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Q62074 (KPCI_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 154. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·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=aPKC-lambda/iota
nPKC-iota
Gene names
Name:Prkci
Synonyms:Pkcl
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length595 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 By similarity. Downstream of PI3K is required for insulin-stimulated glucose transport. Activates RAB4A and promotes its association with KIF3A which is required for the insulin-induced SLC2A4/GLUT4 translocation in adipocytes. Is essential in early embryogenesis and development of differentiating photoreceptors by playing a role in the establishment of epithelial and neuronal polarity. Ref.3 Ref.6 Ref.7 Ref.8 Ref.9

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-411 (activation loop of the kinase domain) and Thr-563 (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.

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) By similarity. Ref.4 Ref.5

Subcellular location

Cytoplasm By similarity. Membrane By similarity. Endosome By similarity. Nucleus By similarity. 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 By similarity.

Domain

The OPR domain mediates interaction with SQSTM1.

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

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.

Post-translational modification

Upon neuronal growth factor (NGF) stimulation, phosphorylated by SRC at Tyr-264, Tyr-279 and Tyr-333. Phosphorylation on Tyr-264 facilitates binding to KPNB1/importin-beta regulating entry of PRKCI into the nucleus. Phosphorylation on Tyr-333 is important for NF-kappa-B stimulation By similarity. Phosphorylation at Thr-411 in the activation loop is not mandatory for activation. Ref.11

Disruption phenotype

Embryonic lethal at 9.5 dpc. Ref.7

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.

Sequence caution

The sequence AAH21630.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAA32499.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Cellular componentCytoplasm
Endosome
Membrane
Nucleus
   DiseaseProto-oncogene
Tumor suppressor
   DomainZinc-finger
   LigandATP-binding
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionDevelopmental protein
Kinase
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 mutant phenotype Ref.7. Source: MGI

cell migration

Inferred from electronic annotation. Source: Ensembl

cell-cell junction organization

Inferred from sequence or structural similarity. Source: UniProtKB

cellular protein localization

Inferred from electronic annotation. Source: Ensembl

cellular response to insulin stimulus

Inferred from mutant phenotype PubMed 9819385. Source: BHF-UCL

establishment of apical/basal cell polarity

Inferred from mutant phenotype Ref.9. Source: MGI

eye photoreceptor cell development

Inferred from mutant phenotype Ref.9. Source: MGI

intracellular signal transduction

Inferred from electronic annotation. Source: InterPro

negative regulation of glial cell apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of neuron apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of NF-kappaB transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of endothelial cell apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of establishment of protein localization to plasma membrane

Inferred from mutant phenotype PubMed 9819385. Source: BHF-UCL

positive regulation of glial cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of glucose import

Inferred from mutant phenotype PubMed 9819385. Source: BHF-UCL

positive regulation of neuron projection development

Inferred from sequence or structural similarity. Source: UniProtKB

protein phosphorylation

Inferred from direct assay PubMed 9819385. Source: BHF-UCL

response to interleukin-1

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi membrane

Inferred from electronic annotation. Source: GOC

Schmidt-Lanterman incisure

Inferred from direct assay PubMed 20237282. Source: BHF-UCL

apical part of cell

Inferred from direct assay PubMed 14758363. Source: MGI

apical plasma membrane

Inferred from direct assay PubMed 16892058. Source: MGI

cell leading edge

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay PubMed 10882525PubMed 14685273. Source: MGI

cytosol

Inferred from sequence or structural similarity. Source: UniProtKB

endosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

protein complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

phospholipid binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein kinase C activity

Inferred from direct assay PubMed 9819385. Source: BHF-UCL

protein kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from sequence or structural similarity. 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 By similarity
Chain2 – 595594Protein kinase C iota type
PRO_0000055711

Regions

Domain25 – 10884OPR
Domain253 – 521269Protein kinase
Domain522 – 59574AGC-kinase C-terminal
Zinc finger140 – 19051Phorbol-ester/DAG-type
Nucleotide binding259 – 2679ATP By similarity
Region2 – 252251Regulatory domain By similarity
Region2 – 2827Required for interaction with RAB2 By similarity
Region72 – 9120Interaction with PARD6A By similarity
Motif125 – 13410Pseudosubstrate

