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P41743 (KPCI_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 162. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein kinase C iota type

EC=2.7.11.13
Alternative name(s):
Atypical protein kinase C-lambda/iota
Short name=PRKC-lambda/iota
Short name=aPKC-lambda/iota
nPKC-iota
Gene names
Name:PRKCI
Synonyms:DXS1179E
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length596 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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 (PI3K) 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. Ref.1 Ref.6 Ref.8 Ref.9 Ref.10 Ref.11 Ref.14 Ref.19 Ref.21 Ref.22 Ref.25 Ref.29 Ref.34 Ref.35

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

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. Ref.5

Subunit structure

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). Ref.5 Ref.7 Ref.9 Ref.12 Ref.13 Ref.14 Ref.16 Ref.17 Ref.18 Ref.20 Ref.23 Ref.24 Ref.30 Ref.37

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. Ref.7 Ref.16 Ref.23 Ref.24

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. Ref.1 Ref.2 Ref.22

Domain

The OPR domain mediates interaction with SQSTM1 By similarity.

The C1 zinc finger does not bind diacylglycerol (DAG).

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 By similarity.

Post-translational modification

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. Ref.15 Ref.16 Ref.24 Ref.39

Sequence similarities

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 zinc finger.

Contains 1 protein kinase domain.

Biophysicochemical properties

Kinetic parameters:

KM=13.5 µM for ATP (for recombinant purified PRKCI) Ref.10

Vmax=7.4 pmol/min/mg enzyme

Sequence caution

The sequence AAA60171.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence AAB17011.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence AAH22016.3 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Cellular componentCytoplasm
Endosome
Membrane
Nucleus
   Coding sequence diversityPolymorphism
   DiseaseProto-oncogene
Tumor suppressor
   DomainZinc-finger
   LigandATP-binding
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processGolgi vesicle budding

Inferred from electronic annotation. Source: Ensembl

actin filament organization

Inferred from electronic annotation. Source: Ensembl

cell junction assembly

Traceable author statement. Source: Reactome

cell migration

Inferred from electronic annotation. Source: Ensembl

cell-cell junction organization

Inferred from mutant phenotype Ref.13. Source: UniProtKB

cellular response to insulin stimulus

Inferred from sequence or structural similarity. Source: BHF-UCL

cytoskeleton organization

Non-traceable author statement Ref.13. Source: UniProtKB

establishment of apical/basal cell polarity

Inferred from electronic annotation. Source: Ensembl

establishment or maintenance of epithelial cell apical/basal polarity

Traceable author statement PubMed 14676191. Source: UniProtKB

eye photoreceptor cell development

Inferred from electronic annotation. Source: Ensembl

intracellular signal transduction

Inferred from electronic annotation. Source: InterPro

membrane organization

Non-traceable author statement Ref.13. Source: UniProtKB

negative regulation of apoptotic process

Traceable author statement. Source: Reactome

negative regulation of glial cell apoptotic process

Inferred from mutant phenotype Ref.34. Source: UniProtKB

negative regulation of neuron apoptotic process

Inferred from direct assay Ref.8. Source: UniProtKB

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

positive regulation of NF-kappaB transcription factor activity

Inferred from direct assay Ref.8. Source: UniProtKB

positive regulation of endothelial cell apoptotic process

Inferred from mutant phenotype Ref.29. Source: UniProtKB

positive regulation of establishment of protein localization to plasma membrane

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of glial cell proliferation

Inferred from mutant phenotype Ref.34. Source: UniProtKB

positive regulation of glucose import

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of neuron projection development

Inferred from mutant phenotype Ref.8. Source: UniProtKB

protein phosphorylation

Inferred from direct assay Ref.1. Source: UniProtKB

protein targeting to membrane

Non-traceable author statement Ref.13. Source: UniProtKB

response to interleukin-1

Inferred from electronic annotation. Source: Ensembl

secretion

Non-traceable author statement Ref.1. Source: UniProtKB

tight junction assembly

Traceable author statement. Source: Reactome

vesicle-mediated transport

Traceable author statement Ref.13. Source: UniProtKB

   Cellular_componentGolgi membrane

Inferred from electronic annotation. Source: GOC

Schmidt-Lanterman incisure

Inferred from electronic annotation. Source: Ensembl

apical plasma membrane

Inferred from electronic annotation. Source: Ensembl

cell leading edge

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay. Source: HPA

cytosol

Inferred from direct assay Ref.13Ref.34. Source: UniProtKB

endosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

intercellular bridge

Inferred from direct assay. Source: HPA

microtubule cytoskeleton

Inferred from direct assay. Source: HPA

nucleus

Inferred from direct assay Ref.12Ref.34. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

polarisome

Traceable author statement PubMed 14676191. Source: UniProtKB

   Molecular_functionATP binding

Traceable author statement Ref.1. Source: UniProtKB

phospholipid binding

Inferred from direct assay Ref.1. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.14Ref.18Ref.17PubMed 14676191Ref.30. Source: UniProtKB

protein kinase C activity

Inferred from sequence or structural similarity. Source: BHF-UCL

protein kinase activity

Inferred from direct assay Ref.14. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay Ref.1. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed
Chain2 – 596595Protein kinase C iota type
PRO_0000055710

Regions

Domain25 – 10884OPR
Domain254 – 522269Protein kinase
Domain523 – 59472AGC-kinase C-terminal
Zinc finger140 – 19051Phorbol-ester/DAG-type
Nucleotide binding260 – 2689ATP By similarity
Region2 – 253252Regulatory domain
Region2 – 2827Required for interaction with RAB2
Region72 – 9120Interaction with PARD6A
Motif125 – 13410Pseudosubstrate By similarity

Sites

Active site3781Proton acceptor By similarity
Binding site2831ATP By similarity

Amino acid modifications

Modified residue21N-acetylproline Ref.32
Modified residue31Phosphothreonine Ref.32
Modified residue71Phosphoserine Ref.32
Modified residue81Phosphoserine Ref.32
Modified residue91Phosphothreonine Ref.32
Modified residue2651Phosphotyrosine; by SRC Ref.15 Ref.16
Modified residue2801Phosphotyrosine; by SRC Ref.15
Modified residue3341Phosphotyrosine; by SRC Ref.15
Modified residue4121Phosphothreonine; by PDPK1 Probable
Modified residue5641Phosphothreonine Ref.36 Ref.39

Natural variations

Natural variant1181P → L in a metastatic melanoma sample; somatic mutation. Ref.40
VAR_042322
Natural variant1301R → C. Ref.40
VAR_042323

Experimental info

Mutagenesis291K → A: No effect on interaction with SQSTM1. Ref.37
Mutagenesis721D → A: Loss of interaction with ECT2, PARD6A and with SQSTM1. Ref.30 Ref.37 Ref.38
Mutagenesis851E → A: Slight decrease of interaction with PARD6A. Loss of interaction with PARD6A; when associated with A-91. Ref.38
Mutagenesis911R → A: Slight decrease of interaction with PARD6A. Loss of interaction with PARD6A; when associated with A-85. Ref.38
Mutagenesis2651Y → 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. Ref.15 Ref.16
Mutagenesis2741K → R: No effect on activity. Ref.10
Mutagenesis2741K → W: Abolishes activity. Ref.10
Mutagenesis2801Y → 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. Ref.15
Mutagenesis3341Y → 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. Ref.15
Sequence conflict4851L → M in AAH22016. Ref.4
Sequence conflict5081H → L in AAH22016. Ref.4
Sequence conflict5601P → R in AAH22016. Ref.4

Secondary structure

.............................................................................. 596
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P41743 [UniParc].

Last modified June 16, 2009. Version 2.
Checksum: 1E3F8C1D4BFC734F

FASTA59668,262
        10         20         30         40         50         60 
MPTQRDSSTM SHTVAGGGSG DHSHQVRVKA YYRGDIMITH FEPSISFEGL CNEVRDMCSF 

        70         80         90        100        110        120 
DNEQLFTMKW IDEEGDPCTV SSQLELEEAF RLYELNKDSE LLIHVFPCVP ERPGMPCPGE 

       130        140        150        160        170        180 
DKSIYRRGAR RWRKLYCANG HTFQAKRFNR RAHCAICTDR IWGLGRQGYK CINCKLLVHK 

       190        200        210        220        230        240 
KCHKLVTIEC GRHSLPQEPV MPMDQSSMHS DHAQTVIPYN PSSHESLDQV GEEKEAMNTR 

       250        260        270        280        290        300 
ESGKASSSLG LQDFDLLRVI GRGSYAKVLL VRLKKTDRIY AMKVVKKELV NDDEDIDWVQ 

       310        320        330        340        350        360 
TEKHVFEQAS NHPFLVGLHS CFQTESRLFF VIEYVNGGDL MFHMQRQRKL PEEHARFYSA 

       370        380        390        400        410        420 
EISLALNYLH ERGIIYRDLK LDNVLLDSEG HIKLTDYGMC KEGLRPGDTT STFCGTPNYI 

       430        440        450        460        470        480 
APEILRGEDY GFSVDWWALG VLMFEMMAGR SPFDIVGSSD NPDQNTEDYL FQVILEKQIR 

       490        500        510        520        530        540 
IPRSLSVKAA SVLKSFLNKD PKERLGCHPQ TGFADIQGHP FFRNVDWDMM EQKQVVPPFK 

       550        560        570        580        590 
PNISGEFGLD NFDSQFTNEP VQLTPDDDDI VRKIDQSEFE GFEYINPLLM SAEECV 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and characterization of PKC iota, an atypical isoform of protein kinase C derived from insulin-secreting cells."
Selbie L.A., Schmitz-Peiffer C., Sheng Y., Biden T.J.
J. Biol. Chem. 268:24296-24302(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
Tissue: Kidney.
[2]"Human protein kinase C iota gene (PRKCI) is closely linked to the BTK gene in Xq21.3."
Mazzarella R., Ciccodicola A., Esposito T., Arcucci A., Migliaccio C., Jones C., Schlessinger D., D'Urso M., D'Esposito M.
Genomics 26:629-631(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Tissue: Teratocarcinoma.
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Testis.
[5]"Lambda-interacting protein, a novel protein that specifically interacts with the zinc finger domain of the atypical protein kinase C isotype lambda/iota and stimulates its kinase activity in vitro and in vivo."
Diaz-Meco M.T., Municio M.M., Sanchez P., Lozano J., Moscat J.
Mol. Cell. Biol. 16:105-114(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SMG1, ENZYME REGULATION.
[6]"Atypical protein kinase C iota protects human leukemia cells against drug-induced apoptosis."
Murray N.R., Fields A.P.
J. Biol. Chem. 272:27521-27524(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL SURVIVAL.
[7]"Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62."
Sanchez P., De Carcer G., Sandoval I.V., Moscat J., Diaz-Meco M.T.
Mol. Cell. Biol. 18:3069-3080(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SQSTM1, SUBCELLULAR LOCATION.
[8]"Overexpression of atypical PKC in PC12 cells enhances NGF-responsiveness and survival through an NF-kappaB dependent pathway."
Wooten M.W., Seibenhener M.L., Zhou G., Vandenplas M.L., Tan T.H.
Cell Death Differ. 6:753-764(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL SURVIVAL.
[9]"The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation."
Sanz L., Sanchez P., Lallena M.-J., Diaz-Meco M.T., Moscat J.
EMBO J. 18:3044-3053(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SQSTM1 AND IKBKB, FUNCTION.
[10]"Unique structural and functional properties of the ATP-binding domain of atypical protein kinase C-iota."
Spitaler M., Villunger A., Grunicke H., Uberall F.
J. Biol. Chem. 275:33289-33296(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF LYS-274.
[11]"Protein kinase C iota protects neural cells against apoptosis induced by amyloid beta-peptide."
Xie J., Guo Q., Zhu H., Wooten M.W., Mattson M.P.
Brain Res. Mol. Brain Res. 82:107-113(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL SURVIVAL.
[12]"Human homologues of the Caenorhabditis elegans cell polarity protein PAR6 as an adaptor that links the small GTPases Rac and Cdc42 to atypical protein kinase C."
Noda Y., Takeya R., Ohno S., Naito S., Ito T., Sumimoto H.
Genes Cells 6:107-119(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PARD6A; PARD6B AND PARD6G, SUBUNIT OF A COMPLEX CONTAINING PARD6B AND CDC42/RAC1.
[13]"Atypical protein kinase C is involved in the evolutionarily conserved par protein complex and plays a critical role in establishing epithelia-specific junctional structures."
Suzuki A., Yamanaka T., Hirose T., Manabe N., Mizuno K., Shimizu M., Akimoto K., Izumi Y., Ohnishi T., Ohno S.
J. Cell Biol. 152:1183-1196(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PARD3 AND PARD6B IN THE TERNARY AKPC/PAR3/PAR6 COMPLEX.
[14]"Glyceraldehyde-3-phosphate dehydrogenase is phosphorylated by protein kinase Ciota /lambda and plays a role in microtubule dynamics in the early secretory pathway."
Tisdale E.J.
J. Biol. Chem. 277:3334-3341(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH GAPDH.
[15]"Nerve growth factor stimulates multisite tyrosine phosphorylation and activation of the atypical protein kinase C's via a src kinase pathway."
Wooten M.W., Vandenplas M.L., Seibenhener M.L., Geetha T., Diaz-Meco M.T.
Mol. Cell. Biol. 21:8414-8427(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-265; TYR-280 AND TYR-334, MUTAGENESIS OF TYR-265; TYR-280 AND TYR-334.
[16]"Phosphorylation of tyrosine 256 facilitates nuclear import of atypical protein kinase C."
White W.O., Seibenhener M.L., Wooten M.W.
J. Cell. Biochem. 85:42-53(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH KPNB1, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-265, MUTAGENESIS OF TYR-265.
[17]"Centaurin-alpha(1) associates with and is phosphorylated by isoforms of protein kinase C."
Zemlickova E., Dubois T., Kerai P., Clokie S., Cronshaw A.D., Wakefield R.I.D., Johannes F.-J., Aitken A.
Biochem. Biophys. Res. Commun. 307:459-465(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ADAP1.
[18]"Mammalian Lgl forms a protein complex with PAR-6 and aPKC independently of PAR-3 to regulate epithelial cell polarity."
Yamanaka T., Horikoshi Y., Sugiyama Y., Ishiyama C., Suzuki A., Hirose T., Iwamatsu A., Shinohara A., Ohno S.
Curr. Biol. 13:734-743(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PARD6B/PAR-6 AND LLGL1.
[19]"Atypical protein kinase C plays a critical role in protein transport from pre-Golgi intermediates."
Tisdale E.J., Wang J., Silver R.B., Artalejo C.R.
J. Biol. Chem. 278:38015-38021(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[20]"Rab2 interacts directly with atypical protein kinase C (aPKC) iota/lambda and inhibits aPKCiota/lambda-dependent glyceraldehyde-3-phosphate dehydrogenase phosphorylation."
Tisdale E.J.
J. Biol. Chem. 278:52524-52530(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAB2A.
[21]"Regulation of interleukin receptor-associated kinase (IRAK) phosphorylation and signaling by iota protein kinase C."
Mamidipudi V., Lin C., Seibenhener M.L., Wooten M.W.
J. Biol. Chem. 279:4161-4165(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF IRAK1.
[22]"Atypical protein kinase Ciota plays a critical role in human lung cancer cell growth and tumorigenicity."
Regala R.P., Weems C., Jamieson L., Copland J.A., Thompson E.A., Fields A.P.
J. Biol. Chem. 280:31109-31115(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[23]"Cyclin-dependent kinase activating kinase/Cdk7 co-localizes with PKC-iota in human glioma cells."
Bicaku E., Patel R., Acevedo-Duncan M.
Tissue Cell 37:53-58(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CDK7, SUBCELLULAR LOCATION.
[24]"Src-dependent protein kinase C iota/lambda (aPKCiota/lambda) tyrosine phosphorylation is required for aPKCiota/lambda association with Rab2 and glyceraldehyde-3-phosphate dehydrogenase on pre-Golgi intermediates."
Tisdale E.J., Artalejo C.R.
J. Biol. Chem. 281:8436-8442(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAB2A AND GADPH, PHOSPHORYLATION, SUBCELLULAR LOCATION.
[25]"Atypical protein kinase C (iota) activates ezrin in the apical domain of intestinal epithelial cells."
Wald F.A., Oriolo A.S., Mashukova A., Fregien N.L., Langshaw A.H., Salas P.J.
J. Cell Sci. 121:644-654(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF EZR.
[26]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[27]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[28]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[29]"Protein kinase C iota mediates lipid-induced apoptosis of human coronary artery endothelial cells."
Staiger K., Schatz U., Staiger H., Weyrich P., Haas C., Guirguis A., Machicao F., Haering H.U., Kellerer M.
Microvasc. Res. 78:40-44(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN APOPTOSIS.
[30]"Ect2 links the PKCiota-Par6alpha complex to Rac1 activation and cellular transformation."
Justilien V., Fields A.P.
Oncogene 28:3597-3607(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ECT2 AND PARD6A, MUTAGENESIS OF ASP-72.
[31]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[32]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT PRO-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-3; SER-7; SER-8 AND THR-9, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[33]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[34]"PKC-? promotes glioblastoma cell survival by phosphorylating and inhibiting BAD through a phosphatidylinositol 3-kinase pathway."
Desai S., Pillai P., Win-Piazza H., Acevedo-Duncan M.
Biochim. Biophys. Acta 1813:1190-1197(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF BAD.
[35]"Oncogenic activity of Ect2 is regulated through protein kinase C iota-mediated phosphorylation."
Justilien V., Jameison L., Der C.J., Rossman K.L., Fields A.P.
J. Biol. Chem. 286:8149-8157(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF ECT2.
[36]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-564, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[37]"Solution structure of atypical protein kinase C PB1 domain and its mode of interaction with ZIP/p62 and MEK5."
Hirano Y., Yoshinaga S., Ogura K., Yokochi M., Noda Y., Sumimoto H., Inagaki F.
J. Biol. Chem. 279:31883-31890(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 25-108, INTERACTION WITH SQSTM1 AND MAP2K5, MUTAGENESIS OF LYS-29 AND ASP-72.
[38]"Structure of a cell polarity regulator, a complex between atypical PKC and Par6 PB1 domains."
Hirano Y., Yoshinaga S., Takeya R., Suzuki N.N., Horiuchi M., Kohjima M., Sumimoto H., Inagaki F.
J. Biol. Chem. 280:9653-9661(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 25-108 IN COMPLEX WITH PARD6A, MUTAGENESIS OF ASP-72; GLU-85 AND ARG-91.
[39]"Crystal structure of the catalytic domain of human atypical protein kinase C-iota reveals interaction mode of phosphorylation site in turn motif."
Messerschmidt A., Macieira S., Velarde M., Baedeker M., Benda C., Jestel A., Brandstetter H., Neuefeind T., Blaesse M.
J. Mol. Biol. 352:918-931(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 233-596, IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION AT THR-412 AND THR-564.
[40]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-118 AND CYS-130.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L18964 mRNA. Translation: AAA60171.1. Different initiation.
L33881 mRNA. Translation: AAB17011.1. Different initiation.
CH471052 Genomic DNA. Translation: EAW78513.1.
CH471052 Genomic DNA. Translation: EAW78515.1.
BC022016 mRNA. Translation: AAH22016.3. Different initiation.
CCDSCCDS3212.2.
PIRA49509.
RefSeqNP_002731.4. NM_002740.5.
UniGeneHs.478199.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1VD2NMR-A25-108[»]
1WMHX-ray1.50A25-108[»]
1ZRZX-ray3.00A233-596[»]
3A8WX-ray2.10A/B249-588[»]
3A8XX-ray2.00A/B249-588[»]
3ZH8X-ray2.74A/B/C248-594[»]
ProteinModelPortalP41743.
SMRP41743. Positions 25-192, 201-588.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111570. 59 interactions.
DIPDIP-31311N.
IntActP41743. 39 interactions.
MINTMINT-5004219.
STRING9606.ENSP00000295797.

Chemistry

BindingDBP41743.
ChEMBLCHEMBL2093867.
GuidetoPHARMACOLOGY1490.

PTM databases

PhosphoSiteP41743.

Polymorphism databases

DMDM239938658.

Proteomic databases

MaxQBP41743.
PaxDbP41743.
PRIDEP41743.

Protocols and materials databases

DNASU5584.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000295797; ENSP00000295797; ENSG00000163558.
GeneID5584.
KEGGhsa:5584.
UCSCuc003fgs.2. human.

Organism-specific databases

CTD5584.
GeneCardsGC03P169940.
HGNCHGNC:9404. PRKCI.
HPAHPA026574.
HPA038635.
MIM600539. gene.
neXtProtNX_P41743.
PharmGKBPA33768.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233033.
HOVERGENHBG108317.
InParanoidP41743.
KOK06069.
OMAFEPSISY.
OrthoDBEOG7HF1J3.
PhylomeDBP41743.
TreeFamTF102004.

Enzyme and pathway databases

BRENDA2.7.11.13. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_111155. Cell-Cell communication.
SignaLinkP41743.

Gene expression databases

BgeeP41743.
CleanExHS_PRKCI.
GenevestigatorP41743.

Family and domain databases

InterProIPR000961. AGC-kinase_C.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR000270. OPR_PB1.
IPR012233. PKC_zeta.
IPR017892. Pkinase_C.
IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERPTHR24357:SF60. PTHR24357:SF60. 1 hit.
PfamPF00130. C1_1. 1 hit.
PF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFPIRSF000554. PKC_zeta. 1 hit.
PRINTSPR00008. DAGPEDOMAIN.
SMARTSM00109. C1. 1 hit.
SM00666. PB1. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS00479. ZF_DAG_PE_1. 1 hit.
PS50081. ZF_DAG_PE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPRKCI. human.
EvolutionaryTraceP41743.
GeneWikiPRKCI.
GenomeRNAi5584.
NextBio21656.
PROP41743.
SOURCESearch...

Entry information

Entry nameKPCI_HUMAN
AccessionPrimary (citable) accession number: P41743
Secondary accession number(s): D3DNQ4, Q8WW06
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: June 16, 2009
Last modified: July 9, 2014
This is version 162 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM