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Reviewed, UniProtKB/Swiss-Prot P41743 (KPCI_HUMAN)

Last modified November 25, 2008. Version 96. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Protein kinase C iota type
    EC=2.7.11.13
Alternative name(s):
    nPKC-iota
    Atypical protein kinase C-lambda/iota
      Short name=aPKC-lambda/iota
      Short name=PRKC-lambda/iota
Gene names
Name: PRKCI
Synonyms: DXS1179E
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length587 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Calcium-independent, phospholipid-dependent, serine- and threonine-specific kinase. May play a role in the secretory response to nutrients. Involved in cell polarization processes and the formation of epithelial tight junctions. Implicated in the activation of several signaling pathways including Ras, c-Src and NF-kappa-B pathways. Functions in both pro- and anti-apoptotic pathways. Functions in the RAC1/ERK signaling required for transformed growth. Plays a role in microtubule dynamics through interaction with RAB2 and GAPDH and recruitment to vesicular tubular clusters (VTCs).

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Might be a target for novel lipid activators that are elevated during nutrient-stimulated insulin secretion. Two specific sites, Thr-403 (activation loop of the kinase domain) and Thr-555 (turn motif), need to be phosphorylated for its full activation By similarity. Atypical PCKs are not regulated by diacylglycerol, phorbol esters nor calcium ions.

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 CENTA1. Interaction with SMG1, through the ZN-finger domain, activates the kinase activity. Interacts with CDK7. Forms a complex with RAB2 and GAPDH involved in recruitment onto the membrane of vesicular tubular clusters (VTCs).

Subcellular location

Cytoplasm. Membrane. Endosome. Nucleus. Note= Transported into the endosome through interaction with SQSTM1/p62. After phosphorylation by cSrc, transported into the nucleus through interaction with KPNB1. Colocalizes with CDK7 in the cytoplasm and nucleus. Vesicular tubular clusters. Transported to VTCs through interaction with Rab2.

Tissue specificity

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.

Domain

The OPR domain mediates interaction with SQSTM1 By similarity.

The C1 domain does not bind diacylglycerol (DAG).

Post-translational modification

On neuronal growth factor (NGF) stimulation, phosphorylated by Src on Tyr-256, Tyr-271 and Tyr-325. Phosphorylation on Tyr-256 facilitates binding to KPNB1/importin-beta regulating entry of PRKCI into the nucleus. Phosphorylation on Tyr-325 is important for NF-kappa-B stimulation.

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
   Coding sequence diversityPolymorphism
   DomainPhorbol-ester binding
Zinc-finger
   LigandATP-binding
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionKinase
Oncogene
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical term3D-structure

Gene Ontology (GO)

   Biological processcell-cell junction organization Ref.8

Inferred from mutant phenotype. Source: UniProtKB

cytoskeleton organization Ref.8

Non-traceable author statement. Source: UniProtKB

establishment or maintenance of epithelial cell apical/basal polarity

Traceable author statement. Source: UniProtKB

intracellular signaling cascade

Inferred from electronic annotation. Source: InterPro

membrane organization Ref.8

Non-traceable author statement. Source: UniProtKB

protein amino acid phosphorylation Ref.1

Traceable author statement. Source: ProtInc

protein targeting to membrane Ref.8

Non-traceable author statement. Source: UniProtKB

secretion Ref.1

Non-traceable author statement. Source: UniProtKB

vesicle-mediated transport Ref.8

Traceable author statement. Source: UniProtKB

   Cellular componentcytosol Ref.8

Inferred from direct assay. Source: UniProtKB

endosome

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Inferred from electronic annotation. Source: UniProtKB-KW

nucleus Ref.7

Inferred from direct assay. Source: UniProtKB

polarisome

Traceable author statement. Source: UniProtKB

   Molecular functionATP binding Ref.1

Traceable author statement. Source: UniProtKB

atypical protein kinase C activity Ref.1

Inferred from direct assay. Source: UniProtKB

diacylglycerol binding

Inferred from electronic annotation. Source: UniProtKB-KW

phospholipid binding Ref.1

Inferred from direct assay. Source: UniProtKB

protein binding Ref.7 Ref.12 Ref.20

Inferred from physical interaction. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 587587Protein kinase C iota type
PRO_0000055710

Regions

Domain16 – 9984OPR
Domain245 – 513269Protein kinase
Domain514 – 58572AGC-kinase C-terminal
Zinc finger131 – 18151Phorbol-ester/DAG-type
Nucleotide binding251 – 2599ATP By similarity
Region1 – 244244Regulatory domain
Region1 – 1919Required for interaction with RAB2
Region63 – 8220Interaction with PARD6A

Sites

Active site3691Proton acceptor By similarity
Binding site2741ATP By similarity

Amino acid modifications

Modified residue2561Phosphotyrosine; by Src
Modified residue2711Phosphotyrosine; by Src
Modified residue3251Phosphotyrosine; by Src
Modified residue4031Phosphothreonine
Modified residue5551Phosphothreonine

Natural variations

Natural variant1091P → L in a metastatic melanoma sample; somatic mutation.
VAR_042322
Natural variant1211R → C
VAR_042323

Experimental info

Mutagenesis201K → A: No effect on interaction with SQSTM1
Mutagenesis631D → A: Loss of interaction with PARD6A and with SQSTM1
Mutagenesis761E → A: Slight decrease of interaction with PARD6A. Loss of interaction with PARD6A; when associated with A-82
Mutagenesis821R → A: Slight decrease of interaction with PARD6A. Loss of interaction with PARD6A; when associated with A-76
Mutagenesis2561Y → 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
Mutagenesis2711Y → 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
Mutagenesis3251Y → 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
Sequence conflict4761L → M in AAH22016. Ref.3
Sequence conflict4991H → L in AAH22016. Ref.3
Sequence conflict5511P → R in AAH22016. Ref.3

Secondary structure

.................................................................. 587
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P41743-1 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: 2A72B2FC983EDB4C

FASTA58767,258
        10         20         30         40         50         60 
MSHTVAGGGS GDHSHQVRVK AYYRGDIMIT HFEPSISFEG LCNEVRDMCS FDNEQLFTMK 

        70         80         90        100        110        120 
WIDEEGDPCT VSSQLELEEA FRLYELNKDS ELLIHVFPCV PERPGMPCPG EDKSIYRRGA 

       130        140        150        160        170        180 
RRWRKLYCAN GHTFQAKRFN RRAHCAICTD RIWGLGRQGY KCINCKLLVH KKCHKLVTIE 

       190        200        210        220        230        240 
CGRHSLPQEP VMPMDQSSMH SDHAQTVIPY NPSSHESLDQ VGEEKEAMNT RESGKASSSL 

       250        260        270        280        290        300 
GLQDFDLLRV IGRGSYAKVL LVRLKKTDRI YAMKVVKKEL VNDDEDIDWV QTEKHVFEQA 

       310        320        330        340        350        360 
SNHPFLVGLH SCFQTESRLF FVIEYVNGGD LMFHMQRQRK LPEEHARFYS AEISLALNYL 

       370        380        390        400        410        420 
HERGIIYRDL KLDNVLLDSE GHIKLTDYGM CKEGLRPGDT TSTFCGTPNY IAPEILRGED 

       430        440        450        460        470        480 
YGFSVDWWAL GVLMFEMMAG RSPFDIVGSS DNPDQNTEDY LFQVILEKQI RIPRSLSVKA 

       490        500        510        520        530        540 
ASVLKSFLNK DPKERLGCHP QTGFADIQGH PFFRNVDWDM MEQKQVVPPF KPNISGEFGL 

       550        560        570        580 
DNFDSQFTNE PVQLTPDDDD IVRKIDQSEF EGFEYINPLL MSAEECV 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and characterization of PKC iota, an atypical isoform of protein kinase C derived from insulin-secreting cells."
Selbie L.A., Schmitz-Peiffer C., Sheng Y., Biden T.J.
J. Biol. Chem. 268:24296-24302(1993) [PubMed: 8226978] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
Tissue: Kidney.
[2]"Human protein kinase C iota gene (PRKCI) is closely linked to the BTK gene in Xq21.3."
Mazzarella R., Ciccodicola A., Esposito T., Arcucci A., Migliaccio C., Jones C., Schlessinger D., D'Urso M., D'Esposito M.
Genomics 26:629-631(1995) [PubMed: 7607695] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Tissue: Teratocarcinoma.
[3]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Testis.
[4]"Lambda-interacting protein, a novel protein that specifically interacts with the zinc finger domain of the atypical protein kinase C isotype lambda/iota and stimulates its kinase activity in vitro and in vivo."
Diaz-Meco M.T., Municio M.M., Sanchez P., Lozano J., Moscat J.
Mol. Cell. Biol. 16:105-114(1996) [PubMed: 8524286] [Abstract]
Cited for: INTERACTION WITH SMG1, ENZYME REGULATION.
[5]"Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62."
Sanchez P., De Carcer G., Sandoval I.V., Moscat J., Diaz-Meco M.T.
Mol. Cell. Biol. 18:3069-3080(1998) [PubMed: 9566925] [Abstract]
Cited for: INTERACTION WITH SQSTM1, SUBCELLULAR LOCATION.
[6]"The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation."
Sanz L., Sanchez P., Lallena M.-J., Diaz-Meco M.T., Moscat J.
EMBO J. 18:3044-3053(1999) [PubMed: 10356400] [Abstract]
Cited for: INTERACTION WITH SQSTM1 AND IKBKB, FUNCTION.
[7]"Human homologues of the Caenorhabditis elegans cell polarity protein PAR6 as an adaptor that links the small GTPases Rac and Cdc42 to atypical protein kinase C."
Noda Y., Takeya R., Ohno S., Naito S., Ito T., Sumimoto H.
Genes Cells 6:107-119(2001) [PubMed: 11260256] [Abstract]
Cited for: INTERACTION WITH PARD6A; PARD6B AND PARD6G, SUBUNIT OF A COMPLEX CONTAINING PARD6B AND CDC42/RAC1.
[8]"Atypical protein kinase C is involved in the evolutionarily conserved par protein complex and plays a critical role in establishing epithelia-specific junctional structures."
Suzuki A., Yamanaka T.,