Protein detail
NTRK1
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)
Protein symbol NTRK1 | UniProt ID | EVMP score 0.25 |
Frequency 1 | Transmembrane count 1 | Protein classification Cancer-related genesDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPredicted intracellular proteinsPredicted membrane proteinsRAS pathway related proteins |
Basic Information
Protein Names
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)
Protein Class
Cancer-related genesDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPredicted intracellular proteinsPredicted membrane proteinsRAS pathway related proteins
Protein Function
- Human disease related genes:Cancers:Cancers of eye, brain, and central nervous system
- Human disease related genes:Nervous system diseases:Other nervous and sensory system diseases
- Predicted intracellular proteins
- ENZYME proteins:Transferases
- Human disease related genes:Cancers:Cancers of endocrine organs
- RAS pathway related proteins
- Enzymes
- Cancer-related genes:Candidate cancer biomarkers
- Kinases:Tyr protein kinases
- Disease related genes
- FDA approved drug targets:Small molecule drugs
Transmembrane
424..439; Helical
Transmembrane Count
1
Ensembl
Entrez Gene Symbol
Gene Synonym
MTCTRKTRKA
Gene Description
Neurotrophic receptor tyrosine kinase 1
Chromosome
1
Position
156815636-156881850
Frequency
1
EVMP Score
0.25
Fluorescence & Localization
Cell SpecificNeutrophil progenitorsSingle-Nuclei Brain Specificleukocyte
Function & Pathway
Protein Function
- Human disease related genes:Cancers:Cancers of eye, brain, and central nervous system
- Human disease related genes:Nervous system diseases:Other nervous and sensory system diseases
- Predicted intracellular proteins
- ENZYME proteins:Transferases
- Human disease related genes:Cancers:Cancers of endocrine organs
- RAS pathway related proteins
- Enzymes
- Cancer-related genes:Candidate cancer biomarkers
- Kinases:Tyr protein kinases
- Disease related genes
- FDA approved drug targets:Small molecule drugs
Cellular Component
- GO:0005739 mitochondrion
- GO:0005769 early endosome
- GO:0005770 late endosome
- GO:0005886 plasma membrane
- GO:0009986 cell surface
- GO:0010008 endosome membrane
- GO:0030424 axon
- GO:0030425 dendrite
- GO:0031901 early endosome membrane
- GO:0031902 late endosome membrane
- GO:0032991 protein-containing complex
- GO:0043025 neuronal cell body
- GO:0043235 receptor complex
- GO:0055038 recycling endosome membrane
Molecular Function
- GO:0004713 protein tyrosine kinase activity
- GO:0004714 transmembrane receptor protein tyrosine kinase activity
- GO:0005004 GPI-linked ephrin receptor activity
- GO:0005030 neurotrophin receptor activity
- GO:0005166 neurotrophin p75 receptor binding
- GO:0005515 protein binding
- GO:0005524 ATP binding
- GO:0010465 nerve growth factor receptor activity
- GO:0019900 kinase binding
- GO:0042802 identical protein binding
- GO:0042803 protein homodimerization activity
- GO:0043121 neurotrophin binding
- GO:0048406 nerve growth factor binding
Biological Process
KEGG
- hsa04010 MAPK signaling pathway
- KEGG:hsa04014 Ras signaling pathway
- KEGG:hsa04020 Calcium signaling pathway
- KEGG:hsa04151 PI3K-Akt signaling pathway
- KEGG:hsa04210 Apoptosis
- KEGG:hsa04722 Neurotrophin signaling pathway
- KEGG:hsa04750 Inflammatory mediator regulation of TRP channels
- KEGG:hsa05200 Pathways in cancer
- KEGG:hsa05202 Transcriptional misregulation in cancer
- KEGG:hsa05216 Thyroid cancer
- KEGG:hsa05230 Central carbon metabolism in cancer
Reactome
- R-hsa-187015 activation of trka receptors
- R-hsa-170984 arms mediated activation
- R-hsa-187024 ngf independant trka activation
- R-hsa-198203 pi3k akt activation
- R-hsa-169893 prolonged erk activation events
- R-hsa-177504 retrograde neurotrophin signalling
- R-hsa-166520 signaling by ntrks
- R-hsa-9006934 signaling by receptor tyrosine kinases
- R-hsa-187687 signalling to erks
- R-hsa-187706 signalling to p38 via rit and rin
- R-hsa-167044 signalling to ras
Mediation Categories
Clinical-translation mediationFusion and delivery mediationImmune mediationReceptor-signaling mediation
Relations & Evidence
Enzyme-Mediated Modification
22 records.
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Ligand-Receptor Signaling
66 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| receptor | receptor | Baccin2019 | No | Yes | No | Yes | No |
| receptor | receptor | SignaLink_function | No | Yes | No | Yes | No |
| kinase | receptor | Almen2009 | No | Yes | No | Yes | No |
| neurotrophin | receptor | Almen2009 | No | Yes | No | Yes | No |
| growth_factor | receptor | Baccin2019 | No | Yes | No | Yes | No |
| receptor_tyrosine_kinases_rtk | receptor | HPMR | No | Yes | No | Yes | No |
| ngfr_ntr_trk | receptor | HPMR | No | Yes | No | Yes | No |
| kinase | receptor | Surfaceome | No | Yes | No | Yes | No |
| neutrophin | receptor | Surfaceome | No | Yes | No | Yes | No |
| receptor | receptor | OmniPath | No | Yes | No | Yes | No |
Regulatory Interaction Network
22 records.
| Source Protein Symbol | Source UniProt ID | Target Protein Symbol | Target UniProt ID | Is Directed | Is Stimulation | Is Inhibition | Database | References |
|---|---|---|---|---|---|---|---|---|
| NTRK1 | P04629 | SH2B1 | Q9NRF2 | Yes | Yes | No | PhosphoPointSIGNORProtMapperHPRDHINTSignaLink3WangLit-BM-17PhosphoSitePhosphoSite_ProtMapper | Lit-BM-17:9856458SIGNOR:15082760PhosphoSite:29229648HPRD:9856458HPRD:10708759SignaLink3:9856458SignaLink3:23331499SignaLink3:15082760Lit-BM-17:10708759HINT:10708759HINT:9856458 |
| NTRK1 | P04629 | SH2B2 | O14492 | Yes | Yes | No | PhosphoPointSIGNORHPRDSignaLink3WangLit-BM-17 | Lit-BM-17:9856458SIGNOR:9856458Lit-BM-17:25921289HPRD:9856458SignaLink3:9856458SignaLink3:23331499 |
| NTRK1 | P04629 | SHC3 | Q92529 | Yes | Yes | No | PhosphoSite_MIMPMIMPiPTMnetPhosphoPointSIGNORHPRDWangPhosphoSite | SIGNOR:11791173HPRD:9507002PhosphoSite:11791173 |
| PTN6 | P29350 | NTRK1 | P04629 | Yes | No | Yes | SIGNORProtMapperDEPODSIGNOR_ProtMapperSPIKE_LC | ProtMapper:14662744DEPOD:14662744SPIKE_LC:15557341SIGNOR:14662744 |
| PTN1 | P18031 | NTRK1 | P04629 | Yes | No | Yes | DOMINOSIGNORHPRDInnateDBSPIKE_LC | InnateDB:12237455HPRD:12237455DOMINO:12237455SIGNOR:28919207SPIKE_LC:12237455 |
| NTRK1 | P04629 | CTNB1 | P35222 | Yes | Yes | No | Sparser_ProtMapperiPTMnetSIGNORProtMapperREACH_ProtMapperPhosphoSite_ProtMapper | ProtMapper:21970630ProtMapper:22558232SIGNOR:22558232 |
| SRC | P12931 | NTRK1 | P04629 | Yes | Yes | No | Sparser_ProtMapperSIGNORProtMapperKEALi2012REACH_ProtMapperNetworKIN_KEA | KEA:17570479ProtMapper:23319303ProtMapper:16860569SIGNOR:20219970 |
| FYN | P06241 | NTRK1 | P04629 | Yes | Yes | No | SIGNOR | SIGNOR:16860569 |
| DUS26 | Q9BV47 | NTRK1 | P04629 | Yes | No | Yes | SIGNOR | SIGNOR:28701747 |
| RAB7A | P51149 | NTRK1 | P04629 | Yes | No | Yes | SIGNOR | SIGNOR:16306406 |
Protein Complex Composition
3 records.
