Phosphatidylinositol 3-kinase catalytic subunit type 3

Details

Name
Phosphatidylinositol 3-kinase catalytic subunit type 3
Synonyms
  • 2.7.1.137
  • hVps34
  • Phosphatidylinositol 3-kinase p100 subunit
  • Phosphoinositide-3-kinase class 3
  • PI3-kinase type 3
  • VPS34
Gene Name
PIK3C3
Organism
Humans
Amino acid sequence
>lcl|BSEQ0019463|Phosphatidylinositol 3-kinase catalytic subunit type 3
MGEAEKFHYIYSCDLDINVQLKIGSLEGKREQKSYKAVLEDPMLKFSGLYQETCSDLYVT
CQVFAEGKPLALPVRTSYKAFSTRWNWNEWLKLPVKYPDLPRNAQVALTIWDVYGPGKAV
PVGGTTVSLFGKYGMFRQGMHDLKVWPNVEADGSEPTKTPGRTSSTLSEDQMSRLAKLTK
AHRQGHMVKVDWLDRLTFREIEMINESEKRSSNFMYLMVEFRCVKCDDKEYGIVYYEKDG
DESSPILTSFELVKVPDPQMSMENLVESKHHKLARSLRSGPSDHDLKPNAATRDQLNIIV
SYPPTKQLTYEEQDLVWKFRYYLTNQEKALTKFLKCVNWDLPQEAKQALELLGKWKPMDV
EDSLELLSSHYTNPTVRRYAVARLRQADDEDLLMYLLQLVQALKYENFDDIKNGLEPTKK
DSQSSVSENVSNSGINSAEIDSSQIITSPLPSVSSPPPASKTKEVPDGENLEQDLCTFLI
SRACKNSTLANYLYWYVIVECEDQDTQQRDPKTHEMYLNVMRRFSQALLKGDKSVRVMRS
LLAAQQTFVDRLVHLMKAVQRESGNRKKKNERLQALLGDNEKMNLSDVELIPLPLEPQVK
IRGIIPETATLFKSALMPAQLFFKTEDGGKYPVIFKHGDDLRQDQLILQIISLMDKLLRK
ENLDLKLTPYKVLATSTKHGFMQFIQSVPVAEVLDTEGSIQNFFRKYAPSENGPNGISAE
VMDTYVKSCAGYCVITYILGVGDRHLDNLLLTKTGKLFHIDFGYILGRDPKPLPPPMKLN
KEMVEGMGGTQSEQYQEFRKQCYTAFLHLRRYSNLILNLFSLMVDANIPDIALEPDKTVK
KVQDKFRLDLSDEEAVHYMQSLIDESVHALFAAVVEQIHKFAQYWRK
Number of residues
887
Molecular Weight
101548.63
Theoretical pI
6.79
GO Classification
Functions
1-phosphatidylinositol-3-kinase activity / ATP binding / protein kinase activity
Processes
autophagosome assembly / cellular response to glucose starvation / cytokinesis / early endosome to late endosome transport / endosome organization / innate immune response / insulin receptor signaling pathway / macroautophagy / phosphatidylinositol biosynthetic process / phosphatidylinositol-3-phosphate biosynthetic process / phosphatidylinositol-mediated signaling / phospholipid metabolic process / protein processing / regulation of cytokinesis / regulation of protein secretion / response to leucine / small molecule metabolic process / toll-like receptor 9 signaling pathway / toll-like receptor signaling pathway
Components
autophagosome / axoneme / cytosol / late endosome / membrane / midbody / phagocytic vesicle / phosphatidylinositol 3-kinase complex / phosphatidylinositol 3-kinase complex, class III
General Function
Protein kinase activity
Specific Function
Catalytic subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis. Involved in regulation of degradative endocytic trafficking and required for the abcission step in cytokinesis, probably in the context of PI3KC3-C2 (PubMed:20643123, PubMed:20208530). Involved in the transport of lysosomal enzyme precursors to lysosomes. Required for transport from early to late endosomes (By similarity).
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Midbody
Gene sequence
>lcl|BSEQ0007162|2664 bp
ATGGGGGAAGCAGAGAAGTTTCACTACATCTATAGTTGTGACCTGGATATCAACGTCCAG
CTTAAGATAGGAAGCTTGGAAGGGAAGAGAGAACAAAAGAGTTATAACGCTGTCCTGGAA
GACCCAATGTTGAAGTTCTCAGGACTATATCAAGAGACATGCTCTGATCTTTATGTTACT
TGTCAAGTTTTTGCAGAAGGGAAGCCTTCGGCCTTGCCAGTGAGAACATCCTACAAAGCA
TTTAGTACAAGATGGAACTGGAATGAATGGCTGAAACTACCAGTAAAATACCCTGACCTG
CCCAGGAATGCCCAAGTGGCCCTCACCATATGGGATGTGTATGGTCCCGGAAAAGCAGTG
CCTGTAGGAGGAACAACGGTTTCGCTCTTTGGAAAATACGGCATGTCTCGCCAAGGGATG
CATGACTTGAAAGTCTGGCCTAATGTAGAAGCAGATGGATCAGAACCCACAAATACTCCT
GGCAGAACAAGTAGCACTCTCTCAGAAGATCAGATGAGCCGTCTTGCCAAGCTCACCAAA
GCTCATCGACAAGGACACATGGTGAAAGTAGATTGGCTGGATAGATTGACATTTAGAGAA
ATAGAAATGATAAATGAGAGTGTGAAACGAAGTTCTAATTTCATGTACCTGATGGGTGGA
TTTCGATGTGTCAAGTGTGATGATAAGGAATATGGTATTGTTTATTATGAAAAGGACGGT
GATGAATCATCTCCAATTTTAACAAGTTTTGAATTAGTGAAAGTTCCTGACCCCCAGATG
TCCCTGGAGAATTTAGTTGAGAGCAAACACCACAACCTTCCCCGGAGTTTAAGAAGTGGA
CCTTCTGACCACGATCTGAAACCCTATCCTTCCCCGAGAGATCAGTTAAAAAATATTGTG
AGTTATCCTCCATCCAAGCCACCCACATATGAAGAACAAGATCTTGTTTGGGAGTTTAGA
TATTATCTTACGAATCAAGATAAAGCCTTGACCAAAATCCTGACATCTGTTATTTGGGAT
CTACCTCAGGGGGCCAAACAGGCCTTGGCACTTCTGGGGAAATGGAACCCGATGGATGTA
GAGGACTCCTTGGAGCTGATATCCTCTCATTACACCAACCCAACTGTGAGGCGTTATGCT
GTTGCCCGGTTGCGACAGGCCGATGATGAGGATTTGTTGATGTACCTATCACAATTGGTC
CAGGCTCTCAAATATGAAAATTTTGATGATATAAAGAATGGATTGGAACCTACCAAGAAG
GATAGTCAGAGTTCAGTGTCAGGAAATGTGTCAAATTCTGGAATAAATTCTGCAGAAATA
GATAGCTCCCAAATTATAACCAGCCCCCTTCCTTCAGTCTCTTCACCTCCTCCTGCATCA
AAAACAAAAGAAGTTCCAGATGGCGAAAATCTGGAACAAGATCTCTGTACCTTCTTGATA
TCGAGAGCCTCCAAAAACTCAACACTGGCTAATTATTTATACTGGTATGTGATAGTGGAA
TGTGAAGATCAAGATACTCAGCAGAGAGATCCAAAGACCCATGAGATGTACTTGAACGTA
ATGAGAAGATTCAGCCAAGCATTGTTGAAGGGTGATAAGTCTGTCAGAGTTATGCGTTCT
TTGCTGGCTGCACAACAGACATTTGTAGATCGGTTGGTGCATCTAATGAAGGCAGTACAA
CGCGAAAGTGGAAATCGTAAGAAAAAGAATGAGAGACTACAGGCATTGCTTGGAGATAAT
GAAAAGATGAATTTGTCAGATGTGGAACTTATCCCGTTGCCTTTAGAACCCCAAGTGAAA
ATTAGAGGAATAATTCCGGAAACAGCTACACTGTTTAAAAGTGCCCTTATGCCTGCACAG
TTGTTTTTTAAGACGGAAGATGGAGGCAAATATCCAGTTATATTTAAGCATGGAGATGAT
TTACGTCAAGATCAACTTATTCTTCAAATCATTTCACTCATGGACAAGCTGTTACGGAAA
GAAAATCTGGACTTGAAATTGACACCTTATAAGGTGTTAGCCACCAGTACAAAACATGGC
TTCATGCAGTTTATCCAGTCAGTTCCTGTGGCTGAAGTTCTTGATACAGAGGGAAGCATT
CAGAACTTTTTTAGAAAATATGCACCAAGTGAGAATGGGCCAAATGGGATTAGTGCTGAG
GTCATGGACACTTACGTTAAAAGCTGTGCTGGATATTGCGTGATCACCTATATACTTGGA
GTTGGAGACAGGCACCTGGATAACCTTGTGCTAACAAAAACAGGCAAACTCTTCCACATA
GACTTTGGATATATTTTGGGTCGGGATCCAAAGCCTCTTCCTCCACCAATGAAGCTGAAT
AAAGAAATGGTAGAAGGAATGGGGGGCACACAGAGTGAGCAGTACCAAGAGTTCCGTAAA
CAGTGTTACACGGCTTTCCTCCACCTGCGGAGGTATTCTAATCTGATTTTGAACTTGTTT
TCCTTGATGGTTGATCCAAACATTCCAGATATTGCACTTGAACCAGATAAAACTGTGAAA
AAGGTTCAGGATAAATTCCGCTTAGACCTGTCGGATGAAGAGGCTGTGCATTACATGCAG
AGTCTGATTGATGAGAGTGTCCATGCTCTTTTTGCTGCAGTGGTGGAACAGATTCACAAG
TTTGCCCAGTACTGGAGAAAATGA
Chromosome Location
Not Available
Locus
18q12.3
External Identifiers
ResourceLink
UniProtKB IDQ8NEB9
UniProtKB Entry NamePK3C3_HUMAN
GenBank Protein ID987948
GenBank Gene IDZ46973
HGNC IDHGNC:8974
General References
  1. Volinia S, Dhand R, Vanhaesebroeck B, MacDougall LK, Stein R, Zvelebil MJ, Domin J, Panaretou C, Waterfield MD: A human phosphatidylinositol 3-kinase complex related to the yeast Vps34p-Vps15p protein sorting system. EMBO J. 1995 Jul 17;14(14):3339-48. [Article]
  2. 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. [Article]
  3. Stein MP, Feng Y, Cooper KL, Welford AM, Wandinger-Ness A: Human VPS34 and p150 are Rab7 interacting partners. Traffic. 2003 Nov;4(11):754-71. [Article]
  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. [Article]
  5. Sun Q, Fan W, Chen K, Ding X, Chen S, Zhong Q: Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class III phosphatidylinositol 3-kinase. Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19211-6. doi: 10.1073/pnas.0810452105. Epub 2008 Dec 2. [Article]
  6. 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. [Article]
  7. Thoresen SB, Pedersen NM, Liestol K, Stenmark H: A phosphatidylinositol 3-kinase class III sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1 regulates cytokinesis and degradative endocytic traffic. Exp Cell Res. 2010 Dec 10;316(20):3368-78. doi: 10.1016/j.yexcr.2010.07.008. Epub 2010 Jul 17. [Article]
  8. Matsunaga K, Saitoh T, Tabata K, Omori H, Satoh T, Kurotori N, Maejima I, Shirahama-Noda K, Ichimura T, Isobe T, Akira S, Noda T, Yoshimori T: Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages. Nat Cell Biol. 2009 Apr;11(4):385-96. doi: 10.1038/ncb1846. Epub 2009 Mar 8. [Article]
  9. Sagona AP, Nezis IP, Pedersen NM, Liestol K, Poulton J, Rusten TE, Skotheim RI, Raiborg C, Stenmark H: PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment of FYVE-CENT to the midbody. Nat Cell Biol. 2010 Apr;12(4):362-71. doi: 10.1038/ncb2036. Epub 2010 Mar 7. [Article]
  10. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  11. Ma C, Wang N, Detre C, Wang G, O'Keeffe M, Terhorst C: Receptor signaling lymphocyte-activation molecule family 1 (Slamf1) regulates membrane fusion and NADPH oxidase 2 (NOX2) activity by recruiting a Beclin-1/Vps34/ultraviolet radiation resistance-associated gene (UVRAG) complex. J Biol Chem. 2012 May 25;287(22):18359-65. doi: 10.1074/jbc.M112.367060. Epub 2012 Apr 9. [Article]
  12. He C, Wei Y, Sun K, Li B, Dong X, Zou Z, Liu Y, Kinch LN, Khan S, Sinha S, Xavier RJ, Grishin NV, Xiao G, Eskelinen EL, Scherer PE, Whistler JL, Levine B: Beclin 2 functions in autophagy, degradation of G protein-coupled receptors, and metabolism. Cell. 2013 Aug 29;154(5):1085-99. doi: 10.1016/j.cell.2013.07.035. Epub 2013 Aug 15. [Article]
  13. Fogel AI, Dlouhy BJ, Wang C, Ryu SW, Neutzner A, Hasson SA, Sideris DP, Abeliovich H, Youle RJ: Role of membrane association and Atg14-dependent phosphorylation in beclin-1-mediated autophagy. Mol Cell Biol. 2013 Sep;33(18):3675-88. doi: 10.1128/MCB.00079-13. Epub 2013 Jul 22. [Article]
  14. Baskaran S, Carlson LA, Stjepanovic G, Young LN, Kim do J, Grob P, Stanley RE, Nogales E, Hurley JH: Architecture and dynamics of the autophagic phosphatidylinositol 3-kinase complex. Elife. 2014 Dec 9;3. doi: 10.7554/eLife.05115. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB06836N-(5-{4-Chloro-3-[(2-hydroxyethyl)sulfamoyl]phenyl}-4-methyl-1,3-thiazol-2-yl)acetamideexperimentalunknownDetails
DB11962GSK-1059615investigationalyesinhibitorDetails