Protein O-GlcNAcase

Details

Name
Protein O-GlcNAcase
Synonyms
  • 3.2.1.169
  • Beta-hexosaminidase
  • Beta-N-acetylglucosaminidase
  • Beta-N-acetylhexosaminidase
  • HEXC
  • KIAA0679
  • MEA5
  • Meningioma-expressed antigen 5
  • N-acetyl-beta-D-glucosaminidase
  • N-acetyl-beta-glucosaminidase
  • NCOAT
  • Nuclear cytoplasmic O-GlcNAcase and acetyltransferase
  • OGA
Gene Name
MGEA5
Organism
Humans
Amino acid sequence
>lcl|BSEQ0009856|Protein O-GlcNAcase
MVQKESQATLEERESELSSNPAASAGASLEPPAAPAPGEDNPAGAGGAAVAGAAGGARRF
LCGVVEGFYGRPWVMEQRKELFRRLQKWELNTYLYAPKDDYKHRMFWREMYSVEEAEQLM
TLISAAREYEIEFIYAISPGLDITFSNPKEVSTLKRKLDQVSQFGCRSFALLFDDIDHNM
CAADKEVFSSFAHAQVSITNEIYQYLGEPETFLFCPTEYCGTFCYPNVSQSPYLRTVGEK
LLPGIEVLWTGPKVVSKEIPVESIEEVSKIIKRAPVIWDNIHANDYDQKRLFLGPYKGRS
TELIPRLKGVLTNPNCEFEANYVAIHTLATWYKSNMNGVRKDVVMTDSEDSTVSIQIKLE
NEGSDEDIETDVLYSPQMALKLALTEWLQEFGVPHQYSSRQVAHSGAKASVVDGTPLVAA
PSLNATTVVTTVYQEPIMSQGAALSGEPTTLTKEEEKKQPDEEPMDMVVEKQEETDHKND
NQILSEIVEAKMAEELKPMDTDKESIAESKSPEMSMQEDCISDIAPMQTDEQTNKEQFVP
GPNEKPLYTAEPVTLEDLQLLADLFYLPYEHGPKGAQMLREFQWLRANSSVVSVNCKGKD
SEKIEEWRSRAAKFEEMCGLVMGMFTRLSNCANRTILYDMYSYVWDIKSIMSMVKSFVQW
LGCRSHSSAQFLIGDQEPWAFRGGLAGEFQRLLPIDGANDLFFQPPPLTPTSKVYTIRPY
FPKDEASVYKICREMYDDGVGLPFQSQPDLIGDKLVGGLLSLSLDYCFVLEDEDGICGYA
LGTVDVTPFIKKCKISWIPFMQEKYTKPNGDKELSEAEKIMLSFHEEQEVLPETFLANFP
SLIKMDIHKKVTDPSVAKSMMACLLSSLKANGSRGAFCEVRPDDKRILEFYSKLGCFEIA
KMEGFPKDVVILGRSL
Number of residues
916
Molecular Weight
102914.215
Theoretical pI
Not Available
GO Classification
Functions
beta-N-acetylglucosaminidase activity / histone acetyltransferase activity / hyalurononglucosaminidase activity
Processes
aging / dATP metabolic process / glycoprotein catabolic process / N-acetylglucosamine metabolic process / necrotic cell death / negative regulation of cardiac muscle adaptation / negative regulation of protein glycosylation / positive regulation of calcium ion transport into cytosol / positive regulation of cell killing / positive regulation of DNA metabolic process / positive regulation of glucose import / positive regulation of growth hormone secretion / positive regulation of insulin secretion / positive regulation of mitochondrial depolarization / positive regulation of protein complex disassembly / positive regulation of proteolysis / protein deglycosylation / protein targeting to membrane / response to steroid hormone
Components
cytosol / membrane / mitochondrion / nucleus
General Function
Hyalurononglucosaminidase activity
Specific Function
Isoform 1: Cleaves GlcNAc but not GalNAc from O-glycosylated proteins. Can use p-nitrophenyl-beta-GlcNAc and 4-methylumbelliferone-GlcNAc as substrates but not p-nitrophenyl-beta-GalNAc or p-nitrophenyl-alpha-GlcNAc (in vitro) (PubMed:11148210). Does not bind acetyl-CoA and does not have histone acetyltransferase activity (PubMed:24088714).Isoform 3: Cleaves GlcNAc but not GalNAc from O-glycosylated proteins. Can use p-nitrophenyl-beta-GlcNAc as substrate but not p-nitrophenyl-beta-GalNAc or p-nitrophenyl-alpha-GlcNAc (in vitro), but has about six times lower specific activity than isoform 1.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0020912|Protein O-GlcNAcase (MGEA5)
ATGGTGCAGAAGGAGAGTCAAGCGACGTTGGAGGAGCGGGAGAGCGAGCTCAGCTCCAAC
CCTGCCGCCTCTGCGGGGGCATCGCTGGAGCCGCCGGCAGCTCCGGCACCCGGAGAAGAC
AACCCCGCCGGGGCTGGGGGAGCGGCGGTGGCCGGGGCTGCAGGAGGGGCTCGGCGGTTC
CTCTGCGGTGTGGTGGAAGGATTTTATGGAAGACCTTGGGTTATGGAACAGAGAAAAGAA
CTCTTTAGAAGGCTCCAGAAATGGGAATTAAATACATACTTGTATGCCCCAAAAGATGAC
TACAAACATAGGATGTTTTGGCGAGAGATGTATTCAGTGGAGGAAGCTGAGCAACTTATG
ACTCTCATCTCTGCTGCACGAGAATATGAGATAGAGTTCATCTATGCGATCTCACCTGGA
TTGGATATCACTTTTTCTAACCCCAAGGAAGTATCCACATTGAAACGTAAATTGGACCAG
GTTTCTCAGTTTGGGTGCAGATCATTTGCTTTGCTTTTTGATGATATAGACCATAATATG
TGTGCAGCAGACAAAGAGGTATTCAGTTCTTTTGCTCATGCCCAAGTCTCCATCACAAAT
GAAATCTATCAGTACCTAGGAGAGCCAGAAACTTTCCTCTTCTGTCCCACAGAATACTGT
GGCACTTTCTGTTATCCAAATGTGTCTCAGTCTCCATATTTAAGGACTGTGGGTGAAAAG
CTTCTACCTGGAATTGAAGTGCTTTGGACAGGTCCCAAAGTTGTTTCTAAAGAAATTCCA
GTAGAGTCCATCGAAGAGGTTTCTAAGATTATTAAGAGAGCTCCAGTAATCTGGGATAAC
ATTCATGCTAATGATTATGATCAGAAGAGACTGTTTCTGGGCCCGTACAAAGGAAGATCC
ACAGAACTCATCCCACGGTTAAAAGGAGTCCTCACTAATCCAAATTGTGAATTTGAAGCC
AACTACGTTGCTATCCACACCCTTGCCACCTGGTACAAATCAAACATGAATGGAGTGAGA
AAAGATGTAGTGATGAGTAGGCAAGTTGCACACAGTGGAGCTAAAGCAAGTGTAGTTGAT
GGGACTCCTTTAGTTGCAGCACCCTCTTTAAATGCCACAACCGTAGTAACAACAGTTTAT
CAGGAGCCCATTATGAGCCAGGGAGCAGCCTTGAGTGGTGAGCCTACTACTCTGACCAAG
GAAGAAGAAAAGAAACAGCCTGATGAAGAACCCATGGACATGGTGGTGGAAAAACAAGAA
GAAACGGACCACAAGAATGACAATCAAATACTGAGTGAAATTGTTGAAGCGAAAATGGCA
GAGGAATTGAAACCAATGGACACTGATAAAGAGAGCATAGCTGAATCAAAATCCCCAGAG
ATGTCCATGCAAGAAGATTGTATTAGTGACATTGCCCCCATGCAAACTGATGAACAGACA
AACAAGGAGCAGTTTGTGCCAGGTCCAAATGAAAAGCCTTTGTACACTGCGGAACCAGTG
ACCCTGGAGGATTTGCAGTTACTTGCTGATCTATTCTACCTTCCTTACGAGCATGGACCC
AAAGGAGCACAGATGTTACGGGAATTTCAATGGCTTCGAGCAAATAGTAGTGTTGTCAGT
GTCAATTGCAAAGGAAAAGACTCTGAAAAAATTGAAGAATGGCGGTCACGAGCAGCCAAG
TTTGAAGAGATGTGTGGACTAGTGATGGGAATGTTCACTCGGCTCTCCAATTGTGCCAAC
AGGACAATTCTTTATGACATGTACTCCTATGTTTGGGATATCAAGAGTATAATGTCTATG
GTGAAGTCTTTTGTACAGTGGTTAGGGTGTCGTAGTCATTCTTCAGCACAATTCTTAATT
GGAGACCAAGAACCCTGGGCCTTTAGAGGTGGTCTAGCAGGAGAGTTCCAGCGTTTGCTG
CCAATTGATGGGGCAAATGATCTCTTTTTTCAGCCACCTCCACTGACTCCTACCTCCAAA
GTTTATACTATCAGACCTTATTTTCCTAAGGATGAGGCATCCGTGTACAAGATTTGCAGA
GAAATGTATGACGATGGAGTGGGTTTACCCTTTCAAAGTCAGCCTGATCTTATTGGAGAC
AAGTTAGTAGGAGGGCTGCTTTCCCTCAGCCTGGATTACTGCTTTGTCCTAGAAGATGAA
GATGGCATATGTGGTTATGCCTTGGGCACTGTAGATGTGACCCCCTTTATTAAAAAATGT
AAAATTTCCTGGATCCCCTTCATGCAGGAGAAGTATACCAAGCCAAATGGTGACAAGGAA
CTCTCTGAGGCTGAGAAAATAATGTTGAGTTTCCATGAAGAACAGGAAGTACTGCCAGAA
ACTTTCCTTGCTAATTTCCCTTCTCTGATAAAGATGGACATTCACAAAAAAGTAACTGAC
CCAAGTGTGGCCAAAAGCATGATGGCTTGCCTCCTGTCTTCACTGAAGGCTAATGGCTCC
CGGGGAGCTTTCTGTGAAGTGAGACCAGATGATAAAAGAATTCTGGAATTTTACAGCAAG
TTAGGATGTTTTGAAATTGCAAAAATGGAAGGATTTCCAAAGGATGTGGTTATACTTGGT
CGGAGCCTGTGA
Chromosome Location
10
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDO60502
UniProtKB Entry NameOGA_HUMAN
HGNC IDHGNC:7056
General References
  1. Heckel D, Comtesse N, Brass N, Blin N, Zang KD, Meese E: Novel immunogenic antigen homologous to hyaluronidase in meningioma. Hum Mol Genet. 1998 Nov;7(12):1859-72. [PubMed:9811929]
  2. Comtesse N, Maldener E, Meese E: Identification of a nuclear variant of MGEA5, a cytoplasmic hyaluronidase and a beta-N-acetylglucosaminidase. Biochem Biophys Res Commun. 2001 May 11;283(3):634-40. [PubMed:11341771]
  3. Gao Y, Wells L, Comer FI, Parker GJ, Hart GW: Dynamic O-glycosylation of nuclear and cytosolic proteins: cloning and characterization of a neutral, cytosolic beta-N-acetylglucosaminidase from human brain. J Biol Chem. 2001 Mar 30;276(13):9838-45. Epub 2001 Jan 8. [PubMed:11148210]
  4. Ishikawa K, Nagase T, Suyama M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O: Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. DNA Res. 1998 Jun 30;5(3):169-76. [PubMed:9734811]
  5. Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T: Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones. DNA Res. 2002 Jun 30;9(3):99-106. [PubMed:12168954]
  6. Deloukas P, Earthrowl ME, Grafham DV, Rubenfield M, French L, Steward CA, Sims SK, Jones MC, Searle S, Scott C, Howe K, Hunt SE, Andrews TD, Gilbert JG, Swarbreck D, Ashurst JL, Taylor A, Battles J, Bird CP, Ainscough R, Almeida JP, Ashwell RI, Ambrose KD, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Bates K, Beasley H, Bray-Allen S, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Cahill P, Camire D, Carter NP, Chapman JC, Clark SY, Clarke G, Clee CM, Clegg S, Corby N, Coulson A, Dhami P, Dutta I, Dunn M, Faulkner L, Frankish A, Frankland JA, Garner P, Garnett J, Gribble S, Griffiths C, Grocock R, Gustafson E, Hammond S, Harley JL, Hart E, Heath PD, Ho TP, Hopkins B, Horne J, Howden PJ, Huckle E, Hynds C, Johnson C, Johnson D, Kana A, Kay M, Kimberley AM, Kershaw JK, Kokkinaki M, Laird GK, Lawlor S, Lee HM, Leongamornlert DA, Laird G, Lloyd C, Lloyd DM, Loveland J, Lovell J, McLaren S, McLay KE, McMurray A, Mashreghi-Mohammadi M, Matthews L, Milne S, Nickerson T, Nguyen M, Overton-Larty E, Palmer SA, Pearce AV, Peck AI, Pelan S, Phillimore B, Porter K, Rice CM, Rogosin A, Ross MT, Sarafidou T, Sehra HK, Shownkeen R, Skuce CD, Smith M, Standring L, Sycamore N, Tester J, Thorpe A, Torcasso W, Tracey A, Tromans A, Tsolas J, Wall M, Walsh J, Wang H, Weinstock K, West AP, Willey DL, Whitehead SL, Wilming L, Wray PW, Young L, Chen Y, Lovering RC, Moschonas NK, Siebert R, Fechtel K, Bentley D, Durbin R, Hubbard T, Doucette-Stamm L, Beck S, Smith DR, Rogers J: The DNA sequence and comparative analysis of human chromosome 10. Nature. 2004 May 27;429(6990):375-81. [PubMed:15164054]
  7. 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]
  8. Wells L, Gao Y, Mahoney JA, Vosseller K, Chen C, Rosen A, Hart GW: Dynamic O-glycosylation of nuclear and cytosolic proteins: further characterization of the nucleocytoplasmic beta-N-acetylglucosaminidase, O-GlcNAcase. J Biol Chem. 2002 Jan 18;277(3):1755-61. [PubMed:11788610]
  9. Cetinbas N, Macauley MS, Stubbs KA, Drapala R, Vocadlo DJ: Identification of Asp174 and Asp175 as the key catalytic residues of human O-GlcNAcase by functional analysis of site-directed mutants. Biochemistry. 2006 Mar 21;45(11):3835-44. [PubMed:16533067]
  10. Butkinaree C, Cheung WD, Park S, Park K, Barber M, Hart GW: Characterization of beta-N-acetylglucosaminidase cleavage by caspase-3 during apoptosis. J Biol Chem. 2008 Aug 29;283(35):23557-66. doi: 10.1074/jbc.M804116200. Epub 2008 Jun 27. [PubMed:18586680]
  11. 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]
  12. 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]
  13. 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]
  14. Schimpl M, Schuttelkopf AW, Borodkin VS, van Aalten DM: Human OGA binds substrates in a conserved peptide recognition groove. Biochem J. 2010 Nov 15;432(1):1-7. doi: 10.1042/BJ20101338. [PubMed:20863279]
  15. Li J, Huang CL, Zhang LW, Lin L, Li ZH, Zhang FW, Wang P: Isoforms of human O-GlcNAcase show distinct catalytic efficiencies. Biochemistry (Mosc). 2010 Jul;75(7):938-43. [PubMed:20673219]
  16. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [PubMed:20068231]
  17. 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. [PubMed:21269460]
  18. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. [PubMed:21406692]
  19. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. [PubMed:22814378]
  20. Rao FV, Schuttelkopf AW, Dorfmueller HC, Ferenbach AT, Navratilova I, van Aalten DM: Structure of a bacterial putative acetyltransferase defines the fold of the human O-GlcNAcase C-terminal domain. Open Biol. 2013 Oct 2;3(10):130021. doi: 10.1098/rsob.130021. [PubMed:24088714]
  21. Schimpl M, Borodkin VS, Gray LJ, van Aalten DM: Synergy of peptide and sugar in O-GlcNAcase substrate recognition. Chem Biol. 2012 Feb 24;19(2):173-8. doi: 10.1016/j.chembiol.2012.01.011. [PubMed:22365600]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00428Streptozocinapproved, investigationalunknownDetails