产品: 磷酸化 TrkA (Tyr680+Tyr681) 抗体
货号: AF3072
描述: Rabbit polyclonal antibody to Phospho-TrkA (Tyr680+Tyr681)
应用: WB IHC
反应: Human, Mouse, Rat
预测: Pig, Zebrafish, Bovine, Sheep, Rabbit, Dog, Chicken
分子量: 87kDa; 87kD(Calculated).
蛋白号: P04629
RRID: AB_2834509

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产品描述

来源:
Rabbit
应用:
WB 1:500-1:2000, IHC 1:50-1:500
*The optimal dilutions should be determined by the end user.
*Tips:

WB: 适用于变性蛋白样本的免疫印迹检测. IHC: 适用于组织样本的石蜡(IHC-p)或冰冻(IHC-f)切片样本的免疫组化/荧光检测. IF/ICC: 适用于细胞样本的荧光检测. ELISA(peptide): 适用于抗原肽的ELISA检测.

反应:
Human,Mouse,Rat
预测:
Pig(100%), Zebrafish(100%), Bovine(100%), Sheep(100%), Rabbit(100%), Dog(100%), Chicken(100%)
克隆:
Polyclonal
特异性:
Phospho-TrkA (Tyr680+Tyr681) Antibody detects endogenous levels of TrkA only when phosphorylated at Tyrosine 680+Tyrosine 681.
RRID:
AB_2834509
引用格式: Affinity Biosciences Cat# AF3072, RRID:AB_2834509.
偶联:
Unconjugated.
纯化:
The antibody is from purified rabbit serum by affinity purification via sequential chromatography on phospho-peptide and non-phospho-peptide affinity columns.
保存:
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.
别名:

展开/折叠

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;

抗原和靶标

免疫原:
Uniprot:
基因/基因ID:
表达:
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.

描述:
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, mental retardation and cancer. Alternate transcriptional splice variants of this gene have been found, but only three have been characterized to date.
序列:
MLRGGRRGQLGWHSWAAGPGSLLAWLILASAGAAPCPDACCPHGSSGLRCTRDGALDSLHHLPGAENLTELYIENQQHLQHLELRDLRGLGELRNLTIVKSGLRFVAPDAFHFTPRLSRLNLSFNALESLSWKTVQGLSLQELVLSGNPLHCSCALRWLQRWEEEGLGGVPEQKLQCHGQGPLAHMPNASCGVPTLKVQVPNASVDVGDDVLLRCQVEGRGLEQAGWILTELEQSATVMKSGGLPSLGLTLANVTSDLNRKNVTCWAENDVGRAEVSVQVNVSFPASVQLHTAVEMHHWCIPFSVDGQPAPSLRWLFNGSVLNETSFIFTEFLEPAANETVRHGCLRLNQPTHVNNGNYTLLAANPFGQASASIMAAFMDNPFEFNPEDPIPVSFSPVDTNSTSGDPVEKKDETPFGVSVAVGLAVFACLFLSTLLLVLNKCGRRNKFGINRPAVLAPEDGLAMSLHFMTLGGSSLSPTEGKGSGLQGHIIENPQYFSDACVHHIKRRDIVLKWELGEGAFGKVFLAECHNLLPEQDKMLVAVKALKEASESARQDFQREAELLTMLQHQHIVRFFGVCTEGRPLLMVFEYMRHGDLNRFLRSHGPDAKLLAGGEDVAPGPLGLGQLLAVASQVAAGMVYLAGLHFVHRDLATRNCLVGQGLVVKIGDFGMSRDIYSTDYYRVGGRTMLPIRWMPPESILYRKFTTESDVWSFGVVLWEIFTYGKQPWYQLSNTEAIDCITQGRELERPRACPPEVYAIMRGCWQREPQQRHSIKDVHARLQALAQAPPVYLDVLG

种属预测

种属预测:

score>80的预测可信度较高,可尝试用于WB检测。*预测模型主要基于免疫原序列比对,结果仅作参考,不作为质保凭据。

Species
Results
Score
Pig
100
Bovine
100
Sheep
100
Dog
100
Zebrafish
100
Chicken
100
Rabbit
100
Horse
0
Xenopus
0
Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

翻译修饰 - P04629 作为底物

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)

翻译修饰 - P04629 作为激酶

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

研究背景

功能:

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.

翻译修饰:

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).

细胞定位:

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
组织特异性:

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.

亚基结构:

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.

蛋白家族:

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.

研究领域

· 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 > 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)

文献引用

1). Liu Y et al. Oligo-Porphyran Ameliorates Neurobehavioral Deficits in Parkinsonian Mice by Regulating the PI3K/Akt/Bcl-2 Pathway. Marine Drugs 2018 Mar 6;16(3) (PubMed: 29509717) [IF=5.4]

Application: WB    Species: mouse    Sample: striatum

Figure 6. |Effects of OP on nerve growth factor (NGF) and tropomyosin receptor kinase A (TrkA),expression. After pretreated with MPTP for 7 days, the C57BL/6 mice were administrated with MA or different concentrations of OP for the followed 7 days.(A) Original bands of NGF, pTrkA, TrkA, andβ-actin.

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