Reviewed, UniProtKB/Swiss-Prot Q62074 (KPCI_MOUSE)

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

Gene names

Name:	Prkci
Synonyms:	Pkcl

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	595 AA.
Sequence status	Complete.
Protein existence	Evidence 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 RAB2A and GAPDH and recruitment to vesicular tubular clusters (VTCs) By similarity.
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-411 (activation loop of the kinase domain) and Thr-563 (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 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) By similarity. Ref.3 Ref.4
Subcellular location	Cytoplasm By similarity. Membrane By similarity. Endosome By similarity. Nucleus By similarity. 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 RAB2A By similarity.
Domain	The OPR domain mediates interaction with SQSTM1. The C1 domain does not bind diacylglycerol (DAG) By similarity.
Post-translational modification	On neuronal growth factor (NGF) stimulation, phosphorylated on tyrosine residues by Src. Phosphorylation on Tyr-264 facilitates binding to KPNB1/importin-beta regulating entry of PRKCI into the nucleus. Phosphorylation on Tyr-333 is important for NF-kappa-B stimulation By similarity.
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 component	Cytoplasm Endosome Membrane Nucleus
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	Phosphoprotein
Gene Ontology (GO)
Biological process	actin filament organization Inferred from mutant phenotype. Source: MGI cell-cell junction organization Inferred from sequence or structural similarity. Source: UniProtKB cellular response to insulin stimulus Inferred from mutant phenotype. Source: UniProtKB establishment of apical/basal cell polarity Inferred from mutant phenotype. Source: MGI eye photoreceptor cell development Inferred from mutant phenotype. Source: MGI intracellular signaling cascade Inferred from electronic annotation. Source: InterPro positive regulation of establishment of protein localization in plasma membrane Inferred from mutant phenotype. Source: UniProtKB positive regulation of glucose import Inferred from mutant phenotype. Source: UniProtKB protein amino acid phosphorylation Inferred from direct assay. Source: UniProtKB
Cellular component	apical plasma membrane Inferred from direct assay. Source: MGI 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
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW phospholipid binding Inferred from sequence or structural similarity. Source: UniProtKB protein kinase C activity Inferred from direct assay. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 595	595	Protein kinase C iota type		PRO_0000055711
Regions
	Domain	25 – 108	84	OPR
	Domain	253 – 521	269	Protein kinase
	Domain	522 – 595	74	AGC-kinase C-terminal
	Zinc finger	140 – 190	51	Phorbol-ester/DAG-type
	Nucleotide binding	259 – 267	9	ATP By similarity
	Region	1 – 252	252	Regulatory domain By similarity
	Region	1 – 28	28	Required for interaction with RAB2 By similarity
	Region	72 – 91	20	Interaction with PARD6A By similarity
Sites
	Active site	377	1	Proton acceptor By similarity
	Binding site	282	1	ATP By similarity
Amino acid modifications
	Modified residue	264	1	Phosphotyrosine; by Src By similarity
	Modified residue	279	1	Phosphotyrosine; by Src By similarity
	Modified residue	333	1	Phosphotyrosine; by Src By similarity
	Modified residue	411	1	Phosphothreonine Probable
	Modified residue	563	1	Phosphothreonine Probable
Experimental info
	Mutagenesis	27	1	R → A: No effect on interaction with SQSTM1. Ref.4
	Mutagenesis	28	1	V → A: No effect on interaction with SQSTM1; when associated with A-29. Ref.4
	Mutagenesis	29	1	K → A: No effect on interaction with SQSTM1; when associated with A-118. Ref.4
	Mutagenesis	70	1	W → A: Loss of interaction with SQSTM1. Ref.4
	Mutagenesis	72	1	D → A: Loss of interaction with SQSTM1. Ref.4
