Scientific Background: 14-3-3ζ (also known as tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide) is a member of the 14-3-3 family of proteins which mediate signal transduction by binding to phosphoserine-containing proteins. 14-3-3ζ protein plays a key role in cancer biology by being an important regulator of major cellular processes such as proliferation, differentiation, senescence and apoptosis (1). 14-3-3ζ protein has been shown to interact with the IRS1 protein, suggesting a role for this protein in regulating insulin sensitivity by interrupting the association between the insulin receptor and IRS1 (2).
2. Niemantsverdriet, M. et al: Cellular functions of 14-3-3 zeta in apoptosis and cell adhesion emphasize its oncogenic character. Oncogene. 2008;27(9):1315-9. 2007.
NCBI and Uniprot Product Information
NCBI Description
This gene product belongs to the 14-3-3 family of proteins which mediate signal transduction by binding to phosphoserine-containing proteins. This highly conserved protein family is found in both plants and mammals, and this protein is 99% identical to the mouse, rat and sheep orthologs. The encoded protein interacts with IRS1 protein, suggesting a role in regulating insulin sensitivity. Several transcript variants that differ in the 5' UTR but that encode the same protein have been identified for this gene. [provided by RefSeq, Oct 2008]
Uniprot Description
Function: Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Ref.9 Ref.14 Ref.15 Ref.21 Ref.23
Subunit structure: Interacts with CDK16 and BSPRY
By similarity. Interacts with WEE1 (C-terminal). Interacts with SAMSN1
By similarity. Interacts with MLF1 (phosphorylated form); the interaction retains it in the cytoplasm
By similarity. Interacts with Thr-phosphorylated ITGB2
By similarity. Interacts with BCL2L11
By similarity. Homodimer. Heterodimerizes with YWHAE. Homo- and hetero-dimerization is inhibited by phosphorylation on Ser-58. Interacts with FOXO4, NOXA1, SSH1 and ARHGEF2. Interacts with Pseudomonas aeruginosa exoS (unphosphorylated form). Interacts with BAX; the interaction occurs in the cytoplasm. Under stress conditions, MAPK8-mediated phosphorylation releases BAX to mitochondria. Interacts with phosphorylated RAF1; the interaction is inhibited when YWHAZ is phosphorylated on Thr-232. Interacts with TP53; the interaction enhances p53 transcriptional activity. The Ser-58 phosphorylated form inhibits this interaction and p53 transcriptional activity. Interacts with ABL1 (phosphorylated form); the interaction retains ABL1 in the cytoplasm. Interacts with PKA-phosphorylated AANAT; the interaction modulates AANAT enzymatic activity by increasing affinity for arylalkylamines and acetyl-CoA and protecting the enzyme from dephosphorylation and proteasomal degradation. It may also prevent thiol-dependent inactivation. Interacts with AKT1; the interaction phosphorylates YWHAZ and modulates dimerization. Interacts with GAB2 and TLK2. Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.20 Ref.21 Ref.23 Ref.25 Ref.26 Ref.27
Subcellular location: Cytoplasm. Melanosome. Note: Located to stage I to stage IV melanosomes. Ref.24
Post-translational modification: The delta, brain-specific form differs from the zeta form in being phosphorylated
By similarity. Phosphorylation on Ser-184 by MAPK8; promotes dissociation of BAX and translocation of BAX to mitochondria. Phosphorylation on Thr-232; inhibits binding of RAF1. Phosphorylated on Ser-58 by PKA and protein kinase C delta type catalytic subunit in a sphingosine-dependent fashion. Phosphorylation on Ser-58 by PKA; disrupts homodimerization and heterodimerization with YHAE and TP53. Ref.9 Ref.12 Ref.13 Ref.15 Ref.19 Ref.20 Ref.23
Sequence similarities: Belongs to the 14-3-3 family.
Caution: Was originally (Ref.1) thought to have phospholipase A2 activity.
Sequence caution: The sequence AAH51814.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.The sequence AAH73141.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.
Research Articles on 14-3-3 zeta
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Product Notes
The 14-3-3 zeta ywhaz (Catalog #AAA515276) is a Recombinant Protein produced from E Coli and is intended for research purposes only. The product is available for immediate purchase. The tag for this protein is GST tag!!Expression System||E.coli!!Source Note||Recombinant full-length human tag-free 14-3-3zeta was expressed in E. coli cells. AAA Biotech's 14-3-3 zeta can be used in a range of immunoassay formats including, but not limited to, Western Blot (WB). Researchers should empirically determine the suitability of the 14-3-3 zeta ywhaz for an application not listed in the data sheet. Researchers commonly develop new applications and it is an integral, important part of the investigative research process. It is sometimes possible for the material contained within the vial of "14-3-3 zeta, Recombinant Protein" to become dispersed throughout the inside of the vial, particularly around the seal of said vial, during shipment and storage. We always suggest centrifuging these vials to consolidate all of the liquid away from the lid and to the bottom of the vial prior to opening. Please be advised that certain products may require dry ice for shipping and that, if this is the case, an additional dry ice fee may also be required.Precautions
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