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Protein

Protein kinase C iota type

Gene

Prkci

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 establishment of protein localization to plasma membrane Source: BHF-UCL
  • 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
  • protein phosphorylation Source: BHF-UCL
  • response to interleukin-1 Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAi2.7.11.13. 3474.
ReactomeiR-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:99260. Prkci.

Subcellular locationi

  • 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

GO - Cellular componenti

  • apical part of cell Source: MGI
  • apical plasma membrane Source: MGI
  • bicellular tight junction Source: Ensembl
  • cell leading edge Source: Ensembl
  • cytoplasm Source: MGI
  • cytosol Source: UniProtKB
  • endosome Source: UniProtKB-SubCell
  • extracellular exosome Source: MGI
  • Golgi membrane Source: GOC
  • intercellular bridge Source: MGI
  • microtubule cytoskeleton Source: MGI
  • nucleus Source: UniProtKB
  • protein complex Source: Ensembl
  • Schmidt-Lanterman incisure Source: BHF-UCL
Complete GO annotation...

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

Protein-protein interaction databases

BioGridi202200. 30 interactors.
DIPiDIP-32555N.
IntActiQ62074. 31 interactors.
MINTiMINT-4100000.
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

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 1 PB1 domain.PROSITE-ProRule annotation
Contains 1 phorbol-ester/DAG-type zinc finger.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

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.
OMAiKLVTVEC.
OrthoDBiEOG091G03Q9.
TreeFamiTF102004.

Family and domain databases

CDDicd00029. C1. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
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.
[Graphical view]
PfamiPF00130. C1_1. 1 hit.
PF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFiPIRSF000554. PKC_zeta. 1 hit.
PRINTSiPR00008. DAGPEDOMAIN.
SMARTiSM00109. C1. 1 hit.
SM00666. PB1. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51285. 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.
[Graphical view]

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.

Cross-referencesi

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.

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...

Protein-protein interaction databases

BioGridi202200. 30 interactors.
DIPiDIP-32555N.
IntActiQ62074. 31 interactors.
MINTiMINT-4100000.
STRINGi10090.ENSMUSP00000103884.

PTM databases

iPTMnetiQ62074.
PhosphoSitePlusiQ62074.

Proteomic databases

EPDiQ62074.
MaxQBiQ62074.
PaxDbiQ62074.
PRIDEiQ62074.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi5584.
MGIiMGI:99260. Prkci.

Phylogenomic databases

eggNOGiKOG0695. Eukaryota.
ENOG410ZMG2. LUCA.
GeneTreeiENSGT00820000126964.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiQ62074.
KOiK06069.
OMAiKLVTVEC.
OrthoDBiEOG091G03Q9.
TreeFamiTF102004.

Enzyme and pathway databases

BRENDAi2.7.11.13. 3474.
ReactomeiR-MMU-209543. p75NTR recruits signalling complexes.
R-MMU-420029. Tight junction interactions.

Miscellaneous databases

PROiQ62074.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000037643.
CleanExiMM_PRKCI.
ExpressionAtlasiQ62074. baseline and differential.
GenevisibleiQ62074. MM.

Family and domain databases

CDDicd00029. C1. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
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.
[Graphical view]
PfamiPF00130. C1_1. 1 hit.
PF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFiPIRSF000554. PKC_zeta. 1 hit.
PRINTSiPR00008. DAGPEDOMAIN.
SMARTiSM00109. C1. 1 hit.
SM00666. PB1. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51285. 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.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKPCI_MOUSE
AccessioniPrimary (citable) accession number: Q62074
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: June 16, 2009
Last modified: November 30, 2016
This is version 180 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.