Q9Z1E3 (IKBA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
NF-kappa-B inhibitor alpha

Alternative name(s):
I-kappa-B-alpha
Short name=IkB-alpha
Short name=IkappaBalpha

Gene names

Name:	Nfkbia
Synonyms:	Ikba

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	314 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL dimers in the cytoplasm through masking of their nuclear localization signals. On cellular stimulation by immune and proinflammatory responses, becomes phosphorylated promoting ubiquitination and degradation, enabling the dimeric RELA to translocate to the nucleus and activate transcription. Ref.5 Ref.6
Subunit structure	Interacts with PRMT2 By similarity. Interacts with RELA; the interaction requires the nuclear import signal. Interacts with NKIRAS1 and NKIRAS2. Part of a 70-90 kDa complex at least consisting of CHUK, IKBKB, NFKBIA, RELA, IKBKAP and MAP3K14. Interacts with HBV protein X. Interacts with RWDD3; the interaction enhances sumoylation. Interacts (when phosphorylated at the 2 serine residues in the destruction motif D-S-G-X(2,3,4)-S) with BTRC. Associates with the SCF(BTRC) complex, composed of SKP1, CUL1 and BTRC; the association is mediated via interaction with BTRC. Part of a SCF(BTRC)-like complex lacking CUL1, which is associated with RELA; RELA interacts directly with NFKBIA. Interacts with PRKACA in platelets; this interaction is disrupted by thrombin and collagen. Interacts with HIF1AN By similarity. Ref.4 Ref.5 Ref.6
Subcellular location	Cytoplasm. Nucleus. Note: Shuttles between the nucleus and the cytoplasm by a nuclear localization signal (NLS) and a CRM1-dependent nuclear export By similarity.
Tissue specificity	Highly expressed in lymph node, thymus followed by liver, brain, muscle, kidney, gastrointestinal and reproductive tract.
Post-translational modification	Phosphorylated; disables inhibition of NF-kappa-B DNA-binding activity. Phosphorylation at positions 32 and 36 is prerequisite to recognition by UBE2D3 leading to polyubiquitination and subsequent degradation By similarity. Ref.4 Ref.5 Ref.6 Sumoylated; sumoylation requires the presence of the nuclear import signal By similarity. Monoubiquitinated at Lys-21 and/or Lys-22 by UBE2D3. Ubiquitin chain elongation is then performed by CDC34 in cooperation with the SCF(FBXW11) E3 ligase complex, building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin. The resulting polyubiquitination leads to protein degradation. Also ubiquitinated by SCF(BTRC) following stimulus-dependent phosphorylation at Ser-32 and Ser-36 By similarity.
Sequence similarities	Belongs to the NF-kappa-B inhibitor family. Contains 5 ANK repeats.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Domain	ANK repeat Repeat
PTM	Hydroxylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cytoplasmic sequestering of NF-kappaB Inferred from electronic annotation. Source: Compara lipopolysaccharide-mediated signaling pathway Inferred from direct assay PubMed 12872135PubMed 18261938. Source: MGI negative regulation of NF-kappaB transcription factor activity Inferred from electronic annotation. Source: Compara negative regulation of Notch signaling pathway Inferred from mutant phenotype PubMed 15845452. Source: MGI negative regulation of lipid storage Inferred from electronic annotation. Source: Compara negative regulation of macrophage derived foam cell differentiation Inferred from electronic annotation. Source: Compara negative regulation of myeloid cell differentiation Inferred from mutant phenotype PubMed 15845452. Source: MGI nucleotide-binding oligomerization domain containing 1 signaling pathway Inferred from direct assay PubMed 18261938. Source: MGI nucleotide-binding oligomerization domain containing 2 signaling pathway Inferred from direct assay PubMed 18261938. Source: MGI positive regulation of cellular protein metabolic process Inferred from electronic annotation. Source: Compara positive regulation of cholesterol efflux Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara positive regulation of transcription, DNA-dependent Inferred from mutant phenotype PubMed 18505784. Source: MGI protein import into nucleus, translocation Inferred from direct assay PubMed 11799106. Source: MGI regulation of cell proliferation Inferred from direct assay PubMed 11799106. Source: MGI response to exogenous dsRNA Inferred from direct assay PubMed 12872135. Source: MGI response to muramyl dipeptide Inferred from direct assay PubMed 15692051. Source: MGI toll-like receptor 4 signaling pathway Inferred from direct assay PubMed 18261938. Source: MGI
Cellular_component	cytosol Inferred from direct assay PubMed 11799106. Source: MGI nucleus Inferred from direct assay PubMed 11799106. Source: MGI plasma membrane Inferred from electronic annotation. Source: Compara protein complex Inferred from electronic annotation. Source: Compara
Molecular_function	nuclear localization sequence binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Hdac3	O88895	2	EBI-644427,EBI-302263
Rela	Q04207	3	EBI-644427,EBI-644400

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 314	314	NF-kappa-B inhibitor alpha		PRO_0000067000
Regions
	Repeat	73 – 103	31	ANK 1
	Repeat	110 – 139	30	ANK 2
	Repeat	143 – 172	30	ANK 3
	Repeat	182 – 211	30	ANK 4
	Repeat	216 – 245	30	ANK 5
	Motif	30 – 36	7	Destruction motif
	Motif	45 – 54	10	Nuclear export signal By similarity
	Motif	110 – 120	11	Nuclear import signal By similarity
Amino acid modifications
	Modified residue	32	1	Phosphoserine; by IKKB Ref.4 Ref.5 Ref.6
	Modified residue	36	1	Phosphoserine; by IKKA, IKKB, IKKE and TBK1 By similarity
	Modified residue	42	1	Phosphotyrosine By similarity
	Modified residue	210	1	(3S)-3-hydroxyasparagine; by HIF1AN By similarity
	Modified residue	244	1	(3S)-3-hydroxyasparagine; by HIF1AN By similarity
	Modified residue	283	1	Phosphoserine; by CK2 By similarity
	Modified residue	288	1	Phosphoserine; by CK2 By similarity
	Modified residue	291	1	Phosphothreonine; by CK2 By similarity
	Modified residue	293	1	Phosphoserine; by CK2 By similarity
	Modified residue	296	1	Phosphothreonine By similarity
	Cross-link	21		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.5
	Cross-link	22		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.5
Experimental info
	Sequence conflict	132	1	K → R in BAE30547. Ref.1
	Sequence conflict	192	1	I → T in AAD10341. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q9Z1E3 [UniParc]. Last modified October 25, 2004. Version 2. Checksum: E1783F8E1BA93813	FASTA	314	35,071
	10 20 30 40 50 60 MFQPAGHGQD WAMEGPRDGL KKERLVDDRH DSGLDSMKDE EYEQMVKELR EIRLQPQEAP 70 80 90 100 110 120 LAAEPWKQQL TEDGDSFLHL AIIHEEKPLT MEVIGQVKGD LAFLNFQNNL QQTPLHLAVI 130 140 150 160 170 180 TNQPGIAEAL LKAGCDPELR DFRGNTPLHL ACEQGCLASV AVLTQTCTPQ HLHSVLQATN 190 200 210 220 230 240 YNGHTCLHLA SIHGYLAIVE HLVTLGADVN AQEPCNGRTA LHLAVDLQNP DLVSLLLKCG 250 260 270 280 290 300 ADVNRVTYQG YSPYQLTWGR PSTRIQQQLG QLTLENLQML PESEDEESYD TESEFTEDEL 310 PYDDCVFGGQ RLTL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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. , 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Bone marrow.
[2]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6. Tissue: Brain.
[3]	"Structural analysis, expression, and chromosomal localization of the mouse ikba gene." Rupec R.A., Poujol D., Grosgeorge J., Carle G.F., Livolsi A., Peyron J.-F., Schmid R.M., Baeuerle P.A., Messer G. Immunogenetics 49:395-403(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 77-314. Strain: 129/Sv. Tissue: Liver.
[4]	"Identification of the receptor component of the IkappaBalpha-ubiquitin ligase." Yaron A., Hatzubai A., Davis M., Lavon I., Amit S., Manning A.M., Andersen J.S., Mann M., Mercurio F., Ben-Neriah Y. Nature 396:590-594(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BTRC, PHOSPHORYLATION AT SER-32 AND SER-36, UBIQUITINATION.
[5]	"Signal-induced ubiquitination of IkappaBalpha by the F-box protein Slimb/beta-TrCP." Spencer E., Jiang J., Chen Z.J. Genes Dev. 13:284-294(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH BTRC; SKP1 AND RELA, PHOSPHORYLATION AT SER-32 AND SER-36, UBIQUITINATION AT LYS-21 AND LYS-22.
[6]	"Ubiquitin-dependent degradation of IkappaBalpha is mediated by a ubiquitin ligase Skp1/Cul 1/F-box protein FWD1." Hatakeyama S., Kitagawa M., Nakayama K., Shirane M., Matsumoto M., Hattori K., Higashi H., Nakano H., Okumura K., Onoe K., Good R.A., Nakayama K. Proc. Natl. Acad. Sci. U.S.A. 96:3859-3863(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH BTRC; SKP1 AND CUL1, PHOSPHORYLATION AT SER-32 AND SER-36, UBIQUITINATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK151115 mRNA. Translation: BAE30124.1. AK151608 mRNA. Translation: BAE30547.1. BC046754 mRNA. Translation: AAH46754.1. U57524 Genomic DNA. Translation: AAD10341.1.
IPI	IPI00331017.
RefSeq	NP_035037.2. NM_010907.2.
UniGene	Mm.170515.
3D structure databases
ProteinModelPortal	Q9Z1E3.
SMR	Q9Z1E3. Positions 70-281.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-36160N.
IntAct	Q9Z1E3. 2 interactions.
MINT	MINT-1523813.
PTM databases
PhosphoSite	Q9Z1E3.
Proteomic databases
PaxDb	Q9Z1E3.
PRIDE	Q9Z1E3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000021413; ENSMUSP00000021413; ENSMUSG00000021025.
GeneID	18035.
KEGG	mmu:18035.
UCSC	uc007nor.2. mouse.
Organism-specific databases
CTD	4792.
MGI	MGI:104741. Nfkbia.
Phylogenomic databases
eggNOG	COG0666.
GeneTree	ENSGT00550000074527.
HOGENOM	HOG000059576.
HOVERGEN	HBG018875.
InParanoid	Q9Z1E3.
KO	K04734.
OMA	SIHGYLA.
OrthoDB	EOG40CHHR.
Gene expression databases
Bgee	Q9Z1E3.
Genevestigator	Q9Z1E3.
GermOnline	ENSMUSG00000021025. Mus musculus.
Family and domain databases
Gene3D	1.25.40.20. 1 hit.
InterPro	IPR002110. Ankyrin_rpt. IPR020683. Ankyrin_rpt-contain_dom. [Graphical view]
Pfam	PF12796. Ank_2. 2 hits. [Graphical view]
PRINTS	PR01415. ANKYRIN.
SMART	SM00248. ANK. 5 hits. [Graphical view]
SUPFAM	SSF48403. ANK. 1 hit.
PROSITE	PS50297. ANK_REP_REGION. 1 hit. PS50088. ANK_REPEAT. 3 hits. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL1926493.
NextBio	293129.
SOURCE	Search...

Entry information

Entry name

IKBA_MOUSE

Accession

Primary (citable) accession number: Q9Z1E3
Secondary accession number(s): Q3U9W9, Q3UB40, Q80ZX5

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2001
Last sequence update:	October 25, 2004
Last modified:	May 29, 2013
This is version 107 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program