Inhibitor of nuclear factor kappa-B kinase subunit alpha

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Q95KV1 (IKKA_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 81. History...

Clusters with 100%, 90%, 50% identity |

Documents (1) |

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

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
EC=2.7.11.10

Alternative name(s):
I-kappa-B kinase 1
Short name=IKK1
Nuclear factor NF-kappa-B inhibitor kinase alpha
Short name=NFKBIKA

Gene names

Name:	CHUK
Synonyms:	IKKA

Organism

Bos taurus (Bovine) [Reference proteome]

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	740 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 By similarity.
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. May interact with TRAF2. Interacts with NALP2. May interact with MAVS/IPS1. Interacts with ARRB1 and ARRB2 By similarity. Interacts with NLRC5; prevents CHUK phosphorylation and kinase activity. Interacts with PIAS1; this interaction induces PIAS1 phosphorylation By similarity. Ref.1
Subcellular location	Cytoplasm. Nucleus. Note: Shuttles between the cytoplasm and the nucleus By similarity.
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 By similarity.
Post-translational modification	Phosphorylated by MAP3K14/NIK, AKT and to a lesser extent by MEKK1, and dephosphorylated by PP2A. Autophosphorylated By similarity.
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
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	I-kappaB phosphorylation Inferred from electronic annotation. Source: GOC 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 odontogenesis of dentin-containing tooth Inferred from electronic annotation. Source: Compara osteoclast differentiation Inferred from electronic annotation. Source: Compara positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm 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 Inferred from electronic annotation. Source: EC protein kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 740

740

Inhibitor of nuclear factor kappa-B kinase subunit alpha

PRO_0000268159

Regions

Domain

15 – 302

288

Protein kinase

Nucleotide binding

21 – 29

ATP By similarity

Region

455 – 476

Leucine-zipper

Region

733 – 738

NEMO-binding By similarity

Sites

Active site

144

Proton acceptor By similarity

Binding site

ATP By similarity

Amino acid modifications

Modified residue

Phosphothreonine; by PKB/AKT1 By similarity

Modified residue

176

Phosphoserine; by MAP3K14 By similarity

Modified residue

180

Phosphoserine By similarity

Sequences

Sequence

Length

Mass (Da)

Tools

Q95KV1 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: 01903BE11F44D176
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FASTA

740

84,344

        10         20         30         40         50         60 
MERPPGLRPG AGGPWEMRER LGTGGFGNVC LYQHRELDLK IAIKSCRLEL STKNRERWCH 

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

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

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

       250        260        270        280        290        300 
CIFACEEMTG EVRFSSHLPQ PNSLCSLIVE PMENWLQLML NWDPQQRGGP VDLTLKQPRC 

       310        320        330        340        350        360 
FVLMDHILNL KIVHILNMTS AKIISFLLPP DESLHSLQSR IERETGINTG SQELLSEMGI 

       370        380        390        400        410        420 
SLDPRKPASQ CVLDGVRGCD SYMVYLFDKS KTVYEGPFAS RSLSDCVNYI VQDSKIQLPI 

       430        440        450        460        470        480 
IQLRKVWAEA VHYVSGLKED YSRLFQGQRA AMLSLLRYNT NLTKMKNTLI SASQQLKAKL 

       490        500        510        520        530        540 
EFFHKSIQLD LERYSEQMTY GISSEKMLKA WKEMEEKAIH YAEVGVIGYL EDQIMSLHTE 

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

       610        620        630        640        650        660 
LKELFGHLSK LLGCKQKIID LLPKVEMALS NIKEADSTVM FMQGKRQKEI WHLLKIACTQ 

       670        680        690        700        710        720 
SSARSLVGSS LEGVTPQLPP TSAEREHPLS CVVTPQDGET LAQMIEENLN CLGHLSTIIH 

       730        740 
EANEKQGNNM MSLDWSWLTE

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of the bovine IkappaB kinases (IKK)alpha and IKKbeta, the regulatory subunit NEMO and their substrate IkappaBalpha." Rottenberg S., Schmuckli-Maurer J., Grimm S., Heussler V.T., Dobbelaere D.A.E. Gene 299:293-300(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH IKKB AND IKBKG.
[2]	NIH - Mammalian Gene Collection (MGC) project Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Hereford. Tissue: Ascending colon.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ414555 mRNA. Translation: CAC93686.1. BC134510 mRNA. Translation: AAI34511.1.
IPI	IPI00694206.
RefSeq	NP_776446.1. NM_174021.2.
UniGene	Bt.63925.
3D structure databases
ProteinModelPortal	Q95KV1.
ModBase	Search...
Proteomic databases
PRIDE	Q95KV1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSBTAT00000009985; ENSBTAP00000009985; ENSBTAG00000007591.
GeneID	281073.
KEGG	bta:281073.
Organism-specific databases
CTD	1147.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00530000063051.
HOGENOM	HOG000038048.
HOVERGEN	HBG018241.
InParanoid	Q95KV1.
KO	K04467.
OMA	EREHPLS.
OrthoDB	EOG4SJ5D7.
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
NextBio	20805154.

Entry information

Entry name

IKKA_BOVIN

Accession

Primary (citable) accession number: Q95KV1
Secondary accession number(s): A7YWD1

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 12, 2006
Last sequence update:	December 1, 2001
Last modified:	April 3, 2013
This is version 81 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Sequences

References

Cross-references

Sequence databases

3D structure databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Family and domain databases

Other

Entry information

Relevant documents