Q15653 (IKBB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
NF-kappa-B inhibitor beta
Short name=NF-kappa-BIB

Alternative name(s):
I-kappa-B-beta
Short name=IkB-B
Short name=IkB-beta
Short name=IkappaBbeta
Thyroid receptor-interacting protein 9
Short name=TR-interacting protein 9
Short name=TRIP-9

Gene names

Name:	NFKBIB
Synonyms:	IKBB, TRIP9

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	356 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Inhibits NF-kappa-B by complexing with and trapping it in the cytoplasm. However, the unphosphorylated form resynthesized after cell stimulation is able to bind NF-kappa-B allowing its transport to the nucleus and protecting it to further NFKBIA-dependent inactivation. Association with inhibitor kappa B-interacting NKIRAS1 and NKIRAS2 prevent its phosphorylation rendering it more resistant to degradation, explaining its slower degradation.
Subunit structure	Interacts with THRB (via ligand-binding domain). Interacts with RELA and REL. Interacts with COMMD1 and inhibitor kappa B-interacting Ras-like NKIRAS1 and NKIRAS2. Ref.8 Ref.11 Ref.12 Ref.13
Subcellular location	Cytoplasm By similarity. Nucleus By similarity.
Tissue specificity	Expressed in all tissues examined.
Post-translational modification	Phosphorylated by RPS6KA1; followed by degradation. Interaction with NKIRAS1 and NKIRAS2 probably prevents phosphorylation. Ref.9 Ref.10
Sequence similarities	Belongs to the NF-kappa-B inhibitor family. Contains 6 ANK repeats.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	ANK repeat Repeat
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	MyD88-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome TRIF-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome Toll signaling pathway Traceable author statement. Source: Reactome innate immune response Traceable author statement. Source: Reactome positive regulation of NF-kappaB transcription factor activity Traceable author statement. Source: Reactome positive regulation of type I interferon production Traceable author statement. Source: Reactome toll-like receptor 1 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 2 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 3 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 4 signaling pathway Traceable author statement. Source: Reactome transcription, DNA-dependent Traceable author statement Ref.1. Source: ProtInc
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	signal transducer activity Traceable author statement Ref.1. Source: ProtInc transcription coactivator activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RELA	Q04206	6	EBI-352889,EBI-73886

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q15653-1)

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: Q15653-2)

The sequence of this isoform differs from the canonical sequence as follows:
     324-338: DEYDDIVVHSSRSQT → VSQEERQGSPAGGSG
     339-356: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 356	356	NF-kappa-B inhibitor beta		PRO_0000067004
Regions
	Repeat	57 – 86	30	ANK 1
	Repeat	93 – 122	30	ANK 2
	Repeat	126 – 155	30	ANK 3
	Repeat	206 – 235	30	ANK 4
	Repeat	240 – 269	30	ANK 5
	Repeat	273 – 302	30	ANK 6
	Compositional bias	186 – 195	10	Asp/Glu-rich (acidic)
Amino acid modifications
	Modified residue	19	1	Phosphoserine; by RPS6KA1 Ref.9
	Modified residue	23	1	Phosphoserine; by RPS6KA1 Ref.9
	Modified residue	313	1	Phosphoserine; by CK2 Ref.10
	Modified residue	315	1	Phosphoserine; by CK2 Ref.10
Natural variations
	Alternative sequence	324 – 338	15	DEYDD…SRSQT → VSQEERQGSPAGGSG in isoform 2.		VSP_012409
	Alternative sequence	339 – 356	18	Missing in isoform 2.		VSP_012410
	Natural variant	339	1	R → W. Ref.3 Corresponds to variant rs17886215 [ dbSNP | Ensembl ].		VAR_020771
Experimental info
	Mutagenesis	19	1	S → A: No degradation; when associated with A-23. Ref.9
	Mutagenesis	23	1	S → A: No degradation; when associated with A-19. Ref.9
	Sequence conflict	19	1	S → T in AAC41742. Ref.1
	Sequence conflict	319	1	S → G in AAC41742. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 4, 2005. Version 2. Checksum: E84575971B6F81CC	FASTA	356	37,771
	10 20 30 40 50 60 MAGVACLGKA ADADEWCDSG LGSLGPDAAA PGGPGLGAEL GPGLSWAPLV FGYVTEDGDT 70 80 90 100 110 120 ALHLAVIHQH EPFLDFLLGF SAGTEYMDLQ NDLGQTALHL AAILGETSTV EKLYAAGAGL 130 140 150 160 170 180 CVAERRGHTA LHLACRVGAH ACARALLQPR PRRPREAPDT YLAQGPDRTP DTNHTPVALY 190 200 210 220 230 240 PDSDLEKEEE ESEEDWKLQL EAENYEGHTP LHVAVIHKDV EMVRLLRDAG ADLDKPEPTC 250 260 270 280 290 300 GRSPLHLAVE AQAADVLELL LRAGANPAAR MYGGRTPLGS AMLRPNPILA RLLRAHGAPE 310 320 330 340 350 PEGEDEKSGP CSSSSDSDSG DEGDEYDDIV VHSSRSQTRL PPTPASKPLP DDPRPV
	Isoform 2 [UniParc]. Checksum: F024666B851DF976	FASTA	338	35,530
	10 20 30 40 50 60 MAGVACLGKA ADADEWCDSG LGSLGPDAAA PGGPGLGAEL GPGLSWAPLV FGYVTEDGDT 70 80 90 100 110 120 ALHLAVIHQH EPFLDFLLGF SAGTEYMDLQ NDLGQTALHL AAILGETSTV EKLYAAGAGL 130 140 150 160 170 180 CVAERRGHTA LHLACRVGAH ACARALLQPR PRRPREAPDT YLAQGPDRTP DTNHTPVALY 190 200 210 220 230 240 PDSDLEKEEE ESEEDWKLQL EAENYEGHTP LHVAVIHKDV EMVRLLRDAG ADLDKPEPTC 250 260 270 280 290 300 GRSPLHLAVE AQAADVLELL LRAGANPAAR MYGGRTPLGS AMLRPNPILA RLLRAHGAPE 310 320 330 PEGEDEKSGP CSSSSDSDSG DEGVSQEERQ GSPAGGSG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Two classes of proteins dependent on either the presence or absence of thyroid hormone for interaction with the thyroid hormone receptor." Lee J.W., Choi H.-S., Gyuris J., Brent R., Moore D.D. Mol. Endocrinol. 9:243-254(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 2). Tissue: Cervix carcinoma.
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]	SeattleSNPs variation discovery resource Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT TRP-339.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Lung.
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 100-338 (ISOFORM 2). Tissue: Pancreas and Uterus.
[7]	"Role of unphosphorylated, newly synthesized IkappaB beta in persistent activation of NF-kappaB." Suyang H., Phillips R.J., Douglas I., Ghosh S. Mol. Cell. Biol. 16:5444-5449(1996) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[8]	"A subclass of Ras proteins that regulate the degradation of IkappaB." Fenwick C., Na S.-Y., Voll R.E., Zhong H., Im S.-Y., Lee J.W., Ghosh S. Science 287:869-873(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NKIRAS1 AND NKIRAS2.
