Names & Taxonomy

Uniprot ID:
P41743
Entry Name:
KPCI_HUMAN
Status:
reviewed
Protein Names:
Protein kinase C iota type (EC 2.7.11.13) (Atypical protein kinase C-lambda/iota) (PRKC-lambda/iota) (aPKC-lambda/iota) (nPKC-iota)
Gene Names:
PRKCI DXS1179E
Gene Names Primary:
PRKCI
Organism:
Homo sapiens (Human)

Structure

Length:
596
Sequence:
MPTQRDSSTMSHTVAGGGSGDHSHQVRVKAYYRGDIMITHFEPSISFEGLCNEVRDMCSFDNEQLFTMKWIDEEGDPCTVSSQLELEEAFRLYELNKDSELLIHVFPCVPERPGMPCPGEDKSIYRRGARRWRKLYCANGHTFQAKRFNRRAHCAICTDRIWGLGRQGYKCINCKLLVHKKCHKLVTIECGRHSLPQEPVMPMDQSSMHSDHAQTVIPYNPSSHESLDQVGEEKEAMNTRESGKASSSLGLQDFDLLRVIGRGSYAKVLLVRLKKTDRIYAMKVVKKELVNDDEDIDWVQTEKHVFEQASNHPFLVGLHSCFQTESRLFFVIEYVNGGDLMFHMQRQRKLPEEHARFYSAEISLALNYLHERGIIYRDLKLDNVLLDSEGHIKLTDYGMCKEGLRPGDTTSTFCGTPNYIAPEILRGEDYGFSVDWWALGVLMFEMMAGRSPFDIVGSSDNPDQNTEDYLFQVILEKQIRIPRSLSVKAASVLKSFLNKDPKERLGCHPQTGFADIQGHPFFRNVDWDMMEQKQVVPPFKPNISGEFGLDNFDSQFTNEPVQLTPDDDDIVRKIDQSEFEGFEYINPLLMSAEECV
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cytoplasm

