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This gene encodes a member of the neurotrophic tyrosine kinase receptor (NTKR) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. The presence of this kinase leads to cell differentiation and may play a role in specifying sensory neuron subtypes. Mutations in this gene have been associated wit... See more...
Aliases for NTRK1 Gene
Aliases for NTRK1 Gene
External Ids for NTRK1 Gene
- HGNC: 8031
- Entrez Gene: 4914
- Ensembl: ENSG00000198400
- OMIM: 191315
- UniProtKB: P04629
Previous GeneCards Identifiers for NTRK1 Gene
- GC01P154699
- GC01P152595
- GC01P153609
- GC01P154047
- GC01P153643
- GC01P155052
- GC01P128143
Summaries for NTRK1 Gene
-
This gene encodes a member of the neurotrophic tyrosine kinase receptor (NTKR) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. The presence of this kinase leads to cell differentiation and may play a role in specifying sensory neuron subtypes. Mutations in this gene have been associated with congenital insensitivity to pain, anhidrosis, self-mutilating behavior, cognitive disability and cancer. Alternate transcriptional splice variants of this gene have been found, but only three have been characterized to date. [provided by RefSeq, Jul 2008]
GeneCards Summary for NTRK1 Gene
NTRK1 (Neurotrophic Receptor Tyrosine Kinase 1) is a Protein Coding gene. Diseases associated with NTRK1 include Insensitivity To Pain, Congenital, With Anhidrosis and Thyroid Carcinoma, Familial Medullary. Among its related pathways are Neuroscience and Transcriptional misregulation in cancer. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and protein kinase activity. An important paralog of this gene is NTRK3.
UniProtKB/Swiss-Prot Summary for NTRK1 Gene
-
Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand (PubMed:1850821, PubMed:1849459, PubMed:1281417, PubMed:8325889, PubMed:15488758, PubMed:22649032, PubMed:17196528, PubMed:27445338). Can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival (By similarity). Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation (PubMed:1281417). Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors.
-
[Isoform TrkA-III]: Resistant to NGF, it constitutively activates AKT1 and NF-kappa-B and is unable to activate the Ras-MAPK signaling cascade. Antagonizes the anti-proliferative NGF-NTRK1 signaling that promotes neuronal precursors differentiation. Isoform TrkA-III promotes angiogenesis and has oncogenic activity when overexpressed.
-
Trk (neurotrophin) receptors are single transmembrane catalytic receptors with intracellular tyrosine kinase activity. Trk receptors are coupled to the Ras, Cdc42/Rac/RhoG, MAPK, PI3K and PLCgamma signaling pathways. Four members of the Trk family have been identified.
Additional gene information for NTRK1 Gene
- HGNC(8031)
- Entrez Gene(4914)
- Ensembl(ENSG00000198400)
- OMIM(191315)
- UniProtKB(P04629)
- Open Targets Platform(ENSG00000198400)
- Monarch Initiative
- Search for NTRK1 at DataMed
- Search for NTRK1 at HumanCyc
No data available for PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NTRK1 Gene
Genomics for NTRK1 Gene
GeneHancer (GH) Regulatory Elements Pubs
Promoters and enhancers for NTRK1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association
Download GeneHancer data from 2017 publication |
Request up-to-date GeneHancer data (full dataset)
GeneHancers around NTRK1 on the GeneHancer Hub at the UCSC Golden Path
Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NTRK1
- Top Transcription factor binding sites by QIAGEN in the NTRK1 gene promoter:
-
- AP-1
- ATF-2
- c-Fos
- c-Jun
- CREB
- deltaCREB
- p53
Genomic Locations for NTRK1 Gene
Genomic Locations for NTRK1 Gene
- chr1:156,815,640-156,881,850
- (GRCh38/hg38)
- Size:
- 66,211 bases
- Orientation:
- Plus strand
- chr1:156,785,432-156,851,642
- (GRCh37/hg19)
- Size:
- 66,211 bases
- Orientation:
- Plus strand
Genomic View for NTRK1 Gene
Genes around NTRK1 on UCSC Golden Path with GeneCards custom track
- Cytogenetic band:
-
- 1q23.1 by HGNC
- 1q23.1 by Entrez Gene
- 1q23.1 by Ensembl
NTRK1 Gene in genomic location: bands according to
Ensembl, locations according to GeneLoc
(and/or Entrez Gene and/or Ensembl if different)
Genomic Neighborhood
• Exon Structure
• Gene Density
RefSeq DNA sequence for NTRK1 Gene
Proteins for NTRK1 Gene
-
Protein details for NTRK1 Gene (UniProtKB/Swiss-Prot)
- Protein Symbol:
- P04629-NTRK1_HUMAN
- Recommended name:
- High affinity nerve growth factor receptor
- Protein Accession:
- P04629
- B2R6T5
- B7ZM34
- P08119
- Q15655
- Q15656
- Q5D056
- Q5VZS2
- Q7Z5C3
- Q9UIU7
Protein attributes for NTRK1 Gene
- Size:
- 796 amino acids
- Molecular mass:
- 87497 Da
- Quaternary structure:
-
- Exists in a dynamic equilibrium between monomeric (low affinity) and dimeric (high affinity) structures. Homodimerization is induced by binding of a NGF dimer (PubMed:1281417, PubMed:10490030, PubMed:17196528). Interacts with SQSTM1; bridges NTRK1 to NGFR (PubMed:11244088). Forms a ternary complex with NGFR and KIDINS220; this complex is affected by the expression levels of KIDINS220 and an increase in KIDINS220 expression leads to a decreased association of NGFR and NTRK1 (By similarity). Interacts with SH2D1A; regulates NTRK1 (By similarity). Interacts (phosphorylated upon activation by NGF) with SHC1; mediates SHC1 phosphorylation and activation (PubMed:8155326, PubMed:15488758). Interacts (phosphorylated upon activation by NGF) with PLCG1; mediates PLCG1 phosphorylation and activation (PubMed:7510697, PubMed:15488758). Interacts (phosphorylated) with SH2B1 and SH2B2 (By similarity). Interacts with GRB2 (PubMed:15488758). Interacts with PIK3R1 (PubMed:15488758). Interacts with FRS2 (PubMed:15488758). Interacts with SORT1; may regulate NTRK1 anterograde axonal transport (PubMed:21102451). Interacts with RAB7A (By similarity). Found in a complex, at least composed of KIDINS220, MAGI2, NTRK1 and RAPGEF2; the complex is mainly formed at late endosomes in a nerve growth factor (NGF)-dependent manner (By similarity). Interacts with RAPGEF2; the interaction is strengthened after NGF stimulation (By similarity). Interacts with PTPRS (By similarity). Interacts with USP36; USP36 does not deubiquitinate NTRK1 (PubMed:27445338). Interacts with GGA3 (PubMed:26446845).
