O14920 (IKKB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Inhibitor of nuclear factor kappa-B kinase subunit beta
Short name=I-kappa-B-kinase beta
Short name=IKK-B
Short name=IKK-beta
Short name=IkBKB
EC=2.7.11.10

Alternative name(s):
I-kappa-B kinase 2
Short name=IKK2
Nuclear factor NF-kappa-B inhibitor kinase beta
Short name=NFKBIKB

Gene names

Name:	IKBKB
Synonyms:	IKKB

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	756 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Also phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation. Ref.16 Ref.32 Ref.35 Ref.42 Ref.43 Ref.45
Catalytic activity	ATP + [I-kappa-B protein] = ADP + [I-kappa-B phosphoprotein].
Subunit structure	Component of the I-kappa-B-kinase (IKK) core complex consisting of CHUK, IKBKB and IKBKG; probably four alpha/CHUK-beta/IKBKB dimers are associated with four gamma/IKBKG subunits. The IKK core complex seems to associate with regulatory or adapter proteins to form a IKK-signalosome holo-complex. The IKK complex associates with TERF2IP/RAP1, leading to promote IKK-mediated phosphorylation of RELA/p65. Part of a complex composed of NCOA2, NCOA3, CHUK/IKKA, IKBKB, IKBKG and CREBBP. Part of a 70-90 kDa complex at least consisting of CHUK/IKKA, IKBKB, NFKBIA, RELA, IKBKAP and MAP3K14. Found in a membrane raft complex, at least composed of BCL10, CARD11, DPP4 and IKBKB. Interacts with SQSTM1 through PRKCZ or PRKCI. Forms an NGF-induced complex with IKBKB, PRKCI and TRAF6. May interact with MAVS/IPS1. Interacts with NALP2. Interacts with TICAM1. Interacts with Yersinia yopJ. Interacts with FAF1; the interaction disrupts the IKK complex formation. Interacts with ATM. Part of a ternary complex consisting of TANK, IKBKB and IKBKG. Interacts with NIBP; the interaction is direct. Interacts with ARRB1 and ARRB2. Interacts with TRIM21. Interacts with NLRC5; prevents IKBKB phosphorylation and kinase activity. Interacts with PDPK1. Ref.12 Ref.17 Ref.20 Ref.21 Ref.22 Ref.24 Ref.25 Ref.27 Ref.28 Ref.29 Ref.31 Ref.35 Ref.39
Subcellular location	Cytoplasm. Nucleus. Membrane raft. Note: Colocalized with DPP4 in membrane rafts. Ref.30 Ref.43
Tissue specificity	Highly expressed in heart, placenta, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis and peripheral blood.
Domain	The kinase domain is located in the N-terminal region. The leucine zipper is important to allow homo- and hetero-dimerization. At the C-terminal region is located the region responsible for the interaction with NEMO/IKBKG. Ref.34
Post-translational modification	Upon cytokine stimulation, phosphorylated on Ser-177 and Ser-181 by MEKK1 and/or MAP3K14/NIK as well as TBK1 and PRKCZ; which enhances activity. Once activated, autophosphorylates on the C-terminal serine cluster; which decreases activity and prevents prolonged activation of the inflammatory response. Phosphorylated by the IKK-related kinases TBK1 and IKBKE, which is associated with reduced CHUK/IKKA and IKBKB activity and NF-kappa-B-dependent gene transcription. Ref.10 Ref.13 Ref.14 Ref.15 Ref.16 Ref.25 Ref.32 Ref.36 Ref.37 Ref.38 Ref.40 Ref.41 Ref.42 Ref.45 Acetylation of Thr-180 by Yersinia yopJ prevents phosphorylation and activation, thus blocking the I-kappa-B pathway. Ubiquitinated. Monoubiquitination involves TRIM21 that leads to inhibition of Tax-induced NF-kappa-B signaling. According to Ref.39, 'Ser-163' does not serve as a monoubiquitination site. According to Ref.26, ubiquitination on 'Ser-163' modulates phosphorylation on C-terminal serine residues. Monoubiquitination by TRIM21 is dirupted by Yersinia yopJ. Ref.26 Ref.39
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cytoplasm Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Isopeptide bond Phosphoprotein S-nitrosylation Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	I-kappaB kinase/NF-kappaB cascade Traceable author statement Ref.34. Source: UniProtKB MyD88-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome MyD88-independent toll-like receptor signaling pathway Traceable author statement. Source: Reactome T cell receptor signaling pathway Traceable author statement. Source: Reactome Toll signaling pathway Traceable author statement. Source: Reactome anti-apoptosis Traceable author statement. Source: Reactome inflammatory response Traceable author statement Ref.34. Source: UniProtKB innate immune response Traceable author statement Ref.34. Source: UniProtKB nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome nucleotide-binding oligomerization domain containing signaling pathway Traceable author statement. Source: Reactome positive regulation of I-kappaB kinase/NF-kappaB cascade Traceable author statement. Source: Reactome positive regulation of NF-kappaB transcription factor activity Traceable author statement Ref.34. Source: UniProtKB positive regulation of transcription, DNA-dependent Non-traceable author statement Ref.1Ref.2Ref.3. Source: UniProtKB response to virus Traceable author statement Ref.34. Source: UniProtKB toll-like receptor 1 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 2 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 3 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 4 signaling pathway Traceable author statement. Source: Reactome
Cellular component	CD40 receptor complex Inferred from sequence or structural similarity. Source: BHF-UCL IkappaB kinase complex Traceable author statement Ref.34. Source: UniProtKB internal side of plasma membrane Inferred from sequence or structural similarity. Source: BHF-UCL membrane raft Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW IkappaB kinase activity Traceable author statement Ref.34. Source: UniProtKB protein binding Inferred from physical interaction Ref.39Ref.35. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CHUK	O15111	5	EBI-81266,EBI-81249
IKBKG	Q9Y6K9	6	EBI-81266,EBI-81279
MAP3K14	Q99558	2	EBI-81266,EBI-358011
NCOA3	Q9Y6Q9	3	EBI-81266,EBI-81196
NFKBIA	P25963	7	EBI-81266,EBI-307386
RPS3	P23396	4	EBI-81266,EBI-351193
STAP2	Q9UGK3	7	EBI-81266,EBI-1553984
TSC1	Q92574	3	EBI-81266,EBI-1047085

