Q5R4K9 (KPCI_PONAB) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein kinase C iota type
EC=2.7.11.13

Alternative name(s):
nPKC-iota

Gene names

Name:

PRKCI

Organism

Pongo abelii (Sumatran orangutan)

Taxonomic identifier

9601 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	596 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript 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 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 By similarity. Might also be a target for novel lipid activators that are elevated during nutrient-stimulated insulin secretion.
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). Interacts with PARD6A By similarity.
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 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 By similarity.
Domain	The OPR domain mediates interaction with SQSTM1 By similarity. The C1 domain does not bind diacylglycerol (DAG) By similarity.
Post-translational modification	On neuronal growth factor (NGF) stimulation, phosphorylated by SRC on Tyr-265, Tyr-280 and Tyr-334. Phosphorylation on 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 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.
Sequence caution	The sequence CAH93307.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

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	intracellular signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	endosome Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase C activity Inferred from electronic annotation. Source: EC 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
	Chain	1 – 596	596	Protein kinase C iota type		PRO_0000055712
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	1 – 253	253	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	378	1	Proton acceptor By similarity
	Binding site	283	1	ATP By similarity
Amino acid modifications
	Modified residue	265	1	Phosphotyrosine; by SRC By similarity
	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 Probable

Sequences

	Sequence		Length	Mass (Da)
	Q5R4K9 [UniParc]. Last modified June 16, 2009. Version 2. Checksum: C514AC89C2D59EA2	FASTA	596	68,263
	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 GRHSLPPEPM 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

[1]	The German cDNA consortium Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain cortex.

Cross-references

Sequence databases
EMBL GenBank DDBJ	CR861237 mRNA. Translation: CAH93307.1. Different initiation.
RefSeq	NP_001126946.1. NM_001133474.1.
UniGene	Pab.1649.
3D structure databases
ProteinModelPortal	Q5R4K9.
ModBase	Search...
Proteomic databases
PRIDE	Q5R4K9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	100173964.
KEGG	pon:100173964.
Organism-specific databases
CTD	5584.
Phylogenomic databases
HOVERGEN	HBG108317.
InParanoid	Q5R4K9.
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. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view]
KO	K06069.
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...

Entry information

Entry name

KPCI_PONAB

Accession

Primary (citable) accession number: Q5R4K9

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 21, 2005
Last sequence update:	June 16, 2009
Last modified:	December 14, 2011
This is version 61 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program