DB code: T00224

RLCP classification 3.103.130000.1161 : Transfer
CATH domain 2.-.-.- :
3.30.200.20 : Phosphorylase Kinase; domain 1
1.10.510.10 : Transferase(Phosphotransferase); domain 1 Catalytic domain
E.C. 2.7.11.30
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
1.10.510.10 : Transferase(Phosphotransferase); domain 1 M00125 M00124 M00131 M00127 M00129 M00130 M00132 M00136 M00196 M00197 M00198 M00304 M00323 M00325 M00326 M00327 M00328 M00329 M00330 M00331 M00332 M00333 M00335 M00339 M00344
3.30.200.20 : Phosphorylase Kinase; domain 1 M00125 M00124 M00131 M00127 M00129 M00130 M00132 M00136 M00196 M00197 M00198 M00304 M00323 M00325 M00326 M00327 M00328 M00329 M00330 M00331 M00332 M00333 M00335 M00339 M00344 D00298

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P36897 TGF-beta receptor type-1
EC 2.7.11.30
Transforming growth factor-beta receptor type I
TGF-beta receptor type I
TGF-beta type I receptor
TbetaR-I
TGFR-1
Serine/threonine-protein kinase receptor R4
SKR4
Activin receptor-like kinase 5
ALK-5
NP_001124388.1 (Protein)
NM_001130916.1 (DNA/RNA sequence)
NP_004603.1 (Protein)
NM_004612.2 (DNA/RNA sequence)
PF01064 (Activin_recp)
PF00069 (Pkinase)
PF08515 (TGF_beta_GS)
[Graphical View]

KEGG enzyme name
receptor protein serine/threonine kinase
activin receptor kinase
receptor type I serine/threonine protein kinase
receptor type II serine/threonine protein kinase
STK13
TGF-beta kinase
receptor serine/threonine protein kinase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P36897 TGFR1_HUMAN ATP + [receptor-protein] = ADP + [receptor- protein] phosphate. Interacts with CD109. The unphosphorylated protein interacts with FKBP1A and is stabilized the inactive conformation. Phosphorylation of the GS region abrogates FKBP1A binding. Interacts with SMAD2 when phosphorylated on several residues in the GS region. Membrane, Single-pass type I membrane protein. Magnesium or manganese (By similarity).

KEGG Pathways
Map code Pathways E.C.

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00002 C00017 C00008 C00562
E.C.
Compound Magnesium ATP [Receptor-protein] ADP [Receptor-protein] phosphate
Type divalent metal (Ca2+, Mg2+) amine group,nucleotide peptide/protein amine group,nucleotide peptide/protein,phosphate group/phosphate ion
ChEBI 18420
15422
16761
PubChem 888
5957
6022
1b6cB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1b6cD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1b6cF01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1b6cH01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1iasA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1iasB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1iasC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1iasD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1iasE01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1b6cB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1b6cD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1b6cF02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1b6cH02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1iasA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1iasB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1iasC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1iasD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1iasE02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P36897, literature [5] & similarity with M00129

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1b6cB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1b6cD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1b6cF01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1b6cH01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1iasA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1iasB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1iasC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1iasD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1iasE01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1b6cB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 333;LYS 335 ASN 338;ASP 351(magnesium binding)
1b6cD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 333;LYS 335 ASN 338;ASP 351(magnesium binding)
1b6cF02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 333;LYS 335 ASN 338;ASP 351(magnesium binding)
1b6cH02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 333;LYS 335 ASN 338;ASP 351(magnesium binding)
1iasA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 333;LYS 335 ASN 338;ASP 351(magnesium binding)
1iasB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 333;LYS 335 ASN 338;ASP 351(magnesium binding)
1iasC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 333;LYS 335 ASN 338;ASP 351(magnesium binding)
1iasD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 333;LYS 335 ASN 338;ASP 351(magnesium binding)
1iasE02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 333;LYS 335 ASN 338;ASP 351(magnesium binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[5]
p.426-427

