Protein kinase C iota type - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot P41743 (KPCI_HUMAN)

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

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	587 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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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.

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Ontologies

Keywords
Cellular component	Cytoplasm Endosome Membrane Nucleus
Coding sequence diversity	Polymorphism
Domain	Phorbol-ester binding Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Oncogene Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell-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 component	cytosol 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 function	ATP 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...

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Binary interactions

With	Entry	#Exp.	IntAct
CDC42	P60953	2	EBI-286199,EBI-81752
PARD6A	Q9NPB6	4	EBI-286199,EBI-81876
PARD6B	Q9BYG5	3	EBI-286199,EBI-295391

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 587

587

Protein kinase C iota type

PRO_0000055710

Regions

Domain

16 – 99

OPR

Domain

245 – 513

269

Protein kinase

Domain

514 – 585

AGC-kinase C-terminal

Zinc finger

131 – 181

Phorbol-ester/DAG-type

Nucleotide binding

251 – 259

ATP By similarity

Region

1 – 244

244

Regulatory domain

Region

1 – 19

Required for interaction with RAB2

Region

63 – 82

Interaction with PARD6A

Sites

Active site

369

Proton acceptor By similarity

Binding site

274

ATP By similarity

Amino acid modifications

Modified residue

256

Phosphotyrosine; by Src

Modified residue

271

Phosphotyrosine; by Src

Modified residue

325

Phosphotyrosine; by Src

Modified residue

403

Phosphothreonine

Modified residue

555

Phosphothreonine

Natural variations

Natural variant

109

P → L in a metastatic melanoma sample; somatic mutation.

VAR_042322

Natural variant

121

R → C

VAR_042323

Experimental info

Mutagenesis

K → A: No effect on interaction with SQSTM1

Mutagenesis

D → A: Loss of interaction with PARD6A and with SQSTM1

Mutagenesis

E → A: Slight decrease of interaction with PARD6A. Loss of interaction with PARD6A; when associated with A-82

Mutagenesis

R → A: Slight decrease of interaction with PARD6A. Loss of interaction with PARD6A; when associated with A-76

Mutagenesis

256

Y → 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

Mutagenesis

271

Y → 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

Mutagenesis

325

Y → 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 conflict

476

L → M in AAH22016. Ref.3

Sequence conflict

499

H → L in AAH22016. Ref.3

Sequence conflict

551

P → R in AAH22016. Ref.3

Secondary structure

587

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P41743-1 [UniParc].

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

587

67,258

        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

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References

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[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.,

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequences

References