- SequenceCaution:
-
- Sequence=CAA27243.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=CAA27243.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=CAA27243.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305}; Sequence=CAA29888.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305}; Sequence=CAA44719.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305}; Sequence=CAA59936.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};
- Miscellaneous:
-
- Trk also stands for tropomyosin-related kinase since it was first isolated as an oncogenic protein which was the result of a fusion between the tropomyosin gene TPM3 and NTRK1.
- [Isoform TrkA-II]: Major isoform.
- [Isoform TrkA-I]: Has enhanced responsiveness to NTF3 neurotrophin.
- [Isoform TrkA-III]: Constitutively active. Does not bind NGF and does not interact with GRB2 and FRS2.
Three dimensional structures from OCA and Proteopedia for NTRK1 Gene
Selected DME Specific Peptides for NTRK1 Gene
- P04629:
-
- RWMPPESI
- HHWCIPF
- HRDLATRN
- RRDIVLK
- FVHRDLATRNC
- PTHVNNGNYTL
- ELGEGAFGKVFLAEC
- GVVLWEI
- FTYGKQPW
- YMRHGDL
- CWQREPQQR
- FVHRDLA
- AVLAPEDGLAMSLHFMTLG
- HGDLNRFLRSHGPDAK
Post-translational modifications for NTRK1 Gene
- Ligand-mediated autophosphorylation (PubMed:2927393, PubMed:1281417, PubMed:15488758, PubMed:7510697, PubMed:8155326, PubMed:8325889, PubMed:27676246, PubMed:28177573). Interaction with SQSTM1 is phosphotyrosine-dependent. Autophosphorylation at Tyr-496 mediates interaction and phosphorylation of SHC1 (PubMed:15488758, PubMed:7510697, PubMed:8155326, PubMed:8325889).
- N-glycosylated (PubMed:2927393). Isoform TrkA-I and isoform TrkA-II are N-glycosylated.
- Ubiquitinated (PubMed:27445338). Undergoes polyubiquitination upon activation; regulated by NGFR (PubMed:27445338). Ubiquitination by NEDD4L leads to degradation (PubMed:27445338). Ubiquitination regulates the internalization of the receptor (By similarity).
-
Glycosylation at Asn95, Asn67, Asn121, Asn188, Asn202, Asn253, Asn318, Asn323, Asn262, Asn338, Asn281, Asn358, and Asn401
- NX_P04629 (NX_P04629-1)
- Modification sites at PhosphoSitePlus
Other Protein References for NTRK1 Gene
- ENSEMBL proteins:
- REFSEQ proteins:
Antibody Products
- LifeSpan BioSciences NTRK1 / TrkA Antibody
- GeneTex Anti-TrkA antibody [EPR1104(2)] and Anti-TrkA antibody
- NSJ Bioreagents TrkA Antibody
- Creative Diagnostics Anti-NTRK1 monoclonal antibody, clone FQ2167Z
-
Creative Biolabs
- Recombinant Anti-Human NTRK1 Antibody
- Chicken Anti-TrkA Polyclonal IgY
- Rabbit Anti-NTRK1 Recombinant Antibody (CBWJN-0811)
- Recombinant Mouse Anti-TrkA Antibody Fab Fragment (MNAC13)
- Recombinant Mouse Anti-Human NTRK1 Antibody (clone 7C3)
- Mouse Anti-NTRK1 Recombinant Antibody (CBYJT-1514)
- Rabbit Anti-NTRK1 Recombinant Antibody (BA0007)
- Recombinant Human Anti-NTRK1 Antibody Fab Fragment (CRB0088)
- Recombinant Human Anti-NTRK1 Antibody scFv Fragment (CRB0084)
- Recombinant Human Anti-NTRK1 Antibody Fab Fragment (CRB0082)
- Recombinant Humanized Anti-NTRK1 Antibody scFv Fragment (BXhVH5VL1)
-
Custom Antibody ServicesOriGene Antibodies for NTRK1
- AM06329SU-N
- AP00067PU-N
- AP06418PU-N
- AP06589PU-N
- AP08798PU-N
- AP09480PU-N
- AP09480PU-S
- AP09509PU-N
- AP09509PU-S
- AP12733PU-N
- AP14434PU-N
- AP18228PU-N
- AP23416PU-N
- AP55689PU-N
- AP55689PU-S
- AP55776PU-N
- AP55776PU-S
- AP55860PU-N
- AP55860PU-S
- CF806413
- TA321258
- TA322998
- TA322999
- TA325755
- TA326155
- TA326161
- TA326181
- TA328905
- TA806413
- TA806413S
- TA890047
- TA890047S
- Novus Biologicals Antibodies for NTRK1
-
Abcam antibodies for NTRK1
- Invitrogen Antibodies for NTRK1 (AFLGC-NTRK1)
- antibodies-online: Show 136 available TRKA Antibodies ranked by validation data
