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HMDB Protein ID HMDBP14107
Secondary Accession Numbers None
Name Inhibitor of growth protein 4
  1. p29ING4
Gene Name ING4
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Component of HBO1 complexes, which specifically mediate acetylation of histone H3 at 'Lys-14' (H3K14ac), and have reduced activity toward histone H4 (PubMed:16387653). Through chromatin acetylation it may function in DNA replication (PubMed:16387653). May inhibit tumor progression by modulating the transcriptional output of signaling pathways which regulate cell proliferation (PubMed:15251430, PubMed:15528276). Can suppress brain tumor angiogenesis through transcriptional repression of RELA/NFKB3 target genes when complexed with RELA (PubMed:15029197). May also specifically suppress loss of contact inhibition elicited by activated oncogenes such as MYC (PubMed:15029197). Represses hypoxia inducible factor's (HIF) activity by interacting with HIF prolyl hydroxylase 2 (EGLN1) (PubMed:15897452). Can enhance apoptosis induced by serum starvation in mammary epithelial cell line HC11 (By similarity).
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
protein acetylation
positive regulation of apoptotic process
cell cycle arrest
apoptotic process
DNA replication
negative regulation of growth
histone H3 acetylation
negative regulation of transcription, DNA-dependent
negative regulation of cell proliferation
DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator
histone H4-K12 acetylation
histone H4-K5 acetylation
histone H4-K8 acetylation
Cellular Component
intermediate filament cytoskeleton
histone acetyltransferase complex
MOZ/MORF histone acetyltransferase complex
Molecular Function
metal ion binding
methylated histone residue binding
transcription coactivator activity
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 249
Molecular Weight 28530.17
Theoretical pI 7.619
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q9UNL4
UniProtKB/Swiss-Prot Entry Name ING4_HUMAN
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
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. Hu RM, Han ZG, Song HD, Peng YD, Huang QH, Ren SX, Gu YJ, Huang CH, Li YB, Jiang CL, Fu G, Zhang QH, Gu BW, Dai M, Mao YF, Gao GF, Rong R, Ye M, Zhou J, Xu SH, Gu J, Shi JX, Jin WR, Zhang CK, Wu TM, Huang GY, Chen Z, Chen MD, Chen JL: Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning. Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9543-8. [PubMed:10931946 ]
  3. 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 ]
  4. Shiseki M, Nagashima M, Pedeux RM, Kitahama-Shiseki M, Miura K, Okamura S, Onogi H, Higashimoto Y, Appella E, Yokota J, Harris CC: p29ING4 and p28ING5 bind to p53 and p300, and enhance p53 activity. Cancer Res. 2003 May 15;63(10):2373-8. [PubMed:12750254 ]
  5. Doyon Y, Cayrou C, Ullah M, Landry AJ, Cote V, Selleck W, Lane WS, Tan S, Yang XJ, Cote J: ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation. Mol Cell. 2006 Jan 6;21(1):51-64. [PubMed:16387653 ]
  6. Ozer A, Wu LC, Bruick RK: The candidate tumor suppressor ING4 represses activation of the hypoxia inducible factor (HIF). Proc Natl Acad Sci U S A. 2005 May 24;102(21):7481-6. Epub 2005 May 16. [PubMed:15897452 ]
  7. Unoki M, Shen JC, Zheng ZM, Harris CC: Novel splice variants of ING4 and their possible roles in the regulation of cell growth and motility. J Biol Chem. 2006 Nov 10;281(45):34677-86. doi: 10.1074/jbc.M606296200. Epub 2006 Sep 13. [PubMed:16973615 ]
  8. Raho G, Miranda C, Tamborini E, Pierotti MA, Greco A: Detection of novel mRNA splice variants of human ING4 tumor suppressor gene. Oncogene. 2007 Aug 9;26(36):5247-57. doi: 10.1038/sj.onc.1210335. Epub 2007 Feb 26. [PubMed:17325660 ]
  9. Zhang X, Xu LS, Wang ZQ, Wang KS, Li N, Cheng ZH, Huang SZ, Wei DZ, Han ZG: ING4 induces G2/M cell cycle arrest and enhances the chemosensitivity to DNA-damage agents in HepG2 cells. FEBS Lett. 2004 Jul 16;570(1-3):7-12. doi: 10.1016/j.febslet.2004.06.010. [PubMed:15251430 ]
  10. Kim S, Chin K, Gray JW, Bishop JM: A screen for genes that suppress loss of contact inhibition: identification of ING4 as a candidate tumor suppressor gene in human cancer. Proc Natl Acad Sci U S A. 2004 Nov 16;101(46):16251-6. doi: 10.1073/pnas.0407158101. Epub 2004 Nov 4. [PubMed:15528276 ]
  11. Zhang X, Wang KS, Wang ZQ, Xu LS, Wang QW, Chen F, Wei DZ, Han ZG: Nuclear localization signal of ING4 plays a key role in its binding to p53. Biochem Biophys Res Commun. 2005 Jun 17;331(4):1032-8. doi: 10.1016/j.bbrc.2005.04.023. [PubMed:15882981 ]
  12. Shi X, Hong T, Walter KL, Ewalt M, Michishita E, Hung T, Carney D, Pena P, Lan F, Kaadige MR, Lacoste N, Cayrou C, Davrazou F, Saha A, Cairns BR, Ayer DE, Kutateladze TG, Shi Y, Cote J, Chua KF, Gozani O: ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression. Nature. 2006 Jul 6;442(7098):96-9. doi: 10.1038/nature04835. Epub 2006 May 21. [PubMed:16728974 ]
  13. Guo Q, Fast W: Citrullination of inhibitor of growth 4 (ING4) by peptidylarginine deminase 4 (PAD4) disrupts the interaction between ING4 and p53. J Biol Chem. 2011 May 13;286(19):17069-78. doi: 10.1074/jbc.M111.230961. Epub 2011 Mar 22. [PubMed:21454715 ]
  14. Palacios A, Munoz IG, Pantoja-Uceda D, Marcaida MJ, Torres D, Martin-Garcia JM, Luque I, Montoya G, Blanco FJ: Molecular basis of histone H3K4me3 recognition by ING4. J Biol Chem. 2008 Jun 6;283(23):15956-64. doi: 10.1074/jbc.M710020200. Epub 2008 Apr 1. [PubMed:18381289 ]
  15. Hung T, Binda O, Champagne KS, Kuo AJ, Johnson K, Chang HY, Simon MD, Kutateladze TG, Gozani O: ING4 mediates crosstalk between histone H3 K4 trimethylation and H3 acetylation to attenuate cellular transformation. Mol Cell. 2009 Jan 30;33(2):248-56. doi: 10.1016/j.molcel.2008.12.016. [PubMed:19187765 ]
  16. Culurgioni S, Munoz IG, Moreno A, Palacios A, Villate M, Palmero I, Montoya G, Blanco FJ: Crystal structure of inhibitor of growth 4 (ING4) dimerization domain reveals functional organization of ING family of chromatin-binding proteins. J Biol Chem. 2012 Mar 30;287(14):10876-84. doi: 10.1074/jbc.M111.330001. Epub 2012 Feb 9. [PubMed:22334692 ]