Gene/Proteome Database (LMPD)

LMPD ID
LMP002189
Gene ID
5584
Species
Homo sapiens (Human)
Gene Name
protein kinase C, iota
Gene Symbol
PRKCI
Synonyms
DXS1179E; PKCI; nPKC-iota
Alternate Names
protein kinase C iota type; PRKC-lambda/iota; aPKC-lambda/iota; atypical protein kinase C-lambda/iota
Chromosome
3
Map Location
3q26.3
EC Number
2.7.11.13
Summary
This gene encodes a member of the protein kinase C (PKC) family of serine/threonine protein kinases. The PKC family comprises at least eight members, which are differentially expressed and are involved in a wide variety of cellular processes. This protein kinase is calcium-independent and phospholipid-dependent. It is not activated by phorbolesters or diacylglycerol. This kinase can be recruited to vesicle tubular clusters (VTCs) by direct interaction with the small GTPase RAB2, where this kinase phosphorylates glyceraldehyde-3-phosphate dehydrogenase (GAPD/GAPDH) and plays a role in microtubule dynamics in the early secretory pathway. This kinase is found to be necessary for BCL-ABL-mediated resistance to drug-induced apoptosis and therefore protects leukemia cells against drug-induced apoptosis. There is a single exon pseudogene mapped on chromosome X. [provided by RefSeq, Jul 2008]
Orthologs
View orthologs and multiple alignments for PRKCI

Proteins

protein kinase C iota type
Refseq ID NP_002731
Protein GI 133908623
UniProt ID P41743
mRNA ID NM_002740
Length 596
RefSeq Status REVIEWED
MPTQRDSSTMSHTVAGGGSGDHSHQVRVKAYYRGDIMITHFEPSISFEGLCNEVRDMCSFDNEQLFTMKWIDEEGDPCTVSSQLELEEAFRLYELNKDSELLIHVFPCVPERPGMPCPGEDKSIYRRGARRWRKLYCANGHTFQAKRFNRRAHCAICTDRIWGLGRQGYKCINCKLLVHKKCHKLVTIECGRHSLPQEPVMPMDQSSMHSDHAQTVIPYNPSSHESLDQVGEEKEAMNTRESGKASSSLGLQDFDLLRVIGRGSYAKVLLVRLKKTDRIYAMKVVKKELVNDDEDIDWVQTEKHVFEQASNHPFLVGLHSCFQTESRLFFVIEYVNGGDLMFHMQRQRKLPEEHARFYSAEISLALNYLHERGIIYRDLKLDNVLLDSEGHIKLTDYGMCKEGLRPGDTTSTFCGTPNYIAPEILRGEDYGFSVDWWALGVLMFEMMAGRSPFDIVGSSDNPDQNTEDYLFQVILEKQIRIPRSLSVKAASVLKSFLNKDPKERLGCHPQTGFADIQGHPFFRNVDWDMMEQKQVVPPFKPNISGEFGLDNFDSQFTNEPVQLTPDDDDIVRKIDQSEFEGFEYINPLLMSAEECV

Gene Information

Entrez Gene ID
5584
Gene Name
protein kinase C, iota
Gene Symbol
PRKCI
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0000139 IEA:GOC C Golgi membrane
GO:0043220 IEA:Ensembl C Schmidt-Lanterman incisure
GO:0016324 IEA:Ensembl C apical plasma membrane
GO:0031252 IEA:Ensembl C cell leading edge
GO:0005737 IDA:HPA C cytoplasm
GO:0005829 IDA:UniProtKB C cytosol
GO:0005768 IEA:UniProtKB-KW C endosome
GO:0070062 IDA:UniProt C extracellular vesicular exosome
GO:0045171 IDA:HPA C intercellular bridge
GO:0015630 IDA:HPA C microtubule cytoskeleton
GO:0005634 IDA:UniProtKB C nucleus
GO:0005886 TAS:Reactome C plasma membrane
GO:0043234 IEA:Ensembl C protein complex
GO:0005524 TAS:UniProtKB F ATP binding
GO:0005543 IDA:UniProtKB F phospholipid binding
GO:0004697 ISS:BHF-UCL F protein kinase C activity
GO:0004672 IDA:UniProtKB F protein kinase activity
GO:0004674 IDA:UniProtKB F protein serine/threonine kinase activity
GO:0008270 IEA:InterPro F zinc ion binding
GO:0048194 IEA:Ensembl P Golgi vesicle budding
GO:0007015 IEA:Ensembl P actin filament organization
GO:0034329 TAS:Reactome P cell junction assembly
GO:0016477 IEA:Ensembl P cell migration
GO:0045216 IMP:UniProtKB P cell-cell junction organization
GO:0032869 ISS:BHF-UCL P cellular response to insulin stimulus
GO:0007010 NAS:UniProtKB P cytoskeleton organization
GO:0035089 IEA:Ensembl P establishment of apical/basal cell polarity
GO:0045197 TAS:UniProtKB P establishment or maintenance of epithelial cell apical/basal polarity
GO:0042462 IEA:Ensembl P eye photoreceptor cell development
GO:0035556 IEA:InterPro P intracellular signal transduction
GO:0061024 NAS:UniProtKB P membrane organization
GO:0043066 TAS:Reactome P negative regulation of apoptotic process
GO:0034351 IMP:UniProtKB P negative regulation of glial cell apoptotic process
GO:0043524 IDA:UniProtKB P negative regulation of neuron apoptotic process
GO:0048011 TAS:Reactome P neurotrophin TRK receptor signaling pathway
GO:0051092 IDA:UniProtKB P positive regulation of NF-kappaB transcription factor activity
GO:2000353 IMP:UniProtKB P positive regulation of endothelial cell apoptotic process
GO:0090004 ISS:BHF-UCL P positive regulation of establishment of protein localization to plasma membrane
GO:0060252 IMP:UniProtKB P positive regulation of glial cell proliferation
GO:0046326 ISS:BHF-UCL P positive regulation of glucose import
GO:0010976 IMP:UniProtKB P positive regulation of neuron projection development
GO:0006468 IDA:UniProtKB P protein phosphorylation
GO:0006612 NAS:UniProtKB P protein targeting to membrane
GO:0070555 IEA:Ensembl P response to interleukin-1
GO:0046903 NAS:UniProtKB P secretion
GO:0070830 TAS:Reactome P tight junction assembly
GO:0016192 TAS:UniProtKB P vesicle-mediated transport

KEGG Pathway Links

KEGG Pathway ID Description
hsa04390 Hippo signaling pathway
hsa04611 Platelet activation
hsa04015 Rap1 signaling pathway

Domain Information

InterPro Annotations

Accession Description
IPR000961 AGC-kinase, C-terminal
IPR020454 Diacylglycerol/phorbol-ester binding
IPR000270 Phox/Bem1p
IPR012233 Protein kinase C
IPR002219 Protein kinase C-like, phorbol ester/diacylglycerol-binding domain
IPR000719 Protein kinase domain
IPR017441 Protein kinase, ATP binding site
IPR017892 Protein kinase, C-terminal
IPR011009 Protein kinase-like domain
IPR008271 Serine/threonine-protein kinase, active site
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain

UniProt Annotations

Entry Information

Gene Name
protein kinase C, iota
Protein Entry
KPCI_HUMAN
UniProt ID
P41743
Species
Human

Comments

Comment Type Description
Biophysicochemical Properties Kinetic parameters: KM=13.5 uM for ATP (for recombinant purified PRKCI) ; Vmax=7.4 pmol/min/mg enzyme ;
Catalytic Activity ATP + a protein = ADP + a phosphoprotein.
Domain The C1 zinc finger does not bind diacylglycerol (DAG).
Domain The OPR domain mediates interaction with SQSTM1.
Domain The pseudosubstrate motif resembles the sequence around sites phosphorylated on target proteins, except the presence of a non-phosphorylatable residue in place of Ser, it modulates activity by competing with substrates.
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. {ECO
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. {ECO
Interaction P60953:CDC42; NbExp=5; IntAct=EBI-286199, EBI-81752; Q96L34:MARK4; NbExp=2; IntAct=EBI-286199, EBI-302319; Q8TEW0:PARD3; NbExp=3; IntAct=EBI-286199, EBI-81968; Q9NPB6:PARD6A; NbExp=11; IntAct=EBI-286199, EBI-81876; Q9BYG5:PARD6B; NbExp=8; IntAct=EBI-286199, EBI-295391; Q9BYG4:PARD6G; NbExp=5; IntAct=EBI-286199, EBI-295417; Q8ND90:PNMA1; NbExp=2; IntAct=EBI-286199, EBI-302345; Q05513:PRKCZ; NbExp=2; IntAct=EBI-286199, EBI-295351; P63000:RAC1; NbExp=3; IntAct=EBI-286199, EBI-413628; P48431:SOX2; NbExp=2; IntAct=EBI-286199, EBI-6124081; Q13501:SQSTM1; NbExp=5; IntAct=EBI-286199, EBI-307104; Q04917:YWHAH; NbExp=3; IntAct=EBI-286199, EBI-306940;
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. Phosphorylation at Tyr-265 facilitates binding to KPNB1/importin-beta regulating entry of PRKCI into the nucleus. Phosphorylation on Tyr-334 is important for NF-kappa-B stimulation. {ECO
Sequence Caution Sequence=AAA60171.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence= ; Sequence=AAB17011.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence= ; Sequence=AAH22016.3; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence= ;
Similarity Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.
Similarity Contains 1 AGC-kinase C-terminal domain.
Similarity Contains 1 OPR domain.
Similarity Contains 1 phorbol-ester/DAG-type zinc finger.
Similarity Contains 1 protein kinase domain.
Subcellular Location Cytoplasm. Membrane. Endosome. Nucleus. 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.
Subunit Forms a complex with SQSTM1 and MP2K5 (By similarity). Interacts directly with SQSTM1 (Probable). Interacts with IKBKB. Interacts with PARD6A, PARD6B and PARD6G. Part of a quaternary complex containing aPKC, PARD3, a PARD6 protein (PARD6A, PARD6B or PARD6G) and a GTPase protein (CDC42 or RAC1). Part of a complex with LLGL1 and PARD6B. Interacts with ADAP1/CENTA1. Interaction with SMG1, through the ZN-finger domain, activates the kinase activity. Interacts with CDK7. Forms a complex with RAB2A and GAPDH involved in recruitment onto the membrane of vesicular tubular clusters (VTCs). Interacts with ECT2 ('Thr-359' phosphorylated form). {ECO
Tissue Specificity Predominantly expressed in lung and brain, but also expressed at lower levels in many tissues including pancreatic islets. Highly expressed in non-small cell lung cancers. {ECO
Web Resource Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/PRKCIID41857ch3q26.html";

Identical and Related Proteins

Unique RefSeq proteins for LMP002189 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
133908623 RefSeq NP_002731 596 protein kinase C iota type

Identical Sequences to LMP002189 proteins

Reference Database Accession Length Protein Name
GI:133908623 GenBank JAA14655.1 596 protein kinase C, iota [Pan troglodytes]
GI:133908623 GenBank JAA14656.1 596 protein kinase C, iota [Pan troglodytes]
GI:133908623 GenBank JAA33047.1 596 protein kinase C, iota [Pan troglodytes]
GI:133908623 GenBank JAA37209.1 596 protein kinase C, iota [Pan troglodytes]
GI:133908623 GenBank JAA37210.1 596 protein kinase C, iota [Pan troglodytes]
GI:133908623 GenBank JAA37211.1 596 protein kinase C, iota [Pan troglodytes]

Related Sequences to LMP002189 proteins

Reference Database Accession Length Protein Name
GI:133908623 GenBank ACM86178.1 655 Sequence 11676 from patent US 6812339
GI:133908623 GenBank AFH33192.1 596 protein kinase C iota type [Macaca mulatta]
GI:133908623 GenBank AFI37704.1 596 protein kinase C iota type [Macaca mulatta]
GI:133908623 GenBank AFI37705.1 596 protein kinase C iota type [Macaca mulatta]
GI:133908623 RefSeq XP_526377.3 690 PREDICTED: protein kinase C iota type [Pan troglodytes]
GI:133908623 RefSeq XP_010373268.1 596 PREDICTED: protein kinase C iota type [Rhinopithecus roxellana]