| Component Name | Component Gene Symbols | Component UniProt ID | Stoichiometry | Database | Database IDs | References |
|---|---|---|---|---|---|---|
| NGF-TrkA complex | NGFNTRK1 | P01138P04629 | 2:2 | CompleatCORUMPDB | PDB:1wwwCORUM:5407PDB:2ifgCompleat:HC1345 | 10490030 |
| NTRK1 | P04629 | 2 | PDB | PDB:6iqnPDB:8ytePDB:4f0iPDB:2n90PDB:1wwaPDB:4aojPDB:6dkwPDB:6pmePDB:7n3t | ||
| NTRK1SHC1 | P04629P29353 | 1:1 | PDB | PDB:1shc |
Isolation & Detection Technology
1 record.
| EV Isolation Method | Detection Method | Number of References | References |
|---|---|---|---|
| Differential UltracentrifugationSize Exclusion Chromatography | Mass spectrometry | 1 | 30875722 |
Sequence, Structure & Domains
Sequences
Length
796
Mass
87,497
Sequence
MLRGGRRGQLGWHSWAAGPGSLLAWLILASAGAAPCPDACCPHGSSGLRCTRDGALDSLHHLPGAENLTELYIENQQHLQHLELRDLRGLGELRNLTIVKSGLRFVAPDAFHFTPRLSRLNLSFNALESLSWKTVQGLSLQELVLSGNPLHCSCALRWLQRWEEEGLGGVPEQKLQCHGQGPLAHMPNASCGVPTLKVQVPNASVDVGDDVLLRCQVEGRGLEQAGWILTELEQSATVMKSGGLPSLGLTLANVTSDLNRKNVTCWAENDVGRAEVSVQVNVSFPASVQLHTAVEMHHWCIPFSVDGQPAPSLRWLFNGSVLNETSFIFTEFLEPAANETVRHGCLRLNQPTHVNNGNYTLLAANPFGQASASIMAAFMDNPFEFNPEDPIPVSFSPVDTNSTSGDPVEKKDETPFGVSVAVGLAVFACLFLSTLLLVLNKCGRRNKFGINRPAVLAPEDGLAMSLHFMTLGGSSLSPTEGKGSGLQGHIIENPQYFSDACVHHIKRRDIVLKWELGEGAFGKVFLAECHNLLPEQDKMLVAVKALKEASESARQDFQREAELLTMLQHQHIVRFFGVCTEGRPLLMVFEYMRHGDLNRFLRSHGPDAKLLAGGEDVAPGPLGLGQLLAVASQVAAGMVYLAGLHFVHRDLATRNCLVGQGLVVKIGDFGMSRDIYSTDYYRVGGRTMLPIRWMPPESILYRKFTTESDVWSFGVVLWEIFTYGKQPWYQLSNTEAIDCITQGRELERPRACPPEVYAIMRGCWQREPQQRHSIKDVHARLQALAQAPPVYLDVLG
Alternative Products
Event=Alternative splicing; Named isoforms=4; Comment=TrkA-I and TrkA-II isoforms have similar biological properties but are differentially expressed.; Name=TrkA-II; Synonyms=TrkAII; IsoId=P04629-1; Sequence=Displayed; Name=TrkA-I; Synonyms=TrkAI; IsoId=P04629-2; Sequence=VSP_002899; Name=3; IsoId=P04629-3; Sequence=VSP_041905, VSP_002899; Name=TrkA-III; Synonyms=TrkAIII; IsoId=P04629-4; Sequence=VSP_042152, VSP_002899
Alternative Sequence
1..71; MLRGGRRGQLGWHSWAAGPGSLLAWLILASAGAAPCPDACCPHGSSGLRCTRDGALDSLHHLPGAENLTEL -> MKEAALICLAPSVPPILTVKSWDTMQLRAARSRCTNLLAAS (in isoform 3); 192..284; GVPTLKVQVPNASVDVGDDVLLRCQVEGRGLEQAGWILTELEQSATVMKSGGLPSLGLTLANVTSDLNRKNVTCWAENDVGRAEVSVQVNVSF -> V (in isoform TrkA-III); 393..398; Missing (in isoform TrkA-I, isoform 3 and isoform TrkA-III)
3D Structural Models
Turn
44..46; 108..113; 494..496; 534..536; 684..686; 722..724; 727..730; 749..751
Helix
