CPLM-006682

Genbank Nucleotide ID

TGF-beta receptor type-1

Protein Synonyms/Alias

TGFR-1; Activin A receptor type II-like protein kinase of 53kD; Activin receptor-like kinase 5; ALK-5; ALK5; Serine/threonine-protein kinase receptor R4; SKR4; TGF-beta type I receptor; Transforming growth factor-beta receptor type I; TGF-beta receptor type I; TbetaR-I

Homo sapiens (Human)

Position	Peptide	Type	References
395	LDDSINMKHFESFKR	ubiquitination	[1]
506	LSQQEGIKM******	ubiquitination	[1, 2, 3]

[1] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
[2] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
[3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]

Functional Description

Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non- canonical, SMAD-independent TGF-beta signaling pathways. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation.

DOMAIN 175 204 GS.
DOMAIN 205 495 Protein kinase.
NP_BIND 211 219 ATP (By similarity).
MOTIF 193 194 FKBP1A-binding.
ACT_SITE 333 333 Proton acceptor (By similarity).
BINDING 232 232 ATP (By similarity).
MOD_RES 165 165 Phosphoserine.
MOD_RES 185 185 Phosphothreonine; by TGFBR2.
MOD_RES 186 186 Phosphothreonine; by TGFBR2.
MOD_RES 187 187 Phosphoserine; by TGFBR2.
MOD_RES 189 189 Phosphoserine; by TGFBR2.
MOD_RES 191 191 Phosphoserine; by TGFBR2.
CARBOHYD 45 45 N-linked (GlcNAc...) (Potential).
DISULFID 36 54
DISULFID 38 41
DISULFID 48 71
DISULFID 86 100
DISULFID 101 106
CROSSLNK 391 391 Glycyl lysine isopeptide (Lys-Gly)

3D-structure; Alternative splicing; Aortic aneurysm; Apoptosis; ATP-binding; Cell junction; Cell membrane; Complete proteome; Craniosynostosis; Differentiation; Direct protein sequencing; Disease mutation; Disulfide bond; Glycoprotein; Growth regulation; Isopeptide bond; Kinase; Magnesium; Manganese; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; Polymorphism; Receptor; Reference proteome; Serine/threonine-protein kinase; Signal; Tight junction; Transferase; Transmembrane; Transmembrane helix; Ubl conjugation.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005923; C:tight junction; IDA:UniProtKB.
GO:0070022; C:transforming growth factor beta receptor homodimeric complex; IC:BHF-UCL.
GO:0005524; F:ATP binding; IDA:HGNC.
GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO:0046332; F:SMAD binding; IDA:BHF-UCL.
GO:0050431; F:transforming growth factor beta binding; IDA:BHF-UCL.
GO:0005025; F:transforming growth factor beta receptor activity, type I; IDA:BHF-UCL.
GO:0005114; F:type II transforming growth factor beta receptor binding; IDA:BHF-UCL.
GO:0000186; P:activation of MAPKK activity; IDA:BHF-UCL.
GO:0001525; P:angiogenesis; IEA:Compara.
GO:0009952; P:anterior/posterior pattern specification; ISS:BHF-UCL.
GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
GO:0048844; P:artery morphogenesis; ISS:BHF-UCL.
GO:0001824; P:blastocyst development; IEA:Compara.
GO:0007050; P:cell cycle arrest; TAS:UniProtKB.
GO:0030199; P:collagen fibril organization; ISS:BHF-UCL.
GO:0048701; P:embryonic cranial skeleton morphogenesis; ISS:BHF-UCL.
GO:0043542; P:endothelial cell migration; IEA:Compara.
GO:0001837; P:epithelial to mesenchymal transition; IDA:UniProtKB.
GO:0008354; P:germ cell migration; ISS:BHF-UCL.
GO:0007507; P:heart development; ISS:BHF-UCL.
GO:0001701; P:in utero embryonic development; ISS:BHF-UCL.
GO:0006917; P:induction of apoptosis; IEA:Compara.
GO:0001822; P:kidney development; ISS:BHF-UCL.
GO:0002088; P:lens development in camera-type eye; IEA:Compara.
GO:0043066; P:negative regulation of apoptotic process; IMP:BHF-UCL.
GO:0032331; P:negative regulation of chondrocyte differentiation; ISS:BHF-UCL.
GO:0001937; P:negative regulation of endothelial cell proliferation; IEA:Compara.
GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; TAS:Reactome.
GO:0048663; P:neuron fate commitment; ISS:BHF-UCL.
GO:0060021; P:palate development; ISS:BHF-UCL.
GO:0060017; P:parathyroid gland development; ISS:BHF-UCL.
GO:0060389; P:pathway-restricted SMAD protein phosphorylation; IDA:BHF-UCL.
GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
GO:0018107; P:peptidyl-threonine phosphorylation; IDA:BHF-UCL.
GO:0060037; P:pharyngeal system development; ISS:BHF-UCL.
GO:0030307; P:positive regulation of cell growth; IDA:BHF-UCL.
GO:0008284; P:positive regulation of cell proliferation; IMP:HGNC.
GO:0051272; P:positive regulation of cellular component movement; IMP:BHF-UCL.
GO:0051491; P:positive regulation of filopodium assembly; IEA:Compara.
GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IDA:BHF-UCL.
GO:0051897; P:positive regulation of protein kinase B signaling cascade; IDA:BHF-UCL.
GO:0060391; P:positive regulation of SMAD protein import into nucleus; IDA:BHF-UCL.
GO:0045893; P:positive regulation of transcription, DNA-dependent; IDA:BHF-UCL.
GO:0009791; P:post-embryonic development; IEA:Compara.
GO:0043393; P:regulation of protein binding; IEA:Compara.
GO:0031396; P:regulation of protein ubiquitination; IDA:UniProtKB.
GO:0070723; P:response to cholesterol; IDA:BHF-UCL.
GO:0048538; P:thymus development; ISS:BHF-UCL.
GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL.
GO:0042060; P:wound healing; TAS:UniProtKB.

IPR000472; Activin_rcpt.
IPR011009; Kinase-like_dom.
IPR000719; Prot_kinase_cat_dom.
IPR017441; Protein_kinase_ATP_BS.
IPR008271; Ser/Thr_kinase_AS.
IPR003605; TGF_beta_rcpt_GS.

PF01064; Activin_recp
PF00069; Pkinase
PF08515; TGF_beta_GS

PS51256; GS
PS00107; PROTEIN_KINASE_ATP
PS50011; PROTEIN_KINASE_DOM
PS00108; PROTEIN_KINASE_ST