NTRK1
entrez
4914
canonical
uniprot
P04629
canonical
ensembl
ENSG00000198400
resolver
ensp
ENSP00000357179
resolver
ensp
ENSP00000376120
resolver
ensp
ENSP00000431418
resolver
genesymbol
NTRK1
resolver
genesymbol_syn
MTC
resolver
genesymbol_syn
TRK
resolver
genesymbol_syn
TRKA
resolver
hgnc
HGNC:8031
resolver
uniprot
B2R6T5
resolver
uniprot
B7ZM34
resolver
uniprot
P08119
resolver
uniprot
Q15655
resolver
uniprot
Q15656
resolver
uniprot
Q5D056
resolver
uniprot
Q5VZS2
resolver
uniprot
Q7Z5C3
resolver
uniprot
Q9UIU7
resolver
uniprot
X5DR71
resolver
uniprot_entry
NTRK1_HUMAN
resolver
uniprot_entry
X5DR71_HUMAN
resolver
uniprot_sec
B2R6T5
resolver
uniprot_sec
B7ZM34
resolver
uniprot_sec
P08119
resolver
uniprot_sec
Q15655
resolver
uniprot_sec
Q15656
resolver
uniprot_sec
Q5D056
resolver
uniprot_sec
Q5VZS2
resolver
uniprot_sec
Q7Z5C3
resolver
uniprot_sec
Q9UIU7
resolver
activity_regulation
ACTIVITY REGULATION: 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). {ECO:0000250|UniProtKB:Q3UFB7}.
uniprot
proteins
amino_acid_sequence
MLRGGRRGQLGWHSWAAGPGSLLAWLILASAGAAPCPDACCPHGSSGLRCTRDGALDSLHHLPGAENLTELYIENQQHLQHLELRDLRGLGELRNLTIVKSGLRFVAPDAFHFTPRLSRLNLSFNALESLSWKTVQGLSLQELVLSGNPLHCSCALRWLQRWEEEGLGGVPEQKLQCHGQGPLAHMPNASCGVPTLKVQVPNASVDVGDDVLLRCQVEGRGLEQAGWILTELEQSATVMKSGGLPSLGLTLANVTSDLNRKNVTCWAENDVGRAEVSVQVNVSFPASVQLHTAVEMHHWCIPFSVDGQPAPSLRWLFNGSVLNETSFIFTEFLEPAANETVRHGCLRLNQPTHVNNGNYTLLAANPFGQASASIMAAFMDNPFEFNPEDPIPVSFSPVDTNSTSGDPVEKKDETPFGVSVAVGLAVFACLFLSTLLLVLNKCGRRNKFGINRPAVLAPEDGLAMSLHFMTLGGSSLSPTEGKGSGLQGHIIENPQYFSDACVHHIKRRDIVLKWELGEGAFGKVFLAECHNLLPEQDKMLVAVKALKEASESARQDFQREAELLTMLQHQHIVRFFGVCTEGRPLLMVFEYMRHGDLNRFLRSHGPDAKLLAGGEDVAPGPLGLGQLLAVASQVAAGMVYLAGLHFVHRDLATRNCLVGQGLVVKIGDFGMSRDIYSTDYYRVGGRTMLPIRWMPPESILYRKFTTESDVWSFGVVLWEIFTYGKQPWYQLSNTEAIDCITQGRELERPRACPPEVYAIMRGCWQREPQQRHSIKDVHARLQALAQAPPVYLDVLG
uniprot
proteins
disease_involvement
DISEASE: 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 intellectual disability. 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 variants affecting the gene represented in this entry.; DISEASE: Note=Chromosomal aberrations involving NTRK1 are found in papillary thyroid carcinomas (PTCs) (PubMed:1532241, PubMed:2869410, PubMed:7565764). 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}.
uniprot
proteins
ec_number
2.7.10.1
uniprot
proteins
function
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:1281417, PubMed:15488758, PubMed:17196528, PubMed:1849459, PubMed:1850821, PubMed:22649032, PubMed:27445338, PubMed:8325889). 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. {ECO:0000250|UniProtKB:P35739, ECO:0000250|UniProtKB:Q3UFB7, ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:1281417, ECO:0000269|PubMed:15488758, ECO:0000269|PubMed:17196528, ECO:0000269|PubMed:1849459, ECO:0000269|PubMed:1850821, ECO:0000269|PubMed:22649032, ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:27676246, ECO:0000269|PubMed:8155326, ECO:0000269|PubMed:8325889}.; 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. {ECO:0000269|PubMed:15488758}.
