CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-010443
UniProt Accession
Genbank Protein ID
 L26110 
Genbank Nucleotide ID
Protein Name
 TGF-beta receptor type-1 
Protein Synonyms/Alias
 TGFR-1; 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 
Gene Name
 Tgfbr1 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Rattus norvegicus (Rat) 
NCBI Taxa ID
 10116 
Lysine Modification
Position
Peptide
Type
References
230RGEEVAVKIFSSREEsumoylation[1]
Reference
 [1] The type I TGF-beta receptor is covalently modified and regulated by sumoylation.
 Kang JS, Saunier EF, Akhurst RJ, Derynck R.
 Nat Cell Biol. 2008 Jun;10(6):654-64. [PMID: 18469808] 
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 (By similarity). 
Sequence Annotation
 DOMAIN 173 202 GS.
 DOMAIN 203 493 Protein kinase.
 NP_BIND 209 217 ATP (By similarity).
 MOTIF 191 192 FKBP1A-binding.
 ACT_SITE 331 331 Proton acceptor (By similarity).
 BINDING 230 230 ATP (By similarity).
 MOD_RES 163 163 Phosphoserine (By similarity).
 MOD_RES 183 183 Phosphothreonine; by TGFBR2 (By
 MOD_RES 184 184 Phosphothreonine; by TGFBR2 (By
 MOD_RES 185 185 Phosphoserine; by TGFBR2 (By similarity).
 MOD_RES 187 187 Phosphoserine; by TGFBR2 (By similarity).
 MOD_RES 189 189 Phosphoserine; by TGFBR2 (By similarity).
 CARBOHYD 41 41 N-linked (GlcNAc...) (Potential).
 DISULFID 32 50 By similarity.
 DISULFID 34 37 By similarity.
 DISULFID 44 67 By similarity.
 DISULFID 82 94 By similarity.
 DISULFID 95 100 By similarity.
 CROSSLNK 389 389 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 Apoptosis; ATP-binding; Cell junction; Cell membrane; Complete proteome; Differentiation; Disulfide bond; Glycoprotein; Growth regulation; Isopeptide bond; Kinase; Magnesium; Manganese; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Serine/threonine-protein kinase; Signal; Tight junction; Transferase; Transmembrane; Transmembrane helix; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 501 AA 
Protein Sequence
MEAASAALRR CLLLIVLVAA ATLLPGAKAL QCFCHLCTKD NFTCETDGLC FVSVTETTDK 60
VIHNSMCIAE IDLIPRDRPF VCAPSSKTGA VTYCCNQDHC NKIELPTTGP FSEKQSAGLG 120
PVELAAVIAG PVCFVCIALM LMVYICHNRT VIHHRVPNEE DPSLDRPFIS EGTTLKDLIY 180
DMTTSGSGSG LPLLVQRTIA RTIVLQESIG KGRFGEVWRG KWRGEEVAVK IFSSREERSW 240
FREAEIYQTV MLRHENILGF IAADNKDNGT WTQLWLVSDY HEHGSLFDYL NRYTVTVEGM 300
IKLALSTASG LAHLHMEIVG TQGKPAIAHR DLKSKNILVK KNGTCCIADL GLAVRHDSAT 360
DTIDIAPNHR VGTKRYMAPE VLDDSINMKH FESFKRADIY AMGLVFWEIA RRCSIGGIHE 420
DYQLPYYDLV PSDPSVEEMR KVVCEQKLRP NIPNRWQSCE ALRVMAKIMR ECWYANGAAR 480
LTALRIKKTL SQLSQQEGIK M 501 
Gene Ontology
 GO:0016324; C:apical plasma membrane; IDA:RGD.
 GO:0016323; C:basolateral plasma membrane; IDA:RGD.
 GO:0005901; C:caveola; IDA:MGI.
 GO:0005923; C:tight junction; IEA:UniProtKB-SubCell.
 GO:0070022; C:transforming growth factor beta receptor homodimeric complex; IC:RGD.
 GO:0005524; F:ATP binding; IMP:RGD.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0046982; F:protein heterodimerization activity; IMP:RGD.
 GO:0050431; F:transforming growth factor beta binding; IDA:RGD.
 GO:0005025; F:transforming growth factor beta receptor activity, type I; IMP:RGD.
 GO:0007568; P:aging; IEP:RGD.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
 GO:0048565; P:digestive tract development; IEP:RGD.
 GO:0009790; P:embryo development; IEP:RGD.
 GO:0007566; P:embryo implantation; IEP:RGD.
 GO:0030324; P:lung development; IEP:RGD.
 GO:0045602; P:negative regulation of endothelial cell differentiation; IMP:RGD.
 GO:0031100; P:organ regeneration; IEP:RGD.
 GO:0046777; P:protein autophosphorylation; IMP:RGD.
 GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
 GO:0051602; P:response to electrical stimulus; IEP:RGD.
 GO:0043627; P:response to estrogen stimulus; IDA:RGD.
 GO:0001666; P:response to hypoxia; IEP:RGD.
 GO:0034695; P:response to prostaglandin E stimulus; IEP:RGD.
 GO:0009636; P:response to toxic substance; IEP:RGD.
 GO:0007179; P:transforming growth factor beta receptor signaling pathway; IMP:RGD. 
Interpro
 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. 
Pfam
 PF01064; Activin_recp
 PF00069; Pkinase
 PF08515; TGF_beta_GS 
SMART
 SM00467; GS 
PROSITE
 PS51256; GS
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 
PRINTS