CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-000059
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform 
Protein Synonyms/Alias
 PI3-kinase subunit delta; PI3K-delta; PI3Kdelta; PtdIns-3-kinase subunit delta; Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit delta; PtdIns-3-kinase subunit p110-delta; p110delta 
Gene Name
 PIK3CD 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
46NANLSTIKQLLWHRAubiquitination[1, 2]
142EVNDFRAKMCQFCEEubiquitination[2]
372VCSEPVWKQRLEFDIubiquitination[2]
449WPSVPDEKGELLNPTubiquitination[2]
528GELYEHEKDLVWKLRubiquitination[2]
557LLVTKWNKHEDVAQMubiquitination[1]
684HHMKVLMKQGEALSKubiquitination[2]
691KQGEALSKLKALNDFubiquitination[2]
693GEALSKLKALNDFVKubiquitination[2]
712KTPKPQTKELMHLCMubiquitination[2]
841IANIQLNKSNMAATAubiquitination[1]
852AATAAFNKDALLNWLubiquitination[2]
862LLNWLKSKNPGEALDubiquitination[2, 3]
1030LRESWKTKVNWLAHNubiquitination[2]
Reference
 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302] 
Functional Description
 Phosphoinositide-3-kinase (PI3K) that phosphorylates PftdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Mediates immune responses. Plays a role in B-cell development, proliferation, migration, and function. Required for B-cell receptor (BCR) signaling. Mediates B-cell proliferation response to anti-IgM, anti-CD40 and IL4 stimulation. Promotes cytokine production in response to TLR4 and TLR9. Required for antibody class switch mediated by TLR9. Involved in the antigen presentation function of B-cells. Involved in B-cell chemotaxis in response to CXCL13 and sphingosine 1-phosphate (S1P). Required for proliferation, signaling and cytokine production of naive, effector and memory T-cells. Required for T-cell receptor (TCR) signaling. Mediates TCR signaling events at the immune synapse. Activation by TCR leads to antigen-dependent memory T-cell migration and retention to antigenic tissues. Together with PIK3CG participates in T-cell development. Contributes to T-helper cell expansion and differentiation. Required for T-cell migration mediated by homing receptors SELL/CD62L, CCR7 and S1PR1 and antigen dependent recruitment of T-cells. Together with PIK3CG is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in NK cell receptor activation. Have a role in NK cell maturation and cytokine production. Together with PIK3CG is involved in neutrophil chemotaxis and extravasation. Together with PIK3CG participates in neutrophil respiratory burst. Have important roles in mast-cell development and mast cell mediated allergic response. Involved in stem cell factor (SCF)-mediated proliferation, adhesion and migration. Required for allergen-IgE-induced degranulation and cytokine release. The lipid kinase activity is required for its biological function. Isoform 2 may be involved in stabilizing total RAS levels, resulting in increased ERK phosphorylation and increased PI3K activity. 
Sequence Annotation
 DOMAIN 16 105 PI3K-ABD.
 DOMAIN 187 278 PI3K-RBD.
 DOMAIN 319 476 C2 PI3K-type.
 DOMAIN 497 674 PIK helical.
 DOMAIN 774 1041 PI3K/PI4K.
 MOD_RES 524 524 Phosphotyrosine.
 MOD_RES 1039 1039 Phosphoserine; by autocatalysis.  
Keyword
 Adaptive immunity; Alternative splicing; ATP-binding; Chemotaxis; Complete proteome; Cytoplasm; Differentiation; Direct protein sequencing; Immunity; Inflammatory response; Innate immunity; Kinase; Nucleotide-binding; Phosphoprotein; Reference proteome; Transferase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1044 AA 
Protein Sequence
MPPGVDCPME FWTKEENQSV VVDFLLPTGV YLNFPVSRNA NLSTIKQLLW HRAQYEPLFH 60