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O14920-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O14920-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-34: MSWSPSLTTQTCGAWEMKERLGTGGFGNVIRWHN → MFSGGCHSPGFGRPSPAFPAPGSPPPAPRPCR

Isoform 3 (identifier: O14920-3)

The sequence of this isoform differs from the canonical sequence as follows:
     231-256: WHSKVRQKSEVDIVVSEDLNGTVKFS → CVRMWPGTVAHSCNPSTLGGRGRWIS
     257-756: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 756

756

Inhibitor of nuclear factor kappa-B kinase subunit beta

PRO_0000086013

Regions

Domain

15 – 300

286

Protein kinase

Domain

458 – 479

22

Leucine-zipper

Nucleotide binding

21 – 29

9

ATP By similarity

Region

737 – 742

6

NEMO-binding

Sites

Active site

145

1

Proton acceptor By similarity

Binding site

44

1

ATP By similarity

Amino acid modifications

Modified residue

23

1

Phosphothreonine By similarity

Modified residue

177

1

Phosphoserine; by TBK1 and PKC/PRKCZ Ref.13 Ref.14 Ref.15

Modified residue

179

1

S-nitrosocysteine Ref.23

Modified residue

180

1

O-acetylthreonine; by Yersinia yopJ

Modified residue

181

1

Phosphoserine; by TBK1, PKC/PRKCZ and PDPK1 Ref.13 Ref.14 Ref.15 Ref.25

Modified residue

670

1

Phosphoserine; by autocatalysis Probable

Modified residue

672

1

Phosphoserine; by autocatalysis Probable

Modified residue

675

1

Phosphoserine; by autocatalysis Probable

Modified residue

682

1

Phosphoserine; by autocatalysis Probable

Modified residue

689

1

Phosphoserine; by autocatalysis Probable

Modified residue

692

1

Phosphoserine; by autocatalysis Probable

Modified residue

695

1

Phosphoserine; by autocatalysis Probable

Modified residue

697

1

Phosphoserine; by autocatalysis Probable

Modified residue

705

1

Phosphoserine; by autocatalysis Probable

Modified residue

733

1

Phosphoserine; by autocatalysis Probable

Modified residue

740

1

Phosphoserine; by autocatalysis Probable

Modified residue

750

1

Phosphoserine; by autocatalysis Probable

Cross-link

163

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.26

Natural variations

Alternative sequence

1 – 34

34

MSWSP…IRWHN → MFSGGCHSPGFGRPSPAFPA PGSPPPAPRPCR in isoform 2.

