EzCatDB: M00132
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DB codeM00132
RLCP classification3.103.130000.1162 : Transfer
CATH domainDomain 12.60.40.10 : Immunoglobulin-like
Domain 22.60.40.10 : Immunoglobulin-like
Domain 33.30.200.20 : Phosphorylase Kinase; domain 1
Domain 41.10.510.10 : Transferase(Phosphotransferase); domain 1Catalytic domain
E.C.2.7.10.1

CATH domainRelated DB codes (homologues)
1.10.510.10 : Transferase(Phosphotransferase); domain 1M00125,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-likeM00131,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 1M00125,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

Enzyme Name
UniProtKBKEGG

P04629
Protein nameHigh affinity nerve growth factor receptorreceptor 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
SynonymsEC 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
RefSeqNP_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)
PfamPF07714 (Pkinase_Tyr)
[Graphical view]


UniProtKB:Accession NumberP04629
Entry nameNTRK1_HUMAN
ActivityATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
SubunitExists 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).
Subcellular locationCell membrane, Single-pass type I membrane protein (By similarity). Note=Endocytosed to the endosomes upon treatment of cells with NGF (By similarity).
Cofactor

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00305C00002C00585C00008C01167
CompoundMagnesiumATP[Protein]-L-tyrosineADP[Protein]-L-tyrosine phosphate
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotidearomatic ring (only carbon atom),peptide/proteinamine group,nucleotidearomatic ring (only carbon atom),peptide/protein,phosphate group/phosphate ion
ChEBI18420
15422

16761

PubChem888
5957

6022

             
1he7AUnboundUnboundUnboundUnboundUnbound
1wwaXUnboundUnboundUnboundUnboundUnbound
1wwaYUnboundUnboundUnboundUnboundUnbound
1wwwXUnboundUnboundUnboundUnboundUnbound
1wwwYUnboundUnboundUnboundUnboundUnbound

Active-site residues
pdb
        
1he7A
1wwaX
1wwaY
1wwwX
1wwwY


references
[1]
CommentsFUNCTION
Medline ID91191557
PubMed ID1849459
JournalCell
Year1991
Volume65
Pages189-97
AuthorsKlein R, Jing SQ, Nanduri V, O'Rourke E, Barbacid M
TitleThe trk proto-oncogene encodes a receptor for nerve growth factor.
Related UniProtKBP04629
[2]
CommentsFUNCTION
Medline ID91218846
PubMed ID1850821
JournalNature
Year1991
Volume350
Pages678-83
AuthorsHempstead BL, Martin-Zanca D, Kaplan DR, Parada LF, Chao MV
TitleHigh-affinity NGF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor.
Related UniProtKBP04629
[3]
CommentsMUTAGENESIS OF TYR-791
Medline ID94179299
PubMed ID7510697
JournalJ Biol Chem
Year1994
Volume269
Pages8901-10
AuthorsLoeb DM, Stephens RM, Copeland T, Kaplan DR, Greene LA
TitleA 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 UniProtKBP04629
[4]
CommentsMUTAGENESIS, AND PHOSPHORYLATION SITES
Medline ID94206546
PubMed ID8155326
JournalNeuron
Year1994
Volume12
Pages691-705
AuthorsStephens RM, Loeb DM, Copeland TD, Pawson T, Greene LA, Kaplan DR
TitleTrk receptors use redundant signal transduction pathways involving SHC and PLC-gamma 1 to mediate NGF responses.
Related UniProtKBP04629
[5]
CommentsSTRUCTURE BY NMR OF 489-500
Medline ID96097066
PubMed ID8524391
JournalNature
Year1995
Volume378
Pages584-92
AuthorsZhou MM, Ravichandran KS, Olejniczak EF, Petros AM, Meadows RP, Sattler M, Harlan JE, Wade WS, Burakoff SJ, Fesik SW
TitleStructure and ligand recognition of the phosphotyrosine binding domain of Shc.
Related UniProtKBP04629
[6]
PubMed ID9278536
JournalJ Neurosci
Year1997
Volume17
Pages7007-16
AuthorsBhattacharyya A, Watson FL, Bradlee TA, Pomeroy SL, Stiles CD, Segal RA
TitleTrk receptors function as rapid retrograde signal carriers in the adult nervous system.
[7]
PubMed ID10103137
JournalEur J Neurosci
Year1999
Volume11
Pages1421-30
AuthorsDiaz-Rodriguez E, Cabrera N, Esparis-Ogando A, Montero JC, Pandiella A
TitleCleavage of the TrkA neurotrophin receptor by multiple metalloproteases generates signalling-competent truncated forms.
[8]
PubMed ID10092678
JournalJ Biol Chem
Year1999
Volume274
Pages9861-70
AuthorsMeakin SO, MacDonald JI, Gryz EA, Kubu CJ, Verdi JM
TitleThe signaling adapter FRS-2 competes with Shc for binding to the nerve growth factor receptor TrkA. A model for discriminating proliferation and differentiation.
[9]
CommentsVARIANT CIPA VAL-587
Medline ID99250414
PubMed ID10233776
JournalJ Invest Dermatol
Year1999
Volume112
Pages810-4
AuthorsYotsumoto S, Setoyama M, Hozumi H, Mizoguchi S, Fukumaru S, Kobayashi K, Saheki T, Kanzaki T
TitleA novel point mutation affecting the tyrosine kinase domain of the TRKA gene in a family with congenital insensitivity to pain with anhidrosis.
Related UniProtKBP04629
[10]
PubMed ID10691301
JournalJ Mol Neurosci
Year1999
Volume13
Pages141-58
AuthorsMacDonald JI, Verdi JM, Meakin SO
TitleActivity-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.
[11]
PubMed ID10490030
JournalNature
Year1999
Volume401
Pages184-8
AuthorsWiesmann C, Ultsch MH, Bass SH, de Vos AM
TitleCrystal structure of nerve growth factor in complex with the ligand-binding domain of the TrkA receptor.
Related PDB1wwa,1www
[12]
PubMed ID10748052
JournalJ Biol Chem
Year2000
Volume275
Pages18225-33
AuthorsMacDonald JI, Gryz EA, Kubu CJ, Verdi JM, Meakin SO
TitleDirect binding of the signaling adapter protein Grb2 to the activation loop tyrosines on the nerve growth factor receptor tyrosine kinase, TrkA.
[13]
PubMed ID10808049
JournalJ Neuroimmunol
Year2000
Volume107
Pages42-9
AuthorsDubus P, Parrens M, El-Mokhtari Y, Ferrer J, Groppi A, Merlio JP
TitleIdentification of novel trkA variants with deletions in leucine-rich motifs of the extracellular domain.
[14]
CommentsX-ray crystallography
PubMed ID11263982
JournalBiochem Biophys Res Commun
Year2001
Volume282
Pages131-41
AuthorsRobertson 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
TitleIdentification and structure of the nerve growth factor binding site on TrkA.
Related PDB1he7
[15]
PubMed ID11376656
JournalFEBS Lett
Year2001
Volume497
Pages20-5
AuthorsBrowes C, Rowe J, Brown A, Montano X
TitleAnalysis of trk A and p53 association.
[16]
PubMed ID11159935
JournalHum Mol Genet
Year2001
Volume10
Pages179-88
AuthorsMardy S, Miura Y, Endo F, Matsuda I, Indo Y
TitleCongenital insensitivity to pain with anhidrosis (CIPA): effect of TRKA (NTRK1) missense mutations on autophosphorylation of the receptor tyrosine kinase for nerve growth factor.
[17]
PubMed ID11147812
JournalJ Cell Physiol
Year2001
Volume186
Pages35-46
AuthorsMiranda C, Greco A, Miele C, Pierotti MA, Van Obberghen E
TitleIRS-1 and IRS-2 are recruited by TrkA receptor and oncogenic TRK-T1.
[18]
PubMed ID11238898
JournalMol Cell Biol
Year2001
Volume21
Pages1613-20
AuthorsQian X, Ginty DD
TitleSH2-B and APS are multimeric adapters that augment TrkA signaling.
[19]
PubMed ID11313867
JournalOncogene
Year2001
Volume20
Pages1229-34
AuthorsArevalo JC, Conde B, Hempstead BI, Chao MV, Martin-Zanca D, Perez P
TitleA novel mutation within the extracellular domain of TrkA causes constitutive receptor activation.
[20]
PubMed ID12446789
JournalMol Cell Biol
Year2002
Volume22
Pages8721-34
AuthorsNakamura T, Komiya M, Sone K, Hirose E, Gotoh N, Morii H, Ohta Y, Mori N
TitleGrit, 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.

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.

createdupdated
2002-12-202009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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