-162582	Signal Transduction
R-HSA-3304356	SMAD2/3 Phosphorylation Motif Mutants in Cancer	Leaf	R-HSA-1643685	Disease
R-HSA-3645790	TGFBR2 Kinase Domain Mutants in Cancer	Leaf	R-HSA-1643685	Disease
R-HSA-3656532	TGFBR1 KD Mutants in Cancer	Leaf	R-HSA-1643685	Disease
R-HSA-3656535	TGFBR1 LBD Mutants in Cancer	Leaf	R-HSA-1643685	Disease
R-HSA-5689603	UCH proteinases	Leaf	R-HSA-392499	Metabolism of proteins
R-HSA-5689880	Ub-specific processing proteases	Leaf	R-HSA-392499	Metabolism of proteins

Subcellular location

Location	ECO term	Pubmed
Cell junction, tight junction	ECO:0000269	PubMed:15761148
Cell membrane	ECO:0000269	PubMed:21791611
Cell membrane	ECO:0000269	PubMed:25893292
Cell membrane	ECO:0000269	PubMed:9472030
Cell surface	ECO:0000269	PubMed:25893292
Membrane raft	ECO:0000269	PubMed:25893292

Interactor | Variant | Drug

Phenotype

HPO ID	HPO name
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000098	Tall stature
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000202	Orofacial cleft
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000272	Malar flattening
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000520	Proptosis
HP:0000525	Abnormality iris morphology
HP:0000577	Exotropia
HP:0000592	Blue sclerae
HP:0000766	Abnormal sternum morphology
HP:0000767	Pectus excavatum
HP:0000768	Pectus carinatum
HP:0000822	Hypertension
HP:0000951	Abnormality of the skin
HP:0000963	Thin skin
HP:0000965	Cutis marmorata
HP:0000977	Soft skin
HP:0000978	Bruising susceptibility
HP:0000987	Atypical scarring of skin
HP:0001065	Striae distensae
HP:0001083	Ectopia lentis
HP:0001162	Postaxial hand polydactyly
HP:0001166	Arachnodactyly
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001297	Stroke
HP:0001363	Craniosynostosis
HP:0001373	Joint dislocation
HP:0001388	Joint laxity
HP:0001519	Disproportionate tall stature
HP:0001631	Atrial septal defect
HP:0001634	Mitral valve prolapse
HP:0001640	Cardiomegaly
HP:0001643	Patent ductus arteriosus
HP:0001647	Bicuspid aortic valve
HP:0001659	Aortic regurgitation
HP:0001677	Coronary artery atherosclerosis
HP:0001695	Cardiac arrest
HP:0001762	Talipes equinovarus
HP:0001763	Pes planus
HP:0001892	Abnormal bleeding
HP:0002105	Hemoptysis
HP:0002107	Pneumothorax
HP:0002138	Subarachnoid hemorrhage
HP:0002140	Ischemic stroke
HP:0002308	Chiari malformation
HP:0002326	Transient ischemic attack
HP:0002616	Aortic root aneurysm
HP:0002617	Vascular dilatation
HP:0002647	Aortic dissection
HP:0002650	Scoliosis
HP:0002664	Neoplasm
HP:0002705	High, narrow palate
HP:0002875	Exertional dyspnea
HP:0003549	Abnormality of connective tissue
HP:0003581	Adult onset
HP:0003621	Juvenile onset
HP:0004933	Ascending aortic dissection
HP:0004937	Pulmonary artery aneurysm
HP:0004942	Aortic aneurysm
HP:0004944	Dilatation of the cerebral artery
HP:0004950	Peripheral arterial stenosis
HP:0004959	Descending thoracic aorta aneurysm
HP:0005112	Abdominal aortic aneurysm
HP:0005116	Arterial tortuosity
HP:0005162	Abnormal left ventricular function
HP:0005182	Bicuspid pulmonary valve
HP:0005294	Arterial dissection
HP:0005692	Joint hyperflexibility
HP:0010646	Cervical spine instability
HP:0010648	Dermal translucency
HP:0011106	Hypovolemia
HP:0012163	Carotid artery dilatation
HP:0012385	Camptodactyly
HP:0012499	Descending aortic dissection
HP:0012763	Paroxysmal dyspnea
HP:0030745	Dilatation of the ductus arteriosus
HP:0100490	Camptodactyly of finger
HP:0100718	Uterine rupture
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

Disease

Disease name	MONDO ID	ICD10	ICD10 chapter	OMIM	Orphanet
ehlers-danlos syndrome, classic type	MONDO:0007522	Q79	chapter17, Congenital malformations, deformations and chromosomal abnormalities		Orphanet:287
multiple self-healing squamous epithelioma	MONDO:0007566	C44	chapter2, Neoplasms	OMIM:132800	Orphanet:65748
marfan syndrome	MONDO:0007947	Q87	chapter17, Congenital malformations, deformations and chromosomal abnormalities	OMIM:154700	Orphanet:284963
marfan syndrome	MONDO:0007947	Q87	chapter17, Congenital malformations, deformations and chromosomal abnormalities	OMIM:154700	Orphanet:558
loeys-dietz syndrome 1	MONDO:0012212	Q87	chapter17, Congenital malformations, deformations and chromosomal abnormalities	OMIM:609192	Orphanet:91387
loeys-dietz syndrome 1	MONDO:0012212	Q87	chapter17, Congenital malformations, deformations and chromosomal abnormalities	OMIM:609192	Orphanet:97295
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 P36897

Gene: TGFBR1, ALK5, SKR4
Protein: TGF-beta receptor type-1

Structure

GO term

InterPro / Pfam

Reactome

Subcellular location

Interactor | Variant | Drug

Phenotype

Tissue and cell type

Disease

Summary of P36897

Gene: TGFBR1, ALK5, SKR4 Protein: TGF-beta receptor type-1

Structure

GO term

InterPro / Pfam

Reactome

Subcellular location

Interactor | Variant | Drug

Phenotype

Tissue and cell type

Disease

Gene: TGFBR1, ALK5, SKR4
Protein: TGF-beta receptor type-1