VSP_041825

Alternative sequence

231 – 256

26

WHSKV…TVKFS → CVRMWPGTVAHSCNPSTLGG RGRWIS in isoform 3.

VSP_041826

Alternative sequence

257 – 756

500

Missing in isoform 3.

VSP_041827

Natural variant

360

1

A → S in breast cancer samples; infiltrating ductal carcinoma; somatic mutation. Ref.47 Ref.48

VAR_035626

Natural variant

369

1

Q → R. Ref.48
Corresponds to variant rs56411242 [ dbSNP | Ensembl ].

VAR_040567

Natural variant

526

1

R → Q. Ref.48
Corresponds to variant rs2272736 [ dbSNP | Ensembl ].

VAR_040568

Natural variant

554

1

R → W. Ref.6
Corresponds to variant rs17875749 [ dbSNP | Ensembl ].

VAR_021124

Natural variant

710

1

A → T. Ref.48
Corresponds to variant rs34309584 [ dbSNP | Ensembl ].

VAR_040569

Natural variant

734

1

F → L. Ref.48
Corresponds to variant rs56301637 [ dbSNP | Ensembl ].

VAR_040570

Natural variant

736

1

A → T.
Corresponds to variant rs17611716 [ dbSNP | Ensembl ].

VAR_051628

Experimental info

Mutagenesis

44

1

K → A: Loss of kinase activity and no effect on binding to NIK. Ref.1 Ref.2

Mutagenesis

163

1

K → R: Monoubiquitinated; when associated with E-177 and E-181. Ref.39

Mutagenesis

177 – 181

5

SLCTS → ALCTA: COmplete loss of TBK1-mediated phosphorylation. Ref.1 Ref.15 Ref.39

Mutagenesis

177

1

S → A: Decrease of activity. Ref.1 Ref.39

Mutagenesis

177

1

S → E: Full activation. Interaction with TRIM21 is enhanced; when associated with E-181. Monoubiquitinated; when associated with R-163 and E-181. Strongly promoted NF-kappa-B gene expression; when associated with E-181. Ref.1 Ref.39

Mutagenesis

181

1

S → A: Decrease of activity. Ref.1 Ref.39

Mutagenesis

181

1

S → E: Full activation. Interaction with TRIM21 is enhanced; when associated with E-177. Monoubiquitinated; when associated with R-163 and E-177. Strongly promoted NF-kappa-B gene expression; when associated with E-177. Ref.1 Ref.39

Sequence conflict

259

1

L → S in BAG63942. Ref.5

Sequence conflict

259

1

L → S in BAH14789. Ref.5

Secondary structure

1

.

.

.

.

.

.

.

756

Helix Strand Turn

Details...

