Product: Phospho-TrkA /TrkB (Tyr785/Tyr816) Antibody
Catalog: AF4390
Description: Rabbit polyclonal antibody to Phospho-TrkA /TrkB (Tyr785/Tyr816)
Application: WB IF/ICC
Reactivity: Human, Mouse, Rat
Prediction: Pig, Bovine, Horse, Sheep, Rabbit, Dog
Mol.Wt.: 87kDa; 87kD,92kD(Calculated).
Uniprot: P04629 | Q16620
RRID: AB_2844455

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Product Info

Source:
Rabbit
Application:
IF/ICC 1:100-1:500, WB 1:500-1:2000
*The optimal dilutions should be determined by the end user.
*Tips:

WB: For western blot detection of denatured protein samples. IHC: For immunohistochemical detection of paraffin sections (IHC-p) or frozen sections (IHC-f) of tissue samples. IF/ICC: For immunofluorescence detection of cell samples. ELISA(peptide): For ELISA detection of antigenic peptide.

Reactivity:
Human,Mouse,Rat
Prediction:
Pig(90%), Bovine(90%), Horse(90%), Sheep(90%), Rabbit(90%), Dog(90%)
Clonality:
Polyclonal
Specificity:
Phospho-TrkA /TrkB (Tyr785/Tyr816) Antibody detects endogenous levels of TrkA /TrkB only when phosphorylated at Tyr785.
RRID:
AB_2844455
Cite Format: Affinity Biosciences Cat# AF4390, RRID:AB_2844455.
Conjugate:
Unconjugated.
Purification:
The antibody is from purified rabbit serum by affinity purification via sequential chromatography on phospho-peptide and non-phospho-peptide affinity columns.
Storage:
Rabbit IgG in phosphate buffered saline , pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
Alias:

Fold/Unfold

gp140trk; High affinity nerve growth factor receptor; High affinity nerve growth factor receptor precursor; MTC; Neurotrophic tyrosine kinase receptor type 1; NTRK1; NTRK1_HUMAN; Oncogene TRK; p14-TrkA; p140 TrkA; p140-TrkA; Slow nerve growth; Trk A; TRK; Trk-A; TRK1; TRK1-transforming tyrosine kinase protein; Tropomyosin-related kinase A; Tyrosine kinase receptor A; Tyrosine kinase receptor;

Immunogens

Immunogen:
Uniprot:
Gene(ID):
Expression:
P04629 NTRK1_HUMAN:

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.

Q16620 NTRK2_HUMAN:

Isoform TrkB is expressed in the central and peripheral nervous system. In the central nervous system (CNS), expression is observed in the cerebral cortex, hippocampus, thalamus, choroid plexus, granular layer of the cerebellum, brain stem, and spinal cord. In the peripheral nervous system, it is expressed in many cranial ganglia, the ophthalmic nerve, the vestibular system, multiple facial structures, the submaxillary glands, and dorsal root ganglia. Isoform TrkB-T1 is mainly expressed in the brain but also detected in other tissues including pancreas, kidney and heart. Isoform TrkB-T-Shc is predominantly expressed in the brain.

Sequence:
MLRGGRRGQLGWHSWAAGPGSLLAWLILASAGAAPCPDACCPHGSSGLRCTRDGALDSLHHLPGAENLTELYIENQQHLQHLELRDLRGLGELRNLTIVKSGLRFVAPDAFHFTPRLSRLNLSFNALESLSWKTVQGLSLQELVLSGNPLHCSCALRWLQRWEEEGLGGVPEQKLQCHGQGPLAHMPNASCGVPTLKVQVPNASVDVGDDVLLRCQVEGRGLEQAGWILTELEQSATVMKSGGLPSLGLTLANVTSDLNRKNVTCWAENDVGRAEVSVQVNVSFPASVQLHTAVEMHHWCIPFSVDGQPAPSLRWLFNGSVLNETSFIFTEFLEPAANETVRHGCLRLNQPTHVNNGNYTLLAANPFGQASASIMAAFMDNPFEFNPEDPIPVSFSPVDTNSTSGDPVEKKDETPFGVSVAVGLAVFACLFLSTLLLVLNKCGRRNKFGINRPAVLAPEDGLAMSLHFMTLGGSSLSPTEGKGSGLQGHIIENPQYFSDACVHHIKRRDIVLKWELGEGAFGKVFLAECHNLLPEQDKMLVAVKALKEASESARQDFQREAELLTMLQHQHIVRFFGVCTEGRPLLMVFEYMRHGDLNRFLRSHGPDAKLLAGGEDVAPGPLGLGQLLAVASQVAAGMVYLAGLHFVHRDLATRNCLVGQGLVVKIGDFGMSRDIYSTDYYRVGGRTMLPIRWMPPESILYRKFTTESDVWSFGVVLWEIFTYGKQPWYQLSNTEAIDCITQGRELERPRACPPEVYAIMRGCWQREPQQRHSIKDVHARLQALAQAPPVYLDVLG

