O15111 (IKKA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Inhibitor of nuclear factor kappa-B kinase subunit alpha
Short name=I-kappa-B kinase alpha
Short name=IKK-A
Short name=IKK-alpha
Short name=IkBKA
Short name=IkappaB kinase
EC=2.7.11.10

Alternative name(s):
Conserved helix-loop-helix ubiquitous kinase
I-kappa-B kinase 1
Short name=IKK1
Nuclear factor NF-kappa-B inhibitor kinase alpha
Short name=NFKBIKA
Transcription factor 16
Short name=TCF-16

Gene names

Name:	CHUK
Synonyms:	IKKA, TCF16

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	745 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 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. Negatively regulates the pathway by phosphorylating the scaffold protein TAXBP1 and thus promoting the assembly of the A20/TNFAIP3 ubiquitin-editing complex (composed of A20/TNFAIP3, TAX1BP1, and the E3 ligases ITCH and RNF11). Therefore, CHUK plays a key role in the negative feedback of NF-kappa-B canonical signaling to limit inflammatory gene activation. As part of the non-canonical pathway of NF-kappa-B activation, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. In turn, these complexes regulate genes encoding molecules involved in B-cell survival and lymphoid organogenesis. Participates also in the negative feedback of the non-canonical NF-kappa-B signaling pathway by phosphorylating and destabilizing MAP3K14/NIK. Within the nucleus, phosphorylates CREBBP and consequently increases both its transcriptional and histone acetyltransferase activities. Modulates chromatin accessibility at NF-kappa-B-responsive promoters by phosphorylating histones H3 at 'Ser-10' that are subsequently acetylated at 'Lys-14' by CREBBP. Additionally, phosphorylates the CREBBP-interacting protein NCOA3. Ref.17 Ref.22 Ref.25 Ref.27 Ref.29
Catalytic activity	ATP + [I-kappa-B protein] = ADP + [I-kappa-B phosphoprotein].
Enzyme regulation	Activated when phosphorylated and inactivated when dephosphorylated.
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. Directly interacts with IKK-gamma/NEMO and TRPC4AP By similarity. May interact with TRAF2. Interacts with NALP2. May interact with MAVS/IPS1. Interacts with ARRB1 and ARRB2. Interacts with NLRC5; prevents CHUK phosphorylation and kinase activity. Interacts with PIAS1; this interaction induces PIAS1 phosphorylation. Ref.9 Ref.15 Ref.18 Ref.19 Ref.20 Ref.21 Ref.25
Subcellular location	Cytoplasm. Nucleus. Note: Shuttles between the cytoplasm and the nucleus. Ref.17
Tissue specificity	Widely expressed.
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.23
Post-translational modification	Phosphorylated by MAP3K14/NIK, AKT and to a lesser extent by MEKK1, and dephosphorylated by PP2A. Autophosphorylated. Ref.10 Ref.11 Ref.13 Ref.24 Acetylation of Thr-179 by Yersinia yopJ prevents phosphorylation and activation, thus blocking the I-kappa-B signaling pathway.
Involvement in disease	Cocoon syndrome (COCOS) [MIM:613630]: A lethal syndrome characterized by multiple fetal malformations including defective face and seemingly absent limbs, which are bound to the trunk and encased under the skin. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.26
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 Nucleus
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	MyD88-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome Rho protein signal transduction Inferred from electronic annotation. Source: Compara T cell receptor signaling pathway Traceable author statement. Source: Reactome TRIF-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome anatomical structure morphogenesis Traceable author statement PubMed 10747982. Source: ProtInc epidermal growth factor receptor signaling pathway Traceable author statement. Source: Reactome fibroblast growth factor receptor signaling pathway Traceable author statement. Source: Reactome inflammatory response Traceable author statement Ref.23. Source: UniProtKB innate immune response Traceable author statement Ref.23. Source: UniProtKB lactation Inferred from electronic annotation. Source: Compara mammary gland alveolus development Inferred from electronic annotation. Source: Compara mammary gland epithelial cell proliferation Inferred from electronic annotation. Source: Compara morphogenesis of an epithelial sheet Inferred from electronic annotation. Source: Compara neurotrophin TRK receptor signaling pathway Traceable author statement. Source: Reactome nucleotide-binding oligomerization domain containing signaling pathway Traceable author statement. Source: Reactome odontogenesis of dentin-containing tooth Inferred from electronic annotation. Source: Compara osteoclast differentiation Inferred from electronic annotation. Source: Compara phosphatidylinositol-mediated signaling 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.23. Source: UniProtKB positive regulation of type I interferon production Traceable author statement. Source: Reactome response to amino acid stimulus Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to hydroperoxide Inferred from electronic annotation. Source: Compara response to lipopolysaccharide Inferred from electronic annotation. Source: Compara response to toxic substance Inferred from electronic annotation. Source: Compara response to virus Traceable author statement Ref.23. Source: UniProtKB skeletal muscle contraction Inferred from electronic annotation. Source: Compara striated muscle cell differentiation Inferred from electronic annotation. Source: Compara toll-like receptor 10 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 toll-like receptor 5 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 9 signaling pathway Traceable author statement. Source: Reactome toll-like receptor TLR1:TLR2 signaling pathway Traceable author statement. Source: Reactome toll-like receptor TLR6:TLR2 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.23. Source: UniProtKB internal side of plasma membrane Inferred from sequence or structural similarity. Source: BHF-UCL nucleus Inferred from direct assay. Source: HPA
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW IkappaB kinase activity Traceable author statement Ref.23. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		6	EBI-81249,EBI-81249
IKBKB	O14920	10	EBI-81249,EBI-81266
IKBKG	Q9Y6K9	13	EBI-81249,EBI-81279
MAP3K14	Q99558	4	EBI-81249,EBI-358011
MYC	P01106	3	EBI-81249,EBI-447544
NFKBIA	P25963	10	EBI-81249,EBI-307386
RELA	Q04206	2	EBI-81249,EBI-73886
TAX1BP1	Q86VP1	2	EBI-81249,EBI-529518
VACWR196	P24772	3	EBI-81249,EBI-4291651	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 745

