Phospho-ERK8 (Thr175+Tyr177) Antibody - #AF0029

Atypical MAPK protein that regulates several process such as autophagy, ciliogenesis, protein trafficking/secretion and genome integrity, in a kinase activity-dependent manner. Controls both, basal and starvation-induced autophagy throught its interaction with GABARAP, MAP1LC3B and GABARAPL1 leading to autophagosome formation, SQSTM1 degradation and reduced MAP1LC3B inhibitory phosphorylation. Regulates primary cilium formation and the localization of ciliary proteins involved in cilium structure, transport, and signaling. Prevents the relocation of the sugar-adding enzymes from the Golgi to the endoplasmic reticulum, thereby restricting the production of sugar-coated proteins. Upon amino-acid starvation, mediates transitional endoplasmic reticulum site disassembly and inhibition of secretion. Binds to chromatin leading to MAPK15 activation and interaction with PCNA, that which protects genomic integrity by inhibiting MDM2-mediated degradation of PCNA. Regulates DA transporter (DAT) activity and protein expression via activation of RhoA. In response to H(2)O(2) treatment phosphorylates ELAVL1, thus preventing it from binding to the PDCD4 3'UTR and rendering the PDCD4 mRNA accessible to miR-21 and leading to its degradation and loss of protein expression. Also functions in a kinase activity-independent manner as a negative regulator of growth (By similarity). Phosphorylates in vitro FOS and MBP. During oocyte maturation, plays a key role in the microtubule organization and meiotic cell cycle progression in oocytes, fertilized eggs, and early embryos (By similarity). Interacts with ESRRA promoting its re-localization from the nucleus to the cytoplasm and then prevents its transcriptional activity.

Autophosphorylated on Thr-175 and Tyr-177; activates the enzyme.

Ubiquitinated. Ubiquitination may allow its tight kinase activity regulation and rapid turnover. May be ubiquitinated by a SCF E3 ligase (By similarity).

Cytoplasm>Cytoskeleton>Cilium basal body. Cell junction>Tight junction. Cytoplasm>Cytoskeleton>Microtubule organizing center>Centrosome>Centriole. Cytoplasmic vesicle>Autophagosome. Golgi apparatus. Nucleus. Cytoplasm. Cytoplasm>Cytoskeleton>Spindle.
Note: Co-localizes to the cytoplasm only in presence of ESRRA (PubMed:21190936). Translocates to the nucleus upon activation (PubMed:20638370). At prometaphase I, metaphase I (MI), anaphase I, telophase I, and metaphase II (MII) stages, is stably detected at the spindle (By similarity).

Widely expressed with a maximal expression in lung and kidney.

Interacts with CSK/c-Src, ABL1, RET and TGFB1I1. Interacts with GABARAP, MAP1LC3B and GABARAPL1; controls, in a kinase-dependent fashion, both basal and starvation-induced autophagy. Interacts with ESRRA; promotes re-localization of ESRRA to the cytoplasm through a XPO1-dependent mechanism then inhibits ESRRA transcriptional activity. Interacts with PCNA; the interaction is chromatin binding- and kinase activity-dependent and prevents MDM2-mediated PCNA destruction by inhibiting the association of PCNA with MDM2. Interacts with DVL2 (By similarity). Interacts with CLIC3; MAPK15 does not phosphorylates CLIC3 (By similarity).

The N-terminal region (1-20) is the minimal region necessary for ubiquitination and further proteasomal degradation.

The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.