MSSWIRWHGPAMARLWGFCWLVVGFWRAAFACPTSCKCSASRIWCSDPSPGIVAFPRLEPNSVDPENITEIFIANQKRLEIINEDDVEAYVGLRNLTIVDSGLKFVAHKAFLKNSNLQHINFTRNKLTSLSRKHFRHLDLSELILVGNPFTCSCDIMWIKTLQEAKSSPDTQDLYCLNESSKNIPLANLQIPNCGLPSANLAAPNLTVEEGKSITLSCSVAGDPVPNMYWDVGNLVSKHMNETSHTQGSLRITNISSDDSGKQISCVAENLVGEDQDSVNLTVHFAPTITFLESPTSDHHWCIPFTVKGNPKPALQWFYNGAILNESKYICTKIHVTNHTEYHGCLQLDNPTHMNNGDYTLIAKNEYGKDEKQISAHFMGWPGIDDGANPNYPDVIYEDYGTAANDIGDTTNRSNEIPSTDVTDKTGREHLSVYAVVVIASVVGFCLLVMLFLLKLARHSKFGMKGPASVISNDDDSASPLHHISNGSNTPSSSEGGPDAVIIGMTKIPVIENPQYFGITNSQLKPDTFVQHIKRHNIVLKRELGEGAFGKVFLAECYNLCPEQDKILVAVKTLKDASDNARKDFHREAELLTNLQHEHIVKFYGVCVEGDPLIMVFEYMKHGDLNKFLRAHGPDAVLMAEGNPPTELTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKIGDFGMSRDVYSTDYYRVGGHTMLPIRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVLQRPRTCPQEVYELMLGCWQREPHMRKNIKGIHTLLQNLAKASPVYLDILG

Predictions

Predictions:

Score>80(red) has high confidence and is suggested to be used for WB detection. *The prediction model is mainly based on the alignment of immunogen sequences, the results are for reference only, not as the basis of quality assurance.

Species
Results
Score
Pig
90
Horse
90
Bovine
90
Sheep
90
Dog
90
Rabbit
90
Zebrafish
75
Chicken
60
Xenopus
0
Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

PTMs - P04629/Q16620 As Substrate

Site PTM Type Enzyme
N95 N-Glycosylation
N121 N-Glycosylation
S123 Phosphorylation
N188 N-Glycosylation
N262 N-Glycosylation
N281 N-Glycosylation
N358 N-Glycosylation
Y490 Phosphorylation
Y496 Phosphorylation P04629 (NTRK1)
Y591 Phosphorylation
Y670 Phosphorylation
S672 Phosphorylation
Y674 Phosphorylation
Y675 Phosphorylation
Y676 Phosphorylation P04629 (NTRK1)
Y680 Phosphorylation P04629 (NTRK1)
Y681 Phosphorylation P04629 (NTRK1)
Y701 Phosphorylation P04629 (NTRK1)
Y729 Phosphorylation
Y757 Phosphorylation
Y785 Phosphorylation
Y791 Phosphorylation P04629 (NTRK1)
Site PTM Type Enzyme
N67 N-Glycosylation
N95 N-Glycosylation
N121 N-Glycosylation
S141 Phosphorylation
T151 Phosphorylation
S153 Phosphorylation
T161 Phosphorylation
N178 N-Glycosylation
N205 N-Glycosylation
N241 N-Glycosylation
T253 Phosphorylation
N254 N-Glycosylation
S256 Phosphorylation
S257 Phosphorylation
S260 Phosphorylation
N280 N-Glycosylation
N338 N-Glycosylation
N412 N-Glycosylation
K461 Acetylation
S479 Phosphorylation
Y490 Phosphorylation
T506 Phosphorylation
Y516 Phosphorylation Q16620 (NTRK2)
Y558 Phosphorylation
T573 Phosphorylation
Y670 Phosphorylation
Y674 Phosphorylation
Y675 Phosphorylation
S698 Phosphorylation
Y702 Phosphorylation
Y706 Phosphorylation
Y707 Phosphorylation
Y785 Phosphorylation
Y817 Phosphorylation

