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F1M7Y5 (KPCI_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified May 14, 2014. Version 31. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | 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
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

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. 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 similarity.

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. Might also be a target for novel lipid activators that are elevated during nutrient-stimulated insulin secretion By similarity.

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.

Subcellular location

Cytoplasm. Membrane By similarity. Endosome By similarity. 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.3

Domain

The OPR domain mediates interaction with SQSTM1 By similarity.

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 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.3

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.

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 termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processGolgi vesicle budding

Inferred from direct assay PubMed 12871960. Source: RGD

actin filament organization

Inferred from electronic annotation. Source: Ensembl

cell migration

Inferred from mutant phenotype PubMed 19885391. Source: RGD

cell-cell junction organization

Inferred from electronic annotation. Source: Ensembl

cellular protein localization

Inferred from mutant phenotype PubMed 19885391. Source: RGD

cellular response to insulin stimulus

Inferred from mutant phenotype PubMed 12975478. Source: RGD

establishment of apical/basal cell polarity

Inferred from electronic annotation. Source: Ensembl

eye photoreceptor cell development

Inferred from electronic annotation. Source: Ensembl

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 electronic annotation. Source: Ensembl

positive regulation of glial cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of glucose import

Inferred from electronic annotation. Source: Ensembl

positive regulation of neuron projection development

Inferred from sequence or structural similarity. Source: UniProtKB

protein phosphorylation

Inferred from direct assay PubMed 19885391. Source: RGD

response to interleukin-1

Inferred from mutant phenotype PubMed 19782155. Source: RGD

response to peptide hormone

Inferred from direct assay PubMed 15649420. Source: RGD

   Cellular_componentGolgi membrane

Inferred from direct assay PubMed 12871960. 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 direct assay PubMed 19885391. Source: RGD

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

plasma membrane

Inferred from direct assay PubMed 18945317. Source: RGD

protein complex

Inferred from direct assay PubMed 19885391. Source: RGD

   Molecular_functionATP binding

Inferred from direct assay PubMed 19885391. Source: RGD

phospholipid binding

Inferred from electronic annotation. Source: Ensembl

protein domain specific binding

Inferred from physical interaction PubMed 19885391. Source: RGD

protein kinase C activity

Inferred from direct assay PubMed 19885391. Source: RGD

protein 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 – 596595Protein kinase C iota type
PRO_0000414090

Regions

Domain26 – 10782OPR
Domain254 – 522269Protein kinase
Domain523 – 59472AGC-kinase C-terminal
Zinc finger140 – 19051Phorbol-ester/DAG-type
Nucleotide binding260 – 2689ATP By similarity
Region2 – 253252Regulatory domain By similarity
Region2 – 2827Required for interaction with RAB2 By similarity
Region72 – 9120Interaction with PARD6A By similarity
Motif125 – 13410Pseudosubstrate By similarity

Sites

Active site3781Proton acceptor By similarity
Binding site2831ATP 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 residue2651Phosphotyrosine; by SRC Ref.3
Modified residue2801Phosphotyrosine; by SRC By similarity
Modified residue3341Phosphotyrosine; by SRC By similarity
Modified residue4121Phosphothreonine; by PDPK1 By similarity
Modified residue5641Phosphothreonine By similarity

Experimental info

Mutagenesis2651Y → F: Loss of phosphorylation and nuclear import. Ref.3
Sequence conflict1711C → R in ACA66272. Ref.2

Sequences

Sequence LengthMass (Da)Tools
F1M7Y5 [UniParc].

Last modified May 3, 2011. Version 1.
Checksum: 60035F56E7547C57

FASTA59668,276
        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 MPMDQSSMHP DHTQTVIPYN 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]"Genome sequence of the Brown Norway rat yields insights into mammalian evolution."
Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. expand/collapse author list , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S.
Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], IDENTIFICATION.
Strain: Brown Norway.
[2]"Expression and localization of atypical PKC isoforms in liver parenchymal cells."
Stross C., Keitel V., Winands E., Haussinger D., Kubitz R.
Biol. Chem. 390:235-244(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 10-596.
Strain: Wistar.
[3]"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: SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-265, MUTAGENESIS OF TYR-265.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
EU517502 mRNA. Translation: ACA66272.1.
RefSeqNP_114448.1. NM_032059.1.
UniGeneRn.1388.

3D structure databases

ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActF1M7Y5. 2 interactions.
STRING10116.ENSRNOP00000012924.

Proteomic databases

PRIDEF1M7Y5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000012924; ENSRNOP00000012924; ENSRNOG00000009652.
GeneID84006.
KEGGrno:84006.
UCSCRGD:620961. rat.

Organism-specific databases

CTD5584.
RGD620961. Prkci.

Phylogenomic databases

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

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

NextBio616517.

Entry information

Entry nameKPCI_RAT
AccessionPrimary (citable) accession number: F1M7Y5
Secondary accession number(s): B1PZT8
Entry history
Integrated into UniProtKB/Swiss-Prot: December 14, 2011
Last sequence update: May 3, 2011
Last modified: May 14, 2014
This is version 31 of the entry and version 1 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