protein kinase C-iota (PRKCI, DXS1179E)

Function: - Ca⁺²-independent, phospholipid-dependent - serine/threonine kinase - may play a role in the secretory response to nutrients - involved in cell polarization processes formation of epithelial tight junctions - implicated in activation of several signaling pathways including Ras, c-Src & NF-kappa-B pathways - functions in both pro- & anti-apoptotic pathways - functions in the RAC1/ERK signaling required for transformed growth - role in microtubule dynamics through interaction with RAB2 & GAPDH & recruitment to vesicular tubular clusters (VTCs) - forms a complex with SQSTM1 & MP2K5 (putative) - interacts directly with SQSTM1 (probable - interacts with IKBKB - interacts with PARD6A, PARD6B & PARD6G - part of a quaternary complex containing aPKC, PARD3, a PARD6 protein (PARD6A, PARD6B or PARD6G) & a GTPase protein (CDC42 or RAC1) - part of a complex with LLGL1 & PARD6B - interacts with CENTA1 - interaction with SMG1, through the ZN-finger domain, activates the kinase activity - interacts with CDK7 - forms a complex with RAB2 & GAPDH involved in recruitment onto the membrane of vesicular tubular clusters (VTCs) - might be a target for novel lipid activators that are elevated during nutrient-stimulated insulin secretion - two specific sites a) Thr-403 (activation loop of the kinase domain) b) Thr-555 (turn motif) need to be phosphorylated for its full activation (putative) - atypical PCKs are not regulated by diacylglycerol, phorbol esters nor Ca⁺² - on neuronal growth factor (NGF) stimulation, phosphorylated by Src on Tyr-256, Tyr-271 & Tyr-325 - phosphorylation on Tyr-256 facilitates binding to KPNB1/ importin-beta regulating entry of PRKCI into the nucleus - phosphorylation on Tyr-325 is important for NF-kappa-B stimulation Structure: - OPR domain mediates interaction with SQSTM1 - C1 domain does not bind diacylglycerol (DAG) - belongs to the protein kinase superfamily, AGC Ser/Thr protein kinase family, PKC subfamily - contains 1 AGC-kinase C-terminal domain - contains 1 OPR domain - contains 1 phorbol-ester/DAG-type Zn⁺² finger - contains 1 protein kinase domain Compartment: - cytoplasm, membrane, endosome, nucleus - transported into the endosome through interaction with SQSTM1/p62 - after phosphorylation by cSrc, transported into the nucleus through interaction with KPNB1 - colocalizes with CDK7 in the cytoplasm & nucleus - vesicular tubular clusters - transported to VTCs through interaction with Rab2 Expression: - expressed in lung & brain > other tissues including pancreatic islets Pathology: - PRKCI is highly expressed in non-small cell lung cancers

Properties

SIZE: entity length = 587 aa MW = 67 kD COMPARTMENT: cytoplasm cell nucleus STATE: active state MOTIF: Regulatory {1-244} MOTIF: RAB2 interaction {1-19} OPR {16-99} PARD6A interaction {63-82} Zinc finger NAME: Zinc finger SITE: 131-181 EFFECTOR-BOUND: Zn+2 kinase domain SITE: 245-513 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 251-259 Tyr phosphorylation site {Y256} Tyr phosphorylation site {Y271} ATP-binding site NAME: ATP-binding site SITE: 274-274 Tyr phosphorylation site {Y325} aspartate residue {D369} Thr phosphorylation site {T403} AGC-kinase C-terminal {514-585} MOTIF: Thr phosphorylation site {T555}

Database Correlations

OMIM 600539 UniProt P41743 PFAM correlations Entrez Gene 5584 Kegg hsa:5584 ENZYME 2.7.11.13

References

UniProt :accession P41743