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Mouse Anti-ZAP70 (Phosphorylated Y292) Recombinant Antibody (A16038A) (PTM-CBMAB-0527LY)


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Summary

Host Animal
Mouse
Specificity
Human, Mouse
Clone
A16038A
Antibody Isotype
IgG2b, κ
Application
WB, ICFC

Basic Information

Immunogen
Human ZAP70 peptide phosphorylated at Y292
Specificity
Human, Mouse
Antibody Isotype
IgG2b, κ
Clonality
Monoclonal
Application Notes
The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.

Formulations & Storage [For reference only, actual COA shall prevail!]

Format
Liquid
Buffer
Phosphate-buffered solution, pH 7.2, containing 0.09% sodium azide
Storage
Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freezethaw cycles.

Target

Full Name
Zeta Chain Of T Cell Receptor Associated Protein Kinase 70
Introduction
This gene encodes an enzyme belonging to the protein tyrosine kinase family, and it plays a role in T-cell development and lymphocyte activation. This enzyme, which is phosphorylated on tyrosine residues upon T-cell antigen receptor (TCR) stimulation, functions in the initial step of TCR-mediated signal transduction in combination with the Src family kinases, Lck and Fyn. This enzyme is also essential for thymocyte development. Mutations in this gene cause selective T-cell defect, a severe combined immunodeficiency disease characterized by a selective absence of CD8-positive T-cells. Two transcript variants that encode different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Entrez Gene ID
Human7535
Mouse22637
UniProt ID
HumanP43403
MouseP43404
Function
Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development. Contributes also to the development and activation of primary B-lymphocytes. When antigen presenting cells (APC) activate T-cell receptor (TCR), a serie of phosphorylations lead to the recruitment of ZAP70 to the doubly phosphorylated TCR component CD247/CD3Z through ITAM motif at the plasma membrane. This recruitment serves to localization to the stimulated TCR and to relieve its autoinhibited conformation. Release of ZAP70 active conformation is further stabilized by phosphorylation mediated by LCK. Subsequently, ZAP70 phosphorylates at least 2 essential adapter proteins: LAT and LCP2. In turn, a large number of signaling molecules are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. Furthermore, ZAP70 controls cytoskeleton modifications, adhesion and mobility of T-lymphocytes, thus ensuring correct delivery of effectors to the APC. ZAP70 is also required for TCR-CD247/CD3Z internalization and degradation through interaction with the E3 ubiquitin-protein ligase CBL and adapter proteins SLA and SLA2. Thus, ZAP70 regulates both T-cell activation switch on and switch off by modulating TCR expression at the T-cell surface. During thymocyte development, ZAP70 promotes survival and cell-cycle progression of developing thymocytes before positive selection (when cells are still CD4/CD8 double negative). Additionally, ZAP70-dependent signaling pathway may also contribute to primary B-cells formation and activation through B-cell receptor (BCR).
Biological Process
Biological Process adaptive immune response Source:UniProtKB1 Publication
Biological Process B cell activation Source:UniProtKB1 Publication
Biological Process beta selection Source:Ensembl
Biological Process calcium-mediated signaling Source:Ensembl
Biological Process cell differentiation Source:GO_Central1 Publication
Biological Process immune response Source:UniProtKB1 Publication
Biological Process innate immune response Source:GO_Central1 Publication
Biological Process intracellular signal transduction Source:UniProtKB1 Publication
Biological Process negative thymic T cell selection Source:Ensembl
Biological Process peptidyl-tyrosine phosphorylation Source:MGI1 Publication
Biological Process positive regulation of alpha-beta T cell differentiation Source:Ensembl
Biological Process positive regulation of alpha-beta T cell proliferation Source:Ensembl
Biological Process positive regulation of calcium-mediated signaling Source:Ensembl
Biological Process positive regulation of T cell differentiation Source:MGI1 Publication
Biological Process positive thymic T cell selection Source:MGI1 Publication
Biological Process protein autophosphorylation Source:Ensembl
Biological Process protein phosphorylation Source:UniProtKB1 Publication
Biological Process T cell activation Source:UniProtKB1 Publication
Biological Process T cell aggregation Source:UniProtKB1 Publication
Biological Process T cell differentiation Source:UniProtKB1 Publication
Biological Process T cell migration Source:UniProtKB1 Publication
Biological Process T cell receptor signaling pathway Source:UniProtKB1 Publication
Biological Process transmembrane receptor protein tyrosine kinase signaling pathway Source:GO_Central1 Publication
Cellular Location
Cytoplasm
Cell membrane
In quiescent T-lymphocytes, it is cytoplasmic. Upon TCR activation, it is recruited at the plasma membrane by interacting with CD247/CD3Z. Colocalizes together with RHOH in the immunological synapse. RHOH is required for its proper localization to the cell membrane and cytoskeleton fractions in the thymocytes (By similarity).
Involvement in disease
Immunodeficiency 48 (IMD48):
A form of severe immunodeficiency characterized by a selective absence of CD8+ T-cells.
Autoimmune disease, multisystem, infantile-onset, 2 (ADMIO2):
An autosomal recessive, autoimmune disorder characterized by systemic manifestations including blistering skin disease, uncontrollable bullous pemphigoid, inflammatory colitis, autoimmune hypothyroidism, proteinuria and nephrotic syndrome.
PTM
Phosphorylated on tyrosine residues upon T-cell antigen receptor (TCR) stimulation. Phosphorylation of Tyr-315 and Tyr-319 are essential for ZAP70 positive function on T-lymphocyte activation whereas Tyr-292 has a negative regulatory role. Within the C-terminal kinase domain, Tyr-492 and Tyr-493 are phosphorylated after TCR induction, Tyr-492 playing a negative regulatory role and Tyr-493 a positive. Tyr-493 is dephosphorylated by PTN22.
Ubiquitinated in response to T cell activation. Deubiquitinated by OTUD7B.
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For research use only. Not intended for any clinical use.

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