DB code: M00132

RLCP classification 3.103.130000.1162 : Transfer
CATH domain 2.60.40.10 : Immunoglobulin-like
2.60.40.10 : 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 M00136 M00196 M00197 M00198 M00304 M00323 M00325 M00326 M00327 M00328 M00329 M00330 M00331 M00332 M00333 M00335 M00339 M00344
2.60.40.10 : Immunoglobulin-like M00131 T00257 T00005 M00113 M00127 M00323 M00325 M00327 M00329 M00330 M00331 M00332 T00307 D00166 D00500 M00112 M00193 T00063 T00065 T00067 T00245
3.30.200.20 : Phosphorylase Kinase; domain 1 M00125 M00124 M00131 T00224 M00127 M00129 M00130 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
P04629 High affinity nerve growth factor receptor
EC 2.7.10.1
Neurotrophic tyrosine kinase receptor type 1
TRK1-transforming tyrosine kinase protein
Tropomyosin-related kinase A
Tyrosine kinase receptor
Tyrosine kinase receptor A
Trk-A
gp140trk
p140-TrkA
NP_001007793.1 (Protein)
NM_001007792.1 (DNA/RNA sequence)
NP_001012331.1 (Protein)
NM_001012331.1 (DNA/RNA sequence)
NP_002520.2 (Protein)
NM_002529.3 (DNA/RNA sequence)
PF07714 (Pkinase_Tyr)
[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
P04629 NTRK1_HUMAN ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Exists in a dynamic equilibrium between monomeric (low affinity) and dimeric (high affinity) structures. Binds SH2B2. Interacts with SQSTM1 which bridges NTRK1 to NGFR. Interacts with ARMS and NGFR. Can form a ternary complex with NGFR and ARMS and this complex is affected by the expression levels of ARMS. An increase in ARMS expression leads to a decreased association of NGFR and NTRK1 (By similarity). Cell membrane, Single-pass type I membrane protein (By similarity). Note=Endocytosed to the endosomes upon treatment of cells with NGF (By similarity).

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
1he7A Unbound Unbound Unbound Unbound Unbound
1wwaX Unbound Unbound Unbound Unbound Unbound
1wwaY Unbound Unbound Unbound Unbound Unbound
1wwwX Unbound Unbound Unbound Unbound Unbound
1wwwY 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
1he7A
1wwaX
1wwaY
1wwwX
1wwwY

