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Details on Person UniProt:P05126-1 PRKCB

Class:IdReferenceIsoform:804973
_chainChangeLoginitiator methionine:1 added on Fri February 6 2015;chain:2-671 added on Fri February 6 2015;initiator methionine:1 for 804973 removed on Fri Nov 03 2023;initiator methionine: for 804973 added on Fri Nov 03 2023;initiator methionine: for 804973 removed on Fri Aug 15 2025;initiator methionine:1 for 804973 added on Fri Aug 15 2025
_displayNameUniProt:P05126-1 PRKCB
_timestamp2026-02-20 21:50:25
chaininitiator methionine:1
chain:2-671
checksum1F31D6A9D3C4C61F
commentFUNCTION Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser-652'. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. Plays a direct role in the negative feedback regulation of the BCR signaling, by down-modulating BTK function via direct phosphorylation of BTK at 'Ser-180', which results in the alteration of BTK plasma membrane localization and in turn inhibition of BTK activity. Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A. In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1-MAPK/ERK signaling cascade. Participates in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Phosphorylates SLC2A1/GLUT1, promoting glucose uptake by SLC2A1/GLUT1. Under high glucose in pancreatic beta-cells, is probably involved in the inhibition of the insulin gene transcription, via regulation of MYC expression. In endothelial cells, activation of PRKCB induces increased phosphorylation of RB1, increased VEGFA-induced cell proliferation, and inhibits PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) regulation by insulin, which causes endothelial dysfunction. Also involved in triglyceride homeostasis. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription (By similarity). Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (By similarity). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (By similarity).FUNCTION Acts as an activator of ferroptosis by mediating phosphorylation and activation of ACSL4. Also stimulates ferroptosis propagation by catalyzing phosphorylation of FOXK1.CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)COFACTOR Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domain.ACTIVITY REGULATION Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-500 (activation loop of the kinase domain), Thr-642 (turn motif) and Ser-661 (hydrophobic region), need to be phosphorylated for its full activation. Specifically inhibited by enzastaurin (LY317615) (By similarity).SUBUNIT Interacts with PDK1. Interacts in vitro with PRKCBP1. Interacts with PHLPP1 and PHLPP2; both proteins mediate its dephosphorylation. Interacts with KDM1A/LSD1, PKN1 and ANDR (By similarity).SUBCELLULAR LOCATION Phosphorylation on Thr-500 within the activation loop renders it competent to autophosphorylate. Subsequent autophosphorylation of Thr-642 maintains catalytic competence, and autophosphorylation on Ser-661 appears to release the kinase into the cytosol. Autophosphorylation on other sites i.e. in the N-terminal and hinge regions have no effect on enzyme activity. Phosphorylation at Tyr-662 by SYK induces binding with GRB2 and contributes to the activation of MAPK/ERK signaling cascade (By similarity).SIMILARITY Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.
created[InstanceEdit:804972] Jupe, S, 2010-05-26
descriptionrecommendedName: Protein kinase C beta type shortName: PKC-B shortName: PKC-beta ecNumber evidence="2"2.7.11.13
geneNamePRKCB
PRKCB1
identifierP05126
isoformParent
isSequenceChangedFALSE
keywordAcetylation
Adaptive immunity
Alternative splicing
Apoptosis
ATP-binding
Calcium
Chromatin regulator
Cytoplasm
Immunity
Kinase
Membrane
Metal-binding
Nucleotide-binding
Nucleus
Phosphoprotein
Reference proteome
Repeat
Serine/threonine-protein kinase
Transcription
Transcription regulation
Transferase
Zinc
Zinc-finger
modified[InstanceEdit:937368] Yung, CK
[InstanceEdit:1042053] Yung, CK
[InstanceEdit:1220657] Yung, CK
[InstanceEdit:1300696] Yung, CK
[InstanceEdit:1301627] Yung, CK
[InstanceEdit:1551960] Weiser, JD
[InstanceEdit:1995863] Weiser, JD
[InstanceEdit:2132304] Weiser, JD
[InstanceEdit:2265580] Weiser, JD
[InstanceEdit:5433710] Weiser, JD
[InstanceEdit:5618415] Weiser, JD
[InstanceEdit:5634237] Weiser, JD
[InstanceEdit:5673015] Weiser, JD
[InstanceEdit:9037114] Weiser, JD
[InstanceEdit:9627708] Weiser, JD
[InstanceEdit:9637257] Weiser, JD
[InstanceEdit:9657908] Weiser, JD
[InstanceEdit:9676415] Weiser, JD
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
[InstanceEdit:9963647] Weiser, Joel, 2025-08-15
[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
namePRKCB
referenceDatabase[ReferenceDatabase:2] UniProt
secondaryIdentifierKPCB_BOVIN
A5D7N0
sequenceLength671
species[Species:48898] Bos taurus
variantIdentifierP05126-1
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No pathways have been reviewed or authored by UniProt:P05126-1 PRKCB (804973)