Helix

707 – 729

23

Helix

734 – 736

3

Helix

740 – 742

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: F9CADF671AE9E14E	FASTA	756	86,564
	10 20 30 40 50 60 MSWSPSLTTQ TCGAWEMKER LGTGGFGNVI RWHNQETGEQ IAIKQCRQEL SPRNRERWCL 70 80 90 100 110 120 EIQIMRRLTH PNVVAARDVP EGMQNLAPND LPLLAMEYCQ GGDLRKYLNQ FENCCGLREG 130 140 150 160 170 180 AILTLLSDIA SALRYLHENR IIHRDLKPEN IVLQQGEQRL IHKIIDLGYA KELDQGSLCT 190 200 210 220 230 240 SFVGTLQYLA PELLEQQKYT VTVDYWSFGT LAFECITGFR PFLPNWQPVQ WHSKVRQKSE 250 260 270 280 290 300 VDIVVSEDLN GTVKFSSSLP YPNNLNSVLA ERLEKWLQLM LMWHPRQRGT DPTYGPNGCF 310 320 330 340 350 360 KALDDILNLK LVHILNMVTG TIHTYPVTED ESLQSLKARI QQDTGIPEED QELLQEAGLA 370 380 390 400 410 420 LIPDKPATQC ISDGKLNEGH TLDMDLVFLF DNSKITYETQ ISPRPQPESV SCILQEPKRN 430 440 450 460 470 480 LAFFQLRKVW GQVWHSIQTL KEDCNRLQQG QRAAMMNLLR NNSCLSKMKN SMASMSQQLK 490 500 510 520 530 540 AKLDFFKTSI QIDLEKYSEQ TEFGITSDKL LLAWREMEQA VELCGRENEV KLLVERMMAL 550 560 570 580 590 600 QTDIVDLQRS PMGRKQGGTL DDLEEQAREL YRRLREKPRD QRTEGDSQEM VRLLLQAIQS 610 620 630 640 650 660 FEKKVRVIYT QLSKTVVCKQ KALELLPKVE EVVSLMNEDE KTVVRLQEKR QKELWNLLKI 670 680 690 700 710 720 ACSKVRGPVS GSPDSMNASR LSQPGQLMSQ PSTASNSLPE PAKKSEELVA EAHNLCTLLE 730 740 750 NAIQDTVREQ DQSFTALDWS WLQTEEEEHS CLEQAS
	Isoform 2 [UniParc]. Checksum: 9C31F5C1DC92661E	FASTA	754	85,945
	10 20 30 40 50 60 MFSGGCHSPG FGRPSPAFPA PGSPPPAPRP CRQETGEQIA IKQCRQELSP RNRERWCLEI 70 80 90 100 110 120 QIMRRLTHPN VVAARDVPEG MQNLAPNDLP LLAMEYCQGG DLRKYLNQFE NCCGLREGAI 130 140 150 160 170 180 LTLLSDIASA LRYLHENRII HRDLKPENIV LQQGEQRLIH KIIDLGYAKE LDQGSLCTSF 190 200 210 220 230 240 VGTLQYLAPE LLEQQKYTVT VDYWSFGTLA FECITGFRPF LPNWQPVQWH SKVRQKSEVD 250 260 270 280 290 300 IVVSEDLNGT VKFSSSLPYP NNLNSVLAER LEKWLQLMLM WHPRQRGTDP TYGPNGCFKA 310 320 330 340 350 360 LDDILNLKLV HILNMVTGTI HTYPVTEDES LQSLKARIQQ DTGIPEEDQE LLQEAGLALI 370 380 390 400 410 420 PDKPATQCIS DGKLNEGHTL DMDLVFLFDN SKITYETQIS PRPQPESVSC ILQEPKRNLA 430 440 450 460 470 480 FFQLRKVWGQ VWHSIQTLKE DCNRLQQGQR AAMMNLLRNN SCLSKMKNSM ASMSQQLKAK 490 500 510 520 530 540 LDFFKTSIQI DLEKYSEQTE FGITSDKLLL AWREMEQAVE LCGRENEVKL LVERMMALQT 550 560 570 580 590 600 DIVDLQRSPM GRKQGGTLDD LEEQARELYR RLREKPRDQR TEGDSQEMVR LLLQAIQSFE 610 620 630 640 650 660 KKVRVIYTQL SKTVVCKQKA LELLPKVEEV VSLMNEDEKT VVRLQEKRQK ELWNLLKIAC 670 680 690 700 710 720 SKVRGPVSGS PDSMNASRLS QPGQLMSQPS TASNSLPEPA KKSEELVAEA HNLCTLLENA 730 740 750 IQDTVREQDQ SFTALDWSWL QTEEEEHSCL EQAS
	Isoform 3 [UniParc]. Checksum: 8B4762DD49F4065A	FASTA	256	29,236
	10 20 30 40 50 60 MSWSPSLTTQ TCGAWEMKER LGTGGFGNVI RWHNQETGEQ IAIKQCRQEL SPRNRERWCL 70 80 90 100 110 120 EIQIMRRLTH PNVVAARDVP EGMQNLAPND LPLLAMEYCQ GGDLRKYLNQ FENCCGLREG 130 140 150 160 170 180 AILTLLSDIA SALRYLHENR IIHRDLKPEN IVLQQGEQRL IHKIIDLGYA KELDQGSLCT 190 200 210 220 230 240 SFVGTLQYLA PELLEQQKYT VTVDYWSFGT LAFECITGFR PFLPNWQPVQ CVRMWPGTVA 250 HSCNPSTLGG RGRWIS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for NF-kappaB activation." Mercurio F., Zhu H., Murray B.W., Shevchenko A., Bennett B.L., Li J.W., Young D.B., Barbosa M., Mann M., Manning A., Rao A. Science 278:860-866(1997) [PubMed: 9346484] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF LYS-44; SER-177 AND SER-181. Tissue: Cervix carcinoma.
[2]	"IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK." Woronicz J.D., Gao X., Cao Z., Rothe M., Goeddel D.V. Science 278:866-869(1997) [PubMed: 9346485] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF LYS-44.
[3]	"IkappaB kinase-alpha and -beta genes are coexpressed in adult and embryonic tissues but localized to different human chromosomes." Hu M.C.-T., Wang Y.-P. Gene 222:31-40(1998) [PubMed: 9813230] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Heart.
