NTRK1 neurotrophic receptor tyrosine kinase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NTRK1provided by HGNC
Official Full Name: neurotrophic receptor tyrosine kinase 1provided by HGNC
Primary source: HGNC:HGNC:8031
See related: Ensembl:ENSG00000198400 MIM:191315; AllianceGenome:HGNC:8031
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MTC; TRK; TRK1; TRKA; Trk-A; p140-TrkA
Summary: 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]
Expression: Biased expression in adrenal (RPKM 3.7), testis (RPKM 1.0) and 10 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q23.1

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (156815750..156881850)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (155952603..156018667)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (156785542..156851642)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

DNA hypermethylation of tumor suppressor genes TWIST1, GATA4, MUS81 and NTRK1 in endometrial hyperplasia.
Title: DNA hypermethylation of tumor suppressor genes TWIST1, GATA4, MUS81 and NTRK1 in endometrial hyperplasia.
Neurotrophic tyrosine receptor kinase gene fusions in adult and pediatric patients with solid tumors: a clinicogenomic biobank and record linkage study of expression frequency and patient characteristics from Finland.
Title: Neurotrophic tyrosine receptor kinase gene fusions in adult and pediatric patients with solid tumors: a clinicogenomic biobank and record linkage study of expression frequency and patient characteristics from Finland.
Molecular Characterization and Inhibition of a Novel Stress-Induced Mitochondrial Protecting Role for Misfolded TrkAIII in Human SH-SY5Y Neuroblastoma Cells.
Title: Molecular Characterization and Inhibition of a Novel Stress-Induced Mitochondrial Protecting Role for Misfolded TrkAIII in Human SH-SY5Y Neuroblastoma Cells.
Acquired NF2 mutation confers resistance to TRK inhibition in an ex vivo LMNA::NTRK1-rearranged soft-tissue sarcoma cell model.
Title: Acquired NF2 mutation confers resistance to TRK inhibition in an ex vivo LMNA::NTRK1-rearranged soft-tissue sarcoma cell model.
A recurrent NTRK1 tyrosine kinase domain mutation pair is characteristic in a subset of dedifferentiated liposarcomas.
Title: A recurrent NTRK1 tyrosine kinase domain mutation pair is characteristic in a subset of dedifferentiated liposarcomas.
TrkA promotes MDM2-mediated AGPS ubiquitination and degradation to trigger prostate cancer progression.
Title: TrkA promotes MDM2-mediated AGPS ubiquitination and degradation to trigger prostate cancer progression.
Pan-TRK immunohistochemistry in gynaecological mesenchymal tumours: diagnostic implications and pitfalls.
Title: Pan-TRK immunohistochemistry in gynaecological mesenchymal tumours: diagnostic implications and pitfalls.
NTRK1 Spitz melanoma presenting clinically as an angioma.
Title: NTRK1 Spitz melanoma presenting clinically as an angioma.
Human TrkAR649W mutation impairs nociception, sweating and cognitive abilities: a mouse model of HSAN IV.
Title: Human TrkAR649W mutation impairs nociception, sweating and cognitive abilities: a mouse model of HSAN IV.
Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors.
Title: Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors.

Submit: New GeneRIF Correction See all GeneRIFs (277)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Professional guidelines

Description
Professional guideline ACMG 2013 The ACMG recommends that laboratories performing clinical sequencing seek and report mutations in NTRK1 that are pathogenic or expected to be pathogenic. GuidelinePubMed

Associated conditions

Description	Tests
Familial medullary thyroid carcinoma MedGen: C1833921 OMIM: 155240 GeneReviews: Multiple Endocrine Neoplasia Type 2	Compare labs
Hereditary insensitivity to pain with anhidrosis MedGen: C0020074 OMIM: 256800 GeneReviews: NTRK1 Congenital Insensitivity to Pain with Anhidrosis, Congenital Insensitivity to Pain Overview	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 Env (gp120) exposure downregulates TrkA, TrkB, and TrkC mRNA levels in dorsal root ganglion neurons	PubMed
Vpr	vpr	Treatment of cultured dorsal root ganglion sensory neurons with HIV-1 Vpr downregulates expression of TrKA and pGSK3beta/GSK3beta proteins and pre-treatment with NGF inhibits this Vpr-induced downregulation of TrKA and pGSK3beta/GSK3beta	PubMed

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:593920 (e-PCR)
- UniSTS:157979

RH70890 (e-PCR)
- UniSTS:85791

D1S506 (e-PCR)
- UniSTS:54122

PMC86471P1 (e-PCR)
- UniSTS:273529

D1S506 (e-PCR)
- UniSTS:88479

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables GPI-linked ephrin receptor activity	IEA Inferred from Electronic Annotation more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables kinase activity	IEA Inferred from Electronic Annotation more info
enables kinase binding	IEA Inferred from Electronic Annotation more info
NOT enables nerve growth factor binding	IDA Inferred from Direct Assay more info	PubMed
enables nerve growth factor binding	IDA Inferred from Direct Assay more info	PubMed
enables nerve growth factor binding	IEA Inferred from Electronic Annotation more info
enables nerve growth factor receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables nerve growth factor receptor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables neurotrophin binding	IBA Inferred from Biological aspect of Ancestor more info
enables neurotrophin binding	TAS Traceable Author Statement more info	PubMed
enables neurotrophin p75 receptor binding	IEA Inferred from Electronic Annotation more info
enables neurotrophin receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables neurotrophin receptor activity	IEA Inferred from Electronic Annotation more info
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
enables protein kinase activity	IEA Inferred from Electronic Annotation more info
enables protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info
enables transferase activity	IEA Inferred from Electronic Annotation more info
enables transmembrane receptor protein tyrosine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables transmembrane receptor protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables transmembrane receptor protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info
enables transmembrane receptor protein tyrosine kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_or_within B cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in Sertoli cell development	IEA Inferred from Electronic Annotation more info
involved_in axon guidance	IEA Inferred from Electronic Annotation more info
involved_in axonogenesis involved in innervation	IEA Inferred from Electronic Annotation more info
involved_in axonogenesis involved in innervation	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within behavioral response to formalin induced pain	IEA Inferred from Electronic Annotation more info
involved_in cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in cell surface receptor protein tyrosine kinase signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell surface receptor protein tyrosine kinase signaling pathway	IEA Inferred from Electronic Annotation more info
NOT involved_in cellular response to amyloid-beta	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within cellular response to growth factor stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to nerve growth factor stimulus	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within cellular response to nerve growth factor stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to nerve growth factor stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to nerve growth factor stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to nerve growth factor stimulus	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to nicotine	IEA Inferred from Electronic Annotation more info
involved_in circadian rhythm	IEA Inferred from Electronic Annotation more info
involved_in detection of mechanical stimulus involved in sensory perception of pain	IEA Inferred from Electronic Annotation more info
involved_in detection of temperature stimulus involved in sensory perception of pain	IEA Inferred from Electronic Annotation more info
involved_in ephrin receptor signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within innervation	IEA Inferred from Electronic Annotation more info
involved_in learning or memory	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within mechanoreceptor differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of apoptotic process	TAS Traceable Author Statement more info	PubMed
NOT involved_in negative regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of neuron apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in nerve growth factor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within nerve growth factor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in nerve growth factor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in nerve growth factor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within nervous system development	IEA Inferred from Electronic Annotation more info
involved_in nervous system development	IEA Inferred from Electronic Annotation more info
acts_upstream_of neuron apoptotic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within neuron development	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within neuron projection development	IDA Inferred from Direct Assay more info	PubMed
involved_in neuron projection development	IEA Inferred from Electronic Annotation more info
involved_in neurotrophin TRK receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in olfactory nerve development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within peptidyl-tyrosine autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in peptidyl-tyrosine autophosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peptidyl-tyrosine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
NOT involved_in positive regulation of ERK1 and ERK2 cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of ERK1 and ERK2 cascade	IDA Inferred from Direct Assay more info	PubMed
NOT involved_in positive regulation of GTPase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of GTPase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of NF-kappaB transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
NOT involved_in positive regulation of Ras protein signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of Ras protein signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of angiogenesis	IDA Inferred from Direct Assay more info	PubMed
NOT involved_in positive regulation of neuron projection development	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of neuron projection development	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of programmed cell death	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of programmed cell death	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of synapse assembly	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of synaptic transmission, glutamatergic	IEA Inferred from Electronic Annotation more info
involved_in programmed cell death involved in cell development	IEA Inferred from Electronic Annotation more info
involved_in programmed cell death involved in cell development	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in response to axon injury	IEA Inferred from Electronic Annotation more info
involved_in response to electrical stimulus	IEA Inferred from Electronic Annotation more info
involved_in response to hydrostatic pressure	IEA Inferred from Electronic Annotation more info
involved_in response to nicotine	IEA Inferred from Electronic Annotation more info
involved_in response to nutrient levels	IEA Inferred from Electronic Annotation more info
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in spermatogenesis	IEA Inferred from Electronic Annotation more info
involved_in sympathetic nervous system development	IEA Inferred from Electronic Annotation more info
involved_in sympathetic nervous system development	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
is_active_in axon	IBA Inferred from Biological aspect of Ancestor more info
located_in axon	IEA Inferred from Electronic Annotation more info
located_in cell surface	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in dendrite	IEA Inferred from Electronic Annotation more info
located_in early endosome	IEA Inferred from Electronic Annotation more info
located_in early endosome	ISS Inferred from Sequence or Structural Similarity more info
located_in early endosome membrane	IEA Inferred from Electronic Annotation more info
located_in endosome	IEA Inferred from Electronic Annotation more info
located_in endosome membrane	TAS Traceable Author Statement more info
located_in late endosome	IEA Inferred from Electronic Annotation more info
located_in late endosome	ISS Inferred from Sequence or Structural Similarity more info
located_in late endosome membrane	IEA Inferred from Electronic Annotation more info
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in mitochondrion	IEA Inferred from Electronic Annotation more info
located_in neuronal cell body	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info
part_of protein-containing complex	IEA Inferred from Electronic Annotation more info
part_of protein-containing complex	ISS Inferred from Sequence or Structural Similarity more info
part_of receptor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of receptor complex	IDA Inferred from Direct Assay more info	PubMed
located_in recycling endosome	IEA Inferred from Electronic Annotation more info
located_in recycling endosome membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: high affinity nerve growth factor receptor