MLSGPEAYVF TCINQTAEQQ ELEDEQRRLC DVQPFLPVLR LVAREGDRVK KLINSQISLL 120
IGKGLHEFDS LCDPEVNDFR AKMCQFCEEA AARRQQLGWE AWLQYSFPLQ LEPSAQTWGP 180
GTLRLPNRAL LVNVKFEGSE ESFTFQVSTK DVPLALMACA LRKKATVFRQ PLVEQPEDYT 240
LQVNGRHEYL YGSYPLCQFQ YICSCLHSGL TPHLTMVHSS SILAMRDEQS NPAPQVQKPR 300
AKPPPIPAKK PSSVSLWSLE QPFRIELIQG SKVNADERMK LVVQAGLFHG NEMLCKTVSS 360
SEVSVCSEPV WKQRLEFDIN ICDLPRMARL CFALYAVIEK AKKARSTKKK SKKADCPIAW 420
ANLMLFDYKD QLKTGERCLY MWPSVPDEKG ELLNPTGTVR SNPNTDSAAA LLICLPEVAP 480
HPVYYPALEK ILELGRHSEC VHVTEEEQLQ LREILERRGS GELYEHEKDL VWKLRHEVQE 540
HFPEALARLL LVTKWNKHED VAQMLYLLCS WPELPVLSAL ELLDFSFPDC HVGSFAIKSL 600
RKLTDDELFQ YLLQLVQVLK YESYLDCELT KFLLDRALAN RKIGHFLFWH LRSEMHVPSV 660
ALRFGLILEA YCRGSTHHMK VLMKQGEALS KLKALNDFVK LSSQKTPKPQ TKELMHLCMR 720
QEAYLEALSH LQSPLDPSTL LAEVCVEQCT FMDSKMKPLW IMYSNEEAGS GGSVGIIFKN 780
GDDLRQDMLT LQMIQLMDVL WKQEGLDLRM TPYGCLPTGD RTGLIEVVLR SDTIANIQLN 840
KSNMAATAAF NKDALLNWLK SKNPGEALDR AIEEFTLSCA GYCVATYVLG IGDRHSDNIM 900
IRESGQLFHI DFGHFLGNFK TKFGINRERV PFILTYDFVH VIQQGKTNNS EKFERFRGYC 960
ERAYTILRRH GLLFLHLFAL MRAAGLPELS CSKDIQYLKD SLALGKTEEE ALKHFRVKFN 1020
EALRESWKTK VNWLAHNVSK DNRQ 1044 
Gene Ontology
 GO:0005942; C:phosphatidylinositol 3-kinase complex; NAS:UniProtKB.
 GO:0005886; C:plasma membrane; TAS:Reactome.
 GO:0016303; F:1-phosphatidylinositol-3-kinase activity; NAS:UniProtKB.
 GO:0035005; F:1-phosphatidylinositol-4-phosphate 3-kinase activity; IBA:RefGenome.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0046934; F:phosphatidylinositol-4,5-bisphosphate 3-kinase activity; IBA:RefGenome.
 GO:0002250; P:adaptive immune response; TAS:UniProtKB.
 GO:0042113; P:B cell activation; TAS:UniProtKB.
 GO:0035754; P:B cell chemotaxis; TAS:UniProtKB.
 GO:0001782; P:B cell homeostasis; IEA:Compara.
 GO:0050853; P:B cell receptor signaling pathway; TAS:UniProtKB.
 GO:0001816; P:cytokine production; TAS:UniProtKB.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0006954; P:inflammatory response; TAS:UniProtKB.
 GO:0045087; P:innate immune response; TAS:UniProtKB.
 GO:0002551; P:mast cell chemotaxis; TAS:UniProtKB.
 GO:0043303; P:mast cell degranulation; TAS:UniProtKB.
 GO:0060374; P:mast cell differentiation; TAS:UniProtKB.
 GO:0035747; P:natural killer cell chemotaxis; TAS:UniProtKB.
 GO:0001779; P:natural killer cell differentiation; TAS:UniProtKB.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0030593; P:neutrophil chemotaxis; TAS:UniProtKB.
 GO:0072672; P:neutrophil extravasation; TAS:UniProtKB.
 GO:0014065; P:phosphatidylinositol 3-kinase cascade; TAS:UniProtKB.
 GO:0006468; P:protein phosphorylation; NAS:UniProtKB.
 GO:0002679; P:respiratory burst involved in defense response; TAS:UniProtKB.
 GO:0044281; P:small molecule metabolic process; TAS:Reactome.
 GO:0010818; P:T cell chemotaxis; TAS:UniProtKB.
 GO:0030217; P:T cell differentiation; TAS:UniProtKB.
 GO:0050852; P:T cell receptor signaling pathway; TAS:UniProtKB. 
Interpro
 IPR016024; ARM-type_fold.
 IPR008973; C2_Ca/lipid-bd_dom_CaLB.
 IPR011009; Kinase-like_dom.
 IPR000403; PI3/4_kinase_cat_dom.
 IPR018936; PI3/4_kinase_CS.
 IPR003113; PI3K_adapt-bd_dom.
 IPR002420; PI3K_C2_dom.
 IPR000341; PI3K_Ras-bd_dom.
 IPR015433; PI_Kinase.
 IPR001263; PInositide-3_kin_accessory_dom. 
Pfam
 PF00454; PI3_PI4_kinase
 PF00792; PI3K_C2
 PF02192; PI3K_p85B
 PF00794; PI3K_rbd
 PF00613; PI3Ka 
SMART
 SM00142; PI3K_C2
 SM00143; PI3K_p85B
 SM00144; PI3K_rbd
 SM00145; PI3Ka
 SM00146; PI3Kc 
PROSITE
 PS00915; PI3_4_KINASE_1
 PS00916; PI3_4_KINASE_2
 PS50290; PI3_4_KINASE_3
 PS51544; PI3K_ABD
 PS51547; PI3K_C2
 PS51546; PI3K_RBD
 PS51545; PIK_HELICAL 
PRINTS