[4]	"Assignment of IkappaB kinase beta (IKBKB) to human chromosome band 8p12-->p11 by in situ hybridization." Shindo M., Nakano H., Sakon S., Yagita H., Mihara M., Okumura K. Cytogenet. Cell Genet. 82:32-33(1998) [PubMed: 9763654] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), GENE MAPPING.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Testis.
[6]	SeattleSNPs variation discovery resource Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT TRP-554.
[7]	"DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S. Nature 439:331-335(2006) [PubMed: 16421571] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Lung.
[9]	"Acetylation of MEK2 and I kappa B kinase (IKK) activation loop residues by YopJ inhibits signaling." Mittal R., Peak-Chew S.Y., McMahon H.T. Proc. Natl. Acad. Sci. U.S.A. 103:18574-18579(2006) [PubMed: 17116858] [Abstract] Cited for: PROTEIN SEQUENCE OF 170-182 (ISOFORM 1), INACTIVATION BY YERSINIA YOPJ, ACETYLATION AT THR-180, MASS SPECTROMETRY.
[10]	"Coordinate regulation of IkappaB kinases by mitogen-activated protein kinase kinase kinase 1 and NF-kappaB-inducing kinase." Nemoto S., DiDonato J.A., Lin A. Mol. Cell. Biol. 18:7336-7343(1998) [PubMed: 9819420] [Abstract] Cited for: IKK PHOSPHORYLATION.
[11]	"IKAP is a scaffold protein of the IkappaB kinase complex." Cohen L., Henzel W.J., Baeuerle P.A. Nature 395:292-296(1998) [PubMed: 9751059] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH CHUK; NFKBIA; RELA; IKBKAP AND MAP3K14.
[12]	"The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation." Sanz L., Sanchez P., Lallena M.-J., Diaz-Meco M.T., Moscat J. EMBO J. 18:3044-3053(1999) [PubMed: 10356400] [Abstract] Cited for: INTERACTION WITH SQSTM1; PRKCZ AND PRKCI.
[13]	"Activation of IkappaB kinase beta by protein kinase C isoforms." Lallena M.J., Diaz-Meco M.T., Bren G., Paya C.V., Moscat J. Mol. Cell. Biol. 19:2180-2188(1999) [PubMed: 10022904] [Abstract] Cited for: PHOSPHORYLATION AT SER-177 AND SER-181.
[14]	"Positive and negative regulation of IkappaB kinase activity through IKKbeta subunit phosphorylation." Delhase M., Hayakawa M., Chen Y., Karin M. Science 284:309-313(1999) [PubMed: 10195894] [Abstract] Cited for: PHOSPHORYLATION AT SER-177; SER-181; SER-670; SER-672; SER-675; SER-682; SER-689; SER-692; SER-695; SER-697; SER-705; SER-733; SER-740 AND SER-750.
[15]	"NAK is an IkappaB kinase-activating kinase." Tojima Y., Fujimoto A., Delhase M., Chen Y., Hatakeyama S., Nakayama K., Kaneko Y., Nimura Y., Motoyama N., Ikeda K., Karin M., Nakanishi M. Nature 404:778-782(2000) [PubMed: 10783893] [Abstract] Cited for: PHOSPHORYLATION AT SER-177 AND SER-181 BY TBK1, MUTAGENESIS OF 177-SER--SER-181.
[16]	"Direct phosphorylation of NF-kappa B1 p105 by the Ikappa B kinase complex on serine 927 is essential for signal-induced p105 proteolysis." Salmeron A., Janzen J., Soneji Y., Bump N., Kamens J., Allen H., Ley S.C. J. Biol. Chem. 276:22215-22222(2001) [PubMed: 11297557] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF NFKB1.
[17]	"Association of the adaptor TANK with the I kappa B kinase (IKK) regulator NEMO connects IKK complexes with IKK epsilon and TBK1 kinases." Chariot A., Leonardi A., Muller J., Bonif M., Brown K., Siebenlist U. J. Biol. Chem. 277:37029-37036(2002) [PubMed: 12133833] [Abstract] Cited for: INTERACTION WITH IKBKG AND TANK.
[18]	"Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) coactivator activity by I kappa B kinase." Wu R.-C., Qin J., Hashimoto Y., Wong J., Xu J., Tsai S.Y., Tsai M.-J., O'Malley B.W. Mol. Cell. Biol. 22:3549-3561(2002) [PubMed: 11971985] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH CREBBP; NCOA2; NCOA3; IKKA AND IKBKG.
