Q62074 (KPCI_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified November 13, 2013. Version 147. History...
Names and origin
|Protein names||Recommended name:|
Protein kinase C iota type
Atypical protein kinase C-lambda/iota
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||595 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 By similarity. 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. Ref.3 Ref.6 Ref.7 Ref.8 Ref.9
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-411 (activation loop of the kinase domain) and Thr-563 (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.
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. Ref.4 Ref.5
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.
The OPR domain mediates interaction with SQSTM1.
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.
Upon neuronal growth factor (NGF) stimulation, phosphorylated by SRC at Tyr-264, Tyr-279 and Tyr-333. 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. Phosphorylation at Thr-411 in the activation loop is not mandatory for activation. Ref.11
Embryonic lethal at 9.5 dpc. Ref.7
Contains 1 AGC-kinase C-terminal domain.
Contains 1 OPR domain.
Contains 1 phorbol-ester/DAG-type zinc finger.
Contains 1 protein kinase domain.
The sequence AAH21630.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.
The sequence BAA32499.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed By similarity|
|Chain||2 – 595||594||Protein kinase C iota type||PRO_0000055711|
|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||2 – 252||251||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|
|Active site||377||1||Proton acceptor By similarity|
|Binding site||282||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||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; alternate Ref.10|
|Modified residue||411||1||Phosphothreonine; by PDPK1; alternate By similarity|
|Modified residue||563||1||Phosphothreonine Ref.11|
|Mutagenesis||27||1||R → A: No effect on interaction with SQSTM1. Ref.5|
|Mutagenesis||28||1||V → A: No effect on interaction with SQSTM1; when associated with A-29. Ref.5|
|Mutagenesis||29||1||K → A: No effect on interaction with SQSTM1; when associated with A-118. Ref.5|
|Mutagenesis||70||1||W → A: Loss of interaction with SQSTM1. Ref.5|
|Mutagenesis||72||1||D → A: Loss of interaction with SQSTM1. Ref.5|
|Mutagenesis||74||1||E → A: Loss of interaction with SQSTM1. Ref.5|
|Mutagenesis||76||1||D → A: Loss of interaction with SQSTM1. Ref.5|
|Mutagenesis||83||1||Q → A: No effect on interaction with SQSTM1. Ref.5|
|Mutagenesis||85||1||E → A: Loss of interaction with SQSTM1. Ref.5|
Helix Strand Turn
|Helix||250 – 252||3|
|Beta strand||253 – 261||9|
|Beta strand||263 – 272||10|
|Turn||273 – 275||3|
|Beta strand||278 – 285||8|
|Helix||286 – 288||3|
|Helix||297 – 308||12|
|Beta strand||317 – 322||6|
|Beta strand||324 – 332||9|
|Helix||339 – 346||8|
|Helix||351 – 370||20|
|Helix||380 – 382||3|
|Beta strand||383 – 385||3|
|Beta strand||391 – 393||3|
|Helix||416 – 418||3|
|Helix||421 – 424||4|
|Helix||432 – 447||16|
|Turn||453 – 456||4|
|Helix||466 – 475||10|
|Helix||486 – 495||10|
|Turn||500 – 502||3|
|Turn||508 – 510||3|
|Helix||511 – 517||7|
|Turn||519 – 523||5|
|Helix||526 – 530||5|
|Helix||548 – 550||3|
|Helix||553 – 556||4|
|Helix||567 – 570||4|
|Helix||575 – 578||4|
|||"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"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].
|||"Evidence that atypical protein kinase C-lambda and atypical protein kinase C-zeta participate in Ras-mediated reorganization of the F-actin cytoskeleton."|
Uberall F., Hellbert K., Kampfer S., Maly K., Villunger A., Spitaler M., Mwanjewe J., Baier-Bitterlich G., Baier G., Grunicke H.H.
J. Cell Biol. 144:413-425(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"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] [Europe PMC] [Abstract]
Cited for: SUBUNIT OF A COMPLEX CONTAINING PARD6B; PARD3 AND CDC42.
|||"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] [Europe PMC] [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.
|||"Insulin-induced GLUT4 translocation involves protein kinase C-lambda-mediated functional coupling between Rab4 and the motor protein kinesin."|
Imamura T., Huang J., Usui I., Satoh H., Bever J., Olefsky J.M.
Mol. Cell. Biol. 23:4892-4900(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"Targeted deletion of protein kinase C lambda reveals a distribution of functions between the two atypical protein kinase C isoforms."|
Soloff R.S., Katayama C., Lin M.Y., Feramisco J.R., Hedrick S.M.
J. Immunol. 173:3250-3260(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
|||"Protein kinase C-lambda knockout in embryonic stem cells and adipocytes impairs insulin-stimulated glucose transport."|
Bandyopadhyay G., Standaert M.L., Sajan M.P., Kanoh Y., Miura A., Braun U., Kruse F., Leitges M., Farese R.V.
Mol. Endocrinol. 18:373-383(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"Function of atypical protein kinase C lambda in differentiating photoreceptors is required for proper lamination of mouse retina."|
Koike C., Nishida A., Akimoto K., Nakaya M.A., Noda T., Ohno S., Furukawa T.
J. Neurosci. 25:10290-10298(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"Large-scale phosphorylation analysis of mouse liver."|
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-411, MASS SPECTROMETRY.
|||"Substrate recognition mechanism of atypical protein kinase Cs revealed by the structure of PKCiota in complex with a substrate peptide from Par-3."|
Wang C., Shang Y., Yu J., Zhang M.
Structure 20:791-801(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 231-595 IN COMPLEX WITH RAT PARD3 PEPTIDE, PHOSPHORYLATION AT THR-563, PSEUDOSUBSTRATE MOTIF.
|+||Additional computationally mapped references.|
|D28577 mRNA. Translation: BAA32499.1. Different initiation.|
BC021630 mRNA. Translation: AAH21630.1. Different initiation.
|RefSeq||NP_032883.2. NM_008857.3. |
3D structure databases
|SMR||Q62074. Positions 25-107, 138-190, 248-587. |
Protein-protein interaction databases
|IntAct||Q62074. 2 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000108249; ENSMUSP00000103884; ENSMUSG00000037643. |
|UCSC||uc008ovs.1. mouse. |
|MGI||MGI:99260. Prkci. |
Enzyme and pathway databases
|BRENDA||220.127.116.11. 3474. |
Gene expression databases
Family and domain databases
|InterPro||IPR000961. AGC-kinase_C. |
|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: Q62074|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
|Human and mouse protein kinases|
Human and mouse protein kinases: classification and index
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
Index of Protein Data Bank (PDB) cross-references
Index of protein domains and families