CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-000077
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha 
Protein Synonyms/Alias
 PI3K-C2-alpha; PtdIns-3-kinase C2 subunit alpha; Phosphoinositide 3-kinase-C2-alpha 
Gene Name
 PIK3C2A 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
41MEAEALAKLQKDRQVubiquitination[1]
94ALDIDVEKLTQAELEacetylation[2]
94ALDIDVEKLTQAELEubiquitination[3]
112LDDSFETKKTPVLPVubiquitination[1, 3]
229DMAKLFDKIASTSEFubiquitination[3, 4, 5, 6, 7]
252DLEITDSKVSNLQVSubiquitination[3, 6]
261SNLQVSPKSEDISKFubiquitination[3]
267PKSEDISKFDWLDLDubiquitination[1, 3, 4, 7]
278LDLDPLSKPKVDNVEubiquitination[1, 3, 6]
280LDPLSKPKVDNVEVLubiquitination[1]
301NVSSLLAKDPWDAVLubiquitination[1, 3]
348IRTTQLAKAQGHISQubiquitination[3]
579RAVDQVIKAVRKICSubiquitination[3]
613AVNLPRSKTADVTSLubiquitination[1, 3, 6]
674TDCAQSSKSVKEAWTubiquitination[6]
872ETLENDIKGKLLDILubiquitination[1, 3]
874LENDIKGKLLDILHKubiquitination[1]
881KLLDILHKDSSLGLSubiquitination[3, 6]
889DSSLGLSKEDKAFLWubiquitination[1, 3]
898DKAFLWEKRYYCFKHubiquitination[6]
1062LLGGVAEKVRQASGSubiquitination[1, 6, 8]
1090QSFFQKNKCRLPLKPubiquitination[6]
1096NKCRLPLKPSLVAKEubiquitination[6]
1162IMDKIWLKEGLDLRMubiquitination[3]
1217PLAEWLRKYNPSEEEubiquitination[3]
1271MFHIDFGKFLGHAQMubiquitination[1]
1414PILSFSPKTYSFRQDubiquitination[1, 6]
1539HPLLRDEKAEGIARSacetylation[9]
1672LKDFNLSKETVKWYQubiquitination[1]
Reference
 [1] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [2] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [4] 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]
 [5] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [6] 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]
 [7] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [8] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [9] Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome.
 Morselli E, Mariño G, Bennetzen MV, Eisenberg T, Megalou E, Schroeder S, Cabrera S, Bénit P, Rustin P, Criollo A, Kepp O, Galluzzi L, Shen S, Malik SA, Maiuri MC, Horio Y, López-Otín C, Andersen JS, Tavernarakis N, Madeo F, Kroemer G.
 J Cell Biol. 2011 Feb 21;192(4):615-29. [PMID: 21339330] 
Functional Description
 Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as second messengers. Has a role in several intracellular trafficking events. Functions in insulin signaling and secretion. Required for translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane and glucose uptake in response to insulin- mediated RHOQ activation. Regulates insulin secretion through two different mechanisms: involved in glucose-induced insulin secretion downstream of insulin receptor in a pathway that involves AKT1 activation and TBC1D4/AS160 phosphorylation, and participates in the late step of insulin granule exocytosis probably in insulin granule fusion. Synthesizes PtdIns3P in response to insulin signaling. Functions in clathrin-coated endocytic vesicle formation and distribution. Regulates dynamin- independent endocytosis, probably by recruiting EEA1 to internalizing vesicles. In neurosecretory cells synthesizes PtdIns3P on large dense core vesicles. Participates in calcium induced contraction of vascular smooth muscle by regulating myosin light chain (MLC) phosphorylation through a mechanism involving Rho kinase-dependent phosphorylation of the MLCP-regulatory subunit MYPT1. May play a role in the EGF signaling cascade. May be involved in mitosis and UV-induced damage response. Required for maintenance of normal renal structure and function by supporting normal podocyte function. 
Sequence Annotation
 DOMAIN 421 509 PI3K-RBD.