[19]	"Tetrameric oligomerization of IkappaB kinase gamma (IKKgamma) is obligatory for IKK complex activity and NF-kappaB activation." Tegethoff S., Behlke J., Scheidereit C. Mol. Cell. Biol. 23:2029-2041(2003) [PubMed: 12612076] [Abstract] Cited for: COMPOSITION OF THE IKK COMPLEX.
[20]	"Mechanisms of the TRIF-induced interferon-stimulated response element and NF-kappaB activation and apoptosis pathways." Han K.J., Su X., Xu L.-G., Bin L.H., Zhang J., Shu H.-B. J. Biol. Chem. 279:15652-15661(2004) [PubMed: 14739303] [Abstract] Cited for: INTERACTION WITH TICAM1.
[21]	"PAN1/NALP2/PYPAF2, an inducible inflammatory mediator that regulates NF-kappaB and caspase-1 activation in macrophages." Bruey J.-M., Bruey-Sedano N., Newman R., Chandler S., Stehlik C., Reed J.C. J. Biol. Chem. 279:51897-51907(2004) [PubMed: 15456791] [Abstract] Cited for: INTERACTION WITH NALP2.
[22]	"beta-Arrestin inhibits NF-kappaB activity by means of its interaction with the NF-kappaB inhibitor IkappaBalpha." Witherow D.S., Garrison T.R., Miller W.E., Lefkowitz R.J. Proc. Natl. Acad. Sci. U.S.A. 101:8603-8607(2004) [PubMed: 15173580] [Abstract] Cited for: INTERACTION WITH ARRB1 AND ARRB2.
[23]	"Nitric oxide represses inhibitory kappaB kinase through S-nitrosylation." Reynaert N.L., Ckless K., Korn S.H., Vos N., Guala A.S., Wouters E.F., van der Vliet A., Janssen-Heininger Y.M. Proc. Natl. Acad. Sci. U.S.A. 101:8945-8950(2004) [PubMed: 15184672] [Abstract] Cited for: S-NITROSYLATION AT CYS-179.
[24]	"NIBP, a novel NIK and IKK(beta)-binding protein that enhances NF-(kappa)B activation." Hu W.-H., Pendergast J.S., Mo X.-M., Brambilla R., Bracchi-Ricard V., Li F., Walters W.M., Blits B., He L., Schaal S.M., Bethea J.R. J. Biol. Chem. 280:29233-29241(2005) [PubMed: 15951441] [Abstract] Cited for: INTERACTION WITH NIBP.
[25]	"3-Phosphoinositide-dependent protein kinase-1-mediated IkappaB kinase beta (IkkB) phosphorylation activates NF-kappaB signaling." Tanaka H., Fujita N., Tsuruo T. J. Biol. Chem. 280:40965-40973(2005) [PubMed: 16207722] [Abstract] Cited for: PHOSPHORYLATION AT SER-181 BY PDPK1, INTERACTION WITH PDPK1.
[26]	"Site-specific monoubiquitination of IkappaB kinase IKKbeta regulates its phosphorylation and persistent activation." Carter R.S., Pennington K.N., Arrate P., Oltz E.M., Ballard D.W. J. Biol. Chem. 280:43272-43279(2005) [PubMed: 16267042] [Abstract] Cited for: UBIQUITINATION AT LYS-163.
[27]	"Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus." Meylan E., Curran J., Hofmann K., Moradpour D., Binder M., Bartenschlager R., Tschopp J. Nature 437:1167-1172(2005) [PubMed: 16177806] [Abstract] Cited for: INTERACTION WITH MAVS.
[28]	"Yersinia YopJ acetylates and inhibits kinase activation by blocking phosphorylation." Mukherjee S., Keitany G., Li Y., Wang Y., Ball H.L., Goldsmith E.J., Orth K. Science 312:1211-1214(2006) [PubMed: 16728640] [Abstract] Cited for: INTERACTION WITH YOPJ, ACETYLATION.
[29]	"Molecular linkage between the kinase ATM and NF-kappaB signaling in response to genotoxic stimuli." Wu Z.H., Shi Y., Tibbetts R.S., Miyamoto S. Science 311:1141-1146(2006) [PubMed: 16497931] [Abstract] Cited for: INTERACTION WITH ATM.
[30]	"Caveolin-1 triggers T-cell activation via CD26 in association with CARMA1." Ohnuma K., Uchiyama M., Yamochi T., Nishibashi K., Hosono O., Takahashi N., Kina S., Tanaka H., Lin X., Dang N.H., Morimoto C. J. Biol. Chem. 282:10117-10131(2007) [PubMed: 17287217] [Abstract] Cited for: IDENTIFICATION IN A MEMBRANE RAFT COMPLEX, SUBCELLULAR LOCATION.
[31]	"FAF1 suppresses IkappaB kinase (IKK) activation by disrupting the IKK complex assembly." Park M.Y., Moon J.H., Lee K.S., Choi H.I., Chung J., Hong H.J., Kim E. J. Biol. Chem. 282:27572-27577(2007) [PubMed: 17684021] [Abstract] Cited for: INTERACTION WITH FAF1.
[32]	"Negative feedback loop in T cell activation through IkappaB kinase-induced phosphorylation and degradation of Bcl10." Lobry C., Lopez T., Israel A., Weil R. Proc. Natl. Acad. Sci. U.S.A. 104:908-913(2007) [PubMed: 17213322] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF BCL10.
[33]	"The I kappa B/NF-kappa B system: a key determinant of mucosal inflammation and protection." Jobin C., Sartor R.B. Am. J. Physiol. 278:C451-C462(2000) [PubMed: 10712233] [Abstract] Cited for: REVIEW.
[34]	"The IkappaB kinase complex: master regulator of NF-kappaB signaling." Solt L.A., May M.J. Immunol. Res. 42:3-18(2008) [PubMed: 18626576] [Abstract] Cited for: REVIEW, DOMAIN.
[35]	"NLRC5 negatively regulates the NF-kappaB and type I interferon signaling pathways." Cui J., Zhu L., Xia X., Wang H.Y., Legras X., Hong J., Ji J., Shen P., Zheng S., Chen Z.J., Wang R.F. Cell 141:483-496(2010) [PubMed: 20434986] [Abstract] Cited for: FUNCTION, INTERACTION WITH NLRC5.
[36]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-672, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[37]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-672, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[38]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-672, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[39]	"Ro52-mediated monoubiquitination of IKK{beta} down-regulates NF-{kappa}B signalling." Wada K., Niida M., Tanaka M., Kamitani T. J. Biochem. 146:821-832(2009) [PubMed: 19675099] [Abstract] Cited for: INTERACTION WITH TRIM21, MONOUBIQUITINATION, UBIQUITINATION INACTIVATION BY YERSINIA YOPJ, MUTAGENESIS OF LYS-163; SER-177 AND SER-181.
[40]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-670 AND SER-672, MASS SPECTROMETRY.
[41]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-672, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[42]	"Respiratory syncytial virus-mediated NF-kappa B p65 phosphorylation at serine 536 is dependent on RIG-I, TRAF6, and IKK beta." Yoboua F., Martel A., Duval A., Mukawera E., Grandvaux N. J. Virol. 84:7267-7277(2010) [PubMed: 20410276] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF RELA.
[43]	"Nuclear IKKbeta is an adaptor protein for IkappaBalpha ubiquitination and degradation in UV-induced NF-kappaB activation." Tsuchiya Y., Asano T., Nakayama K., Kato T. Jr., Karin M., Kamata H. Mol. Cell 39:570-582(2010) [PubMed: 20797629] [Abstract] Cited for: SUBCELLULAR LOCATION, FUNCTION.
[44]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[45]	"Novel cross-talk within the IKK family controls innate immunity." Clark K., Peggie M., Plater L., Sorcek R.J., Young E.R., Madwed J.B., Hough J., McIver E.G., Cohen P. Biochem. J. 434:93-104(2011) [PubMed: 21138416] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION BY TBK1 AND IKBKE.
[46]	"Structure of a NEMO/IKK-associating domain reveals architecture of the interaction site." Rushe M., Silvian L., Bixler S., Chen L.L., Cheung A., Bowes S., Cuervo H., Berkowitz S., Zheng T., Guckian K., Pellegrini M., Lugovskoy A. Structure 16:798-808(2008) [PubMed: 18462684] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 701-742.
[47]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] SER-360.
[48]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., 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 D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-360; ARG-369; GLN-526; THR-710 AND LEU-734.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF029684 mRNA. Translation: AAC51860.1.
AF080158 mRNA. Translation: AAD08997.1.
AF031416 mRNA. Translation: AAC64675.1.
AK302723 mRNA. Translation: BAG63942.1.
AK316418 mRNA. Translation: BAH14789.1.
AY663108 Genomic DNA. Translation: AAT65965.1.
AC083973 Genomic DNA. No translation available.
BC006231 mRNA. Translation: AAH06231.1.

