Reviewed, UniProtKB/Swiss-Prot Q14164 (IKKE_HUMAN)

Names and origin

Protein names

Recommended name:
    Inhibitor of nuclear factor kappa-B kinase subunit epsilon
      Short name=I kappa-B kinase epsilon
      Short name=IkBKE
      Short name=IKK-epsilon
      Short name=IKK-E
    EC=2.7.11.10
Alternative name(s):
    Inducible I kappa-B kinase
      Short name=IKK-i

Gene names

Name:	IKBKE
Synonyms:	IKKE, IKKI, KIAA0151

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	716 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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. May play a special role in the immune response.
Catalytic activity	ATP + [I-kappa-B protein] = ADP + [I-kappa-B phosphoprotein].
Subunit structure	May interact with MAVS/IPS1. Interacts with AZI2. Interacts with SIKE. Interacts with TICAM1/TRIF, IRF3 and DDX58/RIG-I, interactions are disrupted by the interaction between IKBKE and SIKE. Ref.7 Ref.8 Ref.9 Ref.10
Subcellular location	Cytoplasm Probable.
Tissue specificity	Highly expressed in spleen followed by thymus, peripheral blood leukocytes, pancreas, placenta. Weakly expressed in lung, kidney, prostate, ovary and colon.
Post-translational modification	Autophosphorylated.
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
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	immune response Ref.1 Non-traceable author statement. Source: UniProtKB positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from expression pattern. Source: UniProtKB protein amino acid phosphorylation Ref.2 Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Non-traceable author statement. Source: UniProtKB
Molecular function	ATP binding Non-traceable author statement. Source: UniProtKB IkappaB kinase activity Inferred from electronic annotation. Source: EC NF-kappaB-inducing kinase activity Ref.2 Inferred from direct assay. Source: UniProtKB protein binding Ref.10 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ACLY	P53396	1	EBI-307369,EBI-1042794
ATIC	P31939	1	EBI-307369,EBI-1048599
CLTC	Q00610	1	EBI-307369,EBI-354967
DSTYK	Q6XUX3	1	EBI-307369,EBI-1049520
EPRS	P07814	1	EBI-307369,EBI-355315
HYOU1	Q9Y4L1	1	EBI-307369,EBI-1054186
IMPDH2	P12268	1	EBI-307369,EBI-353389
LRPPRC	P42704	1	EBI-307369,EBI-1050853
MAVS	Q7Z434	1	EBI-307369,EBI-995373
MYH10	P35580	1	EBI-307369,EBI-351758
PABPC1	P11940	1	EBI-307369,EBI-81531
PDIA6	Q15084	1	EBI-307369,EBI-1043087
PLS3	P13797	1	EBI-307369,EBI-698052
PPP2R1A	P30153	1	EBI-307369,EBI-302388
PSMA7	O14818	1	EBI-307369,EBI-603272
ROCK2	O75116	1	EBI-307369,EBI-366288
RUVBL2	Q9Y230	1	EBI-307369,EBI-352939
SND1	Q7KZF4	1	EBI-307369,EBI-1044112
VCP	Q5VYM0	1	EBI-307369,EBI-1046421

