Homodimer. Interacts with PAK7/PAK5; leading to inhibit the protein kinase activity (By similarity). Interacts (when phosphorylated at Thr-596) with YWHAZ. In case of infection, interacts with H.pylori CagA, leading to inhibit kinase activity and junctional and polarity defects.
Function:
Serine/threonine-protein kinase involved in cell polarity and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4, MAPT/TAU, and RAB11FIP2. Plays a key role in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Regulates epithelial cell polarity by phosphorylating RAB11FIP2. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Regulates axogenesis by phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3 and inhibiting microtubule-dependent accumulation of KIF13B. Also required for neurite outgrowth and establishment of neuronal polarity. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision to build a columnar versus a hepatic epithelial cell apparently by promoting a switch from a direct to a transcytotic mode of apical protein delivery. Essential for the asymmetric development of membrane domains of polarized epithelial cells.
Subcellular Location:
Cell membrane
Peripheral membrane protein
Cytoplasm
Phosphorylation at Thr-596 by PRKCZ/aPKC and subsequent interaction with 14-3-3 protein YWHAZ promotes relocation from the cell membrane to the cytoplasm.
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Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3);TISSUE SPECIFICITY
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Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6)
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Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4);NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 11-755 (ISOFORM 1)
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Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 28-788 (ISOFORM 4);FUNCTION
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Cited for: FUNCTION;ENZYME REGULATION;PHOSPHORYLATION AT THR-208;MUTAGENESIS OF THR-208
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Cited for: PHOSPHORYLATION AT THR-596;MUTAGENESIS OF THR-596;SUBCELLULAR LOCATION
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Cited for: FUNCTION;SUBCELLULAR LOCATION;PHOSPHORYLATION AT THR-596;MUTAGENESIS OF THR-596;INTERACTION WITH YWHAZ
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Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-486;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456 AND SER-486;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-409; SER-456; SER-486 AND SER-493;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-569;PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-376 (ISOFORMS 13 AND 14);PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-409 (ISOFORMS 15 AND 16);IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-208; SER-409; SER-456; SER-486 AND SER-722;PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-376 (ISOFORMS 13 AND 14);IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-40; SER-486 AND SER-619;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 49-363 IN COMPLEX WITH H.PYLORI CAGA PEPTIDE INHIBITOR