PTMs - P04629/Q16620 As Enzyme

Substrate Site Source
P04629-3 (NTRK1) Y460 Uniprot
P04629-2 (NTRK1) Y490 Uniprot
P04629 (NTRK1) Y496 Uniprot
P04629-2 (NTRK1) Y670 Uniprot
P04629-2 (NTRK1) Y674 Uniprot
P04629-2 (NTRK1) Y675 Uniprot
P04629 (NTRK1) Y676 Uniprot
P04629 (NTRK1) Y680 Uniprot
P04629 (NTRK1) Y681 Uniprot
P04629 (NTRK1) Y701 Uniprot
P04629-2 (NTRK1) Y751 Uniprot
P04629-3 (NTRK1) Y755 Uniprot
P04629-2 (NTRK1) Y785 Uniprot
P04629 (NTRK1) Y791 Uniprot
P05067 (APP) Y757 Uniprot
P29353-2 (SHC1) Y317 Uniprot
P35222 (CTNNB1) Y142 Uniprot
Q92529-2 (SHC3) Y218 Uniprot
Q92529-2 (SHC3) Y219 Uniprot
Q92529-2 (SHC3) Y256 Uniprot
Q92529-2 (SHC3) Y257 Uniprot
Q92529-2 (SHC3) Y283 Uniprot
Q92529-2 (SHC3) Y301 Uniprot
Substrate Site Source
O43559 (FRS3) Y417 Uniprot
O43559 (FRS3) Y455 Uniprot
P22001 (KCNA3) Y161 Uniprot
P22001 (KCNA3) Y162 Uniprot
P22001 (KCNA3) Y163 Uniprot
P22001 (KCNA3) Y499 Uniprot
Q00535 (CDK5) Y15 Uniprot
Q13009 (TIAM1) Y829 Uniprot
Q16620 (NTRK2) Y516 Uniprot
Q16620-4 (NTRK2) Y532 Uniprot
Q16620-1 (NTRK2) Y702 Uniprot
Q16620-1 (NTRK2) Y706 Uniprot
Q16620-1 (NTRK2) Y707 Uniprot
Q16620-4 (NTRK2) Y718 Uniprot
Q16620-4 (NTRK2) Y722 Uniprot
Q16620-4 (NTRK2) Y723 Uniprot
Q16620-1 (NTRK2) Y817 Uniprot
Q16620-4 (NTRK2) Y833 Uniprot
Q92529-2 (SHC3) Y218 Uniprot
Q92529-2 (SHC3) Y219 Uniprot
Q92529-2 (SHC3) Y256 Uniprot
Q92529-2 (SHC3) Y257 Uniprot
Q92529-2 (SHC3) Y283 Uniprot
Q92529-2 (SHC3) Y301 Uniprot

Research Backgrounds

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. 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. 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.

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.

PTMs:

Ligand-mediated autophosphorylation. Interaction with SQSTM1 is phosphotyrosine-dependent. Autophosphorylation at Tyr-496 mediates interaction and phosphorylation of SHC1.

N-glycosylated. Isoform TrkA-I and isoform TrkA-II are N-glycosylated.

Ubiquitinated. Undergoes polyubiquitination upon activation; regulated by NGFR. Ubiquitination by NEDD4L leads to degradation. Ubiquitination regulates the internalization of the receptor (By similarity).

Subcellular Location:

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.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
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.

Subunit Structure:

Exists in a dynamic equilibrium between monomeric (low affinity) and dimeric (high affinity) structures. Homodimerization is induced by binding of a NGF dimer. Interacts with SQSTM1; bridges NTRK1 to NGFR. 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. Interacts (phosphorylated upon activation by NGF) with PLCG1; mediates PLCG1 phosphorylation and activation. Interacts (phosphorylated) with SH2B1 and SH2B2 (By similarity). Interacts with GRB2. Interacts with PIK3R1. Interacts with FRS2. Interacts with SORT1; may regulate NTRK1 anterograde axonal transport. 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. Interacts with GGA3.

Family&Domains:

The transmembrane domain mediates interaction with KIDINS220.

