F1M7Y5 (KPCI_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified May 14, 2014. Version 31. History...
Names and origin
|Protein names||Recommended name:|
Protein kinase C iota type
Atypical protein kinase C-lambda/iota
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||596 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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.
ATP + a protein = ADP + a phosphoprotein.
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.
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.
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
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.
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
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 annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed By similarity|
|Chain||2 – 596||595||Protein kinase C iota type||PRO_0000414090|
|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|
|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|
|Mutagenesis||265||1||Y → F: Loss of phosphorylation and nuclear import. Ref.3|
|Sequence conflict||171||1||C → R in ACA66272. Ref.2|
|||"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. Collins F.S.
Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], IDENTIFICATION.
Strain: Brown Norway.
|||"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.
|||"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.|
|EU517502 mRNA. Translation: ACA66272.1.|
|RefSeq||NP_114448.1. NM_032059.1. |
3D structure databases
Protein-protein interaction databases
|IntAct||F1M7Y5. 2 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSRNOT00000012924; ENSRNOP00000012924; ENSRNOG00000009652. |
|UCSC||RGD:620961. rat. |
|RGD||620961. Prkci. |
Family and domain databases
|InterPro||IPR000961. AGC-kinase_C. |
|PANTHER||PTHR24357:SF60. PTHR24357:SF60. 1 hit. |
|Pfam||PF00130. C1_1. 1 hit. |
PF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
|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.
|SUPFAM||SSF56112. SSF56112. 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.
|Accession||Primary (citable) accession number: F1M7Y5|
Secondary accession number(s): B1PZT8
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families