	Mutagenesis	74	1	E → A: Loss of interaction with SQSTM1. Ref.4
	Mutagenesis	76	1	D → A: Loss of interaction with SQSTM1. Ref.4
	Mutagenesis	83	1	Q → A: No effect on interaction with SQSTM1. Ref.4
	Mutagenesis	85	1	E → A: Loss of interaction with SQSTM1. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q62074-1 [UniParc]. Last modified June 16, 2009. Version 3. Checksum: 6AC612D1E9264825	FASTA	595	68,203
	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 MPMDQTMHPD HTQTVIPYNP SSHESLDQVG EEKEAMNTRE 250 260 270 280 290 300 SGKASSSLGL QDFDLLRVIG RGSYAKVLLV RLKKTDRIYA MKVVKKELVN DDEDIDWVQT 310 320 330 340 350 360 EKHVFEQASN HPFLVGLHSC FQTESRLFFV IEYVNGGDLM FHMQRQRKLP EEHARFYSAE 370 380 390 400 410 420 ISLALNYLHE RGIIYRDLKL DNVLLDSEGH IKLTDYGMCK EGLRPGDTTS TFCGTPNYIA 430 440 450 460 470 480 PEILRGEDYG FSVDWWALGV LMFEMMAGRS PFDIVGSSDN PDQNTEDYLF QVILEKQIRI 490 500 510 520 530 540 PRSLSVKAAS VLKSFLNKDP KERLGCHPQT GFADIQGHPF FRNVDWDMME QKQVVPPFKP 550 560 570 580 590 NISGEFGLDN FDSQFTNEPV QLTPDDDDIV RKIDQSEFEG FEYINPLLMS AEECV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A new member of the third class in the protein kinase C family, PKC lambda, expressed dominantly in an undifferentiated mouse embryonal carcinoma cell line and also in many tissues and cells." Akimoto K., Mizuno K., Osada S., Hirai S., Tanuma S., Suzuki K., Ohno S. J. Biol. Chem. 269:12677-12683(1994) [PubMed: 7513693] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"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].
[3]	"The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42." Joberty G., Petersen C., Gao L., Macara I.G. Nat. Cell Biol. 2:531-539(2000) [PubMed: 10934474] [Abstract] Cited for: SUBUNIT OF A COMPLEX CONTAINING PARD6B; PARD3 AND CDC42.
[4]	"Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins." Lamark T., Perander M., Outzen H., Kristiansen K., Oevervatn A., Michaelsen E., Bjoerkoey G., Johansen T. J. Biol. Chem. 278:34568-34581(2003) [PubMed: 12813044] [Abstract] Cited for: INTERACTION WITH SQSTM1 AND MAP2K5, MUTAGENESIS OF ARG-27; VAL-28; LYS-29; TRP-70; ASP-72; GLU-74; ASP-76; GLN-83 AND GLU-85.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D28577 mRNA. Translation: BAA32499.1. Different initiation. BC021630 mRNA. Translation: AAH21630.1. Different initiation.
IPI	IPI00121084.
PIR	A53758.
RefSeq	NP_032883.2.
UniGene	Mm.291554
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q62074.
PTM databases
PhosphoSite	Q62074.
Proteomic databases
PRIDE	Q62074.
Genome annotation databases
Ensembl	ENSMUST00000046401; ENSMUSP00000041030; ENSMUSG00000037643; Mus musculus. [Genome view] ENSMUST00000108249; ENSMUSP00000103884; ENSMUSG00000037643; Mus musculus. [Genome view]
GeneID	18759.
KEGG	mmu:18759.
Organism-specific databases
CTD	18759.
MGI	MGI:99260. Prkci.
Phylogenomic databases
HOVERGEN	Q62074.
InParanoid	Q62074.
OMA	KGDIMIT.
OrthoDB	EOG93N9ZG.
Enzyme and pathway databases
BRENDA	2.7.11.13. 244.
Gene expression databases
ArrayExpress	Q62074.
Bgee	Q62074.
CleanEx	MM_PRKCI.
Genevestigator	Q62074.
GermOnline	ENSMUSG00000037643. Mus musculus.
Family and domain databases
InterPro	IPR000961. AGC-kinase_C. IPR020454. DAG/PE_bd. IPR011009. Kinase-like_dom. IPR000270. OPR_PB1. IPR015745. PKC. IPR012233. PKC_zeta. IPR017892. Pkinase_C. IPR002219. Prot_Kinase_C-like_PE/DAG_bd. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_prot_kinase-like_dom. IPR008271. Ser/Thr_prot_kinase_AS. IPR002290. Ser/Thr_prot_kinase_dom. [Graphical view]
PANTHER	PTHR22985:SF86. PKC. 1 hit.
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]
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 Resources
SOURCE	Search...

Entry information

Entry name

KPCI_MOUSE

Accession

Primary (citable) accession number: Q62074

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	June 16, 2009
Last modified:	January 19, 2010
This is version 109 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)