ID PK3CD_MOUSE Reviewed; 1043 AA.
AC O35904; Q8CJ28;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 27-MAR-2024, entry version 193.
DE RecName: Full=Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform;
DE Short=PI3-kinase subunit delta;
DE Short=PI3K-delta;
DE Short=PI3Kdelta;
DE Short=PtdIns-3-kinase subunit delta;
DE EC=2.7.1.137 {ECO:0000250|UniProtKB:O00329};
DE EC=2.7.1.153 {ECO:0000250|UniProtKB:O00329};
DE AltName: Full=Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit delta;
DE Short=PtdIns-3-kinase subunit p110-delta;
DE Short=p110delta;
GN Name=Pik3cd;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Spleen;
RX PubMed=9235916; DOI=10.1074/jbc.272.31.19236;
RA Chantry D., Vojtek A., Kashishian A., Holtzman D.A., Wood C., Gray P.W.,
RA Cooper J.A., Hoekstra M.F.;
RT "p110delta, a novel phosphatidylinositol 3-kinase catalytic subunit that
RT associates with p85 and is expressed predominantly in leukocytes.";
RL J. Biol. Chem. 272:19236-19241(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, DISRUPTION PHENOTYPE, AND
RP MUTAGENESIS OF ASP-910.
RC STRAIN=129P2;
RX PubMed=12130661; DOI=10.1126/science.1073560;
RA Okkenhaug K., Bilancio A., Farjot G., Priddle H., Sancho S., Peskett E.,
RA Pearce W., Meek S.E., Salpekar A., Waterfield M.D., Smith A.J.,
RA Vanhaesebroeck B.;
RT "Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase
RT mutant mice.";
RL Science 297:1031-1034(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION IN B-CELLS, AND DISRUPTION PHENOTYPE.
RX PubMed=12235209; DOI=10.1084/jem.20020805;
RA Clayton E., Bardi G., Bell S.E., Chantry D., Downes C.P., Gray A.,
RA Humphries L.A., Rawlings D., Reynolds H., Vigorito E., Turner M.;
RT "A crucial role for the p110delta subunit of phosphatidylinositol 3-kinase
RT in B cell development and activation.";
RL J. Exp. Med. 196:753-763(2002).
RN [6]
RP INTERACTION WITH ERAS.
RX PubMed=12774123; DOI=10.1038/nature01646;
RA Takahashi K., Mitsui K., Yamanaka S.;
RT "Role of Eras in promoting tumor-like properties in mouse embryonic stem
RT cells.";
RL Nature 423:541-545(2003).
RN [7]
RP FUNCTION IN MAST CELLS, ACTIVITY REGULATION, DISRUPTION PHENOTYPE, AND
RP MUTAGENESIS OF ASP-910.
RX PubMed=15496927; DOI=10.1038/nature02991;
RA Ali K., Bilancio A., Thomas M., Pearce W., Gilfillan A.M., Tkaczyk C.,
RA Kuehn N., Gray A., Giddings J., Peskett E., Fox R., Bruce I., Walker C.,
RA Sawyer C., Okkenhaug K., Finan P., Vanhaesebroeck B.;
RT "Essential role for the p110delta phosphoinositide 3-kinase in the allergic
RT response.";
RL Nature 431:1007-1011(2004).
RN [8]
RP FUNCTION IN T-CELL DEVELOPMENT.
RX PubMed=16116162; DOI=10.4049/jimmunol.175.5.2783;
RA Webb L.M.C., Vigorito E., Wymann M.P., Hirsch E., Turner M.;
RT "T cell development requires the combined activities of the p110gamma and
RT p110delta catalytic isoforms of phosphatidylinositol 3-kinase.";
RL J. Immunol. 175:2783-2787(2005).
RN [9]
RP FUNCTION IN T-CELL MIGRATION, ACTIVITY REGULATION, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF ASP-910.
RX PubMed=18259608; DOI=10.1172/jci33267;
RA Jarmin S.J., David R., Ma L., Chai J.-G., Dewchand H., Takesono A.,
RA Ridley A.J., Okkenhaug K., Marelli-Berg F.M.;
RT "T cell receptor-induced phosphoinositide-3-kinase p110delta activity is
RT required for T cell localization to antigenic tissue in mice.";
RL J. Clin. Invest. 118:1154-1164(2008).