References
[1]
Resource
Comments 3D-STRUCTURE MODELING OF 34-114.
Medline ID 96096781
PubMed ID 8521960
Journal FEBS Lett
Year 1995
Volume 376
Pages 31-6
Authors Jokiranta TS, Tissari J, Teleman O, Meri S
Title Extracellular domain of type I receptor for transforming growth factor-beta: molecular modelling using protectin (CD59) as a template.
Related PDB
Related UniProtKB P36897
[2]
Resource
Comments
Medline ID
PubMed ID 8524844
Journal Proc Natl Acad Sci U S A
Year 1995
Volume 92
Pages 11761-5
Authors Luo K, Zhou P, Lodish HF
Title The specificity of the transforming growth factor beta receptor kinases determined by a spatially addressable peptide library.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 9233801
Journal EMBO J
Year 1997
Volume 16
Pages 3912-23
Authors Feng XH, Derynck R
Title A kinase subdomain of transforming growth factor-beta (TGF-beta) type I receptor determines the TGF-beta intracellular signaling specificity.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 9653550
Journal Chem Biol
Year 1998
Volume 5
Pages 321-8
Authors Eyers PA, Craxton M, Morrice N, Cohen P, Goedert M
Title Conversion of SB 203580-insensitive MAP kinase family members to drug-sensitive forms by a single amino-acid substitution.
Related PDB
Related UniProtKB
[5]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10025408
Journal Cell
Year 1999
Volume 96
Pages 425-36
Authors Huse M, Chen YG, Massague J, Kuriyan J
Title Crystal structure of the cytoplasmic domain of the type I TGF beta receptor in complex with FKBP12.
Related PDB 1b6c
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 10075688
Journal J Biol Chem
Year 1999
Volume 274
Pages 7929-35
Authors Armes NA, Neal KA, Smith JC
Title A short loop on the ALK-2 and ALK-4 activin receptors regulates signaling specificity but cannot account for all their effects on early Xenopus development.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 10887089
Journal Development
Year 2000
Volume 127
Pages 3337-47
Authors Gunther CV, Georgi LL, Riddle DL
Title A Caenorhabditis elegans type I TGF beta receptor can function in the absence of type II kinase to promote larval development.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 10973254
Journal Nat Genet
Year 2000
Volume 26
Pages 81-4
Authors Lane KB, Machado RD, Pauciulo MW, Thomson JR, Phillips JA 3rd, Loyd JE, Nichols WC, Trembath RC
Title Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. The International PPH Consortium.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 11251079
Journal Mol Biol Cell
Year 2001
Volume 12
Pages 675-84
Authors Dore JJ Jr, Yao D, Edens M, Garamszegi N, Sholl EL, Leof EB
Title Mechanisms of transforming growth factor-beta receptor endocytosis and intracellular sorting differ between fibroblasts and epithelial cells.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 11583628
Journal Mol Cell
Year 2001
Volume 8
Pages 671-82
Authors Huse M, Muir TW, Xu L, Chen YG, Kuriyan J, Massague J
Title The TGF beta receptor activation process: an inhibitor- to substrate-binding switch.
Related PDB 1ias
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 11904140
Journal FEBS Lett
Year 2002
Volume 513
Pages 147-52
Authors Guimond A, Sulea T, Zwaagstra JC, Ekiel I, O'Connor-McCourt MD
Title Identification of a functional site on the type I TGF-beta receptor by mutational analysis of its ectodomain.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 12015308
Journal J Biol Chem
Year 2002
Volume 277
Pages 29197-209
Authors Guerrero-Esteo M, Sanchez-Elsner T, Letamendia A, Bernabeu C
Title Extracellular and cytoplasmic domains of endoglin interact with the transforming growth factor-beta receptors I and II.
Related PDB
Related UniProtKB

Comments
The E.C. was transferred from 2.7.1.37 to 2.7.11.30.
This enzyme is composed of extracellular domain, transmembrane region, and cytoplasmic kinase domain.
PDB structures, 1b6c & 1ias, correspond to the catalytic kinase domain.
Although the tertiary structure of the catalytic domain has been determined, its catalytic mechanism is still unclear.
However, the active site residues are similar to the homologous tyrosine protein kinases (see M00129), except for arginine residue, which is changed to Lys. Instead, Lys335 seems to occupy the position of arginine residue in the homologous enzymes.

Created Updated
2003-07-22 2009-02-26