P41743 (KPCI_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	PRKCI
Synonyms:	DXS1179E

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	596 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. Ref.1 Ref.6 Ref.8 Ref.9 Ref.10 Ref.11 Ref.14 Ref.19 Ref.21 Ref.22 Ref.25 Ref.29 Ref.34 Ref.35
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 By similarity. Might also be a target for novel lipid activators that are elevated during nutrient-stimulated insulin secretion. Ref.5
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). Ref.5 Ref.7 Ref.9 Ref.12 Ref.13 Ref.14 Ref.16 Ref.17 Ref.18 Ref.20 Ref.23 Ref.24 Ref.30 Ref.37
Subcellular location	Cytoplasm. Membrane. Endosome. 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.7 Ref.16 Ref.23 Ref.24
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. Ref.1 Ref.2 Ref.22
Domain	The OPR 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.
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.15 Ref.16 Ref.24 Ref.39
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.
Biophysicochemical properties	Kinetic parameters: KM=13.5 µM for ATP (for recombinant purified PRKCI) Ref.10 Vmax=7.4 pmol/min/mg enzyme
Sequence caution	The sequence AAA60171.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAB17011.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAH22016.3 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Cellular component	Cytoplasm Endosome Membrane Nucleus
Coding sequence diversity	Polymorphism
Disease	Proto-oncogene Tumor suppressor
Domain	Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Golgi vesicle budding Inferred from electronic annotation. Source: Compara actin filament organization Inferred from electronic annotation. Source: Compara cell migration Inferred from electronic annotation. Source: Compara cellular membrane organization Non-traceable author statement Ref.13. Source: UniProtKB cellular response to insulin stimulus Inferred from sequence or structural similarity. Source: BHF-UCL cytoskeleton organization Non-traceable author statement Ref.13. Source: UniProtKB establishment of apical/basal cell polarity Inferred from electronic annotation. Source: Compara establishment or maintenance of epithelial cell apical/basal polarity Traceable author statement PubMed 14676191. Source: UniProtKB eye photoreceptor cell development Inferred from electronic annotation. Source: Compara intracellular signal transduction Inferred from electronic annotation. Source: InterPro negative regulation of glial cell apoptotic process Inferred from mutant phenotype Ref.34. Source: UniProtKB negative regulation of neuron apoptotic process Inferred from direct assay Ref.8. Source: UniProtKB nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome positive regulation of NF-kappaB transcription factor activity Inferred from direct assay Ref.8. Source: UniProtKB positive regulation of endothelial cell apoptotic process Inferred from mutant phenotype Ref.29. Source: UniProtKB positive regulation of establishment of protein localization to plasma membrane Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of glial cell proliferation Inferred from mutant phenotype Ref.34. Source: UniProtKB positive regulation of glucose import Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of neuron projection development Inferred from mutant phenotype Ref.8. Source: UniProtKB protein targeting to membrane Non-traceable author statement Ref.13. Source: UniProtKB response to interleukin-1 Inferred from electronic annotation. Source: Compara secretion Non-traceable author statement Ref.1. Source: UniProtKB tight junction assembly Traceable author statement. Source: Reactome vesicle-mediated transport Traceable author statement Ref.13. Source: UniProtKB
Cellular_component	Schmidt-Lanterman incisure Inferred from electronic annotation. Source: Compara apical plasma membrane Inferred from electronic annotation. Source: Compara cell leading edge Inferred from electronic annotation. Source: Compara cytosol Inferred from direct assay Ref.13Ref.34. Source: UniProtKB endosome Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay Ref.12Ref.34. Source: UniProtKB plasma membrane Traceable author statement. Source: Reactome polarisome Traceable author statement PubMed 14676191. Source: UniProtKB
Molecular_function	ATP binding Traceable author statement Ref.1. Source: UniProtKB phospholipid binding Inferred from direct assay Ref.1. Source: UniProtKB protein kinase C activity Inferred from sequence or structural similarity. Source: BHF-UCL zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDC42	P60953	5	EBI-286199,EBI-81752
MARK4	Q96L34	2	EBI-286199,EBI-302319
PARD3	Q8TEW0	3	EBI-286199,EBI-81968
PARD6A	Q9NPB6	9	EBI-286199,EBI-81876
PARD6B	Q9BYG5	9	EBI-286199,EBI-295391
PARD6G	Q9BYG4	5	EBI-286199,EBI-295417
PNMA1	Q8ND90	2	EBI-286199,EBI-302345
RAC1	P63000	3	EBI-286199,EBI-413628
YWHAH	Q04917	3	EBI-286199,EBI-306940

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.32

Chain

2 – 596

595

Protein kinase C iota type

PRO_0000055710

Regions

Domain

25 – 108

84

OPR

Domain

254 – 522

269

Protein kinase

Domain

523 – 594

72

AGC-kinase C-terminal

Zinc finger

140 – 190

51

Phorbol-ester/DAG-type

Nucleotide binding

260 – 268

9

ATP By similarity

Region

2 – 253

252

Regulatory domain

Region

2 – 28

27

Required for interaction with RAB2

Region

72 – 91

20

Interaction with PARD6A

Motif

125 – 134

10

Pseudosubstrate By similarity

Sites

Active site

378

1

Proton acceptor By similarity

Binding site

283

1

ATP By similarity

Amino acid modifications

Modified residue

2

1

N-acetylproline Ref.32

Modified residue

3

1

Phosphothreonine Ref.32

Modified residue

7

1

Phosphoserine Ref.32

Modified residue

8

1

Phosphoserine Ref.32

Modified residue

9

1

Phosphothreonine Ref.32

Modified residue

265

1

Phosphotyrosine; by SRC Ref.15 Ref.16

Modified residue

280

1

Phosphotyrosine; by SRC Ref.15

Modified residue

334

1

Phosphotyrosine; by SRC Ref.15

Modified residue

412

1

Phosphothreonine; by PDPK1 Probable

Modified residue

564

1

Phosphothreonine Ref.36 Ref.39

Natural variations

Natural variant

118

1

P → L in a metastatic melanoma sample; somatic mutation. Ref.40

VAR_042322

Natural variant

130

1

R → C. Ref.40

VAR_042323

Experimental info

Mutagenesis

29

1

K → A: No effect on interaction with SQSTM1. Ref.37

Mutagenesis

72

1

D → A: Loss of interaction with ECT2, PARD6A and with SQSTM1. Ref.30 Ref.37 Ref.38

Mutagenesis

85

1

E → A: Slight decrease of interaction with PARD6A. Loss of interaction with PARD6A; when associated with A-91. Ref.38

Mutagenesis

91

1

R → A: Slight decrease of interaction with PARD6A. Loss of interaction with PARD6A; when associated with A-85. Ref.38

Mutagenesis

265

1

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. Ref.15 Ref.16

Mutagenesis

274

1

K → R: No effect on activity. Ref.10

Mutagenesis

274

1

K → W: Abolishes activity. Ref.10

Mutagenesis

280

1

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. Ref.15

Mutagenesis

334

1

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. Ref.15

Sequence conflict

485

1

L → M in AAH22016. Ref.4

Sequence conflict

508

1

H → L in AAH22016. Ref.4

Sequence conflict

560

1

P → R in AAH22016. Ref.4

Secondary structure

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596

Helix Strand Turn

Details...

Beta strand

26 – 32

7

Beta strand

35 – 41

7

Helix

47 – 57

11

Beta strand

67 – 71

5

Beta strand

73 – 75

3

Beta strand

77 – 79

3

Helix

83 – 95

13

Beta strand

101 – 106

6

Helix

251 – 253

3

Beta strand

254 – 262

9

Beta strand

264 – 273

10

Turn

274 – 277

4

Beta strand

278 – 286

9

Helix

287 – 289

3

Helix

293 – 308

16

Turn

309 – 311

3

Beta strand

318 – 323

6

Beta strand

325 – 332

8

Helix

340 – 347

8

Helix

352 – 371

20

Helix

381 – 383

3

Beta strand

384 – 386

3

Beta strand

392 – 394

3

Helix

397 – 399

3

Helix

417 – 419

3

Helix

422 – 425

4

Helix

433 – 448

16

Turn

452 – 457

6

Helix

467 – 476

10

Helix

487 – 496

10

Turn

501 – 503

3

Turn

505 – 507

3

Turn

509 – 511

3

Helix

512 – 517

6

Helix

520 – 522

3

Helix

527 – 531

5

Turn

545 – 547

3

Helix

549 – 551

3

Helix

554 – 557

4

Helix

568 – 571

4

Helix

576 – 579

4

Sequences

	Sequence		Length	Mass (Da)
	P41743 [UniParc]. Last modified June 16, 2009. Version 2. Checksum: 1E3F8C1D4BFC734F	FASTA	596	68,262
	10 20 30 40 50 60 MPTQRDSSTM SHTVAGGGSG DHSHQVRVKA YYRGDIMITH FEPSISFEGL CNEVRDMCSF 70 80 90 100 110 120 DNEQLFTMKW IDEEGDPCTV SSQLELEEAF RLYELNKDSE LLIHVFPCVP ERPGMPCPGE 130 140 150 160 170 180 DKSIYRRGAR RWRKLYCANG HTFQAKRFNR RAHCAICTDR IWGLGRQGYK CINCKLLVHK 190 200 210 220 230 240 KCHKLVTIEC GRHSLPQEPV MPMDQSSMHS DHAQTVIPYN 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

References

	« Hide 'large scale' referencesShow '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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Teratocarcinoma.
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[5]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SMG1, ENZYME REGULATION.
[6]	"Atypical protein kinase C iota protects human leukemia cells against drug-induced apoptosis." Murray N.R., Fields A.P. J. Biol. Chem. 272:27521-27524(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL SURVIVAL.
[7]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SQSTM1, SUBCELLULAR LOCATION.
[8]	"Overexpression of atypical PKC in PC12 cells enhances NGF-responsiveness and survival through an NF-kappaB dependent pathway." Wooten M.W., Seibenhener M.L., Zhou G., Vandenplas M.L., Tan T.H. Cell Death Differ. 6:753-764(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL SURVIVAL.
[9]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SQSTM1 AND IKBKB, FUNCTION.
[10]	"Unique structural and functional properties of the ATP-binding domain of atypical protein kinase C-iota." Spitaler M., Villunger A., Grunicke H., Uberall F. J. Biol. Chem. 275:33289-33296(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF LYS-274.
[11]	"Protein kinase C iota protects neural cells against apoptosis induced by amyloid beta-peptide." Xie J., Guo Q., Zhu H., Wooten M.W., Mattson M.P. Brain Res. Mol. Brain Res. 82:107-113(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL SURVIVAL.
[12]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PARD6A; PARD6B AND PARD6G, SUBUNIT OF A COMPLEX CONTAINING PARD6B AND CDC42/RAC1.
[13]	"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., Hirose T., Manabe N., Mizuno K., Shimizu M., Akimoto K., Izumi Y., Ohnishi T., Ohno S. J. Cell Biol. 152:1183-1196(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PARD3 AND PARD6B IN THE TERNARY AKPC/PAR3/PAR6 COMPLEX.
[14]	"Glyceraldehyde-3-phosphate dehydrogenase is phosphorylated by protein kinase Ciota /lambda and plays a role in microtubule dynamics in the early secretory pathway." Tisdale E.J. J. Biol. Chem. 277:3334-3341(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH GAPDH.
[15]	"Nerve growth factor stimulates multisite tyrosine phosphorylation and activation of the atypical protein kinase C's via a src kinase pathway." Wooten M.W., Vandenplas M.L., Seibenhener M.L., Geetha T., Diaz-Meco M.T. Mol. Cell. Biol. 21:8414-8427(2001) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-265; TYR-280 AND TYR-334, MUTAGENESIS OF TYR-265; TYR-280 AND TYR-334.
[16]	"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: INTERACTION WITH KPNB1, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-265, MUTAGENESIS OF TYR-265.
[17]	"Centaurin-alpha(1) associates with and is phosphorylated by isoforms of protein kinase C." Zemlickova E., Dubois T., Kerai P., Clokie S., Cronshaw A.D., Wakefield R.I.D., Johannes F.-J., Aitken A. Biochem. Biophys. Res. Commun. 307:459-465(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ADAP1.
[18]	"Mammalian Lgl forms a protein complex with PAR-6 and aPKC independently of PAR-3 to regulate epithelial cell polarity." Yamanaka T., Horikoshi Y., Sugiyama Y., Ishiyama C., Suzuki A., Hirose T., Iwamatsu A., Shinohara A., Ohno S. Curr. Biol. 13:734-743(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PARD6B/PAR-6 AND LLGL1.
[19]	"Atypical protein kinase C plays a critical role in protein transport from pre-Golgi intermediates." Tisdale E.J., Wang J., Silver R.B., Artalejo C.R. J. Biol. Chem. 278:38015-38021(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[20]	"Rab2 interacts directly with atypical protein kinase C (aPKC) iota/lambda and inhibits aPKCiota/lambda-dependent glyceraldehyde-3-phosphate dehydrogenase phosphorylation." Tisdale E.J. J. Biol. Chem. 278:52524-52530(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RAB2A.
[21]	"Regulation of interleukin receptor-associated kinase (IRAK) phosphorylation and signaling by iota protein kinase C." Mamidipudi V., Lin C., Seibenhener M.L., Wooten M.W. J. Biol. Chem. 279:4161-4165(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF IRAK1.
[22]	"Atypical protein kinase Ciota plays a critical role in human lung cancer cell growth and tumorigenicity." Regala R.P., Weems C., Jamieson L., Copland J.A., Thompson E.A., Fields A.P. J. Biol. Chem. 280:31109-31115(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[23]	"Cyclin-dependent kinase activating kinase/Cdk7 co-localizes with PKC-iota in human glioma cells." Bicaku E., Patel R., Acevedo-Duncan M. Tissue Cell 37:53-58(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CDK7, SUBCELLULAR LOCATION.
[24]	"Src-dependent protein kinase C iota/lambda (aPKCiota/lambda) tyrosine phosphorylation is required for aPKCiota/lambda association with Rab2 and glyceraldehyde-3-phosphate dehydrogenase on pre-Golgi intermediates." Tisdale E.J., Artalejo C.R. J. Biol. Chem. 281:8436-8442(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RAB2A AND GADPH, PHOSPHORYLATION, SUBCELLULAR LOCATION.
[25]	"Atypical protein kinase C (iota) activates ezrin in the apical domain of intestinal epithelial cells." Wald F.A., Oriolo A.S., Mashukova A., Fregien N.L., Langshaw A.H., Salas P.J. J. Cell Sci. 121:644-654(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF EZR.
[26]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[27]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[28]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[29]	"Protein kinase C iota mediates lipid-induced apoptosis of human coronary artery endothelial cells." Staiger K., Schatz U., Staiger H., Weyrich P., Haas C., Guirguis A., Machicao F., Haering H.U., Kellerer M. Microvasc. Res. 78:40-44(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN APOPTOSIS.
[30]	"Ect2 links the PKCiota-Par6alpha complex to Rac1 activation and cellular transformation." Justilien V., Fields A.P. Oncogene 28:3597-3607(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ECT2 AND PARD6A, MUTAGENESIS OF ASP-72.
[31]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[32]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT PRO-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-3; SER-7; SER-8 AND THR-9, MASS SPECTROMETRY, CLEAVAGE OF INITIATOR METHIONINE. Tissue: Cervix carcinoma.
[33]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[34]	"PKC-? promotes glioblastoma cell survival by phosphorylating and inhibiting BAD through a phosphatidylinositol 3-kinase pathway." Desai S., Pillai P., Win-Piazza H., Acevedo-Duncan M. Biochim. Biophys. Acta 1813:1190-1197(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF BAD.
[35]	"Oncogenic activity of Ect2 is regulated through protein kinase C iota-mediated phosphorylation." Justilien V., Jameison L., Der C.J., Rossman K.L., Fields A.P. J. Biol. Chem. 286:8149-8157(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF ECT2.
[36]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-564, MASS SPECTROMETRY.
[37]	"Solution structure of atypical protein kinase C PB1 domain and its mode of interaction with ZIP/p62 and MEK5." Hirano Y., Yoshinaga S., Ogura K., Yokochi M., Noda Y., Sumimoto H., Inagaki F. J. Biol. Chem. 279:31883-31890(2004) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 25-108, INTERACTION WITH SQSTM1 AND MAP2K5, MUTAGENESIS OF LYS-29 AND ASP-72.
[38]	"Structure of a cell polarity regulator, a complex between atypical PKC and Par6 PB1 domains." Hirano Y., Yoshinaga S., Takeya R., Suzuki N.N., Horiuchi M., Kohjima M., Sumimoto H., Inagaki F. J. Biol. Chem. 280:9653-9661(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 25-108 IN COMPLEX WITH PARD6A, MUTAGENESIS OF ASP-72; GLU-85 AND ARG-91.
[39]	"Crystal structure of the catalytic domain of human atypical protein kinase C-iota reveals interaction mode of phosphorylation site in turn motif." Messerschmidt A., Macieira S., Velarde M., Baedeker M., Benda C., Jestel A., Brandstetter H., Neuefeind T., Blaesse M. J. Mol. Biol. 352:918-931(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 233-596, IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION AT THR-412 AND THR-564.
[40]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-118 AND CYS-130.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00016639.