RN [10]
RP FUNCTION IN NATURAL KILLER CELLS, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP ASP-910.
RX PubMed=18809712; DOI=10.1084/jem.20072327;
RA Guo H., Samarakoon A., Vanhaesebroeck B., Malarkannan S.;
RT "The p110 delta of PI3K plays a critical role in NK cell terminal
RT maturation and cytokine/chemokine generation.";
RL J. Exp. Med. 205:2419-2435(2008).
RN [11]
RP FUNCTION IN NATURAL KILLER CELL MIGRATION, AND ACTIVITY REGULATION.
RX PubMed=19297623; DOI=10.1073/pnas.0808594106;
RA Saudemont A., Garcon F., Yadi H., Roche-Molina M., Kim N.,
RA Segonds-Pichon A., Martin-Fontecha A., Okkenhaug K., Colucci F.;
RT "p110gamma and p110delta isoforms of phosphoinositide 3-kinase
RT differentially regulate natural killer cell migration in health and
RT disease.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:5795-5800(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [13]
RP ALTERNATIVE SPLICING (ISOFORM 2), AND TISSUE SPECIFICITY.
RC TISSUE=Peripheral blood leukocyte;
RX PubMed=22020336; DOI=10.1038/onc.2011.492;
RA Fransson S., Uv A., Eriksson H., Andersson M.K., Wettergren Y., Bergo M.,
RA Ejeskar K.;
RT "p37delta is a new isoform of PI3K p110delta that increases cell
RT proliferation and is overexpressed in tumors.";
RL Oncogene 31:3277-3286(2012).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 106-1043 IN A COMPLEX WITH
RP IC87114; PIK-39; SW13; SW14; SW30; DL06; DL07; ZSTK474; AS5; GDC-0941;
RP INK654; INK666 AND AS15.
RX PubMed=20081827; DOI=10.1038/nchembio.293;
RA Berndt A., Miller S., Williams O., Le D.D., Houseman B.T., Pacold J.I.,
RA Gorrec F., Hon W.-C., Liu Y., Rommel C., Gaillard P., Ruckle T.,
RA Schwarz M.K., Shokat K.M., Shaw J.P., Williams R.L.;
RT "The p110 delta structure: mechanisms for selectivity and potency of new
RT PI(3)K inhibitors.";
RL Nat. Chem. Biol. 6:117-124(2010).
CC -!- FUNCTION: Phosphoinositide-3-kinase (PI3K) phosphorylates
CC phosphatidylinositol (PI) and its phosphorylated derivatives at
CC position 3 of the inositol ring to produce 3-phosphoinositides. Uses
CC ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to
CC generate phosphatidylinositol 3,4,5-trisphosphate (PIP3)
CC (PubMed:9235916). PIP3 plays a key role by recruiting PH domain-
CC containing proteins to the membrane, including AKT1 and PDPK1,
CC activating signaling cascades involved in cell growth, survival,
CC proliferation, motility and morphology. Mediates immune responses.
CC Plays a role in B-cell development, proliferation, migration, and
CC function. Required for B-cell receptor (BCR) signaling. Mediates B-cell
CC proliferation response to anti-IgM, anti-CD40 and IL4 stimulation.
CC Promotes cytokine production in response to TLR4 and TLR9. Required for
CC antibody class switch mediated by TLR9. Involved in the antigen
CC presentation function of B-cells. Involved in B-cell chemotaxis in
CC response to CXCL13 and sphingosine 1-phosphate (S1P). Required for
CC proliferation, signaling and cytokine production of naive, effector and
CC memory T-cells. Required for T-cell receptor (TCR) signaling. Mediates
CC TCR signaling events at the immune synapse. Activation by TCR leads to
CC antigen-dependent memory T-cell migration and retention to antigenic
CC tissues. Together with PIK3CG participates in T-cell development.
CC Contributes to T-helper cell expansion and differentiation. Required
CC for T-cell migration mediated by homing receptors SELL/CD62L, CCR7 and
CC S1PR1 and antigen dependent recruitment of T-cells. Together with
CC PIK3CG is involved in natural killer (NK) cell development and
CC migration towards the sites of inflammation. Participates in NK cell
CC receptor activation. Plays a role in NK cell maturation and cytokine
CC production. Together with PIK3CG is involved in neutrophil chemotaxis
CC and extravasation. Together with PIK3CG participates in neutrophil
CC respiratory burst. Plays important roles in mast-cell development and
CC mast cell mediated allergic response. Involved in stem cell factor
CC (SCF)-mediated proliferation, adhesion and migration. Required for
CC allergen-IgE-induced degranulation and cytokine release. The lipid
CC kinase activity is required for its biological function.
CC {ECO:0000269|PubMed:12130661, ECO:0000269|PubMed:12235209,
CC ECO:0000269|PubMed:15496927, ECO:0000269|PubMed:16116162,
CC ECO:0000269|PubMed:18259608, ECO:0000269|PubMed:18809712,
CC ECO:0000269|PubMed:19297623, ECO:0000269|PubMed:9235916}.
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:O00329};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21293;
CC Evidence={ECO:0000250|UniProtKB:O00329};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a
CC 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + ADP +
CC H(+); Xref=Rhea:RHEA:12709, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:57880, ChEBI:CHEBI:58088, ChEBI:CHEBI:456216;
CC EC=2.7.1.137; Evidence={ECO:0000250|UniProtKB:O00329};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12710;
CC Evidence={ECO:0000250|UniProtKB:O00329};
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:O00329};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43397;
CC Evidence={ECO:0000250|UniProtKB:O00329};
CC -!- ACTIVITY REGULATION: Activated by growth factors and cytokine receptors
CC through a tyrosine-kinase-dependent mechanism. Activated by RAS.
CC IC87114 inhibits lipid kinase activity and is selective in cells at
CC doses up to 5-10 uM. Among other effects, IC87114 reduces allergic
CC responses, prevents the recruitment of antigen-specific T cells into
CC target tissue, and affects natural killer cell chemotaxis.
CC {ECO:0000269|PubMed:15496927, ECO:0000269|PubMed:18259608,
CC ECO:0000269|PubMed:19297623}.
CC -!- PATHWAY: Phospholipid metabolism; phosphatidylinositol phosphate
CC biosynthesis. {ECO:0000305|PubMed:9235916}.
CC -!- SUBUNIT: Heterodimer of a catalytic subunit PIK3CD and a p85 regulatory
CC subunit (PIK3R1, PIK3R2 or PIK3R3). Interacts with ERAS and HRAS.
CC {ECO:0000269|PubMed:12774123}.
CC -!- INTERACTION:
CC O35904-2; P26450: Pik3r1; NbExp=2; IntAct=EBI-6470774, EBI-641764;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=p110-delta;
CC IsoId=O35904-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O35904-2; Sequence=VSP_044411, VSP_044412;
CC -!- TISSUE SPECIFICITY: Abundantly expressed in adult mouse spleen as well
CC as in testis (PubMed:9235916). Isoform 1 is expressed in spleen and
CC lung (at protein level). Isoform 1 is expressed predominantly in
CC leukocytes. {ECO:0000269|PubMed:22020336, ECO:0000269|PubMed:9235916}.
CC -!- PTM: Autophosphorylation on Ser-1038 results in the almost complete
CC inactivation of the lipid kinase activity. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Null mutants are viable and fertile but display
CC defective adaptive and innate immune responses due to signaling defects
CC in multiple cell types including B-, T- and mast and natural killer
CC cells. {ECO:0000269|PubMed:12130661, ECO:0000269|PubMed:12235209,
CC ECO:0000269|PubMed:15496927, ECO:0000269|PubMed:18259608,
CC ECO:0000269|PubMed:18809712}.
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; U86587; AAC25676.1; -; mRNA.
DR EMBL; AF532989; AAN05615.1; -; Genomic_DNA.
DR EMBL; AL607078; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CU207384; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466594; EDL14872.1; -; Genomic_DNA.
DR CCDS; CCDS51380.1; -. [O35904-1]
DR PIR; T43502; T43502.
DR RefSeq; NP_001157524.1; NM_001164052.1. [O35904-1]
DR RefSeq; XP_006538715.1; XM_006538652.3. [O35904-1]
DR PDB; 2WXF; X-ray; 1.90 A; A=106-1043.
DR PDB; 2WXG; X-ray; 2.00 A; A=106-1043.
DR PDB; 2WXH; X-ray; 1.90 A; A=106-1043.
DR PDB; 2WXI; X-ray; 2.80 A; A=106-1043.
DR PDB; 2WXJ; X-ray; 2.60 A; A=106-1043.
DR PDB; 2WXK; X-ray; 2.90 A; A=106-1043.
DR PDB; 2WXL; X-ray; 1.99 A; A=106-1043.
DR PDB; 2WXM; X-ray; 2.80 A; A=106-1043.
DR PDB; 2WXN; X-ray; 2.60 A; A=106-1043.
DR PDB; 2WXO; X-ray; 2.49 A; A=106-1043.
DR PDB; 2WXP; X-ray; 2.30 A; A=106-1043.
DR PDB; 2WXQ; X-ray; 2.70 A; A=106-1043.
DR PDB; 2WXR; X-ray; 2.50 A; A=106-1043.
DR PDB; 2X38; X-ray; 2.20 A; A=106-1043.
DR PDB; 4AJW; X-ray; 2.80 A; A/B=110-1043.
DR PDB; 4V0I; X-ray; 2.54 A; A/B=106-1043.
DR PDB; 4XE0; X-ray; 2.43 A; A=106-1043.
DR PDB; 5AE8; X-ray; 2.42 A; A=106-1043.
DR PDB; 5AE9; X-ray; 2.44 A; A=106-1043.
DR PDB; 5I4U; X-ray; 2.37 A; A=106-1043.
DR PDB; 5I6U; X-ray; 2.84 A; A=106-1043.
DR PDB; 5IS5; X-ray; 2.85 A; A=1-1043.
DR PDB; 5L72; X-ray; 3.06 A; A=106-1043.
DR PDB; 5NCY; X-ray; 1.90 A; A=106-507, A=509-1043.
DR PDB; 5NCZ; X-ray; 1.94 A; A=106-1043.
DR PDB; 5NGB; X-ray; 2.90 A; A=1-1043.
DR PDB; 5O83; X-ray; 2.90 A; A=106-1043.
DR PDB; 5T27; X-ray; 2.60 A; A=106-1043.
DR PDB; 5T28; X-ray; 2.80 A; A=106-507, A=509-1043.
DR PDB; 5T2B; X-ray; 2.30 A; A=106-1043.
DR PDB; 5T2D; X-ray; 2.90 A; A=106-1043.
DR PDB; 5T2G; X-ray; 2.55 A; A=106-1043.
DR PDB; 5T2I; X-ray; 2.30 A; A=106-1043.
DR PDB; 5T2L; X-ray; 2.55 A; A=106-1043.
DR PDB; 5T2M; X-ray; 2.80 A; A=106-1043.
DR PDB; 5T7F; X-ray; 2.60 A; A/B=106-1043.
DR PDB; 5T8I; X-ray; 2.60 A; A=106-1043.
DR PDB; 6DGT; X-ray; 2.60 A; A=106-1043.
DR PDB; 6EYZ; X-ray; 2.20 A; A=1-1043.
DR PDB; 6EZ6; X-ray; 2.04 A; A=1-1043.
DR PDB; 6GY0; X-ray; 2.55 A; A=106-1043.
DR PDB; 6HI9; X-ray; 2.08 A; A=106-1043.
DR PDB; 6MUL; X-ray; 3.09 A; A/B=106-1043.
DR PDB; 6MUM; X-ray; 3.06 A; A/B=106-1043.
DR PDBsum; 2WXF; -.
DR PDBsum; 2WXG; -.
DR PDBsum; 2WXH; -.
DR PDBsum; 2WXI; -.
DR PDBsum; 2WXJ; -.
DR PDBsum; 2WXK; -.
DR PDBsum; 2WXL; -.
DR PDBsum; 2WXM; -.
DR PDBsum; 2WXN; -.
DR PDBsum; 2WXO; -.
DR PDBsum; 2WXP; -.
DR PDBsum; 2WXQ; -.
DR PDBsum; 2WXR; -.
DR PDBsum; 2X38; -.
DR PDBsum; 4AJW; -.
DR PDBsum; 4V0I; -.
DR PDBsum; 4XE0; -.
DR PDBsum; 5AE8; -.
DR PDBsum; 5AE9; -.
DR PDBsum; 5I4U; -.
DR PDBsum; 5I6U; -.
DR PDBsum; 5IS5; -.
DR PDBsum; 5L72; -.
DR PDBsum; 5NCY; -.
DR PDBsum; 5NCZ; -.
DR PDBsum; 5NGB; -.
DR PDBsum; 5O83; -.
DR PDBsum; 5T27; -.
DR PDBsum; 5T28; -.
DR PDBsum; 5T2B; -.
DR PDBsum; 5T2D; -.
DR PDBsum; 5T2G; -.
DR PDBsum; 5T2I; -.
DR PDBsum; 5T2L; -.
DR PDBsum; 5T2M; -.
DR PDBsum; 5T7F; -.
DR PDBsum; 5T8I; -.
DR PDBsum; 6DGT; -.
DR PDBsum; 6EYZ; -.
DR PDBsum; 6EZ6; -.
DR PDBsum; 6GY0; -.
DR PDBsum; 6HI9; -.
DR PDBsum; 6MUL; -.
DR PDBsum; 6MUM; -.
DR AlphaFoldDB; O35904; -.
DR SMR; O35904; -.
DR BioGRID; 202161; 6.
DR DIP; DIP-39841N; -.
DR IntAct; O35904; 8.
DR STRING; 10090.ENSMUSP00000101315; -.
DR BindingDB; O35904; -.
DR ChEMBL; CHEMBL2216745; -.
DR iPTMnet; O35904; -.
DR PhosphoSitePlus; O35904; -.
DR SwissPalm; O35904; -.
DR EPD; O35904; -.
DR MaxQB; O35904; -.
DR PaxDb; 10090-ENSMUSP00000101315; -.
DR ProteomicsDB; 289600; -. [O35904-1]
DR ProteomicsDB; 289601; -. [O35904-2]
DR Antibodypedia; 4215; 677 antibodies from 38 providers.
DR DNASU; 18707; -.
DR Ensembl; ENSMUST00000105689.8; ENSMUSP00000101314.2; ENSMUSG00000039936.19. [O35904-1]
DR GeneID; 18707; -.
DR KEGG; mmu:18707; -.
DR UCSC; uc008vwq.1; mouse. [O35904-1]
DR AGR; MGI:1098211; -.
DR CTD; 5293; -.
DR MGI; MGI:1098211; Pik3cd.
DR VEuPathDB; HostDB:ENSMUSG00000039936; -.
DR eggNOG; KOG0904; Eukaryota.
DR GeneTree; ENSGT00940000159079; -.
DR InParanoid; O35904; -.
DR OrthoDB; 10350at2759; -.
DR BRENDA; 2.7.1.153; 3474.
DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR Reactome; R-MMU-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-MMU-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling.
DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-MMU-8853659; RET signaling.
DR Reactome; R-MMU-9027276; Erythropoietin activates Phosphoinositide-3-kinase (PI3K).
DR Reactome; R-MMU-912526; Interleukin receptor SHC signaling.
DR Reactome; R-MMU-912631; Regulation of signaling by CBL.
DR Reactome; R-MMU-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR UniPathway; UPA00220; -.
DR BioGRID-ORCS; 18707; 1 hit in 80 CRISPR screens.
DR ChiTaRS; Pik3cd; mouse.
DR EvolutionaryTrace; O35904; -.
DR PRO; PR:O35904; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; O35904; Protein.
DR Bgee; ENSMUSG00000039936; Expressed in granulocyte and 170 other cell types or tissues.
DR ExpressionAtlas; O35904; baseline and differential.
DR Genevisible; O35904; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; IBA:GO_Central.
DR GO; GO:0005943; C:phosphatidylinositol 3-kinase complex, class IA; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; IBA:GO_Central.
DR GO; GO:0046934; F:1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity; IEA:UniProtKB-EC.
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:0016301; F:kinase activity; ISO:MGI.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0042113; P:B cell activation; IMP:MGI.
DR GO; GO:0001782; P:B cell homeostasis; IMP:MGI.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IMP:MGI.
DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR GO; GO:0050832; P:defense response to fungus; IMP:MGI.
DR GO; GO:0048872; P:homeostasis of number of cells; IMP:MGI.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:BHF-UCL.
DR GO; GO:0036092; P:phosphatidylinositol-3-phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; ISO:MGI.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:BHF-UCL.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:0038089; P:positive regulation of cell migration by vascular endothelial growth factor signaling pathway; ISO:MGI.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; ISO:MGI.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISO:MGI.
DR GO; GO:1905278; P:positive regulation of epithelial tube formation; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:MGI.
DR GO; GO:0033031; P:positive regulation of neutrophil apoptotic process; ISO:MGI.
DR CDD; cd08693; C2_PI3K_class_I_beta_delta; 1.
DR CDD; cd05174; PI3Kc_IA_delta; 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; IPR037703; PI3Kdelta_dom.
DR InterPro; IPR015433; PI_Kinase.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR10048:SF35; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE 3-KINASE CATALYTIC SUBUNIT DELTA 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 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; ATP-binding;
KW Chemotaxis; Cytoplasm; Differentiation; Immunity; Inflammatory response;
KW Innate immunity; Kinase; Lipid metabolism; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..1043
FT /note="Phosphatidylinositol 4,5-bisphosphate 3-kinase
FT catalytic subunit delta isoform"
FT /id="PRO_0000088791"
FT DOMAIN 16..105
FT /note="PI3K-ABD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00877"
FT DOMAIN 187..278
FT /note="PI3K-RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00879"
FT DOMAIN 319..476
FT /note="C2 PI3K-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00880"
FT DOMAIN 496..673
FT /note="PIK helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00878"
FT DOMAIN 744..1026
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 287..312
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 750..756
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 889..897
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 908..934
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT MOD_RES 523
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O00329"
FT MOD_RES 1038
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O00329"
FT VAR_SEQ 201..212
FT /note="ESFTFQVSTKDM -> VSPSPIPSPSSI (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_044411"
FT VAR_SEQ 213..1043
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_044412"
FT MUTAGEN 910
FT /note="D->A: Inhibits lipid kinase activity. Mice are
FT viable and fertile but display defective adaptive and
FT innate immune responses Signaling defects in B-cells, T-
FT cells, mast cells and natural killer cells. Reduced B and
FT T-cell receptor signaling. Affects development and
FT differentiation of B -ells. Reduced memory T-cell number.
FT Affects B- and T-cell proliferation. Attenuates immune
FT responses in vivo. Induces inflammatory bowel disease
FT development. Lost TCR-induced migration and localization to
FT antigenic tissue. Affects natural killer cell maturation
FT and cytokine production."
FT /evidence="ECO:0000269|PubMed:12130661,
FT ECO:0000269|PubMed:15496927, ECO:0000269|PubMed:18259608,
FT ECO:0000269|PubMed:18809712"
FT CONFLICT 122
FT /note="G -> A (in Ref. 1; AAC25676)"
FT /evidence="ECO:0000305"
FT CONFLICT 584
FT /note="F -> S (in Ref. 1; AAC25676)"
FT /evidence="ECO:0000305"
FT CONFLICT 651
FT /note="R -> H (in Ref. 1; AAC25676)"
FT /evidence="ECO:0000305"
FT HELIX 110..121
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 126..130
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 134..154
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 159..166
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 173..175
FT /evidence="ECO:0007829|PDB:6EZ6"
FT STRAND 189..198
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 202..208
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 213..227
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 236..238
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 239..243
FT /evidence="ECO:0007829|PDB:2WXF"
FT TURN 244..247
FT /evidence="ECO:0007829|PDB:5O83"
FT STRAND 248..250
FT /evidence="ECO:0007829|PDB:5O83"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:5NCZ"
FT HELIX 256..258
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 260..268
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 273..278
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 279..288
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 316..318
FT /evidence="ECO:0007829|PDB:6EZ6"
FT STRAND 321..331
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 340..349
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 352..355
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 363..365
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 370..380
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 381..383
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 389..397
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 416..426
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 430..432
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 435..440
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 455..457
FT /evidence="ECO:0007829|PDB:4V0I"
FT TURN 465..467
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 470..475
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 479..481
FT /evidence="ECO:0007829|PDB:6EZ6"
FT HELIX 488..493
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 511..514
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 524..532
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 534..540
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 542..544
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 545..549
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 554..556
FT /evidence="ECO:0007829|PDB:4XE0"
FT HELIX 557..568
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 575..581
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 589..599
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 604..617
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 618..620
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 622..625
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 627..638
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 640..651
FT /evidence="ECO:0007829|PDB:2WXF"
FT TURN 652..655
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 657..673
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 675..701
FT /evidence="ECO:0007829|PDB:2WXF"
FT TURN 702..704
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 707..718
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 721..727
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 728..732
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 735..740
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 745..747
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 753..755
FT /evidence="ECO:0007829|PDB:2WXR"
FT STRAND 758..763
FT /evidence="ECO:0007829|PDB:2WXF"
FT TURN 765..767
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 768..771
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 773..781
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 784..802
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 814..818
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 821..825
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 828..832
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 833..837
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 841..843
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 850..852
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 853..861
FT /evidence="ECO:0007829|PDB:2WXF"
FT TURN 863..865
FT /evidence="ECO:0007829|PDB:2WXK"
FT HELIX 866..888
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 897..901
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 906..908
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 935..941
FT /evidence="ECO:0007829|PDB:2WXF"
FT TURN 942..944
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 949..968
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 970..980
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 981..983
FT /evidence="ECO:0007829|PDB:2WXF"
FT STRAND 988..990
FT /evidence="ECO:0007829|PDB:5NCZ"
FT HELIX 991..1001
FT /evidence="ECO:0007829|PDB:2WXF"
FT TURN 1002..1004
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 1007..1024
FT /evidence="ECO:0007829|PDB:2WXF"
FT HELIX 1026..1030
FT /evidence="ECO:0007829|PDB:5L72"
SQ SEQUENCE 1043 AA; 119712 MW; AD8DE07D8F847795 CRC64;
MPPGVDCPME FWTKEESQSV VVDFLLPTGV YLNFPVSRNA NLSTIKQVLW HRAQYEPLFH
MLSDPEAYVF TCVNQTAEQQ ELEDEQRRLC DIQPFLPVLR LVAREGDRVK KLINSQISLL
IGKGLHEFDS LRDPEVNDFR TKMRQFCEEA AAHRQQLGWV EWLQYSFPLQ LEPSARGWRA
GLLRVSNRAL LVNVKFEGSE ESFTFQVSTK DMPLALMACA LRKKATVFRQ PLVEQPEEYA
LQVNGRHEYL YGNYPLCHFQ YICSCLHSGL TPHLTMVHSS SILAMRDEQS NPAPQVQKPR
AKPPPIPAKK PSSVSLWSLE QPFSIELIEG RKVNADERMK LVVQAGLFHG NEMLCKTVSS
SEVNVCSEPV WKQRLEFDIS VCDLPRMARL CFALYAVVEK AKKARSTKKK SKKADCPIAW
ANLMLFDYKD QLKTGERCLY MWPSVPDEKG ELLNPAGTVR GNPNTESAAA LVIYLPEVAP
HPVYFPALEK ILELGRHGER GRITEEELQL REILERRGSG ELYEHEKDLV WKMRHEVQEH
FPEALARLLL VTKWNKHEDV AQMLYLLCSW PELPVLSALE LLDFSFPDCY VGSFAIKSLR
KLTDDELFQY LLQLVQVLKY ESYLDCELTK FLLGRALANR KIGHFLFWHL RSEMHVPSVA
LRFGLIMEAY CRGSTHHMKV LMKQGEALSK LKALNDFVKV SSQKTTKPQT KEMMHMCMRQ
ETYMEALSHL QSPLDPSTLL EEVCVEQCTF MDSKMKPLWI MYSSEEAGSA GNVGIIFKNG
DDLRQDMLTL QMIQLMDVLW KQEGLDLRMT PYGCLPTGDR TGLIEVVLHS DTIANIQLNK
SNMAATAAFN KDALLNWLKS KNPGEALDRA IEEFTLSCAG YCVATYVLGI GDRHSDNIMI
RESGQLFHID FGHFLGNFKT KFGINRERVP FILTYDFVHV IQQGKTNNSE KFERFRGYCE
RAYTILRRHG LLFLHLFALM RAAGLPELSC SKDIQYLKDS LALGKTEEEA LKHFRVKFNE
ALRESWKTKV NWLAHNVSKD NRQ
//
