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Identification
HMDB Protein ID HMDBP03120
Secondary Accession Numbers
  • 8662
Name Phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing subunit alpha
Synonyms
  1. PI3K-C2-alpha
  2. Phosphoinositide 3-kinase-C2-alpha
  3. PtdIns-3-kinase C2 subunit alpha
Gene Name PIK3C2A
Protein Type Unknown
Biological Properties
General Function Involved in binding
Specific Function Phosphorylates PtdIns, PtdIns4P and PtdIns(4,5)P2. May play a role in clathrin-coated endocytic vesicle formation and EGF signaling cascade. May be involved in mitosis and UV-induced damage response. May be a downstream effector in insulin signaling cascade
Pathways
  • Joubert syndrome
  • Phosphatidylinositol Phosphate Metabolism
Reactions Not Available
GO Classification
Component
macromolecular complex
protein complex
phosphoinositide 3-kinase complex
Function
binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
phosphotransferase activity, alcohol group as acceptor
protein binding
inositol or phosphatidylinositol kinase activity
lipid binding
phospholipid binding
phosphoinositide binding
lipid kinase activity
phosphoinositide 3-kinase activity
1-phosphatidylinositol-3-kinase activity
Process
metabolic process
cellular process
biological regulation
regulation of biological process
regulation of cellular process
signal transduction
intracellular signal transduction
organophosphate metabolic process
phospholipid metabolic process
cell communication
second-messenger-mediated signaling
phosphoinositide-mediated signaling
glycerophospholipid metabolic process
phosphoinositide metabolic process
phosphoinositide phosphorylation
Cellular Location
  1. Cell membrane
  2. Nucleus
  3. Cytoplasm
  4. Cytoplasmic vesicle
  5. Golgi apparatus
  6. clathrin-coated vesicle
Gene Properties
Chromosome Location Chromosome:1
Locus 11p15.5-p14
SNPs PIK3C2A
Gene Sequence
>5061 bp
ATGGCTCAGATATCTAGCAACAGCGGATTTAAAGAATGTCCATCTTCACATCCGGAACCA
ACAAGAGCAAAAGATGTGGACAAAGAAGAAGCATTACAGATGGAAGCAGAGGCTTTAGCA
AAACTGCAAAAGGATAGACAAGTGACTGACAATCAGAGAGGCTTTGAGTTGTCAAGCAGC
ACCAGAAAAAAAGCACAGGTTTATAACAAGCAGGATTATGATCTCATGGTGTTTCCTGAA
TCAGATTCCCAAAAAAGAGCATTAGATATTGATGTAGAAAAGCTCACCCAAGCTGAACTT
GAGAAACTATTGCTGGATGACAGTTTCGAGACTAAAAAAACACCTGTATTACCAGTTACT
CCTATTCTGAGCCCTTCCTTTTCAGCACAGCTCTATTTTAGACCTACTATTCAGAGAGGA