 DOMAIN 682 841 C2 PI3K-type.
 DOMAIN 861 1037 PIK helical.
 DOMAIN 1133 1397 PI3K/PI4K.
 DOMAIN 1422 1538 PX.
 DOMAIN 1559 1662 C2.
 REGION 2 142 Interaction with clathrin; sufficient to
 REGION 1488 1493 Interaction with PtdIns(4,5)P2-containing
 MOTIF 1608 1619 Nuclear localization signal.
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 60 60 Phosphoserine.
 MOD_RES 108 108 Phosphoserine.
 MOD_RES 259 259 Phosphoserine.
 MOD_RES 327 327 Phosphoserine.
 MOD_RES 338 338 Phosphoserine.  
Keyword
 3D-structure; Acetylation; ATP-binding; Cell membrane; Complete proteome; Cytoplasm; Cytoplasmic vesicle; Endocytosis; Exocytosis; Golgi apparatus; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Transferase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1686 AA 
Protein Sequence
MAQISSNSGF KECPSSHPEP TRAKDVDKEE ALQMEAEALA KLQKDRQVTD NQRGFELSSS 60
TRKKAQVYNK QDYDLMVFPE SDSQKRALDI DVEKLTQAEL EKLLLDDSFE TKKTPVLPVT 120
PILSPSFSAQ LYFRPTIQRG QWPPGLPGPS TYALPSIYPS TYSKQAAFQN GFNPRMPTFP 180
STEPIYLSLP GQSPYFSYPL TPATPFHPQG SLPIYRPVVS TDMAKLFDKI ASTSEFLKNG 240
KARTDLEITD SKVSNLQVSP KSEDISKFDW LDLDPLSKPK VDNVEVLDHE EEKNVSSLLA 300
KDPWDAVLLE ERSTANCHLE RKVNGKSLSV ATVTRSQSLN IRTTQLAKAQ GHISQKDPNG 360
TSSLPTGSSL LQEVEVQNEE MAAFCRSITK LKTKFPYTNH RTNPGYLLSP VTAQRNICGE 420
NASVKVSIDI EGFQLPVTFT CDVSSTVEII IMQALCWVHD DLNQVDVGSY VLKVCGQEEV 480
LQNNHCLGSH EHIQNCRKWD TEIRLQLLTF SAMCQNLART AEDDETPVDL NKHLYQIEKP 540
CKEAMTRHPV EELLDSYHNQ VELALQIENQ HRAVDQVIKA VRKICSALDG VETLAITESV 600
KKLKRAVNLP RSKTADVTSL FGGEDTSRSS TRGSLNPENP VQVSINQLTA AIYDLLRLHA 660
NSGRSPTDCA QSSKSVKEAW TTTEQLQFTI FAAHGISSNW VSNYEKYYLI CSLSHNGKDL 720
FKPIQSKKVG TYKNFFYLIK WDELIIFPIQ ISQLPLESVL HLTLFGILNQ SSGSSPDSNK 780
QRKGPEALGK VSLPLFDFKR FLTCGTKLLY LWTSSHTNSV PGTVTKKGYV MERIVLQVDF 840
PSPAFDIIYT TPQVDRSIIQ QHNLETLEND IKGKLLDILH KDSSLGLSKE DKAFLWEKRY 900
YCFKHPNCLP KILASAPNWK WVNLAKTYSL LHQWPALYPL IALELLDSKF ADQEVRSLAV 960
TWIEAISDDE LTDLLPQFVQ ALKYEIYLNS SLVQFLLSRA LGNIQIAHNL YWLLKDALHD 1020
VQFSTRYEHV LGALLSVGGK RLREELLKQT KLVQLLGGVA EKVRQASGSA RQVVLQRSME 1080
RVQSFFQKNK CRLPLKPSLV AKELNIKSCS FFSSNAVPLK VTMVNADPMG EEINVMFKVG 1140
EDLRQDMLAL QMIKIMDKIW LKEGLDLRMV IFKCLSTGRD RGMVELVPAS DTLRKIQVEY 1200
GVTGSFKDKP LAEWLRKYNP SEEEYEKASE NFIYSCAGCC VATYVLGICD RHNDNIMLRS 1260
TGHMFHIDFG KFLGHAQMFG SFKRDRAPFV LTSDMAYVIN GGEKPTIRFQ LFVDLCCQAY 1320
NLIRKQTNLF LNLLSLMIPS GLPELTSIQD LKYVRDALQP QTTDAEATIF FTRLIESSLG 1380
SIATKFNFFI HNLAQLRFSG LPSNDEPILS FSPKTYSFRQ DGRIKEVSVF TYHKKYNPDK 1440
HYIYVVRILR EGQIEPSFVF RTFDEFQELH NKLSIIFPLW KLPGFPNRMV LGRTHIKDVA 1500
AKRKIELNSY LQSLMNASTD VAECDLVCTF FHPLLRDEKA EGIARSADAG SFSPTPGQIG 1560
GAVKLSISYR NGTLFIMVMH IKDLVTEDGA DPNPYVKTYL LPDNHKTSKR KTKISRKTRN 1620
PTFNEMLVYS GYSKETLRQR ELQLSVLSAE SLRENFFLGG VTLPLKDFNL SKETVKWYQL 1680
TAATYL 1686 
Gene Ontology
 GO:0030136; C:clathrin-coated vesicle; IEA:UniProtKB-SubCell.
 GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0005942; C:phosphatidylinositol 3-kinase complex; IBA:RefGenome.
 GO:0005886; C:plasma membrane; IDA:UniProtKB.
 GO:0031982; C:vesicle; IDA:UniProtKB.
 GO:0016303; F:1-phosphatidylinositol-3-kinase activity; IBA:RefGenome.
 GO:0035005; F:1-phosphatidylinositol-4-phosphate 3-kinase activity; TAS:Reactome.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0035091; F:phosphatidylinositol binding; IEA:InterPro.
 GO:0048268; P:clathrin coat assembly; TAS:UniProtKB.
 GO:0006897; P:endocytosis; IMP:UniProtKB.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:UniProtKB.
 GO:0006887; P:exocytosis; TAS:UniProtKB.
 GO:0008286; P:insulin receptor signaling pathway; TAS:UniProtKB.
 GO:0048015; P:phosphatidylinositol-mediated signaling; IEA:InterPro.
 GO:0048008; P:platelet-derived growth factor receptor signaling pathway; TAS:UniProtKB.
 GO:0044281; P:small molecule metabolic process; TAS:Reactome.
 GO:0014829; P:vascular smooth muscle contraction; TAS:UniProtKB. 
Interpro
 IPR016024; ARM-type_fold.
 IPR000008; C2_Ca-dep.
 IPR008973; C2_Ca/lipid-bd_dom_CaLB.
 IPR018029; C2_membr_targeting.
 IPR011009; Kinase-like_dom.
 IPR001683; Phox.
 IPR000403; PI3/4_kinase_cat_dom.
 IPR018936; PI3/4_kinase_CS.
 IPR002420; PI3K_C2_dom.
 IPR000341; PI3K_Ras-bd_dom.
 IPR015433; PI_Kinase.
 IPR001263; PInositide-3_kin_accessory_dom. 
Pfam
 PF00168; C2
 PF00454; PI3_PI4_kinase
 PF00792; PI3K_C2
 PF00794; PI3K_rbd
 PF00613; PI3Ka
 PF00787; PX 
SMART
 SM00239; C2
 SM00142; PI3K_C2
 SM00144; PI3K_rbd
 SM00145; PI3Ka
 SM00146; PI3Kc
 SM00312; PX 
PROSITE
 PS50004; C2
 PS00915; PI3_4_KINASE_1
 PS00916; PI3_4_KINASE_2
 PS50290; PI3_4_KINASE_3
 PS51547; PI3K_C2
 PS51546; PI3K_RBD
 PS51545; PIK_HELICAL
 PS50195; PX 
PRINTS