You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Identification
HMDB Protein ID HMDBP01302
Secondary Accession Numbers
  • 6598
Name Inhibitor of nuclear factor kappa-B kinase subunit beta
Synonyms
  1. I-kappa-B kinase 2
  2. I-kappa-B-kinase beta
  3. IKK-B
  4. IKK-beta
  5. IKK2
  6. IkBKB
  7. NFKBIKB
  8. Nuclear factor NF-kappa-B inhibitor kinase beta
Gene Name IKBKB
Protein Type Enzyme
Biological Properties
General Function Involved in protein kinase activity
Specific Function Acts as part of the IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF- kappa-B complex and ultimately the degradation of the inhibitor. Also phosphorylates NCOA3
Pathways
  • Intracellular Signalling Through Adenosine Receptor A2a and Adenosine
  • Intracellular Signalling Through Adenosine Receptor A2b and Adenosine
Reactions Not Available
GO Classification
Function
binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
protein kinase activity
protein serine/threonine kinase activity
Process
phosphorus metabolic process
phosphate metabolic process
metabolic process
cellular metabolic process
protein amino acid phosphorylation
phosphorylation
Cellular Location
  1. Cytoplasm
  2. Membrane raft
Gene Properties
Chromosome Location Chromosome:8
Locus 8p11.2
SNPs IKBKB
Gene Sequence
>2268 bp
ATGAGCTGGTCACCTTCCCTGACAACGCAGACATGTGGGGCCTGGGAAATGAAAGAGCGC
CTTGGGACAGGGGGATTTGGAAATGTCATCCGATGGCACAATCAGGAAACAGGTGAGCAG
ATTGCCATCAAGCAGTGCCGGCAGGAGCTCAGCCCCCGGAACCGAGAGCGGTGGTGCCTG
GAGATCCAGATCATGAGAAGGCTGACCCACCCCAATGTGGTGGCTGCCCGAGATGTCCCT
GAGGGGATGCAGAACTTGGCGCCCAATGACCTGCCCCTGCTGGCCATGGAGTACTGCCAA
GGAGGAGATCTCCGGAAGTACCTGAACCAGTTTGAGAACTGCTGTGGTCTGCGGGAAGGT
GCCATCCTCACCTTGCTGAGTGACATTGCCTCTGCGCTTAGATACCTTCATGAAAACAGA
ATCATCCATCGGGATCTAAAGCCAGAAAACATCGTCCTGCAGCAAGGAGAACAGAGGTTA
ATACACAAAATTATTGACCTAGGATATGCCAAGGAGCTGGATCAGGGCAGTCTTTGCACA
TCATTCGTGGGGACCCTGCAGTACCTGGCCCCAGAGCTACTGGAGCAGCAGAAGTACACA
GTGACCGTCGACTACTGGAGCTTCGGCACCCTGGCCTTTGAGTGCATCACGGGCTTCCGG
CCCTTCCTCCCCAACTGGCAGCCCGTGCAGTGGCATTCAAAAGTGCGGCAGAAGAGTGAG
GTGGACATTGTTGTTAGCGAAGACTTGAATGGAACGGTGAAGTTTTCAAGCTCTTTACCC
TACCCCAATAATCTTAACAGTGTCCTGGCTGAGCGACTGGAGAAGTGGCTGCAACTGATG
CTGATGTGGCACCCCCGACAGAGGGGCACGGATCCCACGTATGGGCCCAATGGCTGCTTC
AAGGCCCTGGATGACATCTTAAACTTAAAGCTGGTTCATATCTTGAACATGGTCACGGGC
ACCATCCACACCTACCCTGTGACAGAGGATGAGAGTCTGCAGAGCTTGAAGGCCAGAATC
CAACAGGACACGGGCATCCCAGAGGAGGACCAGGAGCTGCTGCAGGAAGCGGGCCTGGCG
TTGATCCCCGATAAGCCTGCCACTCAGTGTATTTCAGACGGCAAGTTAAATGAGGGCCAC
ACATTGGACATGGATCTTGTTTTTCTCTTTGACAACAGTAAAATCACCTATGAGACTCAG
ATCTCCCCACGGCCCCAACCTGAAAGTGTCAGCTGTATCCTTCAAGAGCCCAAGAGGAAT
CTCGCCTTCTTCCAGCTGAGGAAGGTGTGGGGCCAGGTCTGGCACAGCATCCAGACCCTG
AAGGAAGATTGCAACCGGCTGCAGCAGGGACAGCGAGCCGCCATGATGAATCTCCTCCGA
AACAACAGCTGCCTCTCCAAAATGAAGAATTCCATGGCTTCCATGTCTCAGCAGCTCAAG