Function

Function:
Calcium- and diacylglycerol-independent serine/ threonine-protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differentiation and polarity, and contributes to the regulation of microtubule dynamics in the early secretory pathway. Is necessary for BCR-ABL oncogene-mediated resistance to apoptotic drug in leukemia cells, protecting leukemia cells against drug-induced apoptosis. In cultured neurons, prevents amyloid beta protein-induced apoptosis by interrupting cell death process at a very early step. In glioblastoma cells, may function downstream of phosphatidylinositol 3-kinase (PI(3)K) and PDPK1 in the promotion of cell survival by phosphorylating and inhibiting the pro-apoptotic factor BAD. Can form a protein complex in non-small cell lung cancer (NSCLC) cells with PARD6A and ECT2 and regulate ECT2 oncogenic activity by phosphorylation, which in turn promotes transformed growth and invasion. In response to nerve growth factor (NGF), acts downstream of SRC to phosphorylate and activate IRAK1, allowing the subsequent activation of NF-kappa-B and neuronal cell survival. Functions in the organization of the apical domain in epithelial cells by phosphorylating EZR. This step is crucial for activation and normal distribution of EZR at the early stages of intestinal epithelial cell differentiation. Forms a protein complex with LLGL1 and PARD6B independently of PARD3 to regulate epithelial cell polarity. Plays a role in microtubule dynamics in the early secretory pathway through interaction with RAB2A and GAPDH and recruitment to vesicular tubular clusters (VTCs). In human coronary artery endothelial cells (HCAEC), is activated by saturated fatty acids and mediates lipid-induced apoptosis.
Catalytic Activity:
ATP + a protein = ADP + a phosphoprotein.
Kinetics:
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=13.5 uM for ATP (for recombinant purified PRKCI)
Enzyme Regulation:
ENZYME REGULATION: Atypical PKCs (PRKCI and PRKCZ) exhibit an elevated basal enzymatic activity (that may be due to the interaction with SMG1 or SQSTM1) and are not regulated by diacylglycerol, phosphatidylserine, phorbol esters or calcium ions. Two specific sites, Thr-412 (activation loop of the kinase domain) and Thr-564 (turn motif), need to be phosphorylated for its full activation (By similarity). Might also be a target for novel lipid activators that are elevated during nutrient-stimulated insulin secretion.
Active Site:
ACT_SITE 378 378 Proton acceptor.
Cross Reference Drug Bank:
DB00675
Gene Ontology Go:
apical plasma membrane
bicellular tight junction
cell leading edge
cytoplasm
cytosol
endosome
extracellular exosome
Golgi membrane
intercellular bridge
microtubule cytoskeleton
nucleus
plasma membrane
protein complex
Schmidt-Lanterman incisure
ATP binding
metal ion binding
phospholipid binding
protein kinase activity
protein kinase C activity
protein serine/threonine kinase activity
actin filament organization
bicellular tight junction assembly
cell junction assembly
cell migration
cell-cell junction organization
cellular response to insulin stimulus
cytoskeleton organization
establishment of apical/basal cell polarity
establishment or maintenance of epithelial cell apical/basal polarity
eye photoreceptor cell development
Golgi vesicle budding
intracellular signal transduction
membrane organization
negative regulation of apoptotic process
negative regulation of glial cell apoptotic process
negative regulation of neuron apoptotic process
neurotrophin TRK receptor signaling pathway
peptidyl-serine phosphorylation
positive regulation of endothelial cell apoptotic process
positive regulation of establishment of protein localization to plasma membrane
positive regulation of glial cell proliferation
positive regulation of glucose import
positive regulation of neuron projection development
positive regulation of NF-kappaB transcription factor activity
protein phosphorylation
protein targeting to membrane
response to interleukin-1
secretion
vesicle-mediated transport
Gene Ontology Biological Process:
actin filament organization
bicellular tight junction assembly
cell-cell junction organization
cell junction assembly
cell migration
cellular response to insulin stimulus
cytoskeleton organization
establishment of apical/basal cell polarity
establishment or maintenance of epithelial cell apical/basal polarity
eye photoreceptor cell development
Golgi vesicle budding
intracellular signal transduction
membrane organization
negative regulation of apoptotic process
negative regulation of glial cell apoptotic process
negative regulation of neuron apoptotic process
neurotrophin TRK receptor signaling pathway
peptidyl-serine phosphorylation
positive regulation of endothelial cell apoptotic process
positive regulation of establishment of protein localization to plasma membrane
positive regulation of glial cell proliferation
positive regulation of glucose import
positive regulation of neuron projection development
positive regulation of NF-kappaB transcription factor activity
protein phosphorylation
protein targeting to membrane
response to interleukin-1
secretion
vesicle-mediated transport
Gene Ontology Molecular Function:
ATP binding
metal ion binding
phospholipid binding
protein kinase activity
protein kinase C activity
protein serine/threonine kinase activity
Gene Ontology Cellular Component:
apical plasma membrane
bicellular tight junction
cell leading edge
cytoplasm
cytosol
endosome
extracellular exosome
Golgi membrane
intercellular bridge
microtubule cytoskeleton
nucleus
plasma membrane
protein complex
Schmidt-Lanterman incisure
Keywords:
3D-structure
ATP-binding
Acetylation
Complete proteome
Cytoplasm
Endosome
Kinase
Membrane
Metal-binding
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Proto-oncogene
Reference proteome
Serine/threonine-protein kinase
Transferase
Tumor suppressor
Zinc
Zinc-finger
Interacts With:
P60953; Q96L34; Q8TEW0; Q9NPB6; Q9BYG5; Q9BYG4; Q8ND90; Q05513; P63000; P48431; Q13501; Q04917

Publication

PubMed ID:
8226978 7607695 15489334 8524286 9346882 9566925 10467349 10356400 10906326 11042363 11260256 11257119 11724794 11713277 11891849 12893243 12725730 12871960 14570876 14684752 15994303 15695176 16792529 16452474 17313651 18270268 18220336 18691976 18669648 19327373 19617897 19690332 20068231 21269460 21419810 21189248 21406692 24275569 15143057 15590654 16125198 17344846