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Identification
HMDB Protein ID HMDBP07996
Secondary Accession Numbers
  • 13707
Name Protein SET
Synonyms
  1. HLA-DR-associated protein II
  2. I-2PP2A
  3. IGAAD
  4. Inhibitor of granzyme A-activated DNase
  5. PHAPII
  6. Phosphatase 2A inhibitor I2PP2A
  7. TAF-I
  8. Template-activating factor I
Gene Name SET
Protein Type Unknown
Biological Properties
General Function Involved in nucleosome assembly
Specific Function Multitasking protein, involved in apoptosis, transcription, nucleosome assembly and histone binding. Isoform 2 anti-apoptotic activity is mediated by inhibition of the GZMA- activated DNase, NME1. In the course of cytotoxic T-lymphocyte (CTL)-induced apoptosis, GZMA cleaves SET, disrupting its binding to NME1 and releasing NME1 inhibition. Isoform 1 and isoform 2 are potent inhibitors of protein phosphatase 2A. Isoform 1 and isoform 2 inhibit EP300/CREBBP and PCAF-mediated acetylation of histones (HAT) and nucleosomes, most probably by masking the accessibility of lysines of histones to the acetylases. The predominant target for inhibition is histone H4. HAT inhibition leads to silencing of HAT-dependent transcription and prevents active demethylation of DNA. Both isoforms stimulate DNA replication of the adenovirus genome complexed with viral core proteins; however, isoform 2 specific activity is higher
Pathways Not Available
Reactions Not Available
GO Classification
Component
organelle
membrane-bounded organelle
intracellular membrane-bounded organelle
nucleus
Process
cellular process
cellular component organization at cellular level
organelle organization
chromosome organization
chromatin organization
nucleosome assembly
nucleosome organization
Cellular Location
  1. Nucleus
  2. Cytoplasm
  3. Endoplasmic reticulum
  4. cytosol
  5. nucleoplasm
Gene Properties
Chromosome Location Chromosome:9
Locus 9q34
SNPs SET
Gene Sequence
>873 bp
ATGGCCCCTAAACGCCAGTCTCCACTCCCGCCTCAAAAGAAGAAACCAAGACCACCTCCT
GCTCTGGGACCGGAGGAGACATCGGCCTCTGCAGGCTTGCCGAAGAAGGGAGAAAAAGAA
CAGCAAGAAGCGATTGAACACATTGATGAAGTACAAAATGAAATAGACAGACTTAATGAA
CAAGCCAGTGAGGAGATTTTGAAAGTAGAACAGAAATATAACAAACTCCGCCAACCATTT
TTTCAGAAGAGGTCAGAATTGATCGCCAAAATCCCAAATTTTTGGGTAACAACATTTGTC
AACCATCCACAAGTGTCTGCACTGCTTGGGGAGGAAGATGAAGAGGCACTGCATTATTTG
ACCAGAGTTGAAGTGACAGAATTTGAAGATATTAAATCAGGTTACAGAATAGATTTTTAT
TTTGATGAAAATCCTTACTTTGAAAATAAAGTTCTCTCCAAAGAATTTCATCTGAATGAG
AGTGGTGATCCATCTTCGAAGTCCACCGAAATCAAATGGAAATCTGGAAAGGATTTGACG
AAACGTTCGAGTCAAACGCAGAATAAAGCCAGCAGGAAGAGGCAGCATGAGGAACCAGAG
AGCTTCTTTACCTGGTTTACTGACCATTCTGATGCAGGTGCTGATGAGTTAGGAGAGGTC
ATCAAAGATGATATTTGGCCAAACCCATTACAGTACTACTTGGTTCCCGATATGGATGAT
GAAGAAGGAGAAGGAGAAGAAGATGATGATGATGATGAAGAGGAGGAAGGATTAGAAGAT
ATTGACGAAGAAGGGGATGAGGATGAAGGTGAAGAAGATGAAGATGATGATGAAGGGGAG
GAAGGAGAGGAGGATGAAGGAGAAGATGACTAA
Protein Properties
Number of Residues 290
Molecular Weight 33488.6
Theoretical pI 3.95
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Protein SET
MAPKRQSPLPPQKKKPRPPPALGPEETSASAGLPKKGEKEQQEAIEHIDEVQNEIDRLNE
QASEEILKVEQKYNKLRQPFFQKRSELIAKIPNFWVTTFVNHPQVSALLGEEDEEALHYL
TRVEVTEFEDIKSGYRIDFYFDENPYFENKVLSKEFHLNESGDPSSKSTEIKWKSGKDLT
KRSSQTQNKASRKRQHEEPESFFTWFTDHSDAGADELGEVIKDDIWPNPLQYYLVPDMDD
EEGEGEEDDDDDEEEEGLEDIDEEGDEDEGEEDEDDDEGEEGEEDEGEDD
GenBank ID Protein 170763500
UniProtKB/Swiss-Prot ID Q01105
UniProtKB/Swiss-Prot Entry Name SET_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_001122821.1
GeneCard ID SET
GenAtlas ID SET
HGNC ID HGNC:10760
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. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  3. 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 ]
  4. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [PubMed:17081983 ]
  5. Yu LR, Zhu Z, Chan KC, Issaq HJ, Dimitrov DS, Veenstra TD: Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra. J Proteome Res. 2007 Nov;6(11):4150-62. Epub 2007 Oct 9. [PubMed:17924679 ]
  6. Imami K, Sugiyama N, Kyono Y, Tomita M, Ishihama Y: Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column. Anal Sci. 2008 Jan;24(1):161-6. [PubMed:18187866 ]
  7. Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J, Cheng T, Kho Y, Xiao H, Xiao L, Grishin NV, White M, Yang XJ, Zhao Y: Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. Mol Cell. 2006 Aug;23(4):607-18. [PubMed:16916647 ]
  8. Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. [PubMed:15164053 ]
  9. Molina H, Horn DM, Tang N, Mathivanan S, Pandey A: Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry. Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2199-204. Epub 2007 Feb 7. [PubMed:17287340 ]
  10. Fan Z, Beresford PJ, Oh DY, Zhang D, Lieberman J: Tumor suppressor NM23-H1 is a granzyme A-activated DNase during CTL-mediated apoptosis, and the nucleosome assembly protein SET is its inhibitor. Cell. 2003 Mar 7;112(5):659-72. [PubMed:12628186 ]
  11. Meierhofer D, Wang X, Huang L, Kaiser P: Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry. J Proteome Res. 2008 Oct;7(10):4566-76. doi: 10.1021/pr800468j. Epub 2008 Sep 10. [PubMed:18781797 ]
  12. 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 ]
  13. Carrascal M, Ovelleiro D, Casas V, Gay M, Abian J: Phosphorylation analysis of primary human T lymphocytes using sequential IMAC and titanium oxide enrichment. J Proteome Res. 2008 Dec;7(12):5167-76. [PubMed:19367720 ]
  14. Kitajima TS, Sakuno T, Ishiguro K, Iemura S, Natsume T, Kawashima SA, Watanabe Y: Shugoshin collaborates with protein phosphatase 2A to protect cohesin. Nature. 2006 May 4;441(7089):46-52. Epub 2006 Mar 15. [PubMed:16541025 ]
  15. von Lindern M, van Baal S, Wiegant J, Raap A, Hagemeijer A, Grosveld G: Can, a putative oncogene associated with myeloid leukemogenesis, may be activated by fusion of its 3' half to different genes: characterization of the set gene. Mol Cell Biol. 1992 Aug;12(8):3346-55. [PubMed:1630450 ]
  16. Vaesen M, Barnikol-Watanabe S, Gotz H, Awni LA, Cole T, Zimmermann B, Kratzin HD, Hilschmann N: Purification and characterization of two putative HLA class II associated proteins: PHAPI and PHAPII. Biol Chem Hoppe Seyler. 1994 Feb;375(2):113-26. [PubMed:8192856 ]
  17. Nagata K, Kawase H, Handa H, Yano K, Yamasaki M, Ishimi Y, Okuda A, Kikuchi A, Matsumoto K: Replication factor encoded by a putative oncogene, set, associated with myeloid leukemogenesis. Proc Natl Acad Sci U S A. 1995 May 9;92(10):4279-83. [PubMed:7753797 ]
  18. Li M, Makkinje A, Damuni Z: The myeloid leukemia-associated protein SET is a potent inhibitor of protein phosphatase 2A. J Biol Chem. 1996 May 10;271(19):11059-62. [PubMed:8626647 ]
  19. Tsujio I, Zaidi T, Xu J, Kotula L, Grundke-Iqbal I, Iqbal K: Inhibitors of protein phosphatase-2A from human brain structures, immunocytological localization and activities towards dephosphorylation of the Alzheimer type hyperphosphorylated tau. FEBS Lett. 2005 Jan 17;579(2):363-72. [PubMed:15642345 ]
  20. Adachi Y, Pavlakis GN, Copeland TD: Identification and characterization of SET, a nuclear phosphoprotein encoded by the translocation break point in acute undifferentiated leukemia. J Biol Chem. 1994 Jan 21;269(3):2258-62. [PubMed:8294483 ]
  21. Carlson SG, Eng E, Kim EG, Perlman EJ, Copeland TD, Ballermann BJ: Expression of SET, an inhibitor of protein phosphatase 2A, in renal development and Wilms' tumor. J Am Soc Nephrol. 1998 Oct;9(10):1873-80. [PubMed:9773788 ]
  22. Seo SB, McNamara P, Heo S, Turner A, Lane WS, Chakravarti D: Regulation of histone acetylation and transcription by INHAT, a human cellular complex containing the set oncoprotein. Cell. 2001 Jan 12;104(1):119-30. [PubMed:11163245 ]
  23. Minakuchi M, Kakazu N, Gorrin-Rivas MJ, Abe T, Copeland TD, Ueda K, Adachi Y: Identification and characterization of SEB, a novel protein that binds to the acute undifferentiated leukemia-associated protein SET. Eur J Biochem. 2001 Mar;268(5):1340-51. [PubMed:11231286 ]
  24. Fan Z, Beresford PJ, Zhang D, Lieberman J: HMG2 interacts with the nucleosome assembly protein SET and is a target of the cytotoxic T-lymphocyte protease granzyme A. Mol Cell Biol. 2002 Apr;22(8):2810-20. [PubMed:11909973 ]
  25. Kajiwara Y, Akram A, Katsel P, Haroutunian V, Schmeidler J, Beecham G, Haines JL, Pericak-Vance MA, Buxbaum JD: FE65 binds Teashirt, inhibiting expression of the primate-specific caspase-4. PLoS One. 2009;4(4):e5071. doi: 10.1371/journal.pone.0005071. Epub 2009 Apr 3. [PubMed:19343227 ]