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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

CHUK Gene

protein-coding GIFtS: 70
GCID: GC10M101938

Conserved Helix-Loop-Helix Ubiquitous Kinase

(Previous symbol: TCF16)

Microbiology & Infectious Diseases Congress

See related diseases
at

MalaCards

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
About This Section

Aliases
Conserved Helix-Loop-Helix Ubiquitous Kinase¹ ² ³		I-Kappa-B Kinase-Alpha²
TCF16¹ ² ³		IkB Kinase Alpha Subunit²
IKK1² ³ ⁵		IKK-A Kinase²
IKKA² ³ ⁵		Inhibitor Of Nuclear Factor Kappa-B Kinase Subunit Alpha²
NFKBIKA² ³ ⁵		Nuclear Factor NFkappaB Inhibitor Kinase Alpha²
Transcription Factor 16² ³		IKK-A³
IKK-alpha² ³		IkBKA³
TCF-16² ³		I-Kappa-B Kinase Alpha³
I-Kappa-B Kinase 1² ³		IkappaB Kinase³
EC 2.7.11.10³ ⁸		Nuclear Factor NF-Kappa-B Inhibitor Kinase Alpha³
IKBKA² ⁵		EC 2.7.11⁸

External Ids:	HGNC: 1974¹	Entrez Gene: 1147²	Ensembl: ENSG00000213341⁷	OMIM: 600664⁵	UniProtKB: O15111³

Export aliases for CHUK gene to outside databases

Previous GC identifers: GC10M100841 GC10M101181 GC10M102079 GC10M101612 GC10M095577

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for CHUK Gene:

This gene encodes a member of the serine/threonine protein kinase family. The encoded protein, a component of a

cytokine-activated protein complex that is an inhibitor of the essential transcription factor NF-kappa-B complex,

phosphorylates sites that trigger the degradation of the inhibitor via the ubiquination pathway, thereby

activating the transcription factor. (provided by RefSeq, Jul 2008)

GeneCards Summary for CHUK Gene:

CHUK (conserved helix-loop-helix ubiquitous kinase) is a protein-coding gene. Diseases associated with CHUK include cocoon syndrome, and skin papilloma, and among its related super-pathways are DR3 Signaling and RANK Signaling in Osteoclasts. GO annotations related to this gene include protein kinase activity and protein heterodimerization activity. An important paralog of this gene is IKBKB.

UniProtKB/Swiss-Prot: IKKA_HUMAN, O15111

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

summary for CHUK Gene:

IkappaB Kinase (IKK) is an enzyme complex that forms part of the NF-kappaB signaling pathway. The complex is

comprised of three subunits (IKKalpha (IKK1), IKKbeta (IKK2) and IKKgamma (NEMO)), the alpha- and

beta-subunits are catalytically active whereas the gamma-subunit serves a regulatory function. Activation of

NF-kappaB occurs via degradation of IkappaB, a process that is initiated by its phosphorylation by IkappaB

kinase (IKK). Phosphorylated IkappaB becomes dissociated from NF-kappaB, unmasking the NLS. Phosphorylation

also results in IkappaB ubiquitination and targeting to the proteasome. NF-kappaB can now enter the nucleus

and regulate gene expression.

Gene Wiki entry for CHUK Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000010.10 NT_030059.13 NC_018921.2

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the CHUK gene promoter:
Pax-5 FOXO3 POU6F1 (c2) LCR-F1 FOXO3b RORalpha1 PPAR-gamma1 c-Myb FOXO3a PPAR-gamma2
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: CHUK promoter sequence

Search SABiosciences Chromatin IP Primers for CHUK

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat CHUK

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 10q24-q25 Ensembl cytogenetic band: 10q24.31 HGNC cytogenetic band: 10q24-q25

CHUK Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CHUK gene location

GeneLoc information about chromosome 10 GeneLoc Exon Structure

GeneLoc location for GC10M101938: view genomic region (about GC identifiers)

Start:	101,948,055 bp from pter	End:	101,989,376 bp from pter
Size:	41,322 bases	Orientation:	minus strand

(According to UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MAXQB RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

UniProtKB/Swiss-Prot: IKKA_HUMAN, O15111 (See protein sequence)

Recommended Name: Inhibitor of nuclear factor kappa-B kinase subunit alpha

Size: 745 amino acids; 84640 Da

Subunit: 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

Subcellular location: Cytoplasm. Nucleus. Note=Shuttles between the cytoplasm and the nucleus

1 PDB 3D structure from and Proteopedia for CHUK:

3BRT (3D)

Secondary accessions: O14666 Q13132 Q5W0I4 Q92467

Explore the universe of human proteins at neXtProt for CHUK: NX_O15111

Explore proteomics data for CHUK at MOPED

Post-translational modifications:

UniProtKB: Phosphorylated by MAP3K14/NIK, AKT and to a lesser extent by MEKK1, and dephosphorylated by PP2A.