The extracellular domain mediates interaction with NGFR.

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.

Function:

Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticity (By similarity). Receptor for BDNF/brain-derived neurotrophic factor and NTF4/neurotrophin-4. Alternatively can also bind NTF3/neurotrophin-3 which is less efficient in activating the receptor but regulates neuron survival through NTRK2. Upon 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. Through SHC1, FRS2, SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for instance neuronal differentiation including neurite outgrowth. Through the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade that mainly regulates growth and survival. Through PLCG1 and the downstream protein kinase C-regulated pathways controls synaptic plasticity. Thereby, plays a role in learning and memory by regulating both short term synaptic function and long-term potentiation. PLCG1 also leads to NF-Kappa-B activation and the transcription of genes involved in cell survival. Hence, it is able to suppress anoikis, the apoptosis resulting from loss of cell-matrix interactions. May also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia.

PTMs:

Phosphorylated. Undergoes ligand-mediated autophosphorylation that is required for interaction with SHC1 and PLCG1 and other downstream effectors. Isoform TrkB-T-Shc is not phosphorylated.

Ubiquitinated. Undergoes polyubiquitination upon activation; regulated by NGFR. Ubiquitination regulates the internalization of the receptor (By similarity).

Subcellular Location:

Cell membrane>Single-pass type I membrane protein. Endosome membrane>Single-pass type I membrane protein. Early endosome membrane. Cell projection>Axon. Cell projection>Dendrite. Cytoplasm>Perinuclear region. Cell junction>Synapse>Postsynaptic density.
Note: Internalized to endosomes upon ligand-binding.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
Tissue Specificity:

Isoform TrkB is expressed in the central and peripheral nervous system. In the central nervous system (CNS), expression is observed in the cerebral cortex, hippocampus, thalamus, choroid plexus, granular layer of the cerebellum, brain stem, and spinal cord. In the peripheral nervous system, it is expressed in many cranial ganglia, the ophthalmic nerve, the vestibular system, multiple facial structures, the submaxillary glands, and dorsal root ganglia. Isoform TrkB-T1 is mainly expressed in the brain but also detected in other tissues including pancreas, kidney and heart. Isoform TrkB-T-Shc is predominantly expressed in the brain.

Subunit Structure:

Exists in a dynamic equilibrium between monomeric (low affinity) and dimeric (high affinity) structures. Interacts (phosphorylated upon activation by BDNF) with SHC1; mediates SHC1 phosphorylation and activation. Interacts (phosphorylated upon activation by BDNF) with PLCG1 and/or PLCG2; mediates PLCG1 phosphorylation and activation. Interacts with SH2B1 and SH2B2. Interacts with NGFR; may regulate the ligand specificity of the receptor (By similarity). Interacts with SORCS2; this interaction is important for normal targeting to post-synaptic densities in response to high-frequency stimulation (By similarity). Interacts (phosphorylated upon ligand-binding) with SH2D1A; regulates NTRK2. Interacts with SQSTM1 and KIDINS220 (By similarity). Interacts (phosphorylated upon ligand-binding) with FRS2; activates the MAPK signaling pathway. Interacts with APPL1 (By similarity). Interacts with MAPK8IP3/JIP3 and KLC1; interaction with KLC1 is mediated by MAPK8IP3/JIP3 (By similarity). Interacts with SORL1; this interaction facilitates NTRK2 trafficking between synaptic plasma membranes, postsynaptic densities and cell soma, hence positively regulates BDNF signaling (By similarity).

Family&Domains:

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.

Research Fields

· Cellular Processes > Cell growth and death > Apoptosis.   (View pathway)

· Environmental Information Processing > Signal transduction > MAPK signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Ras signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > PI3K-Akt signaling pathway.   (View pathway)

· Human Diseases > Substance dependence > Alcoholism.

· Human Diseases > Cancers: Overview > Pathways in cancer.   (View pathway)

· Human Diseases > Cancers: Overview > Transcriptional misregulation in cancer.

· Human Diseases > Cancers: Specific types > Thyroid cancer.   (View pathway)

· Human Diseases > Cancers: Overview > Central carbon metabolism in cancer.   (View pathway)

· Organismal Systems > Nervous system > Neurotrophin signaling pathway.   (View pathway)

· Organismal Systems > Sensory system > Inflammatory mediator regulation of TRP channels.   (View pathway)

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