- Compare Top TRKA Antibodies
-
Recommended
- 247 WB Antibodies (anti-human)
- 81 IF (p) Antibodies (anti-human)
- 26 FACS Antibodies (anti-human)
- 19 IF Antibodies (anti-human)
- 16 IHC (p) Antibodies (anti-human)
- 14 IHC Antibodies (anti-human)
- 4 IP Antibodies (anti-human)
- 2 DB Antibodies (anti-human)
- 2 IF/ICC Antibodies (anti-human)
- 1 Neut Antibody (anti-human)
- 115 WB Antibodies (anti-rat)
- 69 IF (p) Antibodies (anti-rat)
- 5 IHC Antibodies (anti-rat)
- 2 IF Antibodies (anti-rat)
- 2 IHC (p) Antibodies (anti-rat)
- 1 FACS Antibody (anti-rat)
- 1 IF/ICC Antibody (anti-rat)
- 155 WB Antibodies (anti-mouse)
- 81 IF (p) Antibodies (anti-mouse)
- 7 IHC Antibodies (anti-mouse)
- 5 IHC (p) Antibodies (anti-mouse)
- 2 IF Antibodies (anti-mouse)
- 1 IF/ICC Antibody (anti-mouse)
-
Boster Bio Antibodies for NTRK1
-
Santa Cruz Biotechnology (SCBT) Antibodies for NTRK1
- Sino Biological Antibodies for NTRK1
Protein Products
- Search Origene for MassSpec and Protein Over-expression Lysates for NTRK1
- Origene Custom Protein Services for NTRK1
- Sino Biological Cell Lysates for NTRK1
- Sino Biological Recombinant Proteins for NTRK1
-
Signalway Proteins for NTRK1
-
Abcam proteins for NTRK1
Assay Products
- RayBiotech Human TrkA ELISA
- Creative Diagnostics Human trkA ELISA Kit and Ntrk1 (Rat) ELISA Kit
- Novus Biologicals ELISA Kits for NTRK1
- antibodies-online: Show 38 available TRKA Elisa Kits ranked by validation data
- Compare Top TRKA Elisa Kits
-
Quality Products:
-
Signalway ELISA kits for NTRK1
- Sino Biological Assays for NTRK1
Domains & Families for NTRK1 Gene
Gene Families for NTRK1 Gene
- HGNC:
- IUPHAR :
- Human Protein Atlas (HPA):
-
- Cancer-related genes
- Disease related genes
- Enzymes
- FDA approved drug targets
- Predicted membrane proteins
Protein Domains for NTRK1 Gene
- InterPro:
- Blocks:
-
- Immunoglobulin subtype
- Tyrosine protein kinase, active site
- Cysteine-rich flanking region, C-terminal
- Receptor tyrosine kinase, class II
- ProtoNet:
Suggested Antigen Peptide Sequences for NTRK1 Gene
- GenScript: Design optimal peptide antigens:
-
- Tyrosine-protein kinase receptor (A6NF12_HUMAN)
- p140-TrkA (NTRK1_HUMAN)
Graphical View of Domain Structure for InterPro Entry
P04629UniProtKB/Swiss-Prot:
NTRK1_HUMAN :- The transmembrane domain mediates interaction with KIDINS220.
- Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.
- Domain:
-
- The transmembrane domain mediates interaction with KIDINS220.
- The extracellular domain mediates interaction with NGFR.
- Family:
-
- Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.
Function for NTRK1 Gene
Molecular function for NTRK1 Gene
- UniProtKB/Swiss-Prot Function:
- Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand (PubMed:1850821, PubMed:1849459, PubMed:1281417, PubMed:8325889, PubMed:15488758, PubMed:22649032, PubMed:17196528, PubMed:27445338). Can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival (By similarity). Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation (PubMed:1281417). Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors.
- UniProtKB/Swiss-Prot Function:
- [Isoform TrkA-III]: Resistant to NGF, it constitutively activates AKT1 and NF-kappa-B and is unable to activate the Ras-MAPK signaling cascade. Antagonizes the anti-proliferative NGF-NTRK1 signaling that promotes neuronal precursors differentiation. Isoform TrkA-III promotes angiogenesis and has oncogenic activity when overexpressed.
- UniProtKB/Swiss-Prot CatalyticActivity:
- Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028, ECO:0000269|PubMed:1281417, ECO:0000269|PubMed:2927393};.
- UniProtKB/Swiss-Prot Induction:
- Isoform TrkA-III is up-regulated upon hypoxia in cells normally expressing it.
- UniProtKB/Swiss-Prot EnzymeRegulation:
- The pro-survival signaling effect of NTRK1 in neurons requires its endocytosis into signaling early endosomes and its retrograde axonal transport. This is regulated by different proteins including CFL1, RAC1 and SORT1. NTF3 is unable to induce this signaling probably due to the lability of the NTF3-NTRK1 complex in endosomes. SH2D1A inhibits the autophosphorylation of the receptor, and alters the recruitment and activation of downstream effectors and signaling cascades (By similarity). Regulated by NGFR (By similarity).
- GENATLAS Biochemistry:
- receptor tyrosine kinase A,binding nerve growth factor (NGFA,NGFB,NGFC),with high affinity,involved in the survival differentiation and maintenance of many neural and non neural cell types
Enzyme Numbers (IUBMB) for NTRK1 Gene
Phenotypes From GWAS Catalog for NTRK1 Gene
| GO ID | Qualified GO term | Evidence | PubMed IDs |
|---|---|---|---|
| GO:0000166 | nucleotide binding | IEA | -- |
| GO:0004672 | protein kinase activity | IEA | -- |
| GO:0004713 | protein tyrosine kinase activity | IEA,TAS | -- |
| GO:0004714 | transmembrane receptor protein tyrosine kinase activity | IEA,IMP | 1281417 |
| GO:0005004 | GPI-linked ephrin receptor activity | IEA | -- |
Phenotypes for NTRK1 Gene
- MGI mutant phenotypes for NTRK1:
-
inferred from 12 alleles
- nervous system phenotype
- immune system phenotype
- normal phenotype
- behavior/neurological phenotype
- mortality/aging
- muscle phenotype
- growth/size/body region phenotype
- vision/eye phenotype
- limbs/digits/tail phenotype
- hearing/vestibular/ear phenotype
- hematopoietic system phenotype
- integument phenotype
- pigmentation phenotype
- no phenotypic analysis
- GenomeRNAi human phenotypes for NTRK1:
-
- Increased vaccinia virus (VACV) infection
- no effect
- shRNA abundance <= 50%
- Decreased viability
- Decreased cell migration
- Decreased telomerase activity
- Upregulation of Wnt/beta-catenin pathway after WNT3A stimulation
- Increased shRNA abundance (Z-score > 2)
- Increased replication of vaccinia virus (VACV)
- Decreased substrate adherent cell growth
- Decreased shRNA abundance (Z-score < -2)
- Decreased epidermal growth factor (EGF) endocytosis, increased transferrin (TF) endocytosis
- Decreased senescence-associated beta-galactosidase protein expression after pRB stimulation
- Decreased cell viability after pRB stimulation
Animal Models for NTRK1 Gene
Animal Model Products
-
Taconic Biosciences Mouse Models for NTRK1
CRISPR Products
- Applied Biological Materials (abm): CRISPR Clones for NTRK1 - Select products 50% OFF >
- * NTRK1 CRISPR as ready-to-use vector or virus: ORF | Lenti- | Adeno- | AAV- | Protein Vector - Browse All
- * Gene synthesis, site-directed mutagenesis, subcloning, and more services - Browse All
-
OriGene CRISPR knockouts for NTRK1
- Search GeneCopoeia for CRISPR/Cas9 clones, lentivirus and AAV products for NTRK1
-
Santa Cruz Biotechnology (SCBT) CRISPR for NTRK1
miRNA Products
Inhibitory RNA Products
- Origene shrna, sirna, and RNAi products in human, mouse, rat for NTRK1
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Clone Products
- Applied Biological Materials (abm): Clones for NTRK1 - Select products 50% OFF >
- * NTRK1 as ready-to-use vector or virus: ORF | Lenti- | Retro- | Adeno- | AAV- | Protein Vector - Browse All
- * Gene synthesis, site-directed mutagenesis, subcloning, and more services - Browse All
-
- MG226042
- MR226042
- MR226042L3
- MR226042L4
- RC213047
- RC213047L1
- RC213047L2
- RC213047L3
- RC213047L4
- RC213091
- RC213091L1
- RC213091L2
- RC213091L3
- RC213091L4
- RC220855
- RC220855L1
- RC220855L2
- RC220855L3
- RC220855L4
- RC600033
- RC600034
- RG213047
- RG213091
- RG220855
- RR201103
- RR201103L3
- RR201103L4
- MR226042L3V
- MR226042L4V
- RC213047L1V
- RC213047L2V
- RC213047L3V
- RC213047L4V
- RC213091L1V
- RC213091L2V
- RC213091L3V
- RC213091L4V
- RC220855L1V
- RC220855L2V
- RC220855L3V
- RC220855L4V
- RR201103L3V
- RR201103L4V
- Custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
- Sino Biological Human cDNA Clone for NTRK1
- Addgene plasmids for NTRK1
- Search GeneCopoeia for ORF cDNA, lentivirus, AAV viral particles and/or promoter clone products for NTRK1
Cell Line Products
- ESI BIO PureStem SM30, NCr-fac & Meso-latp Progenitor for NTRK1
-
Horizon Cell Lines for NTRK1
No data available for miRNA , Transcription Factor Targets and HOMER Transcription for NTRK1 Gene
Localization for NTRK1 Gene
Subcellular locations from UniProtKB/Swiss-Prot for NTRK1 Gene
- Cell membrane. Single-pass type I membrane protein. Early endosome membrane. Single-pass type I membrane protein. Late endosome membrane. Single-pass type I membrane protein. Recycling endosome membrane. Single-pass type I membrane protein. Note=Rapidly internalized after NGF binding (PubMed:1281417). Internalized to endosomes upon binding of NGF or NTF3 and further transported to the cell body via a retrograde axonal transport. Localized at cell membrane and early endosomes before nerve growth factor (NGF) stimulation. Recruited to late endosomes after NGF stimulation. Colocalized with RAPGEF2 at late endosomes. {ECO:0000250 UniProtKB:P35739, ECO:0000269 PubMed:1281417}.
| Compartment | Confidence |
|---|---|
| plasma membrane | 5 |
| endosome | 4 |
| golgi apparatus | 4 |
| extracellular | 3 |
| cytoskeleton | 3 |
| mitochondrion | 3 |
| nucleus | 3 |
| cytosol | 3 |
| lysosome | 3 |
| endoplasmic reticulum | 2 |
| peroxisome | 1 |
- Vesicles (3)
- Cytosol (2)
| GO ID | Qualified GO term | Evidence | PubMed IDs |
|---|---|---|---|
| GO:0000139 | Golgi membrane | TAS | -- |
| GO:0005737 | cytoplasm | IEA | -- |
| GO:0005768 | endosome | IEA | -- |
| GO:0005769 | early endosome | IEA,ISS | -- |
| GO:0005770 | late endosome | IEA,ISS | -- |
Pathways & Interactions for NTRK1 Gene
| SuperPathway | Contained pathways | ||
|---|---|---|---|
| 1 | Apoptotic Pathways in Synovial Fibroblasts |
Cellular Apoptosis Pathway
.85
Mitochondrial Apoptosis
.85
Apoptotic Pathways in Synovial Fibroblasts
.84
p53 Mediated Apoptosis
.84
DHA Signaling
.74
Telomerase Components in Cell Signaling
.72
PPAR Pathway
.66
|
Rac1 Pathway
.65
Actin-Based Motility by Rho Family GTPases
.62
ERK5 Signaling
.61
eIF2 Pathway
.60
Rap1 Pathway
.57
Nuclear Receptor Activation by Vitamin-A
.57
|
| 2 | GPCR Pathway |
Paxillin Interactions
.73
Ras Pathway
.73
GPCR Pathway
.62
Pancreatic Adenocarcinoma
.59
|
Breast Cancer Regulation by Stathmin1
.58
NFAT in Immune Response
.58
Estrogen Pathway
.55
P2Y Receptor Signaling
.38
|
| 3 | RET signaling | ||
| 4 | ERK Signaling |
ERK Signaling
.61
Rho Family GTPases
.61
MAPK Signaling
.58
|
Molecular Mechanisms of Cancer
.51
ILK Signaling
.49
|
| 5 | Development HGF signaling pathway |
Development Neurotrophin family signaling
.44
Apoptosis and survival Role of CDK5 in neuronal death and survival
.37
|
Apoptosis and survival NGF signaling pathway
.36
|
Pathways by source for NTRK1 Gene
4 BioSystems pathways for NTRK1 Gene
16 Reactome pathways for NTRK1 Gene
10 KEGG pathways for NTRK1 Gene
4 GeneGo (Thomson Reuters) pathways for NTRK1 Gene
- Apoptosis and survival NGF signaling pathway
- Apoptosis and survival Role of CDK5 in neuronal death and survival
- Development MAG-dependent inhibition of neurite outgrowth
- Development Neurotrophin family signaling
2 R&D Systems pathways for NTRK1 Gene
3 Tocris pathways for NTRK1 Gene
57 Qiagen pathways for NTRK1 Gene
- 14-3-3 Induced Intracellular Signaling
- Actin Nucleation and Branching
- Actin Nucleation by ARP-WASP Complex
- Actin-Based Motility by Rho Family GTPases
- Activation of cAMP-Dependent PKA
2 Cell Signaling Technology pathways for NTRK1 Gene
Interacting Proteins for NTRK1 Gene
Selected Interacting proteins:
P04629-NTRK1_HUMAN
ENSP00000431418
for NTRK1 Gene via
UniProtKB
MINT
STRING
IID
GPS-Prot Interaction Network for NTRK1
SIGNOR curated interactions for NTRK1 Gene
| GO ID | Qualified GO term | Evidence | PubMed IDs |
|---|---|---|---|
| GO:0000186 | activation of MAPKK activity | TAS | -- |
| GO:0001934 | positive regulation of protein phosphorylation | IEA,TAS | 19036963 |
| GO:0006468 | protein phosphorylation | IEA,IDA | 15488758 |
| GO:0007169 | transmembrane receptor protein tyrosine kinase signaling pathway | IEA,IBA | 21873635 |
| GO:0007275 | multicellular organism development | IBA | 21873635 |
Drugs & Compounds for NTRK1 Gene
(67) Drugs for NTRK1 Gene - From: DrugBank, PharmGKB, ClinicalTrials, ApexBio, DGIdb, Tocris, and Novoseek
| Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
|---|---|---|---|---|---|---|
| Entrectinib | Approved, Investigational | Pharma | Target, inhibitor | Orally active inhibitor of ALK kinase | 15 | |
| imatinib | Approved | Pharma | Target, antagonist, inhibitor | Kinase Inhibitors, SRC/BCR-ABL tyrosine kinase inhibitors | 0 | |
| regorafenib | Approved | Pharma | Target, inhibitor | Inhibitor of VEGFR/PDGFR/FGFR/mutant kit/RET/Raf-1, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 0 | |
| Tyrosine | Approved, Investigational | Nutra | 1044 | |||
| Amitriptyline | Approved | Pharma | Antagonist, Target, agonist, activator | 105 |
(4) Tocris Compounds for NTRK1 Gene
| Compound | Action | Cas Number |
|---|---|---|
| AG 879 | TrkA inhibitor | 148741-30-4 |
| BDNF (human) | Activates TrkB and p75 receptors | 218441-99-7 |
| LM11A 31 dihydrochloride | Nonpeptide p75NTR ligand; neuroprotective | 1243259-19-9 |
| TLQP 21 | VGF-derived peptide | 869988-94-3 |
(9) ApexBio Compounds for NTRK1 Gene
| Compound | Action | Cas Number |
|---|---|---|
| 7,8-Dihydroxyflavone | 38183-03-8 | |
| BDNF (human) | 218441-99-7 | |
| Cyclotraxin B | 1203586-72-4 | |
| Danusertib (PHA-739358) | Pan-aurora kinase inhibitor | 827318-97-8 |
| GNF-5837 | Pan-Trk inhibitor | 1033769-28-6 |
| GW441756 | TrkA inhibitor,potent and selective | 504433-23-2 |
| Lestaurtinib | JAK2/FLT3/TrkA inhibitor | 111358-88-4 |
| LM 22A4 | 37988-18-4 | |
| NTR 368 | 197230-90-3 |
Transcripts for NTRK1 Gene
mRNA/cDNA for NTRK1 Gene
- 3 REFSEQ mRNAs :
- 11 NCBI additional mRNA sequence :
- 10 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :
-
- ENST00000358660 2492 nts (view in UCSC)
- ENST00000368196 2701 nts (view in UCSC)
- ENST00000392302 2609 nts (view in UCSC)
- ENST00000489021 570 nts (view in UCSC)
- ENST00000497019 2508 nts (view in UCSC)
CRISPR Products
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-
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miRNA Products
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Clone Products
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- Custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
- Sino Biological Human cDNA Clone for NTRK1
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Relevant External Links for NTRK1 Gene
- GeneLoc Exon Structure for
- NTRK1
Expression for NTRK1 Gene
mRNA expression in embryonic tissues and stem cells from LifeMap Discovery
- Brain (Nervous System)
- Neural Tube (Nervous System)
-
Ovary (Reproductive System)
- Pre-Granulosa Cells Primordial Follicle
-
Eye (Sensory Organs)
- Limbal Basal Epithelial Cells Limbus Epithelium
-
Epithelial Cells
- Limbal Basal Epithelial Cells Limbus Epithelium
-
Blood (Hematopoietic System)
- Hematopoietic Stem Cells Hematopoietic Bone Marrow
Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NTRK1
SOURCE GeneReport for Unigene cluster for NTRK1 Gene:
Hs.406293mRNA Expression by UniProt/SwissProt for NTRK1 Gene:
P04629-NTRK1_HUMAN
Tissue specificity:
Isoform TrkA-I is found in most non-neuronal tissues. Isoform TrkA-II is primarily expressed in neuronal cells. TrkA-III is specifically expressed by pluripotent neural stem and neural crest progenitors.
Evidence on tissue expression from TISSUES for NTRK1 Gene
- Nervous system(4.7)
- Blood(4.6)
- Intestine(4.6)
- Adrenal gland(3.3)
- Heart(3.2)
- Skin(3.1)
- Stomach(2.8)
- Muscle(2.8)
- Kidney(2.8)
- Thyroid gland(2.7)
- Pancreas(2.7)
- Lung(2.7)
- Liver(2.6)
- Eye(2.5)
- Lymph node(2.5)
- Bone marrow(2.5)
- Bone(2.3)
- Spleen(2.2)
Phenotype-based relationships between genes and organs from Gene ORGANizer for NTRK1 Gene
Germ Layers:
- ectoderm
- endoderm
- mesoderm
Systems:
- cardiovascular
- endocrine
- immune
- integumentary
- lymphatic
- nervous
- skeleton
Regions:
Head and neck:
- brain
- ear
- eye
- head
- jaw
- mandible
- maxilla
- mouth
- neck
- scalp
- skull
- thyroid
Thorax:
- chest wall
- clavicle
- heart
- heart valve
- rib
- rib cage
- scapula
- sternum
Pelvis:
- pelvis
Limb:
- ankle
- arm
- digit
- elbow
- femur
- fibula
- finger
- foot
- forearm
- hand
- hip
- humerus
- knee
- lower limb
- nail
- radius
- shin
- shoulder
- thigh
- tibia
- toe
- ulna
- upper limb
- wrist
General:
- blood
- blood vessel
- bone marrow
- hair
- peripheral nerve
- peripheral nervous system
- skin
- spinal column
- spinal cord
- sweat gland
- vertebrae
Primer Products
-
OriGene qPCR primer pairs for NTRK1
Gene Expression Assay Products
No data available for mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein expression and Protein tissue co-expression partners for NTRK1 Gene
Orthologs for NTRK1 Gene
This gene was present in the common ancestor of animals.
