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Protein

Protein kinase C iota type

Gene

PRKCI

Organism
Homo sapiens (Human)
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.14 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-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.By similarity1 Publication

Kineticsi

  1. KM=13.5 µM for ATP (for recombinant purified PRKCI)1 Publication
  1. Vmax=7.4 pmol/min/mg enzyme1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei283ATPPROSITE-ProRule annotation1
Active sitei378Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri140 – 190Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST51
Nucleotide bindingi260 – 268ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • phospholipid binding Source: UniProtKB
  • protein domain specific binding Source: Ensembl
  • protein kinase activity Source: UniProtKB
  • protein kinase C activity Source: BHF-UCL
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • actin filament organization Source: Ensembl
  • bicellular tight junction assembly Source: Reactome
  • cell-cell junction organization Source: UniProtKB
  • cell migration Source: Ensembl
  • cellular response to insulin stimulus Source: BHF-UCL
  • cytoskeleton organization Source: UniProtKB
  • establishment of apical/basal cell polarity Source: Ensembl
  • establishment or maintenance of epithelial cell apical/basal polarity Source: UniProtKB
  • eye photoreceptor cell development Source: Ensembl
  • Golgi vesicle budding Source: Ensembl
  • intracellular signal transduction Source: GO_Central
  • membrane organization Source: UniProtKB
  • negative regulation of apoptotic process Source: Reactome
  • negative regulation of glial cell apoptotic process Source: UniProtKB
  • negative regulation of neuron apoptotic process Source: UniProtKB
  • peptidyl-serine phosphorylation Source: WormBase
  • 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 Notch signaling pathway Source: Reactome
  • positive regulation of protein localization to plasma membrane Source: BHF-UCL
  • protein phosphorylation Source: UniProtKB
  • protein targeting to membrane Source: UniProtKB
  • response to interleukin-1 Source: Ensembl
  • secretion Source: UniProtKB
  • vesicle-mediated transport Source: UniProtKB

Keywordsi

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

Enzyme and pathway databases

BRENDAi2.7.11.13 2681
ReactomeiR-HSA-1912408 Pre-NOTCH Transcription and Translation
R-HSA-209543 p75NTR recruits signalling complexes
R-HSA-420029 Tight junction interactions
SABIO-RKiP41743
SignaLinkiP41743
SIGNORiP41743

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:
PRKC-lambda/iota
Short name:
aPKC-lambda/iota
nPKC-iota
Gene namesi
Name:PRKCI
Synonyms:DXS1179E
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000163558.12
HGNCiHGNC:9404 PRKCI
MIMi600539 gene
neXtProtiNX_P41743

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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi29K → A: No effect on interaction with SQSTM1. 1 Publication1
Mutagenesisi72D → A: Loss of interaction with ECT2, PARD6A and with SQSTM1. 3 Publications1
Mutagenesisi85E → A: Slight decrease of interaction with PARD6A. Loss of interaction with PARD6A; when associated with A-91. 1 Publication1
Mutagenesisi91R → A: Slight decrease of interaction with PARD6A. Loss of interaction with PARD6A; when associated with A-85. 1 Publication1
Mutagenesisi265Y → 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. 2 Publications1
Mutagenesisi274K → R: No effect on activity. 1 Publication1
Mutagenesisi274K → W: Abolishes activity. 1 Publication1
Mutagenesisi280Y → 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. 1 Publication1
Mutagenesisi334Y → 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. 1 Publication1

Keywords - Diseasei

Proto-oncogene, Tumor suppressor

Organism-specific databases

DisGeNETi5584
OpenTargetsiENSG00000163558
PharmGKBiPA33768

Chemistry databases

ChEMBLiCHEMBL2598
DrugBankiDB03777 Rbt205 Inhibitor
DB00675 Tamoxifen
GuidetoPHARMACOLOGYi1490

Polymorphism and mutation databases

BioMutaiPRKCI
DMDMi239938658

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000557102 – 596Protein kinase C iota typeAdd BLAST595

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylprolineCombined sources1
Modified residuei3PhosphothreonineCombined sources1
Modified residuei7PhosphoserineCombined sources1
Modified residuei8PhosphoserineCombined sources1
Modified residuei9PhosphothreonineCombined sources1
Modified residuei265Phosphotyrosine; by SRC2 Publications1
Modified residuei280Phosphotyrosine; by SRC1 Publication1
Modified residuei334Phosphotyrosine; by SRC1 Publication1
Modified residuei412Phosphothreonine; by PDPK11 Publication1
Modified residuei564PhosphothreonineCombined sources1 Publication1

Post-translational modificationi

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.By similarity4 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP41743
MaxQBiP41743
PaxDbiP41743
PeptideAtlasiP41743
PRIDEiP41743

PTM databases

iPTMnetiP41743
PhosphoSitePlusiP41743

Expressioni

Tissue specificityi

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.3 Publications

Gene expression databases

BgeeiENSG00000163558
CleanExiHS_PRKCI
GenevisibleiP41743 HS

Organism-specific databases

HPAiHPA026574
HPA038635

Interactioni

Subunit structurei

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). Interacts with VAMP2 (PubMed:17313651). Interacts with WDFY2 (via WD repeats 1-3) (PubMed:16792529).By similarityCurated17 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111570, 91 interactors
CORUMiP41743
DIPiDIP-31311N
ELMiP41743
IntActiP41743, 56 interactors
MINTiP41743
STRINGi9606.ENSP00000295797

Chemistry databases

BindingDBiP41743

Structurei

Secondary structure

1596
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi26 – 32Combined sources7
Beta strandi35 – 41Combined sources7
Helixi47 – 57Combined sources11
Beta strandi67 – 71Combined sources5
Beta strandi73 – 75Combined sources3
Beta strandi77 – 79Combined sources3
Helixi83 – 95Combined sources13
Beta strandi101 – 106Combined sources6
Helixi251 – 253Combined sources3
Beta strandi254 – 262Combined sources9
Beta strandi264 – 273Combined sources10
Turni274 – 277Combined sources4
Beta strandi279 – 286Combined sources8
Helixi287 – 289Combined sources3
Helixi293 – 309Combined sources17
Beta strandi318 – 323Combined sources6
Beta strandi325 – 332Combined sources8
Helixi340 – 347Combined sources8
Helixi352 – 371Combined sources20
Helixi381 – 383Combined sources3
Beta strandi384 – 386Combined sources3
Beta strandi388 – 390Combined sources3
Beta strandi392 – 394Combined sources3
Helixi397 – 399Combined sources3
Helixi417 – 419Combined sources3
Helixi422 – 425Combined sources4
Helixi433 – 448Combined sources16
Turni452 – 457Combined sources6
Helixi467 – 476Combined sources10
Helixi487 – 496Combined sources10
Turni501 – 503Combined sources3
Turni505 – 507Combined sources3
Turni509 – 511Combined sources3
Helixi512 – 517Combined sources6
Helixi520 – 522Combined sources3
Helixi527 – 531Combined sources5
Turni545 – 547Combined sources3
Helixi549 – 551Combined sources3
Helixi554 – 557Combined sources4
Helixi568 – 571Combined sources4
Helixi576 – 579Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
5LI1X-ray2.00A248-596[»]
5LI9X-ray1.79A248-596[»]
5LIHX-ray3.25A/B248-596[»]
ProteinModelPortaliP41743
SMRiP41743
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP41743

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini25 – 108PB1PROSITE-ProRule annotationAdd BLAST84
Domaini254 – 522Protein kinasePROSITE-ProRule annotationAdd BLAST269
Domaini523 – 594AGC-kinase C-terminalAdd BLAST72

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 253Regulatory domainAdd BLAST252
Regioni2 – 28Required for interaction with RAB2Add BLAST27
Regioni72 – 91Interaction with PARD6AAdd BLAST20

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi125 – 134PseudosubstrateBy similarity10

Domaini

The PB1 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

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
InParanoidiP41743
KOiK06069
OMAiEPMMPMD
OrthoDBiEOG091G03Q9
PhylomeDBiP41743
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.

P41743-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPTQRDSSTM SHTVAGGGSG DHSHQVRVKA YYRGDIMITH FEPSISFEGL
60 70 80 90 100
CNEVRDMCSF DNEQLFTMKW IDEEGDPCTV SSQLELEEAF RLYELNKDSE
110 120 130 140 150
LLIHVFPCVP ERPGMPCPGE DKSIYRRGAR RWRKLYCANG HTFQAKRFNR
160 170 180 190 200
RAHCAICTDR IWGLGRQGYK CINCKLLVHK KCHKLVTIEC GRHSLPQEPV
210 220 230 240 250
MPMDQSSMHS DHAQTVIPYN PSSHESLDQV GEEKEAMNTR ESGKASSSLG
260 270 280 290 300
LQDFDLLRVI GRGSYAKVLL VRLKKTDRIY AMKVVKKELV NDDEDIDWVQ
310 320 330 340 350
TEKHVFEQAS NHPFLVGLHS CFQTESRLFF VIEYVNGGDL MFHMQRQRKL
360 370 380 390 400
PEEHARFYSA EISLALNYLH ERGIIYRDLK LDNVLLDSEG HIKLTDYGMC
410 420 430 440 450
KEGLRPGDTT STFCGTPNYI APEILRGEDY GFSVDWWALG VLMFEMMAGR
460 470 480 490 500
SPFDIVGSSD NPDQNTEDYL FQVILEKQIR IPRSLSVKAA SVLKSFLNKD
510 520 530 540 550
PKERLGCHPQ TGFADIQGHP FFRNVDWDMM EQKQVVPPFK PNISGEFGLD
560 570 580 590
NFDSQFTNEP VQLTPDDDDI VRKIDQSEFE GFEYINPLLM SAEECV
Length:596
Mass (Da):68,262
Last modified:June 16, 2009 - v2
Checksum:i1E3F8C1D4BFC734F
GO

Sequence cautioni

The sequence AAA60171 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAB17011 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH22016 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti485L → M in AAH22016 (PubMed:15489334).Curated1
Sequence conflicti508H → L in AAH22016 (PubMed:15489334).Curated1
Sequence conflicti560P → R in AAH22016 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_042322118P → L in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_042323130R → C1 PublicationCorresponds to variant dbSNP:rs56154494Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3212.2
PIRiA49509
RefSeqiNP_002731.4, NM_002740.5
UniGeneiHs.478199

Genome annotation databases

EnsembliENST00000295797; ENSP00000295797; ENSG00000163558
GeneIDi5584
KEGGihsa:5584
UCSCiuc003fgs.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiKPCI_HUMAN
AccessioniPrimary (citable) accession number: P41743
Secondary accession number(s): D3DNQ4, Q8WW06
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: June 16, 2009
Last modified: April 25, 2018
This is version 203 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health