PRKCI
entrez
5584
canonical
uniprot
P41743
canonical
ensembl
ENSG00000163558
resolver
ensp
ENSP00000295797
resolver
ensp
ENSP00000645981
resolver
enst
ENST00000295797
resolver
genesymbol
PRKCI
resolver
genesymbol_syn
DXS1179E
resolver
hgnc
HGNC:9404
resolver
uniprot
D3DNQ4
resolver
uniprot
Q8WW06
resolver
uniprot_entry
KPCI_HUMAN
resolver
uniprot_sec
D3DNQ4
resolver
uniprot_sec
Q8WW06
resolver
activity_regulation
ACTIVITY 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. {ECO:0000250, ECO:0000269|PubMed:8524286}.
uniprot
proteins
amino_acid_sequence
MPTQRDSSTMSHTVAGGGSGDHSHQVRVKAYYRGDIMITHFEPSISFEGLCNEVRDMCSFDNEQLFTMKWIDEEGDPCTVSSQLELEEAFRLYELNKDSELLIHVFPCVPERPGMPCPGEDKSIYRRGARRWRKLYCANGHTFQAKRFNRRAHCAICTDRIWGLGRQGYKCINCKLLVHKKCHKLVTIECGRHSLPQEPVMPMDQSSMHSDHAQTVIPYNPSSHESLDQVGEEKEAMNTRESGKASSSLGLQDFDLLRVIGRGSYAKVLLVRLKKTDRIYAMKVVKKELVNDDEDIDWVQTEKHVFEQASNHPFLVGLHSCFQTESRLFFVIEYVNGGDLMFHMQRQRKLPEEHARFYSAEISLALNYLHERGIIYRDLKLDNVLLDSEGHIKLTDYGMCKEGLRPGDTTSTFCGTPNYIAPEILRGEDYGFSVDWWALGVLMFEMMAGRSPFDIVGSSDNPDQNTEDYLFQVILEKQIRIPRSLSVKAASVLKSFLNKDPKERLGCHPQTGFADIQGHPFFRNVDWDMMEQKQVVPPFKPNISGEFGLDNFDSQFTNEPVQLTPDDDDIVRKIDQSEFEGFEYINPLLMSAEECV
uniprot
proteins
ec_number
2.7.11.13
uniprot
proteins
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. Involved in early synaptic long term potentiation phase in CA1 hippocampal cells and short term memory formation (By similarity). {ECO:0000250|UniProtKB:F1M7Y5, ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10467349, ECO:0000269|PubMed:10906326, ECO:0000269|PubMed:11042363, ECO:0000269|PubMed:11724794, ECO:0000269|PubMed:12871960, ECO:0000269|PubMed:14684752, ECO:0000269|PubMed:15994303, ECO:0000269|PubMed:18270268, ECO:0000269|PubMed:19327373, ECO:0000269|PubMed:21189248, ECO:0000269|PubMed:21419810, ECO:0000269|PubMed:8226978, ECO:0000269|PubMed:9346882}.
uniprot
proteins
mass_dalton
68262
uniprot
proteins
mutagenesis
MUTAGEN 29; /note="K->A: No effect on interaction with SQSTM1."; /evidence="ECO:0000269|PubMed:15143057"; MUTAGEN 72; /note="D->A: Loss of interaction with ECT2, PARD6A and with SQSTM1."; /evidence="ECO:0000269|PubMed:15143057, ECO:0000269|PubMed:15590654, ECO:0000269|PubMed:19617897"; MUTAGEN 85; /note="E->A: Slight decrease of interaction with PARD6A. Loss of interaction with PARD6A; when associated with A-91."; /evidence="ECO:0000269|PubMed:15590654"; MUTAGEN 91; /note="R->A: Slight decrease of interaction with PARD6A. Loss of interaction with PARD6A; when associated with A-85."; /evidence="ECO:0000269|PubMed:15590654"; MUTAGEN 265; /note="Y->F: No effect on the SRC-mediated phosphorylation state. No effect on SRC-induced enzyme activity. Little effect on TRAF6-mediated activation of NF-kappa-B. Decreased binding to KPNB1/importin-beta."; /evidence="ECO:0000269|PubMed:11713277, ECO:0000269|PubMed:11891849"; MUTAGEN 274; /note="K->R: No effect on activity."; /evidence="ECO:0000269|PubMed:10906326"; MUTAGEN 274; /note="K->W: Abolishes activity."; /evidence="ECO:0000269|PubMed:10906326"; MUTAGEN 280; /note="Y->F: No effect on the SRC-mediated phosphorylation state. No effect on SRC-induced enzyme activity. No effect on TRAF6-mediated activation of NF-kappa-B."; /evidence="ECO:0000269|PubMed:11713277"; MUTAGEN 334; /note="Y->F: No effect on the SRC-mediated phosphorylation state. Significant reduction of SRC-induced enzyme activity. Greatly reduced TRAF6-mediated activation of NF-kappa-B. Reduces NGF-dependent cell survival."; /evidence="ECO:0000269|PubMed:11713277
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Thr-412 in the activation loop is not mandatory for activation (By similarity). Upon neuronal growth factor (NGF) stimulation, phosphorylated by SRC at Tyr-265, Tyr-280 and Tyr-334 (PubMed:11713277, PubMed:16452474). Phosphorylation at Tyr-265 facilitates binding to KPNB1/importin-beta regulating entry of PRKCI into the nucleus (PubMed:11891849). Phosphorylation on Tyr-334 is important for NF-kappa-B stimulation (PubMed:11713277). Phosphorylated at Thr-564 during the initial phase of long term potentiation (By similarity). {ECO:0000250|UniProtKB:F1M7Y5, ECO:0000250|UniProtKB:Q62074, ECO:0000269|PubMed:11713277, ECO:0000269|PubMed:11891849, ECO:0000269|PubMed:16452474}.
uniprot
proteins
protein_family
AGC Ser/Thr protein kinase family
uniprot
proteins
protein_family
PKC subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
10356400
uniprot
proteins
pubmed
10467349
uniprot
proteins
pubmed
10906326
uniprot
proteins
pubmed
11042363
uniprot
proteins
pubmed
11257119
uniprot
proteins
pubmed
11260256
uniprot
proteins
pubmed
11713277
uniprot
proteins
pubmed
11724794
uniprot
proteins
pubmed
11891849
uniprot
proteins
pubmed
12725730
uniprot
proteins
pubmed
12871960
uniprot
proteins
pubmed
12893243
uniprot
proteins
pubmed
14570876
uniprot
proteins
pubmed
14684752
uniprot
proteins
pubmed
15143057
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15590654
uniprot
proteins
pubmed
15695176
uniprot
proteins
pubmed
15994303
uniprot
proteins
pubmed
16125198
uniprot
proteins
pubmed
16452474
uniprot
proteins
pubmed
16792529
uniprot
proteins
pubmed
17313651
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
18220336
uniprot
proteins
pubmed
18270268
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19327373
uniprot
proteins
pubmed
19617897
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21189248
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21419810
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
7607695
uniprot
proteins
pubmed
8226978
uniprot
proteins
pubmed
8524286
uniprot
proteins
pubmed
9346882
uniprot
proteins
pubmed
9566925
uniprot
proteins
sequence_length
596
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11891849, ECO:0000269|PubMed:15695176, ECO:0000269|PubMed:9566925}. Membrane {ECO:0000269|PubMed:16452474}. Endosome {ECO:0000269|PubMed:9566925}. Nucleus {ECO:0000269|PubMed:11891849, ECO:0000269|PubMed:15695176}. Note=Transported into the endosome through interaction with SQSTM1/p62. After phosphorylation by SRC, transported into the nucleus through interaction with KPNB1. Colocalizes with CDK7 in the cytoplasm and nucleus. Transported to vesicular tubular clusters (VTCs) through interaction with RAB2A. {ECO:0000269|PubMed:15695176, ECO:0000269|PubMed:9566925}.
uniprot
proteins