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Protein

Protein kinase C iota type

Gene

Prkci

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.By similarity5 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

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.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei282ATPPROSITE-ProRule annotation1
Active sitei377Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri140 – 190Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST51
Nucleotide bindingi259 – 267ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • actin filament organization Source: MGI
  • cell-cell junction organization Source: UniProtKB
  • cell migration Source: Ensembl
  • cellular protein localization Source: Ensembl
  • cellular response to insulin stimulus Source: BHF-UCL
  • establishment of apical/basal cell polarity Source: MGI
  • eye photoreceptor cell development Source: MGI
  • Golgi vesicle budding Source: Ensembl
  • intracellular signal transduction Source: GO_Central
  • negative regulation of glial cell apoptotic process Source: UniProtKB
  • negative regulation of neuron apoptotic process Source: UniProtKB
  • peptidyl-serine phosphorylation Source: MGI
  • positive regulation of endothelial cell apoptotic process Source: UniProtKB
  • positive regulation of glial cell proliferation Source: UniProtKB
  • positive regulation of glucose import Source: BHF-UCL
  • positive regulation of neuron projection development Source: UniProtKB
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of protein localization to plasma membrane Source: BHF-UCL
  • protein phosphorylation Source: BHF-UCL
  • response to interleukin-1 Source: Ensembl

Keywordsi

Molecular functionDevelopmental protein, Kinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAi2.7.11.13 3474
ReactomeiR-MMU-1912408 Pre-NOTCH Transcription and Translation
R-MMU-209543 p75NTR recruits signalling complexes
R-MMU-420029 Tight junction interactions

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Prkci
Synonyms:Pkcl
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:99260 Prkci

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endosome, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Embryonic lethal at 9.5 dpc.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi27R → A: No effect on interaction with SQSTM1. 1 Publication1
Mutagenesisi28V → A: No effect on interaction with SQSTM1; when associated with A-29. 1 Publication1
Mutagenesisi29K → A: No effect on interaction with SQSTM1; when associated with A-118. 1 Publication1
Mutagenesisi70W → A: Loss of interaction with SQSTM1. 1 Publication1
Mutagenesisi72D → A: Loss of interaction with SQSTM1. 1 Publication1
Mutagenesisi74E → A: Loss of interaction with SQSTM1. 1 Publication1
Mutagenesisi76D → A: Loss of interaction with SQSTM1. 1 Publication1
Mutagenesisi83Q → A: No effect on interaction with SQSTM1. 1 Publication1
Mutagenesisi85E → A: Loss of interaction with SQSTM1. 1 Publication1

Keywords - Diseasei

Proto-oncogene, Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000557112 – 595Protein kinase C iota typeAdd BLAST594

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylprolineBy similarity1
Modified residuei3PhosphothreonineBy similarity1
Modified residuei7PhosphoserineBy similarity1
Modified residuei8PhosphoserineBy similarity1
Modified residuei9PhosphothreonineBy similarity1
Modified residuei264Phosphotyrosine; by SRCBy similarity1
Modified residuei279Phosphotyrosine; by SRCBy similarity1
Modified residuei333Phosphotyrosine; by SRCBy similarity1
Modified residuei411PhosphothreonineCombined sources1
Modified residuei563PhosphothreonineCombined sources1 Publication1

Post-translational modificationi

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.By similarity1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ62074
MaxQBiQ62074
PaxDbiQ62074
PRIDEiQ62074

PTM databases

iPTMnetiQ62074
PhosphoSitePlusiQ62074

Expressioni

Gene expression databases

BgeeiENSMUSG00000037643
CleanExiMM_PRKCI
ExpressionAtlasiQ62074 baseline and differential
GenevisibleiQ62074 MM

Interactioni

Subunit structurei

Forms a complex with SQSTM1 and MP2K5 (PubMed:12813044). 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) (PubMed:10934474). 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). Interacts with VAMP2 (PubMed:17313651). Interacts with WDFY2 (via WD repeats 1-3) (PubMed:16792529).By similarityCurated4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202200, 32 interactors
CORUMiQ62074
DIPiDIP-32555N
IntActiQ62074, 33 interactors
MINTiQ62074
STRINGi10090.ENSMUSP00000103884

Structurei

Secondary structure

1595
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi250 – 252Combined sources3
Beta strandi253 – 261Combined sources9
Beta strandi263 – 272Combined sources10
Turni273 – 275Combined sources3
Beta strandi278 – 285Combined sources8
Helixi286 – 288Combined sources3
Helixi297 – 308Combined sources12
Beta strandi317 – 322Combined sources6
Beta strandi324 – 332Combined sources9
Helixi339 – 346Combined sources8
Helixi351 – 370Combined sources20
Helixi380 – 382Combined sources3
Beta strandi383 – 385Combined sources3
Beta strandi391 – 393Combined sources3
Helixi416 – 418Combined sources3
Helixi421 – 424Combined sources4
Helixi432 – 447Combined sources16
Turni453 – 456Combined sources4
Helixi466 – 475Combined sources10
Helixi486 – 495Combined sources10
Turni500 – 502Combined sources3
Turni508 – 510Combined sources3
Helixi511 – 517Combined sources7
Turni519 – 523Combined sources5
Helixi526 – 530Combined sources5
Helixi548 – 550Combined sources3
Helixi553 – 556Combined sources4
Helixi567 – 570Combined sources4
Helixi575 – 578Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4DC2X-ray2.40A231-595[»]
ProteinModelPortaliQ62074
SMRiQ62074
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini25 – 108PB1PROSITE-ProRule annotationAdd BLAST84
Domaini253 – 521Protein kinasePROSITE-ProRule annotationAdd BLAST269
Domaini522 – 595AGC-kinase C-terminalAdd BLAST74