| Organism | Taxonomy | Gene | Similarity | Type | Details |
|---|---|---|---|---|---|
| Chimpanzee (Pan troglodytes) |
Mammalia | NTRK1 30 31 |
|
OneToOne | |
| Cow (Bos Taurus) |
Mammalia | NTRK1 30 31 |
|
OneToOne | |
| Dog (Canis familiaris) |
Mammalia | NTRK1 30 31 |
|
OneToOne | |
| Mouse (Mus musculus) |
Mammalia | Ntrk1 30 17 31 |
|
OneToOne | |
| Rat (Rattus norvegicus) |
Mammalia | Ntrk1 30 |
|
||
| Oppossum (Monodelphis domestica) |
Mammalia | NTRK1 31 |
|
OneToOne | |
| Chicken (Gallus gallus) |
Aves | NTRK1 30 31 |
|
OneToOne | |
| Lizard (Anolis carolinensis) |
Reptilia | NTRK1 31 |
|
OneToOne | |
| Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | ntrk1 30 |
|
||
| Zebrafish (Danio rerio) |
Actinopterygii | ntrk1 30 31 |
|
OneToOne | |
| Worm (Caenorhabditis elegans) |
Secernentea | trk-1 31 |
|
OneToMany |
- Species where no ortholog for NTRK1 was found in the sources mined by GeneCards:
-
- A. gosspyii yeast (Eremothecium gossypii)
- Actinobacteria (Mycobacterium tuberculosis)
- African clawed frog (Xenopus laevis)
- African malaria mosquito (Anopheles gambiae)
- Alicante grape (Vitis vinifera)
- Alpha proteobacteria (Wolbachia pipientis)
- Amoeba (Dictyostelium discoideum)
- Archea (Pyrococcus horikoshii)
- Baker's yeast (Saccharomyces cerevisiae)
- Barley (Hordeum vulgare)
- Beta proteobacteria (Neisseria meningitidis)
- Bread mold (Neurospora crassa)
- Chromalveolata (Phytophthora infestans)
- Common water flea (Daphnia pulex)
- Corn (Zea mays)
- E. coli (Escherichia coli)
- Filamentous fungi (Aspergillus nidulans)
- Firmicute Bacteria (Streptococcus pneumoniae)
- Fission Yeast (Schizosaccharomyces pombe)
- Fruit Fly (Drosophila melanogaster)
- Green Algae (Chlamydomonas reinhardtii)
- Honey Bee (Apis mellifera)
- K. Lactis Yeast (Kluyveromyces lactis)
- Loblloly Pine (Pinus taeda)
- Malaria Parasite (Plasmodium falciparum)
- Medicago Trunc (Medicago Truncatula)
- Moss (Physcomitrella patens)
- Orangutan (Pongo pygmaeus)
- Pig (Sus scrofa)
- Platypus (Ornithorhynchus anatinus)
- Rainbow Trout (Oncorhynchus mykiss)
- Rice (Oryza sativa)
- Rice Blast Fungus (Magnaporthe grisea)
- Schistosome Parasite (Schistosoma mansoni)
- Sea Anemone (Nematostella vectensis)
- Sea Vase (Ciona intestinalis)
- Sea Squirt (Ciona savignyi)
- Sea Urchin (Strongylocentrotus purpuratus)
- Sorghum (Sorghum bicolor)
- Soybean (Glycine max)
- Stem Rust Fungus (Puccinia graminis)
- Sugarcane (Saccharum officinarum)
- Thale Cress (Arabidopsis thaliana)
- Tomato (Lycopersicon esculentum)
- Toxoplasmosis (Toxoplasma gondii)
- Trichoplax (Trichoplax adhaerens)
- Wheat (Triticum aestivum)
Evolution for NTRK1 Gene
- ENSEMBL:
- Gene Tree for NTRK1 (if available)
- TreeFam:
- Gene Tree for NTRK1 (if available)
- Aminode:
- Evolutionary constrained regions (ECRs) for NTRK1: view image
Paralogs for NTRK1 Gene
Paralogs for NTRK1 Gene
- NTRK3 5
- NTRK2 5
- INSRR 5
- INSR 5
- IGF1R 5
- ALK 5
- ROS1 5
- DDR2 5
- MUSK 5
- DDR1 5
- MST1R 5
- ROR1 5
- TYRO3 5
- ROR2 5
- LTK 5
- FLT4 5
- EPHA8 5
- KDR 5
- FLT1 5
- PDGFRA 5
- KIT 5
- MET 5
- RYK 5
- EPHB3 5
- EPHA1 5
- EPHB1 5
- CSF1R 5
- PDGFRB 5
- FLT3 5
- RET 5
- EPHA3 5
- ERBB3 5
- FGFR1 5
- EPHA2 5
- EPHA5 5
- EPHA6 5
- EPHB2 5
- EGFR 5
- EPHB4 5
- EPHA7 5
- EPHA4 5
- ERBB2 5
- ERBB4 5
- TEK 5
- EPHB6 5
- FGFR3 5
- FGFR2 5
- TIE1 5
- AXL 5
- EPHA10 5
- FGFR4 5
- MERTK 5
- ENSG00000282278 5
- LMTK2 5
(34) SIMAP similar genes for NTRK1 Gene using alignment to 3 proteins:
- NTRK1_HUMAN
- E9PQG0_HUMAN
- J3KP20_HUMAN
Variants for NTRK1 Gene
Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NTRK1 Gene
| SNP ID | Clinical significance and condition | Chr 01 pos | Variation | AA Info | Type |
|---|---|---|---|---|---|
| 637365 | Likely Benign: Charcot-Marie-Tooth disease | 156,868,250(+) | G/A | SPLICE_DONOR_VARIANT | |
| 637366 | Uncertain Significance: Charcot-Marie-Tooth disease | 156,876,133(+) | G/C | MISSENSE_VARIANT | |
| 637367 | Uncertain Significance: Charcot-Marie-Tooth disease | 156,881,559(+) | C/T | NONSENSE | |
| 637368 | Likely Pathogenic: Hereditary insensitivity to pain with anhidrosis; Charcot-Marie-Tooth disease | 156,864,792(+) | AGTCGCCTGT/A | SPLICE_DONOR_VARIANT | |
| 637369 | Uncertain Significance: Charcot-Marie-Tooth disease | 156,868,171(+) | G/T | NONSENSE |
| Variant ID | Type | Subtype | PubMed ID |
|---|---|---|---|