55..59; 65..67; 84..87; 132..135; 154..156; 157..165; 170..173; 183..185; 256..258; 353..355; 418..441; 490..492; 498..501; 507..509; 552..566; 597..603; 608..611; 624..643; 653..655; 660..662; 672..675; 677..679; 691..693; 696..701; 706..721; 733..742; 754..763; 768..770; 774..786; 789..793
Beta Strand
37..43; 47..50; 70..74; 80..82; 95..101; 119..121; 141..144; 180..182; 195..199; 211..218; 224..229; 234..243; 246..253; 263..268; 273..278; 282..290; 294..309; 312..317; 320..323; 326..332; 342..350; 357..365; 368..376; 476..478; 510..517; 520..522; 524..533; 537..545; 575..579; 581..584; 586..590; 605..607; 615..617; 619..621; 646..648; 656..659; 663..666; 680..683; 687..689
3D Structure
NMR spectroscopy (3); X-ray crystallography (62)
Domain & Motif Annotations
Repeat
90..113; LRR 1; 116..137; LRR 2
Motif
537..541; DXXLL; 607..611; DXXLL
Domain (CC)
The transmembrane domain mediates interaction with KIDINS220..; DOMAIN: The extracellular domain mediates interaction with NGFR.
Domain (FT)
148..193; LRRCT; 194..283; Ig-like C2-type 1; 299..365; Ig-like C2-type 2; 510..781; Protein kinase
Region
469..490; Interaction with SQSTM1
Protein Families
- Protein kinase superfamily
- Tyr protein kinase family
- Insulin receptor subfamily
Sequence Similarities
Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.
Clinical Relevance
Disease Involvement
Cancer-related genesDisease variantFDA approved drug targetsProto-oncogene
Drug Targets
FDA approved drug targets
Drugs
REPOTRECTINIBTAVILERMIDESELITRECTINIBNULLRADICICOLVITAMIN B6ACETYLCYSTEINECRIZOTINIBAST-487ANESTHETIC AGENTIMATINIBTHERAPEUTIC ANDROSTANOLONEDEXAMETHASONELAROTRECTINIBASPIRINESTRADIOL VALERATEMETHOTREXATEGAMMA-INTERFERONAZD-7451LESTAURTINIBLAROTRECTINIB SULFATECYTARABINEPILOCARPINE HYDROCHLORIDESURAMINTAMOXIFENCHEMBL:CHEMBL546797ENTRECTINIBGW441756XGAMBOGIC AMIDETHYROXINEGAMBOGIC ACIDMILCICLIBALISERTIBANTIESTROGENPD-0166285SP-600125GZ-389988PEGCANTRATINIBDOVITINIBGLUCARPIDASECENEGERMIN-BKBJREGORAFENIBSTREPTOZOCINALTIRATINIBTHERAPEUTIC GLUCOCORTICOIDCEP-2563 DIHYDROCHLORIDEILORASERTIBWORTMANNINTALETRECTINIBCEP-2563PLX-7486AZD-6918RECOMBINANT CYTOKINEANTINEOPLASTIC AGENTAPAZIQUONETHERAPEUTIC ANDROGENSORAFENIBPRASUGRELCYCLOPHOSPHAMIDE ANHYDROUSHESPERADINRG-1530ENMD-2076GW843682XBMS-754807TOZASERTIBGW-2580ONO-7579IL-6PHENYLEPHRINENERVE GROWTH FACTORPLX7486TRK INHIBITORPF-562271
Interaction Protein
ENSG00000096384ENSG00000134243ENSG00000134259ENSG00000140538ENSG00000161011
Interaction Count
5
Interaction Dataset
intact_biogrid