DB code: M00136

RLCP classification 3.103.130000.358 : Transfer
CATH domain 3.80.20.20 : 24 nucleotide stem-loop, u2 snrnp hairpin iv. U2 a'; Chain A
2.10.220.10 : Hormone Receptor, Insulin-like Growth Factor Receptor 1; Chain A domain 2
3.80.20.20 : 24 nucleotide stem-loop, u2 snrnp hairpin iv. U2 a'; Chain A
-.-.-.- :
2.60.40.30 : Immunoglobulin-like
3.30.200.20 : Phosphorylase Kinase; domain 1
1.10.510.10 : Transferase(Phosphotransferase); domain 1 Catalytic domain
E.C. 2.7.10.1
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
1.10.510.10 : Transferase(Phosphotransferase); domain 1 M00125 M00124 M00131 T00224 M00127 M00129 M00130 M00132 M00196 M00197 M00198 M00304 M00323 M00325 M00326 M00327 M00328 M00329 M00330 M00331 M00332 M00333 M00335 M00339 M00344
2.60.40.30 : Immunoglobulin-like M00124 M00134 M00129 M00149 M00192
3.30.200.20 : Phosphorylase Kinase; domain 1 M00125 M00124 M00131 T00224 M00127 M00129 M00130 M00132 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 Contains RefSeq Pfam
P08069 Insulin-like growth factor 1 receptor (EC 2.7.10.1) (Insulin-like growth factor I receptor) (IGF-I receptor)AltName: CD_antigen=CD221;
None Insulin-like growth factor 1 receptor alpha chain
Insulin-like growth factor 1 receptor beta chain
NP_000866.1 (Protein)
NM_000875.3 (DNA/RNA sequence)
PF00041 (fn3)
PF00757 (Furin-like)
PF07714 (Pkinase_Tyr)
PF01030 (Recep_L_domain)
[Graphical View]

KEGG enzyme name
receptor protein-tyrosine kinase
AATK
AATYK
AATYK2
AATYK3
ACH
ALK
anaplastic lymphoma kinase
ARK
ATP:protein-tyrosine O-phosphotransferase (ambiguous)
AXL
Bek
Bfgfr
BRT
Bsk
C-FMS
CAK
CCK4
CD115
CD135
CDw135
Cek1
Cek10
Cek11
Cek2
Cek3
Cek5
Cek6
Cek7
CFD1
CKIT
CSF1R
DAlk
DDR1
DDR2
Dek
DKFZp434C1418
Drosophila Eph kinase
DRT
DTK
Ebk
ECK
EDDR1
Eek
EGFR
Ehk2
Ehk3
Elk
EPH
EPHA1
EPHA2
EPHA6
EPHA7
EPHA8
EPHB1
EPHB2
EPHB3
EPHB4
EphB5
ephrin-B3 receptor tyrosine kinase
EPHT
EPHT2
EPHT3
EPHX
ERBB
ERBB1
ERBB2
ERBB3
ERBB4
ERK
Eyk
FGFR1
FGFR2
FGFR3
FGFR4
FLG
FLK1
FLK2
FLT1
FLT2
FLT3
FLT4
FMS
Fv2
HBGFR
HEK11
HEK2
HEK3
HEK5
HEK6
HEP
HER2
HER3
HER4
HGFR
HSCR1
HTK
IGF1R
INSR
INSRR
insulin receptor protein-tyrosine kinase
IR
IRR
JTK12
JTK13
JTK14
JWS
K-SAM
KDR
KGFR
KIA0641
KIAA1079
KIAA1459
Kil
Kin15
Kin16
KIT
KLG
LTK
MCF3
Mdk1
Mdk2
Mdk5
MEhk1
MEN2A/B
Mep
MER
MERTK
MET
Mlk1
Mlk2
Mrk
MST1R
MTC1
MUSK
Myk1
N-SAM
NEP
NET
Neu
neurite outgrowth regulating kinase
NGL
NOK
nork
novel oncogene with kinase-domain
Nsk2
NTRK1
NTRK2
NTRK3
NTRK4
NTRKR1
NTRKR2
NTRKR3
Nuk
NYK
PCL
PDGFR
PDGFRA
PDGFRB
PHB6
protein-tyrosine kinase (ambiguous)
protein tyrosine kinase (ambiguous)
PTK
PTK3
PTK7
receptor protein tyrosine kinase
RET
RON
ROR1
ROR2
ROS1
RSE
RTK
RYK
SEA
Sek2
Sek3
Sek4
Sfr
SKY
STK
STK1
TEK
TIE
TIE1
TIE2
TIF
TKT
TRK
TRKA
TRKB
TRKC
TRKE
TYK1
TYRO10
Tyro11
TYRO3
Tyro5
Tyro6
TYRO7
UFO
VEGFR1
VEGFR2
VEGFR3
Vik
YK1
Yrk