| dgv108e212 | CNV | loss | 25503493 |
| dgv37e201 | CNV | deletion | 23290073 |
| esv1001917 | CNV | deletion | 20482838 |
| esv1010343 | CNV | deletion | 20482838 |
| esv1637866 | CNV | deletion | 17803354 |
| esv2718451 | CNV | deletion | 23290073 |
| esv2718462 | CNV | deletion | 23290073 |
| esv3578202 | CNV | loss | 25503493 |
| nsv1006558 | CNV | gain | 25217958 |
| nsv1133913 | CNV | deletion | 24896259 |
| nsv1145375 | CNV | deletion | 24896259 |
| nsv831648 | CNV | loss | 17160897 |
| nsv831659 | CNV | loss | 17160897 |
| nsv998265 | CNV | gain | 25217958 |
Residual Variation Intolerance Score:
68% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score:
5.51;
71.87% of all genes are more intolerant (likely to be disease-causing)
Additional Variant Information for NTRK1 Gene
SNP Genotyping and Copy Number Assay Products
No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NTRK1 Gene
Disorders for NTRK1 Gene
(85) MalaCards diseases for NTRK1 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards
| Disorder | Aliases | PubMed IDs |
|---|---|---|
| insensitivity to pain, congenital, with anhidrosis |
|
|
| thyroid carcinoma, familial medullary |
|
|
| differentiated thyroid carcinoma |
|
|
| charcot-marie-tooth disease/hereditary motor and sensory neuropathy |
|
|
| charcot-marie-tooth disease |
|
|
Search NTRK1 in MalaCards
View complete list of genes associated with diseases
UniProtKB/Swiss-Prot
NTRK1_HUMAN- Congenital insensitivity to pain with anhidrosis (CIPA) [MIM:256800]: Characterized by a congenital insensitivity to pain, anhidrosis (absence of sweating), absence of reaction to noxious stimuli, self-mutilating behavior, and mental retardation. This rare autosomal recessive disorder is also known as congenital sensory neuropathy with anhidrosis or hereditary sensory and autonomic neuropathy type IV or familial dysautonomia type II. {ECO:0000269 PubMed:10090906, ECO:0000269 PubMed:10233776, ECO:0000269 PubMed:10330344, ECO:0000269 PubMed:10567924, ECO:0000269 PubMed:10861667, ECO:0000269 PubMed:10982191, ECO:0000269 PubMed:11159935, ECO:0000269 PubMed:11310631, ECO:0000269 PubMed:18077166, ECO:0000269 PubMed:22302274, ECO:0000269 PubMed:27676246, ECO:0000269 PubMed:28177573, ECO:0000269 PubMed:28328124, ECO:0000269 PubMed:8696348}. Note=The disease is caused by mutations affecting the gene represented in this entry.
- Note=Chromosomal aberrations involving NTRK1 are found in papillary thyroid carcinomas (PTCs) (PubMed:2869410, PubMed:7565764, PubMed:1532241). Translocation t(1;3)(q21;q11) with TFG generates the TRKT3 (TRK-T3) transcript by fusing TFG to the 3'-end of NTRK1 (PubMed:7565764). A rearrangement with TPM3 generates the TRK transcript by fusing TPM3 to the 3'-end of NTRK1 (PubMed:2869410). An intrachromosomal rearrangement that links the protein kinase domain of NTRK1 to the 5'-end of the TPR gene forms the fusion protein TRK-T1. TRK-T1 is a 55 kDa protein reacting with antibodies against the C-terminus of the NTRK1 protein (PubMed:1532241). {ECO:0000269 PubMed:1532241, ECO:0000269 PubMed:2869410, ECO:0000269 PubMed:7565764}.
Additional Disease Information for NTRK1
- Genetic Association Database
- (GAD)
- Human Genome Epidemiology Navigator
- (HuGE)
- ATLAS of Genetics and Cytogenetics in Oncology and Haematology
- Open Targets Platform
No data available for Genatlas for NTRK1 Gene
Publications for NTRK1 Gene
- c.1810C>T polymorphism of NTRK1 gene is associated with reduced survival in neuroblastoma patients. (PMID: 20003389) Lipska BS … Limon J (BMC cancer 2009) 3 23 41
- SNPs in neurotrophin system genes and Alzheimer's disease in an Italian population. (PMID: 18780967) Cozza A … Pellegrini S (Journal of Alzheimer's disease : JAD 2008) 3 23 41
- Structural and mechanistic insights into nerve growth factor interactions with the TrkA and p75 receptors. (PMID: 17196528) Wehrman T … Garcia KC (Neuron 2007) 3 4 23
- Methylation adjacent to negatively regulating AP-1 site reactivates TrkA gene expression during cancer progression. (PMID: 15870692) Fujimoto M … Kitazawa S (Oncogene 2005) 3 4 23
- Lack of association between TrkA single nucleotide polymorphisms and sporadic Alzheimer's disease in a Japanese population. (PMID: 14642435) Sakasegawa Y … Kaneko K (Neuroscience letters 2003) 3 23 41
ExternalLinks
Products for NTRK1 Gene
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