EzCatDB: T00224
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DB codeT00224
RLCP classification3.103.130000.1161 : Transfer
CATH domainDomain 12.-.-.-
Domain 23.30.200.20 : Phosphorylase Kinase; domain 1
Domain 31.10.510.10 : Transferase(Phosphotransferase); domain 1Catalytic domain
E.C.2.7.11.30

CATH domainRelated DB codes (homologues)
1.10.510.10 : Transferase(Phosphotransferase); domain 1M00125,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 1M00125,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

Enzyme Name
UniProtKBKEGG

P36897
Protein nameTGF-beta receptor type-1receptor 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
SynonymsEC 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
RefSeqNP_001124388.1 (Protein)
NM_001130916.1 (DNA/RNA sequence)
NP_004603.1 (Protein)
NM_004612.2 (DNA/RNA sequence)
PfamPF01064 (Activin_recp)
PF00069 (Pkinase)
PF08515 (TGF_beta_GS)
[Graphical view]


UniProtKB:Accession NumberP36897
Entry nameTGFR1_HUMAN
ActivityATP + [receptor-protein] = ADP + [receptor- protein] phosphate.
SubunitInteracts 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.
Subcellular locationMembrane, Single-pass type I membrane protein.
CofactorMagnesium or manganese (By similarity).

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00305C00002C00017C00008C00562
CompoundMagnesiumATP[Receptor-protein]ADP[Receptor-protein] phosphate
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotidepeptide/proteinamine group,nucleotidepeptide/protein,phosphate group/phosphate ion
ChEBI18420
15422

16761

PubChem888
5957

6022

             
1b6cB01UnboundUnboundUnboundUnboundUnbound
1b6cD01UnboundUnboundUnboundUnboundUnbound
1b6cF01UnboundUnboundUnboundUnboundUnbound
1b6cH01UnboundUnboundUnboundUnboundUnbound
1iasA01UnboundUnboundUnboundUnboundUnbound
1iasB01UnboundUnboundUnboundUnboundUnbound
1iasC01UnboundUnboundUnboundUnboundUnbound
1iasD01UnboundUnboundUnboundUnboundUnbound
1iasE01UnboundUnboundUnboundUnboundUnbound
1b6cB02UnboundUnboundUnboundUnboundUnbound
1b6cD02UnboundUnboundUnboundUnboundUnbound
1b6cF02UnboundUnboundUnboundUnboundUnbound
1b6cH02UnboundUnboundUnboundUnboundUnbound
1iasA02UnboundUnboundUnboundUnboundUnbound
1iasB02UnboundUnboundUnboundUnboundUnbound
1iasC02UnboundUnboundUnboundUnboundUnbound
1iasD02UnboundUnboundUnboundUnboundUnbound
1iasE02UnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P36897, literature [5] & similarity with M00129
pdbCatalytic residuesCofactor-binding residues
          
1b6cB01 
 
1b6cD01 
 
1b6cF01 
 
1b6cH01 
 
1iasA01 
 
1iasB01 
 
1iasC01 
 
1iasD01 
 
1iasE01 
 
1b6cB02ASP 333;LYS 335
ASN 338;ASP 351(magnesium binding)
1b6cD02ASP 333;LYS 335
ASN 338;ASP 351(magnesium binding)
1b6cF02ASP 333;LYS 335
ASN 338;ASP 351(magnesium binding)
1b6cH02ASP 333;LYS 335
ASN 338;ASP 351(magnesium binding)
1iasA02ASP 333;LYS 335
ASN 338;ASP 351(magnesium binding)
1iasB02ASP 333;LYS 335
ASN 338;ASP 351(magnesium binding)
1iasC02ASP 333;LYS 335
ASN 338;ASP 351(magnesium binding)
1iasD02ASP 333;LYS 335
ASN 338;ASP 351(magnesium binding)
1iasE02ASP 333;LYS 335
ASN 338;ASP 351(magnesium binding)

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[5]p.426-427

references
[1]
Comments3D-STRUCTURE MODELING OF 34-114.
Medline ID96096781
PubMed ID8521960
JournalFEBS Lett
Year1995
Volume376
Pages31-6
AuthorsJokiranta TS, Tissari J, Teleman O, Meri S
TitleExtracellular domain of type I receptor for transforming growth factor-beta: molecular modelling using protectin (CD59) as a template.
Related UniProtKBP36897
[2]
PubMed ID8524844
JournalProc Natl Acad Sci U S A
Year1995
Volume92
Pages11761-5
AuthorsLuo K, Zhou P, Lodish HF
TitleThe specificity of the transforming growth factor beta receptor kinases determined by a spatially addressable peptide library.
[3]
PubMed ID9233801
JournalEMBO J
Year1997
Volume16
Pages3912-23
AuthorsFeng XH, Derynck R
TitleA kinase subdomain of transforming growth factor-beta (TGF-beta) type I receptor determines the TGF-beta intracellular signaling specificity.
[4]
PubMed ID9653550
JournalChem Biol
Year1998
Volume5
Pages321-8
AuthorsEyers PA, Craxton M, Morrice N, Cohen P, Goedert M
TitleConversion of SB 203580-insensitive MAP kinase family members to drug-sensitive forms by a single amino-acid substitution.
[5]
CommentsX-ray crystallography
PubMed ID10025408
JournalCell
Year1999
Volume96
Pages425-36
AuthorsHuse M, Chen YG, Massague J, Kuriyan J
TitleCrystal structure of the cytoplasmic domain of the type I TGF beta receptor in complex with FKBP12.
Related PDB1b6c
[6]
PubMed ID10075688
JournalJ Biol Chem
Year1999
Volume274
Pages7929-35
AuthorsArmes NA, Neal KA, Smith JC
TitleA 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.
[7]
PubMed ID10887089
JournalDevelopment
Year2000
Volume127
Pages3337-47
AuthorsGunther CV, Georgi LL, Riddle DL
TitleA Caenorhabditis elegans type I TGF beta receptor can function in the absence of type II kinase to promote larval development.
[8]
PubMed ID10973254
JournalNat Genet
Year2000
Volume26
Pages81-4
AuthorsLane KB, Machado RD, Pauciulo MW, Thomson JR, Phillips JA 3rd, Loyd JE, Nichols WC, Trembath RC
TitleHeterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. The International PPH Consortium.
[9]
PubMed ID11251079
JournalMol Biol Cell
Year2001
Volume12
Pages675-84
AuthorsDore JJ Jr, Yao D, Edens M, Garamszegi N, Sholl EL, Leof EB
TitleMechanisms of transforming growth factor-beta receptor endocytosis and intracellular sorting differ between fibroblasts and epithelial cells.
[10]
PubMed ID11583628
JournalMol Cell
Year2001
Volume8
Pages671-82
AuthorsHuse M, Muir TW, Xu L, Chen YG, Kuriyan J, Massague J
TitleThe TGF beta receptor activation process: an inhibitor- to substrate-binding switch.
Related PDB1ias
[11]
PubMed ID11904140
JournalFEBS Lett
Year2002
Volume513
Pages147-52
AuthorsGuimond A, Sulea T, Zwaagstra JC, Ekiel I, O'Connor-McCourt MD
TitleIdentification of a functional site on the type I TGF-beta receptor by mutational analysis of its ectodomain.
[12]
PubMed ID12015308
JournalJ Biol Chem
Year2002
Volume277
Pages29197-209
AuthorsGuerrero-Esteo M, Sanchez-Elsner T, Letamendia A, Bernabeu C
TitleExtracellular and cytoplasmic domains of endoglin interact with the transforming growth factor-beta receptors I and II.

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.

createdupdated
2003-07-222009-02-26


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Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
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Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
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