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P08069 IGF1R_HUMAN ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Tetramer of 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains contribute to the formation of the ligand- binding domain, while the beta chain carries the kinase domain. Interacts with PIK3R1 and with the PTB/PID domains of IRS1 and SHC1 in vitro when autophosphorylated on tyrosine residues. Membrane, Single-pass type I membrane protein.

KEGG Pathways
Map code Pathways E.C.

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00002 C00585 C00008 C01167
E.C.
Compound Magnesium ATP [Protein]-L-tyrosine ADP [Protein]-L-tyrosine phosphate
Type divalent metal (Ca2+, Mg2+) amine group,nucleotide aromatic ring (only carbon atom),peptide/protein amine group,nucleotide aromatic ring (only carbon atom),peptide/protein,phosphate group/phosphate ion
ChEBI 18420
 18420
 		15422
 15422
 		16761
 16761
PubChem 888
 888
 		5957
 5957
 		6022
 6022
1igrA01 Unbound Unbound Unbound Unbound Unbound
1igrA02 Unbound Unbound Unbound Unbound Unbound
1igrA03 Unbound Unbound Unbound Unbound Unbound
1jqhA01 Bound:_MG Analogue:ANP Unbound Unbound Unbound
1jqhB01 Unbound Analogue:ANP Unbound Unbound Unbound
1jqhC01 Unbound Analogue:ANP Unbound Unbound Unbound
1k3aA01 Unbound Analogue:ACP Bound:G-E-Y-V-N-I-E-F (chain B) Unbound Unbound
1m7nA01 Unbound Unbound Unbound Unbound Unbound
1m7nB01 Unbound Unbound Unbound Unbound Unbound
1p4oA01 Unbound Unbound Unbound Unbound Unbound
1p4oB01 Unbound Unbound Unbound Unbound Unbound
1jqhA02 Unbound Unbound Unbound Unbound Unbound
1jqhB02 Unbound Unbound Unbound Unbound Unbound
1jqhC02 Unbound Unbound Unbound Unbound Unbound
1k3aA02 Unbound Unbound Unbound Unbound Unbound
1m7nA02 Unbound Unbound Unbound Unbound Unbound
1m7nB02 Unbound Unbound Unbound Unbound Unbound
1p4oA02 Unbound Unbound Unbound Unbound Unbound
1p4oB02 Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1igrA01
1igrA02
1igrA03
1jqhA01
1jqhB01
1jqhC01
1k3aA01
1m7nA01
1m7nB01
1p4oA01
1p4oB01
1jqhA02 ASP 1135;ARG 1139 ;TYR 1165;TYR 1166(auto-phosphorylation)
1jqhB02 ASP 1135;ARG 1139 ;TYR 1165;TYR 1166(auto-phosphorylation)
1jqhC02 ASP 1135;ARG 1139 ;TYR 1165;TYR 1166(auto-phosphorylation)
1k3aA02 ASP 1105;ARG 1109 PTR 1131;PTR 1135;PTR 1136(auto-phosphorylation)
1m7nA02 ASP 1132;ARG 1136 TYR 1158;TYR 1162;TYR 1163(auto-phosphorylation)
1m7nB02 ASP 1132;ARG 1136 TYR 1158;TYR 1162;TYR 1163(auto-phosphorylation)
1p4oA02 ASP 1105;ARG 1109 TYR 1131;TYR 1135;TYR 1136(auto-phosphorylation)
1p4oB02 ASP 1105;ARG 1109 TYR 1131;TYR 1135;TYR 1136(auto-phosphorylation)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[17]
p.10061
[19]
p.959