PIR

A49509.

RefSeq

NP_002731.4. NM_002740.5.

UniGene

Hs.478199.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1VD2	NMR	-	A	25-108	[»]
1WMH	X-ray	1.50	A	25-108	[»]
1ZRZ	X-ray	3.00	A	233-596	[»]
3A8W	X-ray	2.10	A/B	249-588	[»]
3A8X	X-ray	2.00	A/B	249-588	[»]
3ZH8	X-ray	2.74	A/B/C	248-594	[»]

ProteinModelPortal

P41743.

ModBase

Search...

Protein-protein interaction databases

IntAct

P41743. 33 interactions.

MINT

MINT-5004219.

STRING

9606.ENSP00000295797.

PTM databases

PhosphoSite

P41743.

Polymorphism databases

DMDM

239938658.

Proteomic databases

PaxDb

P41743.

PRIDE

P41743.

Protocols and materials databases

DNASU

5584.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000295797; ENSP00000295797; ENSG00000163558.

GeneID

5584.

KEGG

hsa:5584.

UCSC

uc003fgs.2. human.

Organism-specific databases

CTD

5584.

GeneCards

GC03P169940.

HGNC

HGNC:9404. PRKCI.

HPA

HPA026574.

MIM

600539. gene.

neXtProt

NX_P41743.

PharmGKB

PA33768.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000233033.

HOVERGEN

HBG108317.

InParanoid

P41743.

KO

K06069.

OMA

RVKAYYK.

OrthoDB

EOG4T782V.

Enzyme and pathway databases

BRENDA

2.7.11.13. 2681.

Pathway_Interaction_DB

il1pathway. IL1-mediated signaling events.
insulin_pathway. Insulin Pathway.
insulin_glucose_pathway. Insulin-mediated glucose transport.
trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.
p75ntrpathway. p75(NTR)-mediated signaling.
tnfpathway. TNF receptor signaling pathway.

Reactome

REACT_111102. Signal Transduction.
REACT_111155. Cell-Cell communication.

Gene expression databases

Bgee

P41743.

CleanEx

HS_PRKCI.

Genevestigator

P41743.

Family and domain databases

InterPro

IPR000961. 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_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF00130. C1_1. 1 hit.
PF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]

PIRSF

PIRSF000554. PKC_zeta. 1 hit.

PRINTS

PR00008. DAGPEDOMAIN.

SMART

SM00109. C1. 1 hit.
SM00666. PB1. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS51285. 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]

ProtoNet

Search...

Other

BindingDB

P41743.

ChEMBL

CHEMBL2598.

ChiTaRS

PRKCI. human.

EvolutionaryTrace

P41743.

GenomeRNAi

5584.

NextBio

21656.

SOURCE

Search...

Entry information

Entry name

KPCI_HUMAN

Accession

Primary (citable) accession number: P41743
Secondary accession number(s): D3DNQ4, Q8WW06

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	June 16, 2009
Last modified:	May 1, 2013
This is version 149 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.