Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0009543
UniProt IDP04629
Primary gene name(s)NTRK1
Synonym gene name(s)MTC, TRK, TRKA
Protein nameHigh affinity nerve growth factor receptor
Protein functionReceptor 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, PubMed:27676246. High affinity receptor for NGF which is its primary ligand, it 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. Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation. 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:0000269|PubMed:27676246}.; FUNCTION: Isoform TrkA-III is resistant to NGF, 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.
Subcellular locationCell membrane {ECO:0000269|PubMed:15488758, ECO:0000269|PubMed:27676246};
Single-pass type I membrane protein {ECO:0000269|PubMed:15488758}. Early endosome membrane {ECO:0000250};
Single-pass type I membrane protein {ECO:0000250}. Late endosome membrane {ECO:0000250};
Single-pass type I membrane protein {ECO:0000250}. Note=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, By similarity. {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P04629
Gene Ontology
(Biological Process)
Complete annatation
activation of MAPKK activity [GO:0000186];
aging [GO:0007568];
axon guidance [GO:0007411];
axonogenesis involved in innervation [GO:0060385];
B cell differentiation [GO:0030183];
behavioral response to formalin induced pain [GO:0061368];
cellular response to nerve growth factor stimulus [GO:1990090];
cellular response to nicotine [GO:0071316];
circadian rhythm [GO:0007623];
detection of mechanical stimulus involved in sensory perception of pain [GO:0050966];
detection of temperature stimulus involved in sensory perception of pain [GO:0050965];
learning or memory [GO:0007611];
mechanoreceptor differentiation [GO:0042490];
microtubule-based movement [GO:0007018];
negative regulation of cell proliferation [GO:0008285];
negative regulation of neuron apoptotic process [GO:0043524];
neurotrophin TRK receptor signaling pathway [GO:0048011];
olfactory nerve development [GO:0021553];
phosphatidylinositol-mediated signaling [GO:0048015];
positive regulation of angiogenesis [GO:0045766];
positive regulation of ERK1 and ERK2 cascade [GO:0070374];
positive regulation of GTPase activity [GO:0043547];
positive regulation of neuron projection development [GO:0010976];
positive regulation of NF-kappaB transcription factor activity [GO:0051092];
positive regulation of programmed cell death [GO:0043068];
positive regulation of protein phosphorylation [GO:0001934];
positive regulation of Ras protein signal transduction [GO:0046579];
positive regulation of synapse assembly [GO:0051965];
positive regulation of synaptic transmission, glutamatergic [GO:0051968];
programmed cell death involved in cell development [GO:0010623];
protein autophosphorylation [GO:0046777];
protein phosphorylation [GO:0006468];
response to activity [GO:0014823];
response to axon injury [GO:0048678];
response to drug [GO:0042493];
response to electrical stimulus [GO:0051602];
response to ethanol [GO:0045471];
response to hydrostatic pressure [GO:0051599];
response to nutrient levels [GO:0031667];
response to radiation [GO:0009314];
Sertoli cell development [GO:0060009];
sympathetic nervous system development [GO:0048485]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
GPI-linked ephrin receptor activity [GO:0005004];
nerve growth factor binding [GO:0048406];
nerve growth factor receptor activity [GO:0010465];
neurotrophin binding [GO:0043121];
protein homodimerization activity [GO:0042803];
transmembrane receptor protein tyrosine kinase activity [GO:0004714]
Gene Ontology
(Cellular Component)
Complete annatation
axon [GO:0030424];
cell surface [GO:0009986];
cytoplasmic vesicle [GO:0031410];
dendrite [GO:0030425];
early endosome [GO:0005769];
early endosome membrane [GO:0031901];
endosome [GO:0005768];
integral component of plasma membrane [GO:0005887];
late endosome [GO:0005770];
late endosome membrane [GO:0031902];
neuronal cell body [GO:0043025];
plasma membrane [GO:0005886];
protein complex [GO:0043234];
receptor complex [GO:0043235]
Protein-protein interaction110969
Phylogenetic treeP04629
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD35.5681674180542700
AZA vs. DISU-0.9777936609956680.1422769421240510.717798021069077
AZA vs. IL70.3836409617845750.4958354695772920.999311006273513
AZA vs. SAHA0.1703826781386410.7860816179353680.94343842406271
DISU vs. CD3-6.555745591205100
DISU vs. IL71.34935194014290.03187284456862740.23193245863132
DISU vs. SAHA1.152967278169210.09423385582079160.392103379645265
DMSO vs. AZA0.07978361106061340.8850275105168631
DMSO vs. CD3-5.4897222343931500
DMSO vs. DISU1.058224290865380.08435775028563370.537351983883825
DMSO vs. IL70.3099967014295210.5348484833020980.896696737481162
DMSO vs. SAHA0.08646247565110840.8798898762112030.970710704822084
HIV vs. Mock in Activation0.2123842243866440.7349536877963210.999983755607037
HIV vs. Mock in Latency0.7429905060183170.01861545416305790.499328709268127
IL7 vs. CD3-5.1832994107810100
SAHA vs. CD3-5.4151411289600100
SAHA vs. IL7-0.2110392594767850.7172345123441390.870134777473131
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) unknown
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK -0.130484 0.922593
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
unknown unknown unknown unknown unknown
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB00619 Imatinib approved unknown antagonist
DB00321 Amitriptyline approved unknown agonist
DB08896 Regorafenib approved yes inhibitor

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1HE7 X-ray 2.0Å A=285-413.
1SHC NMR - B=489-500.
1WWA X-ray 2.5Å X/Y=278-386.
1WWW X-ray 2.2Å X/Y=282-382.
2IFG X-ray 3.4Å A/B=36-382.
4AOJ X-ray 2.7Å A/B/C=473-796.
4CRP NMR - A=282-383.
4F0I X-ray 2.3Å A/B=498-796.
4GT5 X-ray 2.4Å A=498-796.
4PMM X-ray 2.0Å A=501-787.
4PMP X-ray 1.8Å A=501-787.
4PMS X-ray 2.8Å A=501-787.
4PMT X-ray 2.1Å A=501-787.
4YNE X-ray 2.0Å A=502-796.
4YPS X-ray 2.1Å A=502-796.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Vpr downregulates 23912036

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04010 MAPK signaling pathway - Homo sapiens (human)
hsa04144 Endocytosis - Homo sapiens (human)
hsa04210 Apoptosis - Homo sapiens (human)
hsa04722 Neurotrophin signaling pathway - Homo sapiens (human)
hsa04750 Inflammatory mediator regulation of TRP channels - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05202 Transcriptional misregulation in cancer - Homo sapiens (human)
hsa05216 Thyroid cancer - Homo sapiens (human)
hsa05230 Central carbon metabolism in cancer - Homo sapiens (human)