References
[1]
Resource
Comments
Medline ID
PubMed ID 7514345
Journal Adv Exp Med Biol
Year 1993
Volume 343
Pages 33-40
Authors Cascieri MA, Bayne ML
Title Analysis of the interaction of IGF-I analogs with the IGF-I receptor and IGF binding proteins.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 7868068
Journal Horm Res
Year 1994
Volume 42
Pages 152-69
Authors De Meyts P, Wallach B, Christoffersen CT, Urso B, Gronskov K, Latus LJ, Yakushiji F, Ilondo MM, Shymko RM
Title The insulin-like growth factor-I receptor. Structure, ligand-binding mechanism and signal transduction.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 9202243
Journal Endocrinology
Year 1997
Volume 138
Pages 2979-88
Authors Esposito DL, Blakesley VA, Koval AP, Scrimgeour AG, LeRoith D
Title Tyrosine residues in the C-terminal domain of the insulin-like growth factor-I receptor mediate mitogenic and tumorigenic signals.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 9416620
Journal Protein Sci
Year 1997
Volume 6
Pages 2663-6
Authors McKern NM, Lou M, Frenkel MJ, Verkuylen A, Bentley JD, Lovrecz GO, Ivancic N, Elleman TC, Garrett TP, Cosgrove LJ, Ward CW
Title Crystallization of the first three domains of the human insulin-like growth factor-1 receptor.
Related PDB
Related UniProtKB
[5]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 9690478
Journal Nature
Year 1998
Volume 394
Pages 395-9
Authors Garrett TP, McKern NM, Lou M, Frenkel MJ, Bentley JD, Lovrecz GO, Elleman TC, Cosgrove LJ, Ward CW
Title Crystal structure of the first three domains of the type-1 insulin-like growth factor receptor.
Related PDB 1igr
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 10026153
Journal J Biol Chem
Year 1999
Volume 274
Pages 5422-8
Authors Arbet-Engels C, Tartare-Deckert S, Eckhart W
Title C-terminal Src kinase associates with ligand-stimulated insulin-like growth factor-I receptor.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 11162456
Journal Biochem Biophys Res Commun
Year 2000
Volume 279
Pages 955-60
Authors Lopaczynski W, Terry C, Nissley P
Title Autophosphorylation of the insulin-like growth factor I receptor cytoplasmic domain.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 10816097
Journal Biochem Soc Trans
Year 2000
Volume 28
Pages 47-51
Authors O'Connor R, Fennelly C, Krause D
Title Regulation of survival signals from the insulin-like growth factor-I receptor.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 11162597
Journal Biochem Biophys Res Commun
Year 2001
Volume 280
Pages 836-41
Authors Maggi D, Cordera R
Title Cys 786 and Cys 776 in the posttranslational processing of the insulin and IGF-I receptors.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 11498020
Journal Biochem Soc Trans
Year 2001
Volume 29
Pages 513-25
Authors Siddle K, Urso B, Niesler CA, Cope DL, Molina L, Surinya KH, Soos MA
Title Specificity in ligand binding and intracellular signalling by insulin and insulin-like growth factor receptors.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 11714281
Journal Biochemistry
Year 2001
Volume 40
Pages 14268-78
Authors Baer K, Al-Hasani H, Parvaresch S, Corona T, Rufer A, Nolle V, Bergschneider E, Klein HW
Title Dimerization-induced activation of soluble insulin/IGF-1 receptor kinases: an alternative mechanism of activation.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 11737239
Journal Eur J Clin Invest
Year 2001
Volume 31
Pages 966-77
Authors Van Obberghen E, Baron V, Delahaye L, Emanuelli B, Filippa N, Giorgetti-Peraldi S, Lebrun P, Mothe-Satney I, Peraldi P, Rocchi S, Sawka-Verhelle D, Tartare-Deckert S, Giudicelli J
Title Surfing the insulin signaling web.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 11445579
Journal J Biol Chem
Year 2001
Volume 276
Pages 33419-27
