KPCI_PONAB
ID KPCI_PONAB Reviewed; 596 AA.
AC Q5R4K9;
DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 16-JUN-2009, sequence version 2.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Protein kinase C iota type;
DE EC=2.7.11.13;
DE AltName: Full=nPKC-iota;
GN Name=PRKCI;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Calcium- and diacylglycerol-independent serine/ threonine-
CC protein kinase that plays a general protective role against apoptotic
CC stimuli, is involved in NF-kappa-B activation, cell survival,
CC differentiation and polarity, and contributes to the regulation of
CC microtubule dynamics in the early secretory pathway. Is necessary for
CC BCR-ABL oncogene-mediated resistance to apoptotic drug in leukemia
CC cells, protecting leukemia cells against drug-induced apoptosis. In
CC cultured neurons, prevents amyloid beta protein-induced apoptosis by
CC interrupting cell death process at a very early step. In glioblastoma
CC cells, may function downstream of phosphatidylinositol 3-kinase
CC (PI(3)K) and PDPK1 in the promotion of cell survival by phosphorylating
CC and inhibiting the pro-apoptotic factor BAD. Can form a protein complex
CC in non-small cell lung cancer (NSCLC) cells with PARD6A and ECT2 and
CC regulate ECT2 oncogenic activity by phosphorylation, which in turn
CC promotes transformed growth and invasion. In response to nerve growth
CC factor (NGF), acts downstream of SRC to phosphorylate and activate
CC IRAK1, allowing the subsequent activation of NF-kappa-B and neuronal
CC cell survival. Functions in the organization of the apical domain in
CC epithelial cells by phosphorylating EZR. This step is crucial for
CC activation and normal distribution of EZR at the early stages of
CC intestinal epithelial cell differentiation. Forms a protein complex
CC with LLGL1 and PARD6B independently of PARD3 to regulate epithelial
CC cell polarity. Plays a role in microtubule dynamics in the early
CC secretory pathway through interaction with RAB2A and GAPDH and
CC recruitment to vesicular tubular clusters (VTCs). In human coronary
CC artery endothelial cells (HCAEC), is activated by saturated fatty acids
CC and mediates lipid-induced apoptosis (By similarity). Involved in early
CC synaptic long term potentiation phase in CA1 hippocampal cells and
CC short term memory formation (By similarity).
CC {ECO:0000250|UniProtKB:F1M7Y5, ECO:0000250|UniProtKB:P41743}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.13;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.13;
CC -!- ACTIVITY REGULATION: Atypical PKCs (PRKCI and PRKCZ) exhibit an
CC elevated basal enzymatic activity (that may be due to the interaction
CC with SMG1 or SQSTM1) and are not regulated by diacylglycerol,
CC phosphatidylserine, phorbol esters or calcium ions. Two specific sites,
CC Thr-412 (activation loop of the kinase domain) and Thr-564 (turn
CC motif), need to be phosphorylated for its full activation (By
CC similarity). Might also be a target for novel lipid activators that are
CC elevated during nutrient-stimulated insulin secretion. {ECO:0000250}.
CC -!- SUBUNIT: Forms a complex with SQSTM1 and MP2K5 (By similarity).
CC Interacts directly with SQSTM1 (Probable). Interacts with IKBKB.
CC Interacts with PARD6A, PARD6B and PARD6G. Part of a quaternary complex
CC containing aPKC, PARD3, a PARD6 protein (PARD6A, PARD6B or PARD6G) and
CC a GTPase protein (CDC42 or RAC1). Part of a complex with LLGL1 and
CC PARD6B. Interacts with ADAP1/CENTA1. Interaction with SMG1, through the
CC ZN-finger domain, activates the kinase activity. Interacts with CDK7.
CC Forms a complex with RAB2A and GAPDH involved in recruitment onto the
CC membrane of vesicular tubular clusters (VTCs). Interacts with ECT2
CC ('Thr-359' phosphorylated form). Interacts with VAMP2. Interacts with
CC WDFY2 (via WD repeats 1-3) (By similarity).
CC {ECO:0000250|UniProtKB:P41743, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P41743}.
CC Membrane {ECO:0000250|UniProtKB:P41743}. Endosome
CC {ECO:0000250|UniProtKB:P41743}. Nucleus {ECO:0000250|UniProtKB:P41743}.
CC Note=Transported into the endosome through interaction with SQSTM1/p62.
CC After phosphorylation by SRC, transported into the nucleus through
CC interaction with KPNB1. Colocalizes with CDK7 in the cytoplasm and
CC nucleus. Transported to vesicular tubular clusters (VTCs) through
CC interaction with RAB2A. {ECO:0000250|UniProtKB:P41743}.
CC -!- DOMAIN: The PB1 domain mediates interaction with SQSTM1. {ECO:0000250}.
CC -!- DOMAIN: The C1 zinc finger does not bind diacylglycerol (DAG).
CC {ECO:0000250}.
CC -!- DOMAIN: The pseudosubstrate motif resembles the sequence around sites
CC phosphorylated on target proteins, except the presence of a non-
CC phosphorylatable residue in place of Ser, it modulates activity by
CC competing with substrates. {ECO:0000250}.
CC -!- PTM: Phosphorylation at Thr-412 in the activation loop is not mandatory
CC for activation (By similarity). Upon neuronal growth factor (NGF)
CC stimulation, phosphorylated by SRC at Tyr-265, Tyr-280 and Tyr-334 (By
CC similarity). Phosphorylation at Tyr-265 facilitates binding to
CC KPNB1/importin-beta regulating entry of PRKCI into the nucleus (By
CC similarity). Phosphorylation on Tyr-334 is important for NF-kappa-B
CC stimulation (By similarity). Phosphorylated at Thr-564 during the
CC initial phase of long term potentiation (By similarity).
CC {ECO:0000250|UniProtKB:F1M7Y5, ECO:0000250|UniProtKB:P41743,
CC ECO:0000250|UniProtKB:Q62074}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. PKC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAH93307.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; CR861237; CAH93307.1; ALT_INIT; mRNA.
DR RefSeq; NP_001126946.1; NM_001133474.1.
DR AlphaFoldDB; Q5R4K9; -.
DR BMRB; Q5R4K9; -.
DR SMR; Q5R4K9; -.
DR STRING; 9601.ENSPPYP00000015972; -.
DR Ensembl; ENSPPYT00000016611; ENSPPYP00000015972; ENSPPYG00000014289.
DR GeneID; 100173964; -.
DR KEGG; pon:100173964; -.
DR CTD; 5584; -.
DR eggNOG; KOG0695; Eukaryota.
DR GeneTree; ENSGT00940000153497; -.
DR InParanoid; Q5R4K9; -.
DR OrthoDB; 614710at2759; -.
DR Proteomes; UP000001595; Chromosome 3.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0045171; C:intercellular bridge; IEA:Ensembl.
DR GO; GO:0015630; C:microtubule cytoskeleton; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0120157; C:PAR polarity complex; IEA:Ensembl.
DR GO; GO:0043220; C:Schmidt-Lanterman incisure; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004698; F:calcium-dependent protein kinase C activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005543; F:phospholipid binding; IEA:Ensembl.
DR GO; GO:0004672; F:protein kinase activity; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0007015; P:actin filament organization; IEA:Ensembl.
DR GO; GO:0045216; P:cell-cell junction organization; IEA:Ensembl.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl.
DR GO; GO:0035089; P:establishment of apical/basal cell polarity; IEA:Ensembl.
DR GO; GO:0045197; P:establishment or maintenance of epithelial cell apical/basal polarity; IEA:Ensembl.
DR GO; GO:0042462; P:eye photoreceptor cell development; IEA:Ensembl.
DR GO; GO:0034351; P:negative regulation of glial cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; ISS:UniProtKB.
DR GO; GO:0046326; P:positive regulation of glucose import; IEA:Ensembl.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IEA:Ensembl.
DR CDD; cd00029; C1; 1.
DR CDD; cd06404; PB1_aPKC; 1.
DR CDD; cd05618; STKc_aPKC_iota; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR034661; aPKC_iota.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR020454; DAG/PE-bd.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR034877; PB1_aPKC.
DR InterPro; IPR000270; PB1_dom.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR012233; PKC.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF00564; PB1; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR PIRSF; PIRSF000554; PKC_zeta; 1.
DR PRINTS; PR00008; DAGPEDOMAIN.
DR SMART; SM00109; C1; 1.
DR SMART; SM00666; PB1; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57889; SSF57889; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS51745; PB1; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 2: Evidence at transcript level;
KW Acetylation; ATP-binding; Cytoplasm; Endosome; Kinase; Membrane;
KW Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Proto-oncogene;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Tumor suppressor; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P41743"
FT CHAIN 2..596
FT /note="Protein kinase C iota type"
FT /id="PRO_0000055712"
FT DOMAIN 25..108
FT /note="PB1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01081"
FT DOMAIN 254..522
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 523..594
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT ZN_FING 140..190
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2..253
FT /note="Regulatory domain"
FT /evidence="ECO:0000250"
FT REGION 2..28
FT /note="Required for interaction with RAB2"
FT /evidence="ECO:0000250"
FT REGION 72..91
FT /note="Interaction with PARD6A"
FT /evidence="ECO:0000250"
FT REGION 221..246
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 125..134
FT /note="Pseudosubstrate"
FT /evidence="ECO:0000250"
FT COMPBIAS 1..18
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 378
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 260..268
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 283
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 2
FT /note="N-acetylproline"
FT /evidence="ECO:0000250|UniProtKB:P41743"
FT MOD_RES 3
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P41743"
FT MOD_RES 7
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P41743"
FT MOD_RES 8
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P41743"
FT MOD_RES 9
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P41743"
FT MOD_RES 265
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:P41743"
FT MOD_RES 280
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:P41743"
FT MOD_RES 334
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:P41743"
FT MOD_RES 412
FT /note="Phosphothreonine; by PDPK1"
FT /evidence="ECO:0000250|UniProtKB:P41743"
FT MOD_RES 564
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P41743"
SQ SEQUENCE 596 AA; 68263 MW; C514AC89C2D59EA2 CRC64;
MPTQRDSSTM SHTVAGGGSG DHSHQVRVKA YYRGDIMITH FEPSISFEGL CNEVRDMCSF
DNEQLFTMKW IDEEGDPCTV SSQLELEEAF RLYELNKDSE LLIHVFPCVP ERPGMPCPGE
DKSIYRRGAR RWRKLYCANG HTFQAKRFNR RAHCAICTDR IWGLGRQGYK CINCKLLVHK
KCHKLVTIEC GRHSLPPEPM MPMDQSSMHS DHAQTVIPYN PSSHESLDQV GEEKEAMNTR
ESGKASSSLG LQDFDLLRVI GRGSYAKVLL VRLKKTDRIY AMKVVKKELV NDDEDIDWVQ
TEKHVFEQAS NHPFLVGLHS CFQTESRLFF VIEYVNGGDL MFHMQRQRKL PEEHARFYSA
EISLALNYLH ERGIIYRDLK LDNVLLDSEG HIKLTDYGMC KEGLRPGDTT STFCGTPNYI
APEILRGEDY GFSVDWWALG VLMFEMMAGR SPFDIVGSSD NPDQNTEDYL FQVILEKQIR
IPRSLSVKAA SVLKSFLNKD PKERLGCHPQ TGFADIQGHP FFRNVDWDMM EQKQVVPPFK
PNISGEFGLD NFDSQFTNEP VQLTPDDDDI VRKIDQSEFE GFEYINPLLM SAEECV