Sites

Active site3771Proton acceptor By similarity
Binding site2821ATP By similarity

Amino acid modifications

Modified residue21N-acetylproline By similarity
Modified residue31Phosphothreonine By similarity
Modified residue71Phosphoserine By similarity
Modified residue81Phosphoserine By similarity
Modified residue91Phosphothreonine By similarity
Modified residue2641Phosphotyrosine; by SRC By similarity
Modified residue2791Phosphotyrosine; by SRC By similarity
Modified residue3331Phosphotyrosine; by SRC By similarity
Modified residue4111Phosphothreonine; alternate Ref.10
Modified residue4111Phosphothreonine; by PDPK1; alternate By similarity
Modified residue5631Phosphothreonine Ref.11

Experimental info

Mutagenesis271R → A: No effect on interaction with SQSTM1. Ref.5
Mutagenesis281V → A: No effect on interaction with SQSTM1; when associated with A-29. Ref.5
Mutagenesis291K → A: No effect on interaction with SQSTM1; when associated with A-118. Ref.5
Mutagenesis701W → A: Loss of interaction with SQSTM1. Ref.5
Mutagenesis721D → A: Loss of interaction with SQSTM1. Ref.5
Mutagenesis741E → A: Loss of interaction with SQSTM1. Ref.5
Mutagenesis761D → A: Loss of interaction with SQSTM1. Ref.5
Mutagenesis831Q → A: No effect on interaction with SQSTM1. Ref.5
Mutagenesis851E → A: Loss of interaction with SQSTM1. Ref.5

Secondary structure

...................................................... 595
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q62074 [UniParc].

Last modified June 16, 2009. Version 3.
Checksum: 6AC612D1E9264825

FASTA59568,203
        10         20         30         40         50         60 
MPTQRDSSTM SHTVACGGGG DHSHQVRVKA YYRGDIMITH FEPSISFEGL CSEVRDMCSF 

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

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

       190        200        210        220        230        240 
KCHKLVTIEC GRHSLPPEPM MPMDQTMHPD HTQTVIPYNP SSHESLDQVG EEKEAMNTRE 

       250        260        270        280        290        300 
SGKASSSLGL QDFDLLRVIG RGSYAKVLLV RLKKTDRIYA MKVVKKELVN DDEDIDWVQT 

       310        320        330        340        350        360 
EKHVFEQASN HPFLVGLHSC FQTESRLFFV IEYVNGGDLM FHMQRQRKLP EEHARFYSAE 

       370        380        390        400        410        420 
ISLALNYLHE RGIIYRDLKL DNVLLDSEGH IKLTDYGMCK EGLRPGDTTS TFCGTPNYIA 

       430        440        450        460        470        480 
PEILRGEDYG FSVDWWALGV LMFEMMAGRS PFDIVGSSDN PDQNTEDYLF QVILEKQIRI 

       490        500        510        520        530        540 
PRSLSVKAAS VLKSFLNKDP KERLGCHPQT GFADIQGHPF FRNVDWDMME QKQVVPPFKP 

       550        560        570        580        590 
NISGEFGLDN FDSQFTNEPV QLTPDDDDIV RKIDQSEFEG FEYINPLLMS AEECV 

« Hide

References

« Hide 'large scale' references
[1]"A new member of the third class in the protein kinase C family, PKC lambda, expressed dominantly in an undifferentiated mouse embryonal carcinoma cell line and also in many tissues and cells."
Akimoto K., Mizuno K., Osada S., Hirai S., Tanuma S., Suzuki K., Ohno S.
J. Biol. Chem. 269:12677-12683(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"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].
[3]"Evidence that atypical protein kinase C-lambda and atypical protein kinase C-zeta participate in Ras-mediated reorganization of the F-actin cytoskeleton."
Uberall F., Hellbert K., Kampfer S., Maly K., Villunger A., Spitaler M., Mwanjewe J., Baier-Bitterlich G., Baier G., Grunicke H.H.
J. Cell Biol. 144:413-425(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[4]"The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42."
Joberty G., Petersen C., Gao L., Macara I.G.
Nat. Cell Biol. 2:531-539(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT OF A COMPLEX CONTAINING PARD6B; PARD3 AND CDC42.
[5]"Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins."
Lamark T., Perander M., Outzen H., Kristiansen K., Oevervatn A., Michaelsen E., Bjoerkoey G., Johansen T.
J. Biol. Chem. 278:34568-34581(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SQSTM1 AND MAP2K5, MUTAGENESIS OF ARG-27; VAL-28; LYS-29; TRP-70; ASP-72; GLU-74; ASP-76; GLN-83 AND GLU-85.
[6]"Insulin-induced GLUT4 translocation involves protein kinase C-lambda-mediated functional coupling between Rab4 and the motor protein kinesin."
Imamura T., Huang J., Usui I., Satoh H., Bever J., Olefsky J.M.
Mol. Cell. Biol. 23:4892-4900(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Targeted deletion of protein kinase C lambda reveals a distribution of functions between the two atypical protein kinase C isoforms."
Soloff R.S., Katayama C., Lin M.Y., Feramisco J.R., Hedrick S.M.
J. Immunol. 173:3250-3260(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[8]"Protein kinase C-lambda knockout in embryonic stem cells and adipocytes impairs insulin-stimulated glucose transport."
Bandyopadhyay G., Standaert M.L., Sajan M.P., Kanoh Y., Miura A., Braun U., Kruse F., Leitges M., Farese R.V.
Mol. Endocrinol. 18:373-383(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Function of atypical protein kinase C lambda in differentiating photoreceptors is required for proper lamination of mouse retina."
Koike C., Nishida A., Akimoto K., Nakaya M.A., Noda T., Ohno S., Furukawa T.
J. Neurosci. 25:10290-10298(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-411, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[11]"Substrate recognition mechanism of atypical protein kinase Cs revealed by the structure of PKCiota in complex with a substrate peptide from Par-3."
Wang C., Shang Y., Yu J., Zhang M.
Structure 20:791-801(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 231-595 IN COMPLEX WITH RAT PARD3 PEPTIDE, PHOSPHORYLATION AT THR-563, PSEUDOSUBSTRATE MOTIF.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D28577 mRNA. Translation: BAA32499.1. Different initiation.
BC021630 mRNA. Translation: AAH21630.1. Different initiation.
CCDSCCDS17289.2.
PIRA53758.
RefSeqNP_032883.2. NM_008857.3.
UniGeneMm.291554.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4DC2X-ray2.40A231-595[»]
ProteinModelPortalQ62074.
SMRQ62074. Positions 25-192, 248-587.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202200. 2 interactions.
DIPDIP-32555N.
IntActQ62074. 2 interactions.
MINTMINT-4100000.

PTM databases

PhosphoSiteQ62074.

Proteomic databases

MaxQBQ62074.
PaxDbQ62074.
PRIDEQ62074.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000108249; ENSMUSP00000103884; ENSMUSG00000037643.
GeneID18759.
KEGGmmu:18759.
UCSCuc008ovs.1. mouse.

Organism-specific databases

CTD5584.
MGIMGI:99260. Prkci.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00750000117322.
HOGENOMHOG000233033.
HOVERGENHBG108317.
InParanoidQ62074.
KOK06069.
OMAFEPSISY.
OrthoDBEOG7HF1J3.
TreeFamTF102004.

Enzyme and pathway databases

BRENDA2.7.11.13. 3474.

Gene expression databases

ArrayExpressQ62074.
BgeeQ62074.
CleanExMM_PRKCI.
GenevestigatorQ62074.

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

NextBio294941.
PROQ62074.
SOURCESearch...

Entry information

Entry nameKPCI_MOUSE
AccessionPrimary (citable) accession number: Q62074
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: June 16, 2009
Last modified: July 9, 2014
This is version 154 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

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

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot