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 18420	15422 15422		16761 16761
PubChem	888 888	5957 5957		6022 6022

1b6cB01	Unbound	Unbound	Unbound	Unbound	Unbound
1b6cD01	Unbound	Unbound	Unbound	Unbound	Unbound
1b6cF01	Unbound	Unbound	Unbound	Unbound	Unbound
1b6cH01	Unbound	Unbound	Unbound	Unbound	Unbound
1iasA01	Unbound	Unbound	Unbound	Unbound	Unbound
1iasB01	Unbound	Unbound	Unbound	Unbound	Unbound
1iasC01	Unbound	Unbound	Unbound	Unbound	Unbound
1iasD01	Unbound	Unbound	Unbound	Unbound	Unbound
1iasE01	Unbound	Unbound	Unbound	Unbound	Unbound
1b6cB02	Unbound	Unbound	Unbound	Unbound	Unbound
1b6cD02	Unbound	Unbound	Unbound	Unbound	Unbound
1b6cF02	Unbound	Unbound	Unbound	Unbound	Unbound
1b6cH02	Unbound	Unbound	Unbound	Unbound	Unbound
1iasA02	Unbound	Unbound	Unbound	Unbound	Unbound
1iasB02	Unbound	Unbound	Unbound	Unbound	Unbound
1iasC02	Unbound	Unbound	Unbound	Unbound	Unbound
1iasD02	Unbound	Unbound	Unbound	Unbound	Unbound
1iasE02	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
1b6cD01
1b6cF01
1b6cH01
1iasA01
1iasB01
1iasC01
1iasD01
1iasE01
1b6cB02	ASP 333;LYS 335	ASN 338;ASP 351(magnesium binding)
1b6cD02	ASP 333;LYS 335	ASN 338;ASP 351(magnesium binding)
1b6cF02	ASP 333;LYS 335	ASN 338;ASP 351(magnesium binding)
1b6cH02	ASP 333;LYS 335	ASN 338;ASP 351(magnesium binding)
1iasA02	ASP 333;LYS 335	ASN 338;ASP 351(magnesium binding)
1iasB02	ASP 333;LYS 335	ASN 338;ASP 351(magnesium binding)
1iasC02	ASP 333;LYS 335	ASN 338;ASP 351(magnesium binding)
1iasD02	ASP 333;LYS 335	ASN 338;ASP 351(magnesium binding)
1iasE02	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.

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