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 252Regulatory domainBy similarityAdd BLAST251
Regioni2 – 28Required for interaction with RAB2By similarityAdd BLAST27
Regioni72 – 91Interaction with PARD6ABy similarityAdd BLAST20

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi125 – 134Pseudosubstrate10

Domaini

The PB1 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.

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri140 – 190Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST51

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0695 Eukaryota
ENOG410ZMG2 LUCA
GeneTreeiENSGT00820000126964
HOGENOMiHOG000233033
HOVERGENiHBG108317
InParanoidiQ62074
KOiK06069
OMAiEPMMPMD
OrthoDBiEOG091G03Q9
TreeFamiTF102004

Family and domain databases

CDDicd00029 C1, 1 hit
cd06404 PB1_aPKC, 1 hit
cd05618 STKc_aPKC_iota, 1 hit
InterProiView protein in InterPro
IPR000961 AGC-kinase_C
IPR034661 aPKC_iota
IPR020454 DAG/PE-bd
IPR011009 Kinase-like_dom_sf
IPR034877 PB1_aPKC
IPR000270 PB1_dom
IPR002219 PE/DAG-bd
IPR012233 PKC
IPR017892 Pkinase_C
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00130 C1_1, 1 hit
PF00564 PB1, 1 hit
PF00069 Pkinase, 1 hit
PF00433 Pkinase_C, 1 hit
PIRSFiPIRSF000554 PKC_zeta, 1 hit
PRINTSiPR00008 DAGPEDOMAIN
SMARTiView protein in SMART
SM00109 C1, 1 hit
SM00666 PB1, 1 hit
SM00133 S_TK_X, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51285 AGC_KINASE_CTER, 1 hit
PS51745 PB1, 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

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q62074-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPTQRDSSTM SHTVACGGGG DHSHQVRVKA YYRGDIMITH FEPSISFEGL
60 70 80 90 100
CSEVRDMCSF DNEQPFTMKW IDEEGDPCTV SSQLELEEAF RLYELNKDSE
110 120 130 140 150
LLIHVFPCVP ERPGMPCPGE DKSIYRRGAR RWRKLYCANG HTFQAKRFNR
160 170 180 190 200
RAHCAICTDR IWGLGRQGYK CINCKLLVHK KCHKLVTIEC GRHSLPPEPM
210 220 230 240 250
MPMDQTMHPD HTQTVIPYNP SSHESLDQVG EEKEAMNTRE SGKASSSLGL
260 270 280 290 300
QDFDLLRVIG RGSYAKVLLV RLKKTDRIYA MKVVKKELVN DDEDIDWVQT
310 320 330 340 350
EKHVFEQASN HPFLVGLHSC FQTESRLFFV IEYVNGGDLM FHMQRQRKLP
360 370 380 390 400
EEHARFYSAE ISLALNYLHE RGIIYRDLKL DNVLLDSEGH IKLTDYGMCK
410 420 430 440 450
EGLRPGDTTS TFCGTPNYIA PEILRGEDYG FSVDWWALGV LMFEMMAGRS
460 470 480 490 500
PFDIVGSSDN PDQNTEDYLF QVILEKQIRI PRSLSVKAAS VLKSFLNKDP
510 520 530 540 550
KERLGCHPQT GFADIQGHPF FRNVDWDMME QKQVVPPFKP NISGEFGLDN
560 570 580 590
FDSQFTNEPV QLTPDDDDIV RKIDQSEFEG FEYINPLLMS AEECV
Length:595
Mass (Da):68,203
Last modified:June 16, 2009 - v3
Checksum:i6AC612D1E9264825
GO

Sequence cautioni

The sequence AAH21630 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAA32499 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D28577 mRNA Translation: BAA32499.1 Different initiation.
BC021630 mRNA Translation: AAH21630.1 Different initiation.
CCDSiCCDS17289.2
PIRiA53758
RefSeqiNP_032883.2, NM_008857.3
UniGeneiMm.291554

Genome annotation databases

EnsembliENSMUST00000108249; ENSMUSP00000103884; ENSMUSG00000037643
GeneIDi18759
KEGGimmu:18759
UCSCiuc008ovs.1 mouse

Similar proteinsi

Entry informationi

Entry nameiKPCI_MOUSE
AccessioniPrimary (citable) accession number: Q62074
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: June 16, 2009
Last modified: April 25, 2018
This is version 193 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health