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Reviewed, UniProtKB/Swiss-Prot Q60680 (IKKA_MOUSE)

Last modified February 9, 2010. Version 105. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Inhibitor of nuclear factor kappa-B kinase subunit alpha
      Short name=I-kappa-B kinase alpha
      Short name=IkBKA
      Short name=IKK-alpha
      Short name=IKK-A
      Short name=IkappaB kinase
    EC=2.7.11.10
Alternative name(s):
    I-kappa-B kinase 1
      Short name=IKK1
    Conserved helix-loop-helix ubiquitous kinase
    Nuclear factor NF-kappa-B inhibitor kinase alpha
      Short name=NFKBIKA
Gene names
Name: Chuk
Synonyms: Ikka
OrganismMus musculus (Mouse)
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

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Protein attributes

Sequence length745 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

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General annotation (Comments)

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. 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. Also phosphorylates NCOA3. Phosphorylates 'Ser-10' of histone H3 at NF-kappa-B-regulated promoters during inflammatory responses triggered by cytokines. Ref.10

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. 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. May interact with TRAF2. Interacts with NALP2. May interact with MAVS/IPS1. Interacts with ARRB1 By similarity. Interacts with ARRB2. Ref.11

Subcellular location

Cytoplasm. Nucleus. Note: Shuttles between the cytoplasm and the nucleus. Ref.10

Tissue specificity

Ubiquitous only for isoform 1, isoforms 2 and 3 are expressed predominantly in brain and T-lymphocytes.

Developmental stage

Maximally expressed at E7 day followed by E11, E15 and E17 days. In the limb development, its expression predominates in the limb buds at E12.5 day.

Post-translational modification

Phosphorylated by MAP3K14/NIK, AKT and to a lesser extent by MEKK1, and dephosphorylated by PP2A. Autophosphorylated. Ref.6 Ref.8

Sequence similarities

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily.

Contains 1 protein kinase domain.

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Binary interactions

With

Entry

#Exp.

IntAct

Notes

Fam92a1Q8BP222EBI-646260,EBI-646638
IKBKBO149201EBI-646245,EBI-81266From a different organism.
IKBKBO149201EBI-646269,EBI-81266From a different organism.
Irf7P704342EBI-646245,EBI-997907
Krt10P025352EBI-646260,EBI-646288
MAP3K14Q995581EBI-646245,EBI-358011From a different organism.
MAP3K14Q995582EBI-646264,EBI-358011From a different organism.
NFKBIAP259631EBI-646245,EBI-307386From a different organism.
NFKBIAP259631EBI-646264,EBI-307386From a different organism.
NFKBIAP259631EBI-646269,EBI-307386From a different organism.
Pex5O090122EBI-646260,EBI-646301
Sestd1Q80UK02EBI-646260,EBI-646282

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Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q60680-1)

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: Q60680-2)

Also known as: Delta LH;

The sequence of this isoform differs from the canonical sequence as follows:
     452-471: MLSLLRYNANLTKMKNTLIS → IFRKNVKSMERNGRKGHSLF
     472-745: Missing.
Isoform 3 (identifier: Q60680-3)

Also known as: Delta H;

The sequence of this isoform differs from the canonical sequence as follows:
     577-584: DHLYSDST → GKTLQSQY
     585-745: Missing.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 745745Inhibitor of nuclear factor kappa-B kinase subunit alpha
PRO_0000086012

Regions

Domain15 – 300286Protein kinase
Domain455 – 47622Leucine-zipper
Nucleotide binding21 – 299ATP By similarity
Region738 – 7436NEMO-binding

Sites

Active site1441Proton acceptor By similarity
Binding site441ATP By similarity

Amino acid modifications

Modified residue231Phosphothreonine; by PKB/AKT1 By similarity
Modified residue1761Phosphoserine; by MAP3K14 By similarity

Natural variations

Alternative sequence452 – 47120MLSLL…NTLIS → IFRKNVKSMERNGRKGHSLF in isoform 2.
VSP_004866
Alternative sequence472 – 745274Missing in isoform 2.
VSP_004867
Alternative sequence577 – 5848DHLYSDST → GKTLQSQY in isoform 3.
VSP_004868
Alternative sequence585 – 745161Missing in isoform 3.
VSP_004869

Experimental info

Sequence conflict2361K → E in BAB31335. Ref.3
Sequence conflict4001S → Y in BAB31335. Ref.3

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 3FEF5582AFF92233

FASTA74584,729
        10         20         30         40         50         60 
MERPPGLRPG AGGPWEMRER LGTGGFGNVS LYQHRELDLK IAIKSCRLEL SSKNRERWCH 

        70         80         90        100        110        120 
EIQIMKKLDH ANVVKACDVP EELNFLINDV PLLAMEYCSG GDLRKLLNKP ENCCGLKESQ 

       130        140        150        160        170        180 
ILSLLSDIGS GIRYLHENKI IHRDLKPENI VLQDVGGKTI HKIIDLGYAK DVDQGSLCTS 

       190        200        210        220        230        240 
FVGTLQYLAP ELFENKPYTA TVDYWSFGTM VFECIAGYRP FLHHLQPFTW HEKIKKKDPK 