GCCAAGTTGGATTTCTTCAAAACCAGCATCCAGATTGACCTGGAGAAGTACAGCGAGCAA
ACCGAGTTTGGGATCACATCAGATAAACTGCTGCTGGCCTGGAGGGAAATGGAGCAGGCT
GTGGAGCTCTGTGGGCGGGAGAACGAAGTGAAACTCCTGGTAGAACGGATGATGGCTCTG
CAGACCGACATTGTGGACTTACAGAGGAGCCCCATGGGCCGGAAGCAGGGGGGAACGCTG
GACGACCTAGAGGAGCAAGCAAGGGAGCTGTACAGGAGACTAAGGGAAAAACCTCGAGAC
CAGCGAACTGAGGGTGACAGTCAGGAAATGGTACGGCTGCTGCTTCAGGCAATTCAGAGC
TTCGAGAAGAAAGTGCGAGTGATCTATACGCAGCTCAGTAAAACTGTGGTTTGCAAGCAG
AAGGCGCTGGAACTGTTGCCCAAGGTGGAAGAGGTGGTGAGCTTAATGAATGAGGATGAG
AAGACTGTTGTCCGGCTGCAGGAGAAGCGGCAGAAGGAGCTCTGGAATCTCCTGAAGATT
GCTTGTAGCAAGGTCCGTGGTCCTGTCAGTGGAAGCCCGGATAGCATGAATGCCTCTCGA
CTTAGCCAGCCTGGGCAGCTGATGTCTCAGCCCTCCACGGCCTCCAACAGCTTACCTGAG
CCAGCCAAGAAGAGTGAAGAACTGGTGGCTGAAGCACATAACCTCTGCACCCTGCTAGAA
AATGCCATACAGGACACTGTGAGGGAACAAGACCAGAGTTTCACGGCCCTAGACTGGAGC
TGGTTACAGACGGAAGAAGAAGAGCACAGCTGCCTGGAGCAGGCCTCA
Protein Properties
Number of Residues 756
Molecular Weight 86563.2
Theoretical pI 5.53
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Inhibitor of nuclear factor kappa-B kinase subunit beta
MSWSPSLTTQTCGAWEMKERLGTGGFGNVIRWHNQETGEQIAIKQCRQELSPRNRERWCL
EIQIMRRLTHPNVVAARDVPEGMQNLAPNDLPLLAMEYCQGGDLRKYLNQFENCCGLREG
AILTLLSDIASALRYLHENRIIHRDLKPENIVLQQGEQRLIHKIIDLGYAKELDQGSLCT
SFVGTLQYLAPELLEQQKYTVTVDYWSFGTLAFECITGFRPFLPNWQPVQWHSKVRQKSE
VDIVVSEDLNGTVKFSSSLPYPNNLNSVLAERLEKWLQLMLMWHPRQRGTDPTYGPNGCF
KALDDILNLKLVHILNMVTGTIHTYPVTEDESLQSLKARIQQDTGIPEEDQELLQEAGLA
LIPDKPATQCISDGKLNEGHTLDMDLVFLFDNSKITYETQISPRPQPESVSCILQEPKRN
LAFFQLRKVWGQVWHSIQTLKEDCNRLQQGQRAAMMNLLRNNSCLSKMKNSMASMSQQLK
AKLDFFKTSIQIDLEKYSEQTEFGITSDKLLLAWREMEQAVELCGRENEVKLLVERMMAL
QTDIVDLQRSPMGRKQGGTLDDLEEQARELYRRLREKPRDQRTEGDSQEMVRLLLQAIQS
FEKKVRVIYTQLSKTVVCKQKALELLPKVEEVVSLMNEDEKTVVRLQEKRQKELWNLLKI
ACSKVRGPVSGSPDSMNASRLSQPGQLMSQPSTASNSLPEPAKKSEELVAEAHNLCTLLE
NAIQDTVREQDQSFTALDWSWLQTEEEEHSCLEQAS
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID O14920
UniProtKB/Swiss-Prot Entry Name IKKB_HUMAN
PDB IDs Not Available
GenBank Gene ID AF029684
GeneCard ID IKBKB
GenAtlas ID IKBKB
HGNC ID HGNC:5960
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. Wu RC, Qin J, Hashimoto Y, Wong J, Xu J, Tsai SY, Tsai MJ, O'Malley BW: Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) Coactivator activity by I kappa B kinase. Mol Cell Biol. 2002 May;22(10):3549-61. [PubMed:11971985 ]
  8. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [PubMed:16959974 ]
  9. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [PubMed:17344846 ]
  10. Witherow DS, Garrison TR, Miller WE, Lefkowitz RJ: beta-Arrestin inhibits NF-kappaB activity by means of its interaction with the NF-kappaB inhibitor IkappaBalpha. Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8603-7. Epub 2004 Jun 1. [PubMed:15173580 ]
  11. Hu WH, Pendergast JS, Mo XM, Brambilla R, Bracchi-Ricard V, Li F, Walters WM, Blits B, He L, Schaal SM, Bethea JR: NIBP, a novel NIK and IKK(beta)-binding protein that enhances NF-(kappa)B activation. J Biol Chem. 2005 Aug 12;280(32):29233-41. Epub 2005 Jun 10. [PubMed:15951441 ]
  12. Mercurio F, Zhu H, Murray BW, Shevchenko A, Bennett BL, Li J, Young DB, Barbosa M, Mann M, Manning A, Rao A: IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for NF-kappaB activation. Science. 1997 Oct 31;278(5339):860-6. [PubMed:9346484 ]
  13. Woronicz JD, Gao X, Cao Z, Rothe M, Goeddel DV: IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK. Science. 1997 Oct 31;278(5339):866-9. [PubMed:9346485 ]
  14. Hu MC, Wang Y: IkappaB kinase-alpha and -beta genes are coexpressed in adult and embryonic tissues but localized to different human chromosomes. Gene. 1998 Nov 5;222(1):31-40. [PubMed:9813230 ]
  15. Shindo M, Nakano H, Sakon S, Yagita H, Mihara M, Okumura K: Assignment of IkappaB kinase beta (IKBKB) to human chromosome band 8p12-->p11 by in situ hybridization. Cytogenet Cell Genet. 1998;82(1-2):32-3. [PubMed:9763654 ]
  16. Mittal R, Peak-Chew SY, McMahon HT: Acetylation of MEK2 and I kappa B kinase (IKK) activation loop residues by YopJ inhibits signaling. Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18574-9. Epub 2006 Nov 20. [PubMed:17116858 ]
  17. Nemoto S, DiDonato JA, Lin A: Coordinate regulation of IkappaB kinases by mitogen-activated protein kinase kinase kinase 1 and NF-kappaB-inducing kinase. Mol Cell Biol. 1998 Dec;18(12):7336-43. [PubMed:9819420 ]
  18. Cohen L, Henzel WJ, Baeuerle PA: IKAP is a scaffold protein of the IkappaB kinase complex. Nature. 1998 Sep 17;395(6699):292-6. [PubMed:9751059 ]
  19. Sanz L, Sanchez P, Lallena MJ, Diaz-Meco MT, Moscat J: The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation. EMBO J. 1999 Jun 1;18(11):3044-53. [PubMed:10356400 ]
  20. Delhase M, Hayakawa M, Chen Y, Karin M: Positive and negative regulation of IkappaB kinase activity through IKKbeta subunit phosphorylation. Science. 1999 Apr 9;284(5412):309-13. [PubMed:10195894 ]
  21. Jobin C, Sartor RB: The I kappa B/NF-kappa B system: a key determinant of mucosalinflammation and protection. Am J Physiol Cell Physiol. 2000 Mar;278(3):C451-62. [PubMed:10712233 ]
  22. Chariot A, Leonardi A, Muller J, Bonif M, Brown K, Siebenlist U: Association of the adaptor TANK with the I kappa B kinase (IKK) regulator NEMO connects IKK complexes with IKK epsilon and TBK1 kinases. J Biol Chem. 2002 Oct 4;277(40):37029-36. Epub 2002 Jul 19. [PubMed:12133833 ]
  23. Tegethoff S, Behlke J, Scheidereit C: Tetrameric oligomerization of IkappaB kinase gamma (IKKgamma) is obligatory for IKK complex activity and NF-kappaB activation. Mol Cell Biol. 2003 Mar;23(6):2029-41. [PubMed:12612076 ]
  24. Han KJ, Su X, Xu LG, Bin LH, Zhang J, Shu HB: Mechanisms of the TRIF-induced interferon-stimulated response element and NF-kappaB activation and apoptosis pathways. J Biol Chem. 2004 Apr 9;279(15):15652-61. Epub 2004 Jan 22. [PubMed:14739303 ]
  25. Bruey JM, Bruey-Sedano N, Newman R, Chandler S, Stehlik C, Reed JC: PAN1/NALP2/PYPAF2, an inducible inflammatory mediator that regulates NF-kappaB and caspase-1 activation in macrophages. J Biol Chem. 2004 Dec 10;279(50):51897-907. Epub 2004 Sep 28. [PubMed:15456791 ]
  26. Reynaert NL, Ckless K, Korn SH, Vos N, Guala AS, Wouters EF, van der Vliet A, Janssen-Heininger YM: Nitric oxide represses inhibitory kappaB kinase through S-nitrosylation. Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):8945-50. Epub 2004 Jun 7. [PubMed:15184672 ]
  27. Carter RS, Pennington KN, Arrate P, Oltz EM, Ballard DW: Site-specific monoubiquitination of IkappaB kinase IKKbeta regulates its phosphorylation and persistent activation. J Biol Chem. 2005 Dec 30;280(52):43272-9. Epub 2005 Nov 1. [PubMed:16267042 ]
  28. Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, Bartenschlager R, Tschopp J: Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature. 2005 Oct 20;437(7062):1167-72. Epub 2005 Sep 21. [PubMed:16177806 ]
  29. Mukherjee S, Keitany G, Li Y, Wang Y, Ball HL, Goldsmith EJ, Orth K: Yersinia YopJ acetylates and inhibits kinase activation by blocking phosphorylation. Science. 2006 May 26;312(5777):1211-4. [PubMed:16728640 ]
  30. Wu ZH, Shi Y, Tibbetts RS, Miyamoto S: Molecular linkage between the kinase ATM and NF-kappaB signaling in response to genotoxic stimuli. Science. 2006 Feb 24;311(5764):1141-6. [PubMed:16497931 ]
  31. Ohnuma K, Uchiyama M, Yamochi T, Nishibashi K, Hosono O, Takahashi N, Kina S, Tanaka H, Lin X, Dang NH, Morimoto C: Caveolin-1 triggers T-cell activation via CD26 in association with CARMA1. J Biol Chem. 2007 Mar 30;282(13):10117-31. Epub 2007 Feb 6. [PubMed:17287217 ]
  32. Park MY, Moon JH, Lee KS, Choi HI, Chung J, Hong HJ, Kim E: FAF1 suppresses IkappaB kinase (IKK) activation by disrupting the IKK complex assembly. J Biol Chem. 2007 Sep 21;282(38):27572-7. Epub 2007 Aug 7. [PubMed:17684021 ]
  33. Cui J, Zhu L, Xia X, Wang HY, Legras X, Hong J, Ji J, Shen P, Zheng S, Chen ZJ, Wang RF: NLRC5 negatively regulates the NF-kappaB and type I interferon signaling pathways. Cell. 2010 Apr 30;141(3):483-96. doi: 10.1016/j.cell.2010.03.040. [PubMed:20434986 ]
  34. Wada K, Niida M, Tanaka M, Kamitani T: Ro52-mediated monoubiquitination of IKK{beta} down-regulates NF-{kappa}B signalling. J Biochem. 2009 Dec;146(6):821-32. doi: 10.1093/jb/mvp127. Epub 2009 Aug 12. [PubMed:19675099 ]