Autophosphorylated

UniProtKB: Acetylation of Thr-179 by Yersinia yopJ prevents phosphorylation and activation, thus blocking the I-kappa-B

signaling pathway

View modification sites using PhosphoSitePlus

View neXtProt modification sites for NX_O15111

4/23 DME Specific Peptides for CHUK (O15111) (see all 23)

QGQRAAM

RDLKPEN

QQLKAKL

NYIVQDSK

CHUK Protein expression data from MOPED¹, PaxDb² and MAXQB³ : About this image

REFSEQ proteins: NP_001269.3

ENSEMBL proteins:

ENSP00000359424

Reactome Protein details: O15111
Human Recombinant Protein Products for CHUK:

	EMD Millipore Purified and/or Recombinant CHUK Protein
	Browse R&D Systems for human recombinant proteins
	Browse recombinant and purified proteins available from Enzo Life Sciences
	Browse OriGene full length recombinant human proteins expressed in human HEK293 cells OriGene Protein Over-expression Lysate for CHUK OriGene Custom MassSpec OriGene Custom Protein Services for CHUK
	GenScript Custom Purified and Recombinant Proteins Services for CHUK
	Novus Biologicals CHUK Proteins Novus Biologicals CHUK Lysate
	Browse Sino Biological Recombinant Proteins Browse Sino Biological Cell Lysates
	Browse ProSpec Recombinant Proteins
	Cloud-Clone Corp. Proteins for CHUK

Gene Ontology (GO): 5/8 cellular component terms (GO ID links to tree view) (see all 8): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005634	nucleus	IDA	--
GO:0005730	NOT nucleolus	IDA	--
GO:0005737	cytoplasm	IDA	--
GO:0005829	cytosol	TAS	--
GO:0008385	IkappaB kinase complex	TAS	18626576

CHUK for ontologies About GeneDecksing

CHUK Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of CHUK
	R&D Systems Antibodies for CHUK (IKK alpha)
	Cell Signaling Technology (CST) Antibodies for CHUK (IKKA)
	OriGene Antibodies for CHUK OriGene Custom Antibody Services for CHUK
	GenScript Superior Antibodies for CHUK
	Novus Biologicals CHUK Antibodies
	Abcam antibodies for CHUK
	Cloud-Clone Corp. Antibodies for CHUK
	ThermoFisher Antibody for CHUK
	LSBio Antibodies in human, mouse, rat for CHUK

Assay Products for CHUK:

	EMD Millipore Kits and Assays for the Analysis of CHUK
	OriGene Custom Assay Services for CHUK
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for CHUK
	Cell Signaling Technology (CST) Sandwich ELISA Kits for CHUK (IKKA)
	Browse Enzo Life Sciences for kits & assays
	Cloud-Clone Corp. ELISAs for CHUK Cloud-Clone Corp. CLIAs for CHUK

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

IUPHAR Guide to PHARMACOLOGY protein family classification: conserved helix-loop-helix ubiquitous kinase

IKK family

5/6 InterPro protein domains (see all 6):

IPR017441 Protein_kinase_ATP_BS

IPR002290 Ser/Thr_dual-sp_kinase_dom

IPR011009 Kinase-like_dom

IPR008271 Ser/Thr_kinase_AS

IPR000719 Prot_kinase_cat_dom

Graphical View of Domain Structure for InterPro Entry O15111

ProtoNet protein and cluster: O15111

UniProtKB/Swiss-Prot: IKKA_HUMAN, O15111

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

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

Similarity: Contains 1 protein kinase domain

CHUK for domains About GeneDecksing

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
About This Section

Molecular Function:

UniProtKB/Swiss-Prot Summary: IKKA_HUMAN, O15111