745

Inhibitor of nuclear factor kappa-B kinase subunit alpha

PRO_0000086011

Regions

Domain

15 – 302

288

Protein kinase

Nucleotide binding

21 – 29

9

ATP By similarity

Region

455 – 476

22

Leucine-zipper

Region

738 – 743

6

NEMO-binding

Sites

Active site

144

1

Proton acceptor By similarity

Binding site

44

1

ATP By similarity

Amino acid modifications

Modified residue

23

1

Phosphothreonine; by PKB/AKT1 and SGK1 Ref.11 Ref.24

Modified residue

176

1

Phosphoserine; by MAP3K14 Ref.10

Modified residue

179

1

O-acetylthreonine; by Yersinia yopJ

Modified residue

180

1

Phosphoserine; by SGK1 Ref.24

Natural variations

Natural variant

126

1

S → C. Ref.30
Corresponds to variant rs34427437 [ dbSNP | Ensembl ].

VAR_040565

Natural variant

155

1

V → A. Ref.30
Corresponds to variant rs2230803 [ dbSNP | Ensembl ].

VAR_040566

Natural variant

268

1

V → I. Ref.1 Ref.2 Ref.4 Ref.6 Ref.7 Ref.30
Corresponds to variant rs2230804 [ dbSNP | Ensembl ].

VAR_021359

Experimental info

Mutagenesis

23

1

T → A: Loss of phosphorylation and decrease of kinase activity. Ref.11

Mutagenesis

44

1

K → A: Loss of kinase activity. Ref.1 Ref.3

Mutagenesis

44

1

K → M: Loss of autophosphorylation. Ref.1 Ref.3

Mutagenesis

176

1

S → A: Loss of phosphorylation and of activity. Ref.3 Ref.10

Mutagenesis

176

1

S → E: Full activation. Ref.3 Ref.10

Mutagenesis

179

1

T → A: No change in phosphorylation. Ref.10

Mutagenesis

180

1

S → A: No change in phosphorylation. Ref.10

Sequence conflict

543

1

E → G in AAC51671. Ref.2

Sequence conflict

604

1

L → R in AAC50713. Ref.7

Sequence conflict

679 – 680

2

TS → AY in AAC50713. Ref.7

Sequence conflict

684

1

P → A no nucleotide entry Ref.3

Sequence conflict

684

1

P → A in AAC50713. Ref.7

Sequence conflict

686 – 687

2

TS → DL in AAC50713. Ref.7

Secondary structure

1

.

.

.

.

.

745

Helix Strand Turn

Details...

Helix

735 – 737

3

Helix

741 – 743

3

Sequences

	Sequence		Length	Mass (Da)
	O15111 [UniParc]. Last modified January 11, 2011. Version 2. Checksum: 4EA55C6FFC66FA16	FASTA	745	84,640
	10 20 30 40 50 60 MERPPGLRPG AGGPWEMRER LGTGGFGNVC LYQHRELDLK IAIKSCRLEL STKNRERWCH 70 80 90 100 110 120 EIQIMKKLNH ANVVKACDVP EELNILIHDV PLLAMEYCSG GDLRKLLNKP ENCCGLKESQ 130 140 150 160 170 180 ILSLLSDIGS GIRYLHENKI IHRDLKPENI VLQDVGGKII HKIIDLGYAK DVDQGSLCTS 190 200 210 220 230 240 FVGTLQYLAP ELFENKPYTA TVDYWSFGTM VFECIAGYRP FLHHLQPFTW HEKIKKKDPK 250 260 270 280 290 300 CIFACEEMSG EVRFSSHLPQ PNSLCSLVVE PMENWLQLML NWDPQQRGGP VDLTLKQPRC 310 320 330 340 350 360 FVLMDHILNL KIVHILNMTS AKIISFLLPP DESLHSLQSR IERETGINTG SQELLSETGI 370 380 390 400 410 420 SLDPRKPASQ CVLDGVRGCD SYMVYLFDKS KTVYEGPFAS RSLSDCVNYI VQDSKIQLPI 430 440 450 460 470 480 IQLRKVWAEA VHYVSGLKED YSRLFQGQRA AMLSLLRYNA NLTKMKNTLI SASQQLKAKL 490 500 510 520 530 540 EFFHKSIQLD LERYSEQMTY GISSEKMLKA WKEMEEKAIH YAEVGVIGYL EDQIMSLHAE 550 560 570 580 590 600 IMELQKSPYG RRQGDLMESL EQRAIDLYKQ LKHRPSDHSY SDSTEMVKII VHTVQSQDRV 610 620 630 640 650 660 LKELFGHLSK LLGCKQKIID LLPKVEVALS NIKEADNTVM FMQGKRQKEI WHLLKIACTQ 670 680 690 700 710 720 SSARSLVGSS LEGAVTPQTS AWLPPTSAEH DHSLSCVVTP QDGETSAQMI EENLNCLGHL 730 740 STIIHEANEE QGNSMMNLDW SWLTE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and characterization of an IkappaB kinase." Regnier C.H., Song H.Y., Gao X., Goeddel D.V., Cao Z., Rothe M. Cell 90:373-383(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF LYS-44, VARIANT ILE-268. Tissue: T-cell.
[2]	"A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB." DiDonato J.A., Hayakawa M., Rothwarf D.M., Zandi E., Karin M. Nature 388:548-554(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, VARIANT ILE-268.
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, MUTAGENESIS OF LYS-44 AND SER-176. Tissue: Cervix carcinoma.
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ILE-268. Tissue: Heart.
[5]	SeattleSNPs variation discovery resource Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., 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 A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ILE-268.
[7]	"CHUK, a new member of the helix-loop-helix and leucine zipper families of interacting proteins, contains a serine-threonine kinase catalytic domain." Connelly M.A., Marcu K.B. Cell. Mol. Biol. Res. 41:537-549(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 32-745, VARIANT ILE-268. Tissue: Cervix carcinoma.
[8]	"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] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 169-181, INACTIVATION BY YERSINIA YOPJ, ACETYLATION AT THR-179, MASS SPECTROMETRY.
[9]	"IKAP is a scaffold protein of the IkappaB kinase complex." Cohen L., Henzel W.J., Baeuerle P.A. Nature 395:292-296(1998) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH IKBKB; NFKBIA; RELA; IKBKAP AND MAP3K14.
[10]	"NF-kappaB-inducing kinase activates IKK-alpha by phosphorylation of Ser-176." Ling L., Cao Z., Goeddel D.V. Proc. Natl. Acad. Sci. U.S.A. 95:3792-3797(1998) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-176, MUTAGENESIS OF SER-176; THR-179 AND SER-180.
[11]	"NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase." Ozes O.N., Mayo L.D., Gustin J.A., Pfeffer S.R., Pfeffer L.M., Donner D.B. Nature 401:82-85(1999) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-23, MUTAGENESIS OF THR-23.
[12]	"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] [Europe PMC] [Abstract] Cited for: IKKA-IKKB BINDING.
[13]	"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] [Europe PMC] [Abstract] Cited for: IKK PHOSPHORYLATION.
[14]	"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] [Europe PMC] [Abstract] Cited for: REVIEW.
[15]	"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] [Europe PMC] [Abstract] Cited for: SUBUNIT OF A COMPLEX CONTAINING CREBBP; NCOA2; NCOA3; IKKB AND IKBKG.
[16]	"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] [Europe PMC] [Abstract] Cited for: COMPOSITION OF THE IKK COMPLEX.
[17]	"Histone H3 phosphorylation by IKK-alpha is critical for cytokine-induced gene expression." Yamamoto Y., Verma U.N., Prajapati S., Kwak Y.T., Gaynor R.B. Nature 423:655-659(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, FUNCTION IN PHOSPHORYLATION OF HISTONE H3.
[18]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NALP2.
[19]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ARRB1 AND ARRB2.
[20]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MAVS.
[21]	"Proinflammatory stimuli induce IKKalpha-mediated phosphorylation of PIAS1 to restrict inflammation and immunity." Liu B., Yang Y., Chernishof V., Loo R.R., Jang H., Tahk S., Yang R., Mink S., Shultz D., Bellone C.J., Loo J.A., Shuai K. Cell 129:903-914(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PIAS1.
[22]	"Phosphorylation of CBP by IKKalpha promotes cell growth by switching the binding preference of CBP from p53 to NF-kappaB." Huang W.C., Ju T.K., Hung M.C., Chen C.C. Mol. Cell 26:75-87(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF CREBBP.
[23]	"The IkappaB kinase complex: master regulator of NF-kappaB signaling." Solt L.A., May M.J. Immunol. Res. 42:3-18(2008) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW, DOMAIN.
[24]	"SGK1 phosphorylation of IkappaB Kinase alpha and p300 Up-regulates NF-kappaB activity and increases N-Methyl-D-aspartate receptor NR2A and NR2B expression." Tai D.J., Su C.C., Ma Y.L., Lee E.H. J. Biol. Chem. 284:4073-4089(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-23 AND SER-180 BY SGK1.
[25]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH NLRC5.
[26]	"Mutant CHUK and severe fetal encasement malformation." Lahtela J., Nousiainen H.O., Stefanovic V., Tallila J., Viskari H., Karikoski R., Gentile M., Saloranta C., Varilo T., Salonen R., Kestila M. N. Engl. J. Med. 363:1631-1637(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN COCOS.
[27]	"Negative feedback in noncanonical NF-kappaB signaling modulates NIK stability through IKKalpha-mediated phosphorylation." Razani B., Zarnegar B., Ytterberg A.J., Shiba T., Dempsey P.W., Ware C.F., Loo J.A., Cheng G. Sci. Signal. 3:RA41-RA41(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN MAP3K14 PHOSPHORYLATION.
[28]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[29]	"The kinase IKKalpha inhibits activation of the transcription factor NF-kappaB by phosphorylating the regulatory molecule TAX1BP1." Shembade N., Pujari R., Harhaj N.S., Abbott D.W., Harhaj E.W. Nat. Immunol. 12:834-843(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF TAX1BP1.
[30]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] CYS-126; ALA-155 AND ILE-268.
[31]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 732-745.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF012890 mRNA. Translation: AAC51662.1.
AF009225 mRNA. Translation: AAC51671.1.
AF080157 mRNA. Translation: AAD08996.1.
AY652653 Genomic DNA. Translation: AAT49098.1.
AL138921 Genomic DNA. Translation: CAH72401.1.
U22512 mRNA. Translation: AAC50713.1.

