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   27-MAR-2024, entry version 165.
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; 10116-ENSRNOP00000022179; -.
DR   GeneID; 85243; -.
DR   KEGG; rno:85243; -.
DR   UCSC; RGD:620917; rat.
DR   AGR; RGD:620917; -.
DR   CTD; 5291; -.
DR   RGD; 620917; Pik3cb.
DR   eggNOG; KOG0904; Eukaryota.
DR   InParanoid; Q9Z1L0; -.
DR   OrthoDB; 10350at2759; -.
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: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:0046934; F:1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity; ISS:UniProtKB.
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: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: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:0006874; P:intracellular calcium ion homeostasis; ISO:RGD.
DR   GO; GO:1903298; P:negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway; ISO:RGD.
DR   GO; GO:0043409; P:negative regulation of MAPK cascade; ISO:RGD.
DR   GO; GO:0051898; P:negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; 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:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; 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: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:0045429; P:positive regulation of nitric oxide biosynthetic process; 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:0003376; P:sphingosine-1-phosphate receptor signaling pathway; ISO:RGD.
DR   CDD; cd08693; C2_PI3K_class_I_beta_delta; 1.
DR   CDD; cd00872; PI3Ka_I; 1.
DR   CDD; cd05173; PI3Kc_IA_beta; 1.
DR   Gene3D; 3.10.20.770; -; 1.
DR   Gene3D; 2.60.40.150; C2 domain; 1.
DR   Gene3D; 1.10.1070.11; Phosphatidylinositol 3-/4-kinase, catalytic domain; 1.
DR   Gene3D; 1.25.40.70; Phosphatidylinositol 3-kinase, accessory domain (PIK); 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:SF33; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE 3-KINASE CATALYTIC SUBUNIT BETA ISOFORM; 1.
DR   PANTHER; PTHR10048; PHOSPHATIDYLINOSITOL KINASE; 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; ARM repeat; 1.
DR   SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   SUPFAM; SSF54236; Ubiquitin-like; 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
//