Names: Oncogene TRK; TRK1-transforming tyrosine kinase protein; gp140trk; neurotrophic tyrosine kinase, receptor, type 1; tropomyosin receptor kinase A; tropomyosin-related kinase A; tyrosine kinase receptor A

NP_001007793.1

EC 2.7.10.1

NP_001012331.1

EC 2.7.10.1

NP_002520.2

EC 2.7.10.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007493.1 RefSeqGene

Range

5001..71101

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_261

mRNA and Protein(s)

NM_001007792.1 → NP_001007793.1 high affinity nerve growth factor receptor isoform 3

See identical proteins and their annotated locations for NP_001007793.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) utilizes alternate 5' exons and lacks an internal in-frame exon, compared to variant 2. Translation initiation occurs at an upstream AUG, resulting in a shorter isoform (3) with a unique N-terminus compared to isoform 2.

Source sequence(s)

AL158169, BC062580

UniProtKB/TrEMBL

A0A6Q8PHG5

Related

ENSP00000376120.3, ENST00000392302.7

Conserved Domains (7) summary

cd04971
Location:269 → 349

Ig_TrKABC_d5; Fifth domain (immunoglobulin-like) of Trk receptors TrkA, TrkB and TrkC

cd04972
Location:165 → 252

Ig_TrkABC_d4; Fourth domain (immunoglobulin-like) of Trk receptors TrkA, TrkB and TrkC

cd05092
Location:468 → 747

PTKc_TrkA; Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A

sd00031
Location:63 → 86

LRR_1; leucine-rich repeat [structural motif]

pfam07714
Location:474 → 745

Pkinase_Tyr; Protein tyrosine kinase

pfam13855
Location:62 → 120

LRR_8; Leucine rich repeat

pfam16920
Location:121 → 162

TPKR_C2; Tyrosine-protein kinase receptor C2 Ig-like domain
NM_001012331.2 → NP_001012331.1 high affinity nerve growth factor receptor isoform 1 precursor

See identical proteins and their annotated locations for NP_001012331.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) lacks an internal, in-frame exon, compared to variant 2, resulting in a shorter isoform (1) lacking an internal segment compared to isoform 2.

Source sequence(s)

AL158169, BC062580, BM685020, M23102

Consensus CDS

CCDS30891.1

UniProtKB/TrEMBL

J3KP20, X5DR71

Related

ENSP00000357179.3, ENST00000368196.7

Conserved Domains (7) summary

cd04971
Location:299 → 379

Ig_TrKABC_d5; Fifth domain (immunoglobulin-like) of Trk receptors TrkA, TrkB and TrkC

cd04972
Location:195 → 282

Ig_TrkABC_d4; Fourth domain (immunoglobulin-like) of Trk receptors TrkA, TrkB and TrkC

cd05092
Location:498 → 777

PTKc_TrkA; Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A

sd00031
Location:68 → 92

LRR_1; leucine-rich repeat [structural motif]

pfam07714
Location:504 → 775

Pkinase_Tyr; Protein tyrosine kinase

pfam13855
Location:92 → 150

LRR_8; Leucine rich repeat

pfam16920
Location:151 → 192

TPKR_C2; Tyrosine-protein kinase receptor C2 Ig-like domain
NM_002529.4 → NP_002520.2 high affinity nerve growth factor receptor isoform 2 precursor

See identical proteins and their annotated locations for NP_002520.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) represents the longest transcript and encodes the longest isoform (2).

Source sequence(s)

AL158169, BC062580, M23102, X06704

Consensus CDS

CCDS1161.1

UniProtKB/Swiss-Prot

B2R6T5, B7ZM34, P04629, P08119, Q15655, Q15656, Q5D056, Q5VZS2, Q7Z5C3, Q9UIU7

UniProtKB/TrEMBL

J3KP20

Related

ENSP00000431418.1, ENST00000524377.7

Conserved Domains (7) summary

cd04971
Location:299 → 379

Ig_TrKABC_d5; Fifth domain (immunoglobulin-like) of Trk receptors TrkA, TrkB and TrkC

cd04972
Location:195 → 282

Ig_TrkABC_d4; Fourth domain (immunoglobulin-like) of Trk receptors TrkA, TrkB and TrkC

cd05092
Location:504 → 783

PTKc_TrkA; Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A

sd00031
Location:68 → 92

LRR_1; leucine-rich repeat [structural motif]

pfam07714
Location:510 → 781

Pkinase_Tyr; Protein tyrosine kinase

pfam13855
Location:92 → 150

LRR_8; Leucine rich repeat

pfam16920
Location:151 → 192

TPKR_C2; Tyrosine-protein kinase receptor C2 Ig-like domain