IPI

IPI00005104.

RefSeq

NP_001269.3. NM_001278.3.

UniGene

Hs.198998.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3BRT	X-ray	2.25	A/C	732-745	[»]

ProteinModelPortal

O15111.

SMR

O15111. Positions 16-660.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-27526N.

IntAct

O15111. 27 interactions.

MINT

MINT-88648.

STRING

9606.ENSP00000359424.

PTM databases

PhosphoSite

O15111.

Proteomic databases

PaxDb

O15111.

PRIDE

O15111.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000370397; ENSP00000359424; ENSG00000213341.

GeneID

1147.

KEGG

hsa:1147.

UCSC

uc001kqp.3. human.

Organism-specific databases

CTD

1147.

GeneCards

GC10M101938.

H-InvDB

HIX0201495.

HGNC

HGNC:1974. CHUK.

HPA

CAB004240.
CAB018564.
HPA001402.

MIM

600664. gene.
613630. phenotype.

neXtProt

NX_O15111.

PharmGKB

PA26510.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000038048.

HOVERGEN

HBG018241.

InParanoid

O15111.

KO

K04467.

OMA

EREHPLS.

OrthoDB

EOG4SJ5D7.

PhylomeDB

O15111.

Enzyme and pathway databases

BRENDA

2.7.11.10. 2681.

Pathway_Interaction_DB

nfkappabalternativepathway. Alternative NF-kappaB pathway.
bcr_5pathway. BCR signaling pathway.
nfkappabcanonicalpathway. Canonical NF-kappaB pathway.
pi3kciaktpathway. Class I PI3K signaling events mediated by Akt.
faspathway. FAS signaling pathway (CD95).
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
foxopathway. FoxO family signaling.
hivnefpathway. HIV-1 Nef: Negative effector of Fas and TNF-alpha.
il1pathway. IL1-mediated signaling events.
avb3_opn_pathway. Osteopontin-mediated 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_116125. Disease.
REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.

SignaLink

O15111.

Gene expression databases

Bgee

O15111.

CleanEx

HS_CHUK.

Genevestigator

O15111.

GermOnline

ENSG00000107566. Homo sapiens.

Family and domain databases

InterPro

IPR022007. IKKbetaNEMObind.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

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

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

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

ProtoNet

Search...

Other

BindingDB

O15111.

ChEMBL

CHEMBL3476.

ChiTaRS

CHUK. human.

EvolutionaryTrace

O15111.

GenomeRNAi

1147.

NextBio

4772.

SOURCE

Search...

Entry information

Entry name

IKKA_HUMAN

Accession

Primary (citable) accession number: O15111
Secondary accession number(s): O14666 , Q13132, Q5W0I4, Q92467

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 2001
Last sequence update:	January 11, 2011
Last modified:	May 29, 2013
This is version 148 of the entry and version 2 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.