uniprot
proteins
mass_dalton
87497
uniprot
proteins
mutagenesis
MUTAGEN 496; /note="Y->F: Loss of interaction with SHC1 and altered phosphorylation of SHC1. Altered neurite outgrowth and altered activation of the MAPK pathway; when associated with F-791."; /evidence="ECO:0000269|PubMed:8155326"; MUTAGEN 540..541; /note="LV->AA: Abolishes interaction with GGA3."; /evidence="ECO:0000269|PubMed:26446845"; MUTAGEN 544; /note="K->A: No effect on interaction with GGA3."; /evidence="ECO:0000269|PubMed:26446845"; MUTAGEN 544; /note="K->N: Loss of kinase activity."; /evidence="ECO:0000269|PubMed:1281417, ECO:0000269|PubMed:8155326"; MUTAGEN 610..611; /note="LL->AA: No effect on interaction with GGA3."; /evidence="ECO:0000269|PubMed:26446845"; MUTAGEN 791; /note="Y->F: Loss of interaction with PLCG1 and altered phosphorylation of PLCG1. Altered neurite outgrowth and altered activation of the MAPK pathway; when associated with F-496."; /evidence="ECO:0000269|PubMed:7510697, ECO:0000269|PubMed:8155326
uniprot
proteins
post_translational_modification
PTM: Ligand-mediated autophosphorylation (PubMed:1281417, PubMed:15488758, PubMed:27676246, PubMed:28177573, PubMed:2927393, PubMed:7510697, PubMed:8155326, PubMed:8325889). Interaction with SQSTM1 is phosphotyrosine-dependent. Autophosphorylation at Tyr-496 mediates interaction and phosphorylation of SHC1 (PubMed:15488758, PubMed:7510697, PubMed:8155326, PubMed:8325889). {ECO:0000269|PubMed:1281417, ECO:0000269|PubMed:15488758, ECO:0000269|PubMed:27676246, ECO:0000269|PubMed:28177573, ECO:0000269|PubMed:2927393, ECO:0000269|PubMed:7510697, ECO:0000269|PubMed:8155326, ECO:0000269|PubMed:8325889}.; PTM: N-glycosylated (PubMed:2927393). Isoform TrkA-I and isoform TrkA-II are N-glycosylated. {ECO:0000269|PubMed:15488758, ECO:0000269|PubMed:17196528, ECO:0000269|PubMed:27676246, ECO:0000269|PubMed:2927393}.; PTM: 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). {ECO:0000250|UniProtKB:Q3UFB7, ECO:0000269|PubMed:27445338}.
uniprot
proteins
protein_family
Insulin receptor subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
10090906
uniprot
proteins
pubmed
10233776
uniprot
proteins
pubmed
10330344
uniprot
proteins
pubmed
10388563
uniprot
proteins
pubmed
10391209
uniprot
proteins
pubmed
10443680
uniprot
proteins
pubmed
10490030
uniprot
proteins
pubmed
10567924
uniprot
proteins
pubmed
10861667
uniprot
proteins
pubmed
10982191
uniprot
proteins
pubmed
11159935
uniprot
proteins
pubmed
11244088
uniprot
proteins
pubmed
11310631
uniprot
proteins
pubmed
1281417
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
1532241
uniprot
proteins
pubmed
15488758
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15870692
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17196528
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
18077166
uniprot
proteins
pubmed
1849459
uniprot
proteins
pubmed
1850821
uniprot
proteins
pubmed
21102451
uniprot
proteins
pubmed
22302274
uniprot
proteins
pubmed
22649032
uniprot
proteins
pubmed
26446845
uniprot
proteins
pubmed
27445338
uniprot
proteins
pubmed
27676246
uniprot
proteins
pubmed
28177573
uniprot
proteins
pubmed
28328124
uniprot
proteins
pubmed
2869410
uniprot
proteins
pubmed
2927393
uniprot
proteins
pubmed
2966065
uniprot
proteins
pubmed
7510697
uniprot
proteins
pubmed
7565764
uniprot
proteins
pubmed
7823156
uniprot
proteins
pubmed
8155326
uniprot
proteins
pubmed
8325889
uniprot
proteins
pubmed
8524391
uniprot
proteins
pubmed
8696348
uniprot
proteins
pubmed
9290260
uniprot
proteins
sequence_length
796
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1281417, ECO:0000269|PubMed:15488758, ECO:0000269|PubMed:17196528, ECO:0000269|PubMed:27676246, ECO:0000269|PubMed:2927393}; Single-pass type I membrane protein {ECO:0000269|PubMed:1281417, ECO:0000269|PubMed:15488758}. Early endosome membrane {ECO:0000250|UniProtKB:P35739}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P35739}. Late endosome membrane {ECO:0000250|UniProtKB:P35739}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P35739}. Recycling endosome membrane {ECO:0000250|UniProtKB:P35739}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P35739}. 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}.
uniprot
proteins
transmembrane_region
TRANSMEM 424..439; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins