KPCA_RABIT
ID KPCA_RABIT Reviewed; 672 AA.
AC P10102;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Protein kinase C alpha type;
DE Short=PKC-A;
DE Short=PKC-alpha;
DE EC=2.7.11.13;
GN Name=PRKCA;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=3808073; DOI=10.1038/325161a0;
RA Ohno S., Kawasaki H., Imajoh S., Suzuki K., Inagaki M., Yokokura H.,
RA Sakoh T., Hidaka H.;
RT "Tissue-specific expression of three distinct types of rabbit protein
RT kinase C.";
RL Nature 325:161-166(1987).
RN [2]
RP REVIEW.
RX PubMed=3045562; DOI=10.1038/334661a0;
RA Nishizuka Y.;
RT "The molecular heterogeneity of protein kinase C and its implications for
RT cellular regulation.";
RL Nature 334:661-665(1988).
CC -!- FUNCTION: Calcium-activated, phospholipid- and diacylglycerol (DAG)-
CC dependent serine/threonine-protein kinase that is involved in positive
CC and negative regulation of cell proliferation, apoptosis,
CC differentiation, migration and adhesion, cardiac hypertrophy,
CC angiogenesis, platelet function and inflammation, by directly
CC phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or
CC activating signaling cascades involving MAPK1/3 (ERK1/2) and RAP1GAP.
CC Depending on the cell type, is involved in cell proliferation and cell
CC growth arrest by positive and negative regulation of the cell cycle.
CC Can promote cell growth by phosphorylating and activating RAF1, which
CC mediates the activation of the MAPK/ERK signaling cascade, and/or by
CC up-regulating CDKN1A, which facilitates active cyclin-dependent kinase
CC (CDK) complex formation. In cells stimulated by the phorbol ester PMA,
CC can trigger a cell cycle arrest program which is associated with the
CC accumulation of the hyper-phosphorylated growth-suppressive form of RB1
CC and induction of the CDK inhibitors CDKN1A and CDKN1B. Depending on the
CC cell type, exhibits anti-apoptotic function and protects cells from
CC apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, or
CC mediates anti-apoptotic action by phosphorylating BCL2. During
CC macrophage differentiation induced by macrophage colony-stimulating
CC factor (CSF1), is translocated to the nucleus and is associated with
CC macrophage development. After wounding, translocates from focal
CC contacts to lamellipodia and participates in the modulation of
CC desmosomal adhesion. Plays a role in cell motility by phosphorylating
CC CSPG4, which induces association of CSPG4 with extensive lamellipodia
CC at the cell periphery and polarization of the cell accompanied by
CC increases in cell motility. During chemokine-induced CD4(+) T cell
CC migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting
CC in its dissociation from LRCH1 and the activation of GTPase CDC42.
CC Negatively regulates myocardial contractility and positively regulates
CC angiogenesis, platelet aggregation and thrombus formation in arteries.
CC Mediates hypertrophic growth of neonatal cardiomyocytes, in part
CC through a MAPK1/3 (ERK1/2)-dependent signaling pathway, and upon PMA
CC treatment, is required to induce cardiomyocyte hypertrophy up to heart
CC failure and death, by increasing protein synthesis, protein-DNA ratio
CC and cell surface area. Regulates cardiomyocyte function by
CC phosphorylating cardiac troponin T (TNNT2/CTNT), which induces
CC significant reduction in actomyosin ATPase activity, myofilament
CC calcium sensitivity and myocardial contractility. In angiogenesis, is
CC required for full endothelial cell migration, adhesion to vitronectin
CC (VTN), and vascular endothelial growth factor A (VEGFA)-dependent
CC regulation of kinase activation and vascular tube formation. Involved
CC in the stabilization of VEGFA mRNA at post-transcriptional level and
CC mediates VEGFA-induced cell proliferation. In the regulation of
CC calcium-induced platelet aggregation, mediates signals from the
CC CD36/GP4 receptor for granule release, and activates the integrin
CC heterodimer ITGA2B-ITGB3 through the RAP1GAP pathway for adhesion.
CC During response to lipopolysaccharides (LPS), may regulate selective
CC LPS-induced macrophage functions involved in host defense and
CC inflammation. But in some inflammatory responses, may negatively
CC regulate NF-kappa-B-induced genes, through IL1A-dependent induction of
CC NF-kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O-
CC tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which
CC modulates EIF4G1 binding to MKNK1 and may be involved in the regulation
CC of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of
CC KIT activity. Phosphorylates ATF2 which promotes cooperation between
CC ATF2 and JUN, activating transcription. Phosphorylates SOCS2 at 'Ser-
CC 52' facilitating its ubiquitination and proteosomal degradation (By
CC similarity). {ECO:0000250|UniProtKB:P17252,
CC ECO:0000250|UniProtKB:P20444}.
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 -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC Note=Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2
CC domain. {ECO:0000250|UniProtKB:P05696};
CC -!- ACTIVITY REGULATION: Classical (or conventional) PKCs (PRKCA, PRKCB and
CC PRKCG) are activated by calcium and diacylglycerol (DAG) in the
CC presence of phosphatidylserine. Three specific sites; Thr-497
CC (activation loop of the kinase domain), Thr-638 (turn motif) and Ser-
CC 657 (hydrophobic region), need to be phosphorylated for its full
CC activation.
CC -!- SUBUNIT: Interacts with ADAP1/CENTA1, CSPG4 and PRKCABP. Binds to
CC CAVIN2 in the presence of phosphatidylserine. Interacts with PICK1 (via
CC PDZ domain). Interacts with TRIM41. Recruited in a circadian manner
CC into a nuclear complex which also includes BMAL1 and RACK1. Interacts
CC with PARD3 (By similarity). Interacts with SOCS2 (By similarity).