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 716	716	Inhibitor of nuclear factor kappa-B kinase subunit epsilon		PRO_0000086017
Regions
	Domain	9 – 315	307	Protein kinase
	Domain	436 – 457	22	Leucine-zipper Potential
	Nucleotide binding	15 – 23	9	ATP By similarity
Sites
	Active site	135	1	Proton acceptor By similarity
	Binding site	38	1	ATP By similarity
Amino acid modifications
	Modified residue	172	1	Phosphoserine
Natural variations
	Natural variant	128	1	E → K Ref.5		VAR_038816
	Natural variant	371	1	A → T: dbSNP rs17021877. Ref.5 Ref.11		VAR_038817
	Natural variant	483	1	T → M Ref.11		VAR_040571
	Natural variant	515	1	E → D Ref.5		VAR_038818
	Natural variant	543	1	I → M Ref.5		VAR_038819
	Natural variant	602	1	A → V: dbSNP rs12059562. Ref.5 Ref.11		VAR_038820
	Natural variant	660	1	G → E Ref.11		VAR_040572
	Natural variant	713	1	P → L: dbSNP rs3748022. Ref.5 Ref.11		VAR_019989
Experimental info
	Mutagenesis	38	1	K → A: Loss of kinase activity. Ref.1
	Mutagenesis	168	1	E → A: Slight decrease of kinase activity. Ref.1
	Mutagenesis	172	1	S → A: Loss of autophosphorylation and of kinase activity. Ref.1
	Mutagenesis	172	1	S → E: Decrease in kinase activity. Ref.1
	Sequence conflict	187	1	R → Q in AAI05925. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Q14164-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 3E5FBE5840734D81	FASTA	716	80,462
	10 20 30 40 50 60 MQSTANYLWH TDDLLGQGAT ASVYKARNKK SGELVAVKVF NTTSYLRPRE VQVREFEVLR 70 80 90 100 110 120 KLNHQNIVKL FAVEETGGSR QKVLVMEYCS SGSLLSVLES PENAFGLPED EFLVVLRCVV 130 140 150 160 170 180 AGMNHLRENG IVHRDIKPGN IMRLVGEEGQ SIYKLTDFGA ARELDDDEKF VSVYGTEEYL 190 200 210 220 230 240 HPDMYERAVL RKPQQKAFGV TVDLWSIGVT LYHAATGSLP FIPFGGPRRN KEIMYRITTE 250 260 270 280 290 300 KPAGAIAGAQ RRENGPLEWS YTLPITCQLS LGLQSQLVPI LANILEVEQA KCWGFDQFFA 310 320 330 340 350 360 ETSDILQRVV VHVFSLSQAV LHHIYIHAHN TIAIFQEAVH KQTSVAPRHQ EYLFEGHLCV 370 380 390 400 410 420 LEPSVSAQHI AHTTASSPLT LFSTAIPKGL AFRDPALDVP KFVPKVDLQA DYNTAKGVLG 430 440 450 460 470 480 AGYQALRLAR ALLDGQELMF RGLHWVMEVL QATCRRTLEV ARTSLLYLSS SLGTERFSSV 490 500 510 520 530 540 AGTPEIQELK AAAELRSRLR TLAEVLSRCS QNITETQESL SSLNRELVKS RDQVHEDRSI 550 560 570 580 590 600 QQIQCCLDKM NFIYKQFKKS RMRPGLGYNE EQIHKLDKVN FSHLAKRLLQ VFQEECVQKY 610 620 630 640 650 660 QASLVTHGKR MRVVHETRNH LRLVGCSVAA CNTEAQGVQE SLSKLLEELS HQLLQDRAKG 670 680 690 700 710 AQASPPPIAP YPSPTRKDLL LHMQELCEGM KLLASDLLDN NRIIERLNRV PAPPDV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"IKK-i, a novel lipopolysaccharide-inducible kinase that is related to IkappaB kinases." Shimada T., Kawai T., Takeda K., Matsumoto M., Inoue J., Tatsumi Y., Kanamaru A., Akira S. Int. Immunol. 11:1357-1362(1999) [PubMed: 10421793] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF LYS-38; GLU-168 AND SER-172.
[2]	"IKK epsilon is part of a novel PMA-inducible IkappaB kinase complex." Peters R.T., Liao S.-M., Maniatis T. Mol. Cell 5:513-522(2000) [PubMed: 10882136] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Leukocyte.
[3]	"Prediction of the coding sequences of unidentified human genes. IV. The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of cDNA clones from human cell line KG-1." Nagase T., Seki N., Tanaka A., Ishikawa K., Nomura N. DNA Res. 2:167-174(1995) [PubMed: 8590280] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Bone marrow.
[4]	SeattleSNPs variation discovery resource Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LYS-128; THR-371; ASP-515; MET-543; VAL-602 AND LEU-713.
[5]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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].
[7]	"Identification of NAP1, a regulatory subunit of IkappaB kinase-related kinases that potentiates NF-kappaB signaling." Fujita F., Taniguchi Y., Kato T., Narita Y., Furuya A., Ogawa T., Sakurai H., Joh T., Itoh M., Delhase M., Karin M., Nakanishi M. Mol. Cell. Biol. 23:7780-7793(2003) [PubMed: 14560022] [Abstract] Cited for: INTERACTION WITH AZI2.
[8]	"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.
[9]	"SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus-triggered IRF-3 activation pathways." Huang J., Liu T., Xu L.-G., Chen D., Zhai Z., Shu H.-B. EMBO J. 24:4018-4028(2005) [PubMed: 16281057] [Abstract] Cited for: INTERACTION WITH SIKE; IRF3; TICAM1 AND DDX58.
[10]	"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.
[11]	"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] THR-371; MET-483; VAL-602; GLU-660 AND LEU-713.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	D63485 mRNA. Translation: BAA09772.2. Different initiation. AB016590 mRNA. Translation: BAA85155.1. AF241789 mRNA. Translation: AAF45307.1. DQ667176 Genomic DNA. Translation: ABG25921.1. AL354681 Genomic DNA. Translation: CAI15250.1. BC105923 mRNA. Translation: AAI05924.1. BC105924 mRNA. Translation: AAI05925.1.
IPI	IPI00029045.
RefSeq	NP_054721.1.
UniGene	Hs.321045
3D structure databases
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:27530N.
IntAct	Q14164. 343 interactions.
PTM databases
PhosphoSite	Q14164.
Proteomic databases
PRIDE	Q14164.
Genome annotation databases
Ensembl	ENSG00000143466. Homo sapiens. [Contig view]
GeneID	9641.
KEGG	hsa:9641.
Organism-specific databases
GeneCards	GC01P204710.
H-InvDB	HIX0001528. HIX0001529.
HGNC	HGNC:14552. IKBKE.
HPA	HPA015788.
MIM	605048. gene.
PharmGKB	PA134962294.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q14164.
HOVERGEN	Q14164.
OMA	Q14164. FLVVLRC.
Enzyme and pathway databases
BRENDA	2.7.11.10. 247.
Gene expression databases
ArrayExpress	Q14164.
Bgee	Q14164.
CleanEx	HS_IKBKE.
GermOnline	ENSG00000143466. Homo sapiens.
Family and domain databases
InterPro	IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	36191.
SOURCE	Search...

Entry information

Entry name

IKKE_HUMAN

Accession

Primary (citable) accession number: Q14164
Secondary accession number(s): Q3KR43, Q5JTS6

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2001
Last sequence update:	November 1, 1996
Last modified:	June 16, 2009
This is version 93 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)