References for Catalytic Mechanism
References Sections No. of steps in catalysis

References
[1]
Resource
Comments FUNCTION
Medline ID 91191557
PubMed ID 1849459
Journal Cell
Year 1991
Volume 65
Pages 189-97
Authors Klein R, Jing SQ, Nanduri V, O'Rourke E, Barbacid M
Title The trk proto-oncogene encodes a receptor for nerve growth factor.
Related PDB
Related UniProtKB P04629
[2]
Resource
Comments FUNCTION
Medline ID 91218846
PubMed ID 1850821
Journal Nature
Year 1991
Volume 350
Pages 678-83
Authors Hempstead BL, Martin-Zanca D, Kaplan DR, Parada LF, Chao MV
Title High-affinity NGF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor.
Related PDB
Related UniProtKB P04629
[3]
Resource
Comments MUTAGENESIS OF TYR-791
Medline ID 94179299
PubMed ID 7510697
Journal J Biol Chem
Year 1994
Volume 269
Pages 8901-10
Authors Loeb DM, Stephens RM, Copeland T, Kaplan DR, Greene LA
Title A Trk nerve growth factor (NGF) receptor point mutation affecting interaction with phospholipase C-gamma 1 abolishes NGF-promoted peripherin induction but not neurite outgrowth.
Related PDB
Related UniProtKB P04629
[4]
Resource
Comments MUTAGENESIS, AND PHOSPHORYLATION SITES
Medline ID 94206546
PubMed ID 8155326
Journal Neuron
Year 1994
Volume 12
Pages 691-705
Authors Stephens RM, Loeb DM, Copeland TD, Pawson T, Greene LA, Kaplan DR
Title Trk receptors use redundant signal transduction pathways involving SHC and PLC-gamma 1 to mediate NGF responses.
Related PDB
Related UniProtKB P04629
[5]
Resource
Comments STRUCTURE BY NMR OF 489-500
Medline ID 96097066
PubMed ID 8524391
Journal Nature
Year 1995
Volume 378
Pages 584-92
Authors Zhou MM, Ravichandran KS, Olejniczak EF, Petros AM, Meadows RP, Sattler M, Harlan JE, Wade WS, Burakoff SJ, Fesik SW
Title Structure and ligand recognition of the phosphotyrosine binding domain of Shc.
Related PDB
Related UniProtKB P04629
[6]
Resource
Comments
Medline ID
PubMed ID 9278536
Journal J Neurosci
Year 1997
Volume 17
Pages 7007-16
Authors Bhattacharyya A, Watson FL, Bradlee TA, Pomeroy SL, Stiles CD, Segal RA
Title Trk receptors function as rapid retrograde signal carriers in the adult nervous system.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 10103137
Journal Eur J Neurosci
Year 1999
Volume 11
Pages 1421-30
Authors Diaz-Rodriguez E, Cabrera N, Esparis-Ogando A, Montero JC, Pandiella A
Title Cleavage of the TrkA neurotrophin receptor by multiple metalloproteases generates signalling-competent truncated forms.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 10092678
Journal J Biol Chem
Year 1999
Volume 274
Pages 9861-70
Authors Meakin SO, MacDonald JI, Gryz EA, Kubu CJ, Verdi JM
Title The signaling adapter FRS-2 competes with Shc for binding to the nerve growth factor receptor TrkA. A model for discriminating proliferation and differentiation.
Related PDB
Related UniProtKB
[9]
Resource
Comments VARIANT CIPA VAL-587
Medline ID 99250414
PubMed ID 10233776
Journal J Invest Dermatol
Year 1999
Volume 112
Pages 810-4
Authors Yotsumoto S, Setoyama M, Hozumi H, Mizoguchi S, Fukumaru S, Kobayashi K, Saheki T, Kanzaki T
Title A novel point mutation affecting the tyrosine kinase domain of the TRKA gene in a family with congenital insensitivity to pain with anhidrosis.
Related PDB
Related UniProtKB P04629
[10]
Resource
Comments
Medline ID
PubMed ID 10691301
Journal J Mol Neurosci
Year 1999
Volume 13
Pages 141-58
Authors MacDonald JI, Verdi JM, Meakin SO
Title Activity-dependent interaction of the intracellular domain of rat trkA with intermediate filament proteins, the beta-6 proteasomal subunit, Ras-GRF1, and the p162 subunit of eIF3.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 10490030
Journal Nature
Year 1999
Volume 401
Pages 184-8
Authors Wiesmann C, Ultsch MH, Bass SH, de Vos AM
Title Crystal structure of nerve growth factor in complex with the ligand-binding domain of the TrkA receptor.
Related PDB 1wwa 1www
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 10748052
Journal J Biol Chem
Year 2000
Volume 275
Pages 18225-33
Authors MacDonald JI, Gryz EA, Kubu CJ, Verdi JM, Meakin SO
Title Direct binding of the signaling adapter protein Grb2 to the activation loop tyrosines on the nerve growth factor receptor tyrosine kinase, TrkA.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 10808049
Journal J Neuroimmunol
Year 2000
Volume 107
Pages 42-9
Authors Dubus P, Parrens M, El-Mokhtari Y, Ferrer J, Groppi A, Merlio JP
Title Identification of novel trkA variants with deletions in leucine-rich motifs of the extracellular domain.
Related PDB
Related UniProtKB
[14]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 11263982
Journal Biochem Biophys Res Commun
Year 2001
Volume 282
Pages 131-41
Authors Robertson AG, Banfield MJ, Allen SJ, Dando JA, Mason GG, Tyler SJ, Bennett GS, Brain SD, Clarke AR, Naylor RL, Wilcock GK, Brady RL, Dawbarn D
Title Identification and structure of the nerve growth factor binding site on TrkA.
Related PDB 1he7
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 11376656
Journal FEBS Lett
Year 2001
Volume 497
Pages 20-5
Authors Browes C, Rowe J, Brown A, Montano X
Title Analysis of trk A and p53 association.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 11159935
Journal Hum Mol Genet
Year 2001
Volume 10
Pages 179-88
Authors Mardy S, Miura Y, Endo F, Matsuda I, Indo Y
Title Congenital insensitivity to pain with anhidrosis (CIPA): effect of TRKA (NTRK1) missense mutations on autophosphorylation of the receptor tyrosine kinase for nerve growth factor.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 11147812
Journal J Cell Physiol
Year 2001
Volume 186
Pages 35-46
Authors Miranda C, Greco A, Miele C, Pierotti MA, Van Obberghen E
Title IRS-1 and IRS-2 are recruited by TrkA receptor and oncogenic TRK-T1.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 11238898
Journal Mol Cell Biol
Year 2001
Volume 21
Pages 1613-20
Authors Qian X, Ginty DD
Title SH2-B and APS are multimeric adapters that augment TrkA signaling.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 11313867
Journal Oncogene
Year 2001
Volume 20
Pages 1229-34
Authors Arevalo JC, Conde B, Hempstead BI, Chao MV, Martin-Zanca D, Perez P
Title A novel mutation within the extracellular domain of TrkA causes constitutive receptor activation.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 12446789
Journal Mol Cell Biol
Year 2002
Volume 22
Pages 8721-34
Authors Nakamura T, Komiya M, Sone K, Hirose E, Gotoh N, Morii H, Ohta Y, Mori N
Title Grit, a GTPase-activating protein for the Rho family, regulates neurite extension through association with the TrkA receptor and N-Shc and CrkL/Crk adapter molecules.
Related PDB
Related UniProtKB

Comments
The E.C. was transferred from 2.7.1.112 to 2.7.10.1.
This receptor enzyme has N-terminal extracellular region, transmembrane region, and C-terminal cytoplasmic region. The extracellular region is composed of two Ig-like C2-type domains, whilst the cytoplasmic region contains protein kinase domain, which is homologous to other tyrosine protein kinase domains (M00129 in EzCatDB). The structure of the catalytic domain has not been obtained, though. This receptor belongs to the Insulin receptor superfamily.
The PDB structures correspond to the second Ig-like C2-type domain.

Created Updated
2002-12-20 2009-02-26