PK3CB_RAT
ID PK3CB_RAT Reviewed; 1070 AA.
AC Q9Z1L0;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform;
DE Short=PI3-kinase subunit beta;
DE Short=PI3K-beta;
DE Short=PI3Kbeta;
DE Short=PtdIns-3-kinase subunit beta;
DE EC=2.7.1.153 {ECO:0000250|UniProtKB:P42338};
DE AltName: Full=Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit beta;
DE Short=PtdIns-3-kinase subunit p110-beta;
DE Short=p110beta;
DE AltName: Full=Serine/threonine protein kinase PIK3CB {ECO:0000250|UniProtKB:P42338};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P42338};
GN Name=Pik3cb;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RA Mulder H., Stenson Holst L., Degerman E.;
RT "Phosphatidylinositol-3 kinase and activation of phosphodiesterase 3B in
RT adipocytes.";
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Phosphoinositide-3-kinase (PI3K) phosphorylates
CC phosphatidylinositol (PI) derivatives at position 3 of the inositol
CC ring to produce 3-phosphoinositides. Uses ATP and PtdIns(4,5)P2
CC (phosphatidylinositol 4,5-bisphosphate) to generate
CC phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role
CC by recruiting PH domain-containing proteins to the membrane, including
CC AKT1 and PDPK1, activating signaling cascades involved in cell growth,
CC survival, proliferation, motility and morphology. Involved in the
CC activation of AKT1 upon stimulation by G-protein coupled receptors
CC (GPCRs) ligands such as CXCL12, sphingosine 1-phosphate, and
CC lysophosphatidic acid. May also act downstream receptor tyrosine
CC kinases. Required in different signaling pathways for stable platelet
CC adhesion and aggregation. Plays a role in platelet activation signaling
CC triggered by GPCRs, alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) and ITAM
CC (immunoreceptor tyrosine-based activation motif)-bearing receptors such
CC as GP6. Regulates the strength of adhesion of ITGA2B/ ITGB3 activated
CC receptors necessary for the cellular transmission of contractile
CC forces. Required for platelet aggregation induced by F2 (thrombin) and
CC thromboxane A2 (TXA2). Has a role in cell survival. May have a role in
CC cell migration. Involved in the early stage of autophagosome formation.
CC Modulates the intracellular level of PtdIns3P (phosphatidylinositol 3-
CC phosphate) and activates PIK3C3 kinase activity. May act as a scaffold,
CC independently of its lipid kinase activity to positively regulate
CC autophagy. May have a role in insulin signaling as scaffolding protein
CC in which the lipid kinase activity is not required. May have a kinase-
CC independent function in regulating cell proliferation and in clathrin-
CC mediated endocytosis. Mediator of oncogenic signal in cell lines
CC lacking PTEN. The lipid kinase activity is necessary for its role in
CC oncogenic transformation. Required for the growth of ERBB2 and RAS
CC driven tumors. Has also a protein kinase activity showing
CC autophosphorylation. {ECO:0000250|UniProtKB:P42338}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-
CC bisphosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-3,4,5-trisphosphate) + ADP + H(+); Xref=Rhea:RHEA:21292,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57836,
CC ChEBI:CHEBI:58456, ChEBI:CHEBI:456216; EC=2.7.1.153;
CC Evidence={ECO:0000250|UniProtKB:P42338};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21293;
CC Evidence={ECO:0000250|UniProtKB:P42338};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-
CC 3-phospho-1D-myo-inositol 4,5-bisphosphate + ATP = 1-octadecanoyl-2-
CC (5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo-
CC inositol 3,4,5-triphosphate) + ADP + H(+); Xref=Rhea:RHEA:43396,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:77137,
CC ChEBI:CHEBI:83243, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:P42338};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43397;
CC Evidence={ECO:0000250|UniProtKB:P42338};
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=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:P42338};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000250|UniProtKB:P42338};
CC -!- PATHWAY: Phospholipid metabolism; phosphatidylinositol phosphate
CC biosynthesis. {ECO:0000250|UniProtKB:P42338}.
CC -!- SUBUNIT: Heterodimer of a catalytic subunit PIK3CB and a p85 regulatory
CC subunit (PIK3R1, PIK3R2 or PIK3R3). Interaction with PIK3R2 is required
CC for nuclear localization and nuclear export (By similarity). Part of a
CC complex with PIK3R1 and PTEN (By similarity). Binding to PTEN may
CC antagonize the lipid kinase activity under normal growth conditions (By
CC similarity). Part of a complex involved in autophagosome formation
CC composed of PIK3C3 and PIK3R4 (By similarity). Interacts with BECN1,
CC ATG14 and RAB5A (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=Interaction with PIK3R2 is required for nuclear localization and
CC export.
CC -!- DOMAIN: The inhibitory interactions with PIK3R1 are mediated by the
CC PI3K-ABD domain and the C2 PI3K-type domain with the iSH2 (inter-SH2)
CC region of PIK3R1; the C2 PI3K-type domain, the PI3K helical domain, and
CC the PI3K/PI4K kinase domain with the nSH2 (N-terminal SH2) region of
CC PIK3R1; and the PI3K/PI4K kinase domain with the cSH2 (C-terminal SH2)
CC region of PIK3R1. The inhibitory interaction between the PI3K-ABD
CC domain and the C2 PI3K-type domain with the iSH2 (inter-SH2) region of
CC PIK3R1 is weak. The nuclear localization signal (NLS) is required for
CC its function in cell survival (By similarity). {ECO:0000250}.
CC -!- PTM: Autophosphorylation at Ser-1070 negatively regulates the
CC phosphatidylinositol-4,5-bisphosphate 3-kinase activity.
CC {ECO:0000250|UniProtKB:P42338}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. {ECO:0000255|PROSITE-
CC ProRule:PRU00877, ECO:0000255|PROSITE-ProRule:PRU00879,
CC ECO:0000255|PROSITE-ProRule:PRU00880}.
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DR EMBL; AJ012482; CAA10046.1; -; mRNA.
DR RefSeq; NP_445933.1; NM_053481.2.
DR AlphaFoldDB; Q9Z1L0; -.
DR SMR; Q9Z1L0; -.
DR IntAct; Q9Z1L0; 9.
DR STRING; 10116.ENSRNOP00000022179; -.
DR BindingDB; Q9Z1L0; -.
DR ChEMBL; CHEMBL3608198; -.
DR iPTMnet; Q9Z1L0; -.
DR PhosphoSitePlus; Q9Z1L0; -.
DR PaxDb; Q9Z1L0; -.
DR PRIDE; Q9Z1L0; -.
DR GeneID; 85243; -.
DR KEGG; rno:85243; -.
DR UCSC; RGD:620917; rat.
DR CTD; 5291; -.
DR RGD; 620917; Pik3cb.
DR eggNOG; KOG0904; Eukaryota.
DR InParanoid; Q9Z1L0; -.
DR PhylomeDB; Q9Z1L0; -.
DR BRENDA; 2.7.1.153; 5301.
DR Reactome; R-RNO-109704; PI3K Cascade.
DR Reactome; R-RNO-112399; IRS-mediated signalling.
DR Reactome; R-RNO-114604; GPVI-mediated activation cascade.
DR Reactome; R-RNO-1257604; PIP3 activates AKT signaling.
DR Reactome; R-RNO-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-RNO-186763; Downstream signal transduction.
DR Reactome; R-RNO-198203; PI3K/AKT activation.
DR Reactome; R-RNO-201556; Signaling by ALK.
DR Reactome; R-RNO-202424; Downstream TCR signaling.
DR Reactome; R-RNO-2029485; Role of phospholipids in phagocytosis.
DR Reactome; R-RNO-210993; Tie2 Signaling.
DR Reactome; R-RNO-2424491; DAP12 signaling.
DR Reactome; R-RNO-2730905; Role of LAT2/NTAL/LAB on calcium mobilization.
DR Reactome; R-RNO-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-RNO-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling.
DR Reactome; R-RNO-5673001; RAF/MAP kinase cascade.
DR Reactome; R-RNO-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-RNO-8853659; RET signaling.
DR Reactome; R-RNO-9027276; Erythropoietin activates Phosphoinositide-3-kinase (PI3K).
DR Reactome; R-RNO-912526; Interleukin receptor SHC signaling.
DR Reactome; R-RNO-912631; Regulation of signaling by CBL.
DR UniPathway; UPA00220; -.
DR PRO; PR:Q9Z1L0; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0031526; C:brush border membrane; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; IDA:RGD.
DR GO; GO:0005943; C:phosphatidylinositol 3-kinase complex, class IA; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; IDA:RGD.
DR GO; GO:0035005; F:1-phosphatidylinositol-4-phosphate 3-kinase activity; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0043560; F:insulin receptor substrate binding; ISO:RGD.
DR GO; GO:0016301; F:kinase activity; ISO:RGD.
DR GO; GO:0035004; F:phosphatidylinositol 3-kinase activity; NAS:RGD.
DR GO; GO:0052742; F:phosphatidylinositol kinase activity; IBA:GO_Central.
DR GO; GO:0052812; F:phosphatidylinositol-3,4-bisphosphate 5-kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0046934; F:phosphatidylinositol-4,5-bisphosphate 3-kinase activity; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; ISS:UniProtKB.
DR GO; GO:0060055; P:angiogenesis involved in wound healing; ISO:RGD.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISO:RGD.
DR GO; GO:0040016; P:embryonic cleavage; ISO:RGD.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0001935; P:endothelial cell proliferation; ISO:RGD.
DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; ISO:RGD.
DR GO; GO:1903298; P:negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; ISO:RGD.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; ISO:RGD.
DR GO; GO:1903671; P:negative regulation of sprouting angiogenesis; ISO:RGD.
DR GO; GO:1900747; P:negative regulation of vascular endothelial growth factor signaling pathway; ISO:RGD.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; ISO:RGD.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IDA:RGD.
DR GO; GO:0036092; P:phosphatidylinositol-3-phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; ISO:RGD.
DR GO; GO:0030168; P:platelet activation; ISO:RGD.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0033031; P:positive regulation of neutrophil apoptotic process; ISO:RGD.
DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; ISO:RGD.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:RGD.
DR GO; GO:0035022; P:positive regulation of Rac protein signal transduction; ISO:RGD.
DR GO; GO:0001952; P:regulation of cell-matrix adhesion; ISO:RGD.
DR GO; GO:0002931; P:response to ischemia; ISO:RGD.
DR GO; GO:0009611; P:response to wounding; ISO:RGD.
DR GO; GO:0003376; P:sphingosine-1-phosphate receptor signaling pathway; ISO:RGD.
DR CDD; cd05173; PI3Kc_IA_beta; 1.
DR Gene3D; 1.10.1070.11; -; 1.
DR Gene3D; 1.25.40.70; -; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR InterPro; IPR036940; PI3/4_kinase_cat_sf.
DR InterPro; IPR018936; PI3/4_kinase_CS.
DR InterPro; IPR002420; PI3K-type_C2_dom.
DR InterPro; IPR003113; PI3K_ABD.
DR InterPro; IPR001263; PI3K_accessory_dom.
DR InterPro; IPR042236; PI3K_accessory_sf.
DR InterPro; IPR000341; PI3K_Ras-bd_dom.
DR InterPro; IPR037702; PI3Kbeta_dom.
DR InterPro; IPR015433; PI_Kinase.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR10048; PTHR10048; 1.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR Pfam; PF00792; PI3K_C2; 1.
DR Pfam; PF02192; PI3K_p85B; 1.
DR Pfam; PF00794; PI3K_rbd; 1.
DR Pfam; PF00613; PI3Ka; 1.
DR SMART; SM00142; PI3K_C2; 1.
DR SMART; SM00143; PI3K_p85B; 1.
DR SMART; SM00144; PI3K_rbd; 1.
DR SMART; SM00145; PI3Ka; 1.
DR SMART; SM00146; PI3Kc; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51547; C2_PI3K; 1.
DR PROSITE; PS00915; PI3_4_KINASE_1; 1.
DR PROSITE; PS00916; PI3_4_KINASE_2; 1.
DR PROSITE; PS50290; PI3_4_KINASE_3; 1.
DR PROSITE; PS51544; PI3K_ABD; 1.
DR PROSITE; PS51546; PI3K_RBD; 1.
DR PROSITE; PS51545; PIK_HELICAL; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Autophagy; Cell adhesion; Cytoplasm; Endocytosis; Kinase;
KW Lipid metabolism; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN 1..1070
FT /note="Phosphatidylinositol 4,5-bisphosphate 3-kinase
FT catalytic subunit beta isoform"
FT /id="PRO_0000088789"
FT DOMAIN 26..115
FT /note="PI3K-ABD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00877"
FT DOMAIN 194..285
FT /note="PI3K-RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00879"
FT DOMAIN 327..496
FT /note="C2 PI3K-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00880"
FT DOMAIN 524..701
FT /note="PIK helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00878"
FT DOMAIN 772..1053
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 778..784
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 916..924
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 935..961
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT MOTIF 410..418
FT /note="Nuclear localization signal (NLS)"
FT /evidence="ECO:0000250"
FT MOD_RES 324
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BTI9"
FT MOD_RES 1070
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P42338"
SQ SEQUENCE 1070 AA; 122608 MW; 4E8EB2333E96E4D5 CRC64;
MCFRSIMPPA MADTLDIWAV DSQIASDGSI SVDFLLPTGI YIQLEVPREA TISYIKQMLW
KQVHNYPMFN LLMDIDSYMF ACVNQTAVYE ELEDETRRLC DVRPFLPVLK LVTRSCDPAE
KLDSKIGVLI GKGLHEFDAL KDPEVNEFRR KMRKFSEDKI QSLVGLSWID WLKHTYPPEH
EPSVLENLED KLYGGKLVVA VHFENSQDVF SFQVSPNLNP IKINELAIQK RLTIRGKEEE
ASPCDYVLQV SGRVEYVFGD HPLIQFQYIR NCVMNRTLPH FILVECCKIK KMYEQEMIAI
EAAINRNSSS LPLPLPPKKT RVISHVWGNN NPFQIVLVKG NKLNTEETVK VHVRAGLFHG
TELLCKTVVS SEISGKNDHI WNEQLEFDIN ICDLPRMARL CFAVYAVLDK VKTKKSTKTI
NPSKYQTIRK AGKVHYPVAW VNTMVFDFKG QLRSGDVILH SWSSFPDELE EMLNPMGTVQ
TNPYAENATA LHIKFPENKK QPYYYPPFDK IIEKAAEIAS GDSANVSSRG GKKFLAVLKE
ILDRDPLSQL CENEMDLIWT LRQDCRENFP QSLPKLLLSI KWNKLEDVAQ LQALLQIWPK
LPPREALELL DFNYPDQYVR EYAVGCLRQM SDEELSQYLL QLVQVLKYEP FLDCALSRFL
LERALDNRRI GQFLFWHLRS EVHTPAVSIQ FGVILEAYCR GSVGHMKVLS KQVEALNKLK
TLNSLIKLNA MKLNRAKGKE AMHTCLKQSA YREALSDLQS PLNPCVILSE LYVEKCRYMD
SKMKPLWLVY SNRAFGEDAV GVIFKNGDDL RQDMLTLQML RLMDLLWKEA GLDLRMLPYG
CLATGDRSGL IEVVSTSETI ADIQLNSSNV AATAAFNKDA LLNWLKEYNS GDDLDRAIEE
FTLSCAGYCV ASYVLGIGDR HSDNIMVKKT GQLFHIDFGH ILGNFKSKFG IKRERVPFIL
TYDFIHVIQQ GKTGNTEKFG RFRQCCEDAY LILRRHGNLF ITLFALMLTA GLPELTSVKD
IQYLKDSLAL GKSEEEALKQ FKQKFDEALR ESWTTKVNWM AHTVRKDYRS