Authors Ligensa T, Krauss S, Demuth D, Schumacher R, Camonis J, Jaques G, Weidner KM
Title A PDZ domain protein interacts with the C-terminal tail of the insulin-like growth factor-1 receptor but not with the insulin receptor.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 11445567
Journal J Biol Chem
Year 2001
Volume 276
Pages 33608-15
Authors Brodt P, Fallavollita L, Khatib AM, Samani AA, Zhang D
Title Cooperative regulation of the invasive and metastatic phenotypes by different domains of the type I insulin-like growth factor receptor beta subunit.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 11500492
Journal J Biol Chem
Year 2001
Volume 276
Pages 43980-6
Authors Whittaker J, Groth AV, Mynarcik DC, Pluzek L, Gadsboll VL, Whittaker LJ
Title Alanine scanning mutagenesis of a type 1 insulin-like growth factor receptor ligand binding site.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 11376122
Journal Mol Pathol
Year 2001
Volume 54
Pages 125-32
Authors Ward CW, Garrett TP, McKern NM, Lou M, Cosgrove LJ, Sparrow LG, Frenkel MJ, Hoyne PA, Elleman TC, Adams TE, Lovrecz GO, Lawrence LJ, Tulloch PA
Title The three dimensional structure of the type I insulin-like growth factor receptor.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 11694888
Journal Nat Struct Biol
Year 2001
Volume 8
Pages 1058-63
Authors Favelyukis S, Till JH, Hubbard SR, Miller WT
Title Structure and autoregulation of the insulin-like growth factor 1 receptor kinase.
Related PDB 1k3a
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 11287679
Journal Protein Eng
Year 2001
Volume 14
Pages 61-5
Authors Geddes S, Holst P, Grotzinger J, Gill R, Nugent P, De Meyts P, Wollmer A, Wood S, Pitts J
Title Structure-function studies of an IGF-I analogue that can be chemically cleaved to a two-chain mini-IGF-I.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 11591350
Journal Structure (Camb)
Year 2001
Volume 9
Pages 955-65
Authors Pautsch A, Zoephel A, Ahorn H, Spevak W, Hauptmann R, Nar H
Title Crystal structure of bisphosphorylated IGF-1 receptor kinase: insight into domain movements upon kinase activation.
Related PDB 1jqh
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 12138114
Journal J Biol Chem
Year 2002
Volume 277
Pages 38797-802
Authors Munshi S, Kornienko M, Hall DL, Reid JC, Waxman L, Stirdivant SM, Darke PL, Kuo LC
Title Crystal structure of the Apo, unactivated insulin-like growth factor-1 receptor kinase. Implication for inhibitor specificity.
Related PDB 1m7n 1p4o
Related UniProtKB

Comments
The E.C. was transferred from 2.7.1.112 to 2.7.10.1.
This protein is a receptor enzyme, insulin-like growth factor I receptor, composed of two chains, alpha and beta. PDB structure, 1igr, corresponds to the N-terminal domains of the alpha chain. The beta chain is composed of an extracellular reagion, transmembrane region, and a cytoplasmic region. The extracellular region contains a fibronectin type-III domain, whilst the cytoplasmic region has got a kinase domain. PDB structures, 1jqh, 1k3a, 1m7n & 1p4o, correspond to the kinase domain.
According to the literature [17] & [19], Asp1105 (of PDB entry 1k3a) seemes to be a general base, which can activate the acceptor group, the hydroxyl group of substrate tyrosine, which in turn would make a nucleophilic attack on the transferred group, gamma-phosphate group of ATP. Arg1109 also seems to interact with both the general base and the acceptor hydroxyl group. Although two magnesium ions are coordinated to the beta- and gamma-phosphates of ATP analogue in a homologous receptor enzyme, Insulin receptor kinase (see M00129), only one magnesium ion is coordinated by the alpha- and gamma-phosphates and two water molecules (see [19]).

Created Updated
2004-03-30 2009-02-26