[9]	"Mapping of the inducible IkappaB phosphorylation sites that signal its ubiquitination and degradation." DiDonato J.A., Mercurio F., Rosette C., Wu-Li J., Suyang H., Ghosh S., Karin M. Mol. Cell. Biol. 16:1295-1304(1996) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF SER-19 AND SER-23, PHOSPHORYLATION AT SER-19 AND SER-23.
[10]	"Basal phosphorylation of the PEST domain in the I(kappa)B(beta) regulates its functional interaction with the c-rel proto-oncogene product." Chu Z.L., McKinsey T.A., Liu L., Qi X., Ballard D.W. Mol. Cell. Biol. 16:5974-5984(1996) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-313 AND SER-315.
[11]	"KappaB-Ras binds to the unique insert within the ankyrin repeat domain of IkappaBbeta and regulates cytoplasmic retention of IkappaBbeta.NF-kappaB complexes." Chen Y., Wu J., Ghosh G. J. Biol. Chem. 278:23101-23106(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NKIRAS1.
[12]	"Inhibition of NF-kappaB activity by IkappaBbeta in association with kappaB-Ras." Chen Y., Vallee S., Wu J., Vu D., Sondek J., Ghosh G. Mol. Cell. Biol. 24:3048-3056(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NKIRAS1.
[13]	"Characterization of COMMD protein-protein interactions in NF-kappaB signalling." de Bie P., van de Sluis B., Burstein E., Duran K.J., Berger R., Duckett C.S., Wijmenga C., Klomp L.W. Biochem. J. 398:63-71(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH COMMD1.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	L40407 Genomic DNA. Translation: AAC41742.1. BT006743 mRNA. Translation: AAP35389.1. AY736284 Genomic DNA. Translation: AAU10088.1. AK290569 mRNA. Translation: BAF83258.1. CH471126 Genomic DNA. Translation: EAW56843.1. BC007197 mRNA. Translation: AAH07197.1. BC015528 mRNA. Translation: AAH15528.1.
IPI	IPI00161119. IPI00514744.
RefSeq	NP_001230045.1. NM_001243116.1. NP_002494.2. NM_002503.4.
UniGene	Hs.9731.
3D structure databases
ProteinModelPortal	Q15653.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-27532N.
IntAct	Q15653. 5 interactions.
MINT	MINT-1131598.
STRING	9606.ENSP00000312988.
PTM databases
PhosphoSite	Q15653.
Polymorphism databases
DMDM	57015399.
Proteomic databases
PaxDb	Q15653.
PRIDE	Q15653.
Protocols and materials databases
DNASU	4793.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000313582; ENSP00000312988; ENSG00000104825. ENST00000572515; ENSP00000459728; ENSG00000104825.
GeneID	4793.
KEGG	hsa:4793.
UCSC	uc002ojw.3. human. uc002ojy.3. human.
Organism-specific databases
CTD	4793.
GeneCards	GC19P039390.
HGNC	HGNC:7798. NFKBIB.
HPA	CAB010447.
MIM	604495. gene.
neXtProt	NX_Q15653.
PharmGKB	PA31602.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG272177.
HOVERGEN	HBG019039.
KO	K02581.
OrthoDB	EOG4229KF.
PhylomeDB	Q15653.
Enzyme and pathway databases
Pathway_Interaction_DB	bcr_5pathway. BCR signaling pathway.
Reactome	REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines. REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q15653.
Bgee	Q15653.
CleanEx	HS_NFKBIB.
Genevestigator	Q15653.
GermOnline	ENSG00000104825. Homo sapiens.
Family and domain databases
Gene3D	1.25.40.20. 2 hits.
InterPro	IPR002110. Ankyrin_rpt. IPR020683. Ankyrin_rpt-contain_dom. [Graphical view]
Pfam	PF00023. Ank. 3 hits. PF12796. Ank_2. 1 hit. [Graphical view]
PRINTS	PR01415. ANKYRIN.
SMART	SM00248. ANK. 6 hits. [Graphical view]
SUPFAM	SSF48403. ANK. 1 hit.
PROSITE	PS50297. ANK_REP_REGION. 1 hit. PS50088. ANK_REPEAT. 4 hits. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q15653.
ChEMBL	CHEMBL3806.
ChiTaRS	NFKBIB. human.
GenomeRNAi	4793.
NextBio	18470.
SOURCE	Search...

Entry information

Entry name

IKBB_HUMAN

Accession

Primary (citable) accession number: Q15653
Secondary accession number(s): A8K3F4, Q96BJ7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	January 4, 2005
Last modified:	May 1, 2013
This is version 132 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.