CAGTGGCCACCTGGATTACCTGGGCCTTCCACTTATGCTTTACCTTCTATTTATCCTTCT
ACTTACAGTAAACAGGCTGCATTCCAAAATGGCTTCAATCCAAGAATGCCCACTTTTCCA
TCTACAGAACCTATATATTTAAGTCTTCCGGGACAATCTCCATATTTCTCATATCCTTTG
ACACCTGCCACACCCTTTCATCCACAAGGAAGCTTACCTATCTATCGTCCAGTAGTCAGT
ACTGACATGGCAAAACTATTTGACAAAATAGCTAGTACATCAGAATTTTTAAAAAATGGG
AAAGCAAGGACTGATTTGGAGATAACAGATTCAAAAGTCAGCAATCTACAGGTATCTCCA
AAGTCTGAGGATATCAGTAAATTTGACTGGTTAGACTTGGATCCTCTAAGTAAGCCTAAG
GTGGATAATGTGGAGGTATTAGACCATGAGGAAGAGAAAAATGTTTCAAGTTTGCTAGCA
AAGGATCCTTGGGATGCTGTTCTTCTTGAAGAGAGATCGACAGCAAATTGTCATCTTGAA
AGAAAGGTGAATGGAAAATCCCTTTCTGTGGCAACTGTTACAAGAAGCCAGTCTTTAAAT
ATTCGAACAACTCAGCTTGCAAAAGCCCAGGGCCATATATCTCAGAAAGACCCAAATGGG
ACCAGTAGTTTGCCAACTGGAAGTTCTCTTCTTCAAGAAGTTGAAGTACAGAATGAGGAG
ATGGCAGCTTTTTGTCGATCCATTACAAAATTGAAGACCAAATTTCCATATACCAATCAC
CGCACAAACCCAGGCTATTTGTTAAGTCCAGTCACAGCGCAAAGAAACATATGCGGAGAA
AATGCTAGTGTGAAGGTCTCCATTGACATTGAAGGATTTCAGCTACCAGTTACTTTTACG
TGTGATGTGAGTTCTACTGTAGAAATCATTATAATGCAAGCCCTTTGCTGGGTACATGAT
GACTTGAATCAAGTAGATGTTGGCAGCTATGTTCTAAAAGTTTGTGGTCAAGAGGAAGTG
CTGCAGAATAATCATTGCCTTGGAAGTCATGAGCATATTCAAAACTGTCGAAAATGGGAC
ACAGAAATTAGACTACAACTCTTGACCTTCAGTGCAATGTGTCAAAATCTGGCCCGAACA
GCAGAAGATGATGAAACACCCGTGGATTTAAACAAACACCTGTATCAAATAGAAAAACCT
TGCAAAGAAGCCATGACGAGACACCCTGTTGAAGAACTCTTAGATTCTTATCACAACCAA
GTAGAACTGGCTCTTCAAATTGAAAACCAACACCGAGCAGTAGATCAAGTAATTAAAGCT
GTAAGAAAAATCTGTAGTGCTTTAGATGGTGTCGAGACTCTTGCCATTACAGAATCAGTA
AAGAAGCTAAAGAGAGCAGTTAATCTTCCAAGGAGTAAAACTGCTGATGTGACTTCTTTG
TTTGGAGGAGAAGACACTAGCAGGAGTTCAACTAGGGGCTCACTTAATCCTGAAAATCCT
GTTCAAGTAAGCATAAACCAATTAACTGCAGCAATTTATGATCTTCTCAGACTCCATGCA
AATTCTGGTAGGAGTCCTACAGACTGTGCCCAAAGTAGCAAGAGTGTCAAGGAAGCATGG
ACTACAACAGAGCAGCTCCAGTTTACTATTTTTGCTGCTCATGGAATTTCAAGTAATTGG
GTATCAAATTATGAAAAATACTACTTGATATGTTCACTGTCTCACAATGGAAAGGATCTT
TTTAAACCTATTCAATCAAAGAAGGTTGGCACTTACAAGAATTTCTTCTATCTTATTAAA
TGGGATGAACTAATCATTTTTCCTATCCAGATATCACAATTGCCATTAGAATCAGTTCTT
CACCTTACTCTTTTTGGAATTTTAAATCAGAGCAGTGGAAGTTCCCCTGATTCTAATAAG
CAGAGAAAGGGACCAGAAGCTTTGGGCAAAGTTTCTTTACCTCTTTTTGACTTTAAACGG
TTTTTAACATGTGGAACTAAACTTCTATATCTTTGGACTTCATCACATACAAATTCTGTT
CCTGGAACAGTTACCAAAAAAGGATATGTCATGGAAAGAATAGTGCTACAGGTTGATTTT
CCTTCTCCTGCATTTGATATTATTTATACAACTCCTCAAGTTGACAGAAGCATTATACAG
CAACATAACTTAGAAACACTAGAGAATGATATAAAAGGGAAACTTCTTGATATTCTTCAT
AAAGACTCATCACTTGGACTTTCTAAAGAAGATAAAGCTTTTTTATGGGAGAAACGTTAT
TATTGCTTCAAACACCCAAATTGTCTTCCTAAAATATTAGCAAGCGCCCCAAACTGGAAA
TGGGTTAATCTTGCCAAAACTTACTCATTGCTTCACCAGTGGCCTGCATTGTACCCACTA
ATTGCATTGGAACTTCTTGATTCAAAATTTGCTGATCAGGAAGTAAGATCCCTAGCTGTG
ACCTGGATTGAGGCCATTAGTGATGATGAGCTAACAGATCTTCTTCCACAGTTTGTACAA
GCTTTGAAATATGAAATTTACTTGAATAGTTCATTAGTGCAATTCCTTTTGTCCAGGGCA
TTGGGAAATATCCAGATAGCACACAATTTATATTGGCTTCTCAAAGATGCCCTGCATGAT
GTACAGTTTAGTACCCGATACGAACATGTTTTGGGTGCTCTCCTGTCAGTAGGAGGAAAA
CGACTTAGAGAAGAACTTCTAAAACAGACGAAACTTGTACAGCTTTTAGGAGGAGTAGCA
GAAAAAGTAAGGCAGGCTAGTGGATCAGCCAGACAGGTTGTTCTCCAAAGAAGTATGGAA
CGAGTACAGTCCTTTTTTCAGAAAAATAAATGCCGTCTCCCTCTCAAGCCAAGTCTAGTG
GCAAAAGAATTAAATATTAAGTCGTGTTCCTTCTTCAGTTCTAATGCTGTCCCCCTAAAA
GTCACAATGGTGAATGCTGACCCTATGGGAGAAGAAATTAATGTCATGTTTAAGGTTGGT
GAAGATCTTCGGCAAGATATGTTAGCTTTACAGATGATAAAGATTATGGATAAGATCTGG
CTTAAAGAAGGACTAGATCTGAGGATGGTAATTTTCAAATGTCTCTCAACTGGCAGAGAT
CGAGGCATGGTGGAGCTGGTTCCTGCTTCCGATACCCTCAGGAAAATCCAAGTGGAATAT
GGTGTGACAGGATCCTTTAAAGATAAACCACTTGCAGAGTGGCTAAGGAAATACAATCCC
TCTGAAGAAGAATATGAAAAGGCTTCAGAGAACTTTATCTATTCCTGTGCTGGATGCTGT
GTAGCCACCTATGTTTTAGGCATCTGTGATCGACACAATGACAATATAATGCTTCGAAGC
ACGGGACACATGTTTCACATTGACTTTGGAAAGTTTTTGGGACATGCACAGATGTTTGGC
AGCTTCAAAAGGGATCGGGCTCCTTTTGTGCTGACCTCTGATATGGCATATGTCATTAAT
GGGGGTGAAAAGCCCACCATTCGTTTTCAGTTGTTTGTGGACCTCTGCTGTCAGGCCTAC
AACTTGATAAGAAAGCAGACAAACCTTTTTCTTAACCTCCTTTCACTGATGATTCCTTCA
GGGTTACCAGAACTTACAAGTATTCAAGATTTGAAATACGTTAGAGATGCACTTCAACCC
CAAACTACAGACGCAGAAGCTACAATTTTCTTTACTAGGCTTATTGAATCAAGTTTGGGA
AGCATTGCCACAAAGTTTAACTTCTTCATTCACAACCTTGCTCAGCTTCGTTTTTCTGGT
CTTCCTTCTAATGATGAGCCCATCCTTTCATTTTCACCTAAAACATACTCCTTTAGACAA
GATGGTCGAATCAAGGAAGTCTCTGTTTTTACATATCATAAGAAATACAACCCAGATAAA
CATTATATTTATGTAGTCCGAATTTTGAGGGAAGGACAGATTGAACCATCATTTGTCTTC
CGAACATTTGACGAATTTCAGGAACTTCACAATAAGCTCAGTATTATTTTTCCACTTTGG
AAGTTACCAGGCTTTCCTAATAGGATGGTTCTAGGAAGAACACACATAAAAGATGTAGCA
GCCAAAAGGAAAATTGAGTTAAACAGTTACTTACAGAGTTTGATGAATGCTTCAACGGAT
GTAGCAGAGTGTGATCTTGTTTGTACTTTCTTCCACCCTTTACTTCGTGATGAGAAAGCT
GAAGGGATAGCTAGGTCTGCAGATGCAGGTTCCTTCAGTCCTACTCCAGGCCAAATAGGA
GGAGCTGTGAAATTATCCATCTCTTACCGAAATGGTACTCTTTTCATCATGGTGATGCAT
ATCAAAGATCTTGTTACTGAAGATGGAGCTGACCCAAATCCATATGTCAAAACATACCTA
CTTCCAGATAACCACAAAACATCCAAACGTAAAACCAAAATTTCACGAAAAACGAGGAAT
CCGACATTCAATGAAATGCTTGTATACAGTGGATATAGCAAAGAAACCCTAAGACAGCGA
GAACTTCAACTAAGTGTACTCAGTGCAGAATCTCTGCGGGAGAATTTTTTCTTGGGTGGA
GTAACCCTGCCTTTGAAAGATTTCAACTTGAGCAAAGAGACGGTTAAATGGTATCAGCTG
ACTGCGGCAACATACTTGTAA
Protein Properties
Number of Residues 1686
Molecular Weight 190677.8
Theoretical pI 8.1
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing subunit alpha
MAQISSNSGFKECPSSHPEPTRAKDVDKEEALQMEAEALAKLQKDRQVTDNQRGFELSSS
TRKKAQVYNKQDYDLMVFPESDSQKRALDIDVEKLTQAELEKLLLDDSFETKKTPVLPVT
PILSPSFSAQLYFRPTIQRGQWPPGLPGPSTYALPSIYPSTYSKQAAFQNGFNPRMPTFP
STEPIYLSLPGQSPYFSYPLTPATPFHPQGSLPIYRPVVSTDMAKLFDKIASTSEFLKNG
KARTDLEITDSKVSNLQVSPKSEDISKFDWLDLDPLSKPKVDNVEVLDHEEEKNVSSLLA
KDPWDAVLLEERSTANCHLERKVNGKSLSVATVTRSQSLNIRTTQLAKAQGHISQKDPNG
TSSLPTGSSLLQEVEVQNEEMAAFCRSITKLKTKFPYTNHRTNPGYLLSPVTAQRNICGE
NASVKVSIDIEGFQLPVTFTCDVSSTVEIIIMQALCWVHDDLNQVDVGSYVLKVCGQEEV
LQNNHCLGSHEHIQNCRKWDTEIRLQLLTFSAMCQNLARTAEDDETPVDLNKHLYQIEKP
CKEAMTRHPVEELLDSYHNQVELALQIENQHRAVDQVIKAVRKICSALDGVETLAITESV
KKLKRAVNLPRSKTADVTSLFGGEDTSRSSTRGSLNPENPVQVSINQLTAAIYDLLRLHA
NSGRSPTDCAQSSKSVKEAWTTTEQLQFTIFAAHGISSNWVSNYEKYYLICSLSHNGKDL
FKPIQSKKVGTYKNFFYLIKWDELIIFPIQISQLPLESVLHLTLFGILNQSSGSSPDSNK
QRKGPEALGKVSLPLFDFKRFLTCGTKLLYLWTSSHTNSVPGTVTKKGYVMERIVLQVDF
PSPAFDIIYTTPQVDRSIIQQHNLETLENDIKGKLLDILHKDSSLGLSKEDKAFLWEKRY
YCFKHPNCLPKILASAPNWKWVNLAKTYSLLHQWPALYPLIALELLDSKFADQEVRSLAV
TWIEAISDDELTDLLPQFVQALKYEIYLNSSLVQFLLSRALGNIQIAHNLYWLLKDALHD
VQFSTRYEHVLGALLSVGGKRLREELLKQTKLVQLLGGVAEKVRQASGSARQVVLQRSME
RVQSFFQKNKCRLPLKPSLVAKELNIKSCSFFSSNAVPLKVTMVNADPMGEEINVMFKVG
EDLRQDMLALQMIKIMDKIWLKEGLDLRMVIFKCLSTGRDRGMVELVPASDTLRKIQVEY
GVTGSFKDKPLAEWLRKYNPSEEEYEKASENFIYSCAGCCVATYVLGICDRHNDNIMLRS
TGHMFHIDFGKFLGHAQMFGSFKRDRAPFVLTSDMAYVINGGEKPTIRFQLFVDLCCQAY
NLIRKQTNLFLNLLSLMIPSGLPELTSIQDLKYVRDALQPQTTDAEATIFFTRLIESSLG
SIATKFNFFIHNLAQLRFSGLPSNDEPILSFSPKTYSFRQDGRIKEVSVFTYHKKYNPDK
HYIYVVRILREGQIEPSFVFRTFDEFQELHNKLSIIFPLWKLPGFPNRMVLGRTHIKDVA
AKRKIELNSYLQSLMNASTDVAECDLVCTFFHPLLRDEKAEGIARSADAGSFSPTPGQIG
GAVKLSISYRNGTLFIMVMHIKDLVTEDGADPNPYVKTYLLPDNHKTSKRKTKISRKTRN
PTFNEMLVYSGYSKETLRQRELQLSVLSAESLRENFFLGGVTLPLKDFNLSKETVKWYQL
TAATYL
GenBank ID Protein 109731357
UniProtKB/Swiss-Prot ID O00443
UniProtKB/Swiss-Prot Entry Name P3C2A_HUMAN
PDB IDs Not Available
GenBank Gene ID BC113658
GeneCard ID PIK3C2A
GenAtlas ID PIK3C2A
HGNC ID HGNC:8971
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  3. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332 ]
  4. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [PubMed:18691976 ]
  5. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [PubMed:19369195 ]
  6. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330 ]
  7. Wang B, Malik R, Nigg EA, Korner R: Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis. Anal Chem. 2008 Dec 15;80(24):9526-33. doi: 10.1021/ac801708p. [PubMed:19007248 ]
  8. Arcaro A, Zvelebil MJ, Wallasch C, Ullrich A, Waterfield MD, Domin J: Class II phosphoinositide 3-kinases are downstream targets of activated polypeptide growth factor receptors. Mol Cell Biol. 2000 Jun;20(11):3817-30. [PubMed:10805725 ]
  9. El Sheikh SS, Domin J, Tomtitchong P, Abel P, Stamp G, Lalani EN: Topographical expression of class IA and class II phosphoinositide 3-kinase enzymes in normal human tissues is consistent with a role in differentiation. BMC Clin Pathol. 2003 Oct 16;3(1):4. [PubMed:14563213 ]
  10. Domin J, Pages F, Volinia S, Rittenhouse SE, Zvelebil MJ, Stein RC, Waterfield MD: Cloning of a human phosphoinositide 3-kinase with a C2 domain that displays reduced sensitivity to the inhibitor wortmannin. Biochem J. 1997 Aug 15;326 ( Pt 1):139-47. [PubMed:9337861 ]
  11. Domin J, Gaidarov I, Smith ME, Keen JH, Waterfield MD: The class II phosphoinositide 3-kinase PI3K-C2alpha is concentrated in the trans-Golgi network and present in clathrin-coated vesicles. J Biol Chem. 2000 Apr 21;275(16):11943-50. [PubMed:10766823 ]
  12. Didichenko SA, Thelen M: Phosphatidylinositol 3-kinase c2alpha contains a nuclear localization sequence and associates with nuclear speckles. J Biol Chem. 2001 Dec 21;276(51):48135-42. Epub 2001 Oct 17. [PubMed:11606566 ]
  13. Gaidarov I, Smith ME, Domin J, Keen JH: The class II phosphoinositide 3-kinase C2alpha is activated by clathrin and regulates clathrin-mediated membrane trafficking. Mol Cell. 2001 Feb;7(2):443-9. [PubMed:11239472 ]
  14. Didichenko SA, Fragoso CM, Thelen M: Mitotic and stress-induced phosphorylation of HsPI3K-C2alpha targets the protein for degradation. J Biol Chem. 2003 Jul 11;278(28):26055-64. Epub 2003 Apr 28. [PubMed:12719431 ]
  15. Stahelin RV, Karathanassis D, Bruzik KS, Waterfield MD, Bravo J, Williams RL, Cho W: Structural and membrane binding analysis of the Phox homology domain of phosphoinositide 3-kinase-C2alpha. J Biol Chem. 2006 Dec 22;281(51):39396-406. Epub 2006 Oct 12. [PubMed:17038310 ]