IPI

IPI00024709.
IPI00798101.
IPI01010552.

RefSeq

NP_001177649.1. NM_001190720.2.
NP_001547.1. NM_001556.2.

UniGene

Hs.597664.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3BRT	X-ray	2.25	A/C	701-730	[»]
3BRV	X-ray	2.20	A/C	701-745	[»]

ProteinModelPortal

O14920.

SMR

O14920. Positions 16-666, 702-743.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-27527N.

IntAct

O14920. 26 interactions.

MINT

MINT-107608.

STRING

O14920.

PTM databases

PhosphoSite

O14920.

Proteomic databases

PRIDE

O14920.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000342222; ENSP00000339151; ENSG00000104365.

GeneID

3551.

KEGG

hsa:3551.

UCSC

uc003xow.1. human.

Organism-specific databases

CTD

3551.

GeneCards

GC08P042146.

H-InvDB

HIX0007480.

HGNC

HGNC:5960. IKBKB.

HPA

CAB004447.
HPA001249.

MIM

603258. gene.

neXtProt

NX_O14920.

PharmGKB

PA29776.

GenAtlas

Search...

Phylogenomic databases

GeneTree

ENSGT00530000063051.

HOGENOM

HBG358635.

HOVERGEN

HBG018241.

InParanoid

O14920.

OMA

PGQLMSQ.

OrthoDB

EOG4PK276.

PhylomeDB

O14920.

Enzyme and pathway databases

BRENDA

2.7.11.10. 2681.

Pathway_Interaction_DB

nfkappabatypicalpathway. Atypical NF-kappaB pathway.
bcr_5pathway. BCR signaling pathway.
nfkappabcanonicalpathway. Canonical NF-kappaB pathway.
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
foxopathway. FoxO family signaling.
il1pathway. IL1-mediated signaling events.
p75ntrpathway. p75(NTR)-mediated signaling.
tcrpathway. TCR signaling in naive CD4+ T cells.
cd8tcrpathway. TCR signaling in naive CD8+ T cells.
tnfpathway. TNF receptor signaling pathway.
trail_pathway. TRAIL signaling pathway.

Reactome

REACT_111102. Signal Transduction.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

O14920.

Bgee

O14920.

CleanEx

HS_IKBKB.

Genevestigator

O14920.

GermOnline

ENSG00000104365. Homo sapiens.

Family and domain databases

InterPro

IPR022007. IKKbetaNEMObind.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017442. Se/Thr_kinase-like_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR019955. Ubiquitin_supergroup.
[Graphical view]

KO

K07209.

Pfam

PF12179. IKKbetaNEMObind. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. False negative.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB01169. Arsenic trioxide.
DB00995. Auranofin.

NextBio

13864.

SOURCE

Search...

Entry information

Entry name

IKKB_HUMAN

Accession

Primary (citable) accession number: O14920
Secondary accession number(s): B4DZ30, O75327

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 2001
Last sequence update:	January 1, 1998
Last modified:	January 25, 2012
This is version 136 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.