       250        260        270        280        290        300 
CIFACEEMTG EVRFSSHLPQ PNSLCSLIVE PMESWLQLML NWDPQQRGGP IDLTLKQPRC 

       310        320        330        340        350        360 
FALMDHILNL KIVHILNMTS AKIISFLLPC 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 
EFFRKSIQLD LERYSEQMTY GISSEKMLKA WKEMEEKAIH YSEVGVIGYL EDQIMSLHTE 

       550        560        570        580        590        600 
IMELQKSPYG RRQGDLMESL EQRAIDLYKQ LKHRPPDHLY SDSTEMVKII VHTVQSQDRV 

       610        620        630        640        650        660 
LKELFGHLSK LLGCKQKIID LLPKVEVALS NIKEADNTVM FMQGKRQKEI WHLLKIACTQ 

       670        680        690        700        710        720 
SSARSLVGSS LEGTVTPPVS AWLPPTLADR EHPLTCVVTP QDGETLAQMI EENLNCLGHL 

       730        740 
STIIREANED QSSSLMSLDW SWLAE

« Hide

Isoform 2 (Delta LH).

Checksum: 14F1EFF71B4A17EE
Show »

FASTA47153,544
Isoform 3 (Delta H).

Checksum: D99BB8A6DF1CA4EB
Show »

FASTA58466,805

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References

« Hide 'large scale' references
[1]"CHUK, a conserved helix-loop-helix ubiquitous kinase, maps to human chromosome 10 and mouse chromosome 19."
Mock B.A., Connelly M.A., McBride O.W., Kozak C.A., Marcu K.B.
Genomics 27:348-351(1995) [PubMed: 7558004] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Strain: BALB/c.
[2]"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: 8777433] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Strain: BALB/c.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Strain: C57BL/6J.
Tissue: Colon.
[4]"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: Eye.
[5]"Functional isoforms of IkappaB kinase alpha (IKKalpha) lacking leucine zipper and helix-loop-helix domains reveal that IKKalpha and IKKbeta have different activation requirements."
McKenzie F.R., Connelly M.A., Balzarano D., Mueller J.R., Geleziunas R., Marcu K.B.
Mol. Cell. Biol. 20:2635-2649(2000) [PubMed: 10733566] [Abstract]
Cited for: ALTERNATIVE SPLICING.
[6]"Differential regulation of IkappaB kinase alpha and beta by two upstream kinases, NF-kappaB-inducing kinase and mitogen-activated protein kinase/ERK kinase kinase-1."
Nakano H., Shindo M., Sakon S., Nishinaka S., Mihara M., Yagita H., Okumura K.
Proc. Natl. Acad. Sci. U.S.A. 95:3537-3542(1998) [PubMed: 9520401] [Abstract]
Cited for: PHOSPHORYLATION BY MAP3K14/NIK.
[7]"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: IKKA-IKKB BINDING.
[8]"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.
[9]"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.
[10]"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: 12789342] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[11]"Beta2-adrenergic receptor regulates Toll-like receptor-4-induced nuclear factor-kappaB activation through beta-arrestin 2."
Kizaki T., Izawa T., Sakurai T., Haga S., Taniguchi N., Tajiri H., Watanabe K., Day N.K., Toba K., Ohno H.
Immunology 124:348-356(2008) [PubMed: 18194271] [Abstract]
Cited for: INTERACTION WITH ARRB2.
+Additional computationally mapped references.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		U12473 mRNA. Translation: AAC52589.1.
AK018671 mRNA. Translation: BAB31335.1.
BC018243 mRNA. Translation: AAH18243.1.
IPIIPI00119213.
IPI00230069.
IPI00400114.
PIRI49101.
UniGeneMm.3996

3D structure databases

SMRQ60680. Positions 19-330.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-29719N.
IntActQ60680. 24 interactions.
STRINGQ60680.

PTM databases

PhosphoSiteQ60680.

Proteomic databases

PRIDEQ60680.

Genome annotation databases

EnsemblENSMUST00000026217; ENSMUSP00000026217; ENSMUSG00000025199; Mus musculus. [Genome view]
ENSMUST00000112015; ENSMUSP00000107646; ENSMUSG00000025199; Mus musculus. [Genome view]
UCSCuc008hpg.1. mouse.
uc008hpi.1. mouse.

Organism-specific databases

MGIMGI:99484. Chuk.

Phylogenomic databases

HOGENOMHBG358635.
HOVERGENQ60680.
InParanoidQ60680.

Enzyme and pathway databases

BRENDA2.7.11.10. 244.

Gene expression databases

ArrayExpressQ60680.
BgeeQ60680.
CleanExMM_CHUK.
GenevestigatorQ60680.
GermOnlineENSMUSG00000025199. Mus musculus.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_prot_kinase-like_dom.
IPR008271. Ser/Thr_prot_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio281918.
SOURCESearch...

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Entry information

Entry nameIKKA_MOUSE
AccessionPrimary (citable) accession number: Q60680
Secondary accession number(s): Q80VU2, Q9D2X3
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: November 1, 1996
Last modified: February 9, 2010
This is version 105 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents