F1M7Y5 (KPCI_RAT) 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=aPKC-lambda/iota
nPKC-iota

Gene names

Name:	Prkci
Synonyms:	Pkcl

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

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. 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 component	Cytoplasm Endosome Membrane Nucleus
Disease	Proto-oncogene Tumor suppressor
Domain	Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Developmental protein Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Golgi vesicle budding Inferred from direct assay PubMed 12871960. Source: RGD actin filament organization Inferred from electronic annotation. Source: Compara cell migration Inferred from mutant phenotype PubMed 19885391. Source: RGD cell-cell junction organization Inferred from electronic annotation. Source: Compara 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: Compara 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 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: Compara positive regulation of glial cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of glucose import Inferred from electronic annotation. Source: Compara positive regulation of neuron projection development Inferred from sequence or structural similarity. Source: UniProtKB response to interleukin-1 Inferred from mutant phenotype PubMed 19782155. Source: RGD
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 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_function	ATP binding Inferred from direct assay PubMed 19885391. Source: RGD phospholipid binding Inferred from electronic annotation. Source: Compara protein kinase C activity Inferred from direct assay PubMed 19885391. Source: RGD zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 596	595	Protein kinase C iota type		PRO_0000414090
Regions
	Domain	26 – 107	82	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 By similarity
	Region	2 – 28	27	Required for interaction with RAB2 By similarity
	Region	72 – 91	20	Interaction with PARD6A By similarity
	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 By similarity
	Modified residue	3	1	Phosphothreonine By similarity
	Modified residue	7	1	Phosphoserine By similarity
	Modified residue	8	1	Phosphoserine By similarity
	Modified residue	9	1	Phosphothreonine By similarity
	Modified residue	265	1	Phosphotyrosine; by SRC Ref.3
	Modified residue	280	1	Phosphotyrosine; by SRC By similarity
	Modified residue	334	1	Phosphotyrosine; by SRC By similarity
	Modified residue	412	1	Phosphothreonine; by PDPK1 By similarity
	Modified residue	564	1	Phosphothreonine By similarity
Experimental info
	Mutagenesis	265	1	Y → F: Loss of phosphorylation and nuclear import. Ref.3
	Sequence conflict	171	1	C → R in ACA66272. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	F1M7Y5 [UniParc]. Last modified May 3, 2011. Version 1. Checksum: 60035F56E7547C57	FASTA	596	68,276
	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

References

	« Hide 'large scale' referencesShow '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. , 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.
IPI	IPI00914259.
RefSeq	NP_114448.1. NM_032059.1.
UniGene	Rn.1388.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000012924.
Proteomic databases
PRIDE	F1M7Y5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000012924; ENSRNOP00000012924; ENSRNOG00000009652.
GeneID	84006.
KEGG	rno:84006.
UCSC	RGD:620961. rat.
Organism-specific databases
CTD	5584.
RGD	620961. Prkci.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00700000104096.
HOGENOM	HOG000233033.
HOVERGEN	HBG108317.
KO	K06069.
OrthoDB	EOG4T782V.
Gene expression databases
ArrayExpress	F1M7Y5.
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
NextBio	616517.

Entry information

Entry name

KPCI_RAT

Accession

Primary (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:	April 3, 2013
This is version 22 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program