CC {ECO:0000250|UniProtKB:P05696, ECO:0000250|UniProtKB:P17252,
CC ECO:0000250|UniProtKB:P20444}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Mitochondrion
CC membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}.
CC Nucleus {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. PKC subfamily. {ECO:0000305}.
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DR EMBL; X04796; CAA28483.1; -; mRNA.
DR PIR; C26037; KIRBC.
DR RefSeq; NP_001095194.1; NM_001101724.1.
DR AlphaFoldDB; P10102; -.
DR SMR; P10102; -.
DR STRING; 9986.ENSOCUP00000025402; -.
DR SwissPalm; P10102; -.
DR PRIDE; P10102; -.
DR GeneID; 100037720; -.
DR KEGG; ocu:100037720; -.
DR CTD; 5578; -.
DR eggNOG; KOG0696; Eukaryota.
DR InParanoid; P10102; -.
DR OrthoDB; 614710at2759; -.
DR BRENDA; 2.7.11.13; 1749.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
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:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0034351; P:negative regulation of glial cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; ISS:UniProtKB.
DR GO; GO:0045785; P:positive regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR GO; GO:2000707; P:positive regulation of dense core granule biogenesis; ISS:UniProtKB.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; ISS:UniProtKB.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0031666; P:positive regulation of lipopolysaccharide-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0045651; P:positive regulation of macrophage differentiation; ISS:UniProtKB.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0090330; P:regulation of platelet aggregation; ISS:UniProtKB.
DR CDD; cd00029; C1; 2.
DR CDD; cd05615; STKc_cPKC_alpha; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR034663; cPKC_alpha.
DR InterPro; IPR020454; DAG/PE-bd.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR014375; Protein_kinase_C_a/b/g.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00130; C1_1; 2.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR PIRSF; PIRSF000550; PKC_alpha; 1.
DR PRINTS; PR00360; C2DOMAIN.
DR PRINTS; PR00008; DAGPEDOMAIN.
DR SMART; SM00109; C1; 2.
DR SMART; SM00239; C2; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57889; SSF57889; 2.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS50004; C2; 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; 2.
DR PROSITE; PS50081; ZF_DAG_PE_2; 2.
PE 2: Evidence at transcript level;
KW Acetylation; Angiogenesis; Apoptosis; ATP-binding; Calcium; Cell adhesion;
KW Cell membrane; Cytoplasm; Kinase; Membrane; Metal-binding; Mitochondrion;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P17252"
FT CHAIN 2..672
FT /note="Protein kinase C alpha type"
FT /id="PRO_0000055681"
FT DOMAIN 158..275
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 339..597
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 598..668
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT ZN_FING 36..86
FT /note="Phorbol-ester/DAG-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ZN_FING 101..151
FT /note="Phorbol-ester/DAG-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ACT_SITE 463
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 186
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 187
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 187
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 193
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 195
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-4,5-bisphosphate)"
FT /ligand_id="ChEBI:CHEBI:58456"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 245
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-4,5-bisphosphate)"
FT /ligand_id="ChEBI:CHEBI:58456"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 246
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 246
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 247
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 248
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 248
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 248
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 252
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 254
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 254
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 345..353
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 368
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P17252"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17252"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17252"
FT MOD_RES 319
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT MOD_RES 494
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04409"
FT MOD_RES 495
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04409"
FT MOD_RES 497
FT /note="Phosphothreonine; by PDPK1"
FT /evidence="ECO:0000250|UniProtKB:P04409"
FT MOD_RES 501
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P05771"
FT MOD_RES 628
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P17252"
FT MOD_RES 631
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P68403, ECO:0000255"
FT MOD_RES 638
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P17252"
FT MOD_RES 651
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17252"
FT MOD_RES 657
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P05771"
FT MOD_RES 658
FT /note="Phosphotyrosine; by SYK"
FT /evidence="ECO:0000250|UniProtKB:P20444"
SQ SEQUENCE 672 AA; 76782 MW; 3D311367D3577A77 CRC64;
MADVFPANDS TASQDVANRF ARKGALRQKN VHEVKDHKFI ARFFKQPTFC SHCTDFIWGF
GKQGFQCQVC CFVVHKRCHE FVTFSCPGAD KGPDTDDPRS KHKFKIHTYG SPTFCDHCGS
LLYGLIHQGM KCDTCDMNVH KQCVINVPSL CGMDHTEKRG RIYLKAEVTD EKLHVTVRDA
KNLIPMDPNG LSDPYVKLKL IPDPKNESKQ KTKTIRSTLN PQWNESFTFK LKPSDKDRRL
SVEIWDWDRT TRNDFMGSLS FGVSELMKMP ASGWYKLLNQ EEGEYYNVPI PEGDEDGNVE
LRQKFEKAKL GPAGNKVISP SEDRKQPSNN LDRVKLTDFN FLMVLGKGSF GKVMLADRKG
TEELYAIKIL KKDVVIQDDD VECTMVEKRV LALMDKPPFL TQLHSCFQTV DRLYFVMEYV
NGGDLMYHIQ QVGKFKEPQA VFYAAEISIG LFFLHKRGII YRDLKLDNVM LDSEGHIKIA
DFGMCKEHMM DGVTTRTFCG TPDYIAPEII AYQPYGKSVD WWAYGVLLYE MLAGQPPFDG
EDEDELFQSI MEHNVSYPKS LSKEAVSICK GLMTKHPAKR LGCGPEGERD VREHAFFRRI
DWEKLENREI QPPFKPKVCG KGAENFDKFF TRGQPVVTPP DQLVIANIDQ SDFEGFSYVN
PQFVHPILQS SV
