Q63746 (IKBA_RAT) 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
RL/IF-1

Gene names

Name:	Nfkbia
Synonyms:	Ikba

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	314 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript 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 tranlocate to the nucleus and activate transcription By similarity.
Subunit structure	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 By similarity. Interacts with PRMT2. Interacts with PRKACA in platlets; this interaction is disrupted by thrombin and collagen By similarity.
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.
Induction	During liver regeneration. Ref.4
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. 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 polyubiquitinatin leads to protein degredation. 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 4 ANK repeats.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Domain	ANK repeat Repeat
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cytoplasmic sequestering of NF-kappaB Inferred from mutant phenotype. Source: RGD
Cellular component	I-kappaB/NF-kappaB complex Inferred by curator. Source: RGD cytosol Inferred from direct assay. Source: RGD nucleus Inferred from direct assay. Source: RGD
Molecular function	NF-kappaB binding Inferred from physical interaction. Source: RGD heat shock protein binding Inferred from physical interaction. Source: RGD
Complete GO annotation...

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_0000067002
Regions
	Repeat	110 – 139	30	ANK 1
	Repeat	143 – 172	30	ANK 2
	Repeat	182 – 211	30	ANK 3
	Repeat	216 – 245	30	ANK 4
	Motif	30 – 36	7	Destruction motif By similarity
	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 IKKA and IKKB By similarity
	Modified residue	36	1	Phosphoserine; by IKKA, IKKB, IKKE and TBK1 By similarity
	Modified residue	42	1	Phosphotyrosine; by Tyr-kinases 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
	Cross-link	21		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
	Cross-link	22		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Potential

Sequences

	Sequence		Length	Mass (Da)
	Q63746 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: CC4C9D0F6CDDA950	FASTA	314	35,017
	10 20 30 40 50 60 MFQPAGHGQD WAMEGPRDGL KKERLVDDRH DSGLDSMKDE DYEQMVKELR EIRLQPQEAP 70 80 90 100 110 120 LAAEPWKQQL TEDGDSFLHL AIIHEEKTLT MEVIGQVKGD LAFLNFQNNL QQTPLHLAVI 130 140 150 160 170 180 TNQPGIAEAL LKAGCDPELR DFRGNTPLHL ACEQGCLASV AVLTQTCTPQ HLHSVLQATN 190 200 210 220 230 240 YNGHTCLHLA SIHGYLGIVE HLVTLGADVN AQEPCNGRTA LHLAVDLQNP DLVSLLLKCG 250 260 270 280 290 300 ADVNRVTYQG YSPYQLTWGR PSTRIQQQLG QLTLENLQTL PESEDEESYD TESEFTEDEL 310 PYDDCVFGGQ RLTL

References

[1]	"Sequence of rat RL/IF-1 encoding an IkappaB, and comparison with related proteins containing Notch-like repeats." Tewari M., Mohn K.L., Yue F.E., Taub R.A. Nucleic Acids Res. 20:607-607(1992) [PubMed: 1741294] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Erratum Tewari M., Mohn K.L., Yue F.E., Taub R.A. Nucleic Acids Res. 20:2624-2624(1992)
[3]	Erratum Tewari M., Mohn K.L., Yue F.E., Taub R.A. Nucleic Acids Res. 20:2931-2931(1992)
[4]	"Rapid induction in regenerating liver of RL/IF-1 (an I kappa B that inhibits NF-kappa B, RelB-p50, and c-Rel-p50) and PHF, a novel kappa B site-binding complex." Tewari M., Dobrzanski P., Mohn K.L., Cressman D.E., Hsu J.C., Bravo R., Taub R. Mol. Cell. Biol. 12:2898-2908(1992) [PubMed: 1588976] [Abstract] Cited for: INDUCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X63594 mRNA. Translation: CAA45138.1.
IPI	IPI00211841.
PIR	A44437.
RefSeq	NP_001099190.2. NM_001105720.2.
UniGene	Rn.12550.
3D structure databases
ProteinModelPortal	Q63746.
SMR	Q63746. Positions 70-281.
ModBase	Search...
Protein-protein interaction databases
STRING	Q63746.
PTM databases
PhosphoSite	Q63746.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000009894; ENSRNOP00000009894; ENSRNOG00000007390.
GeneID	25493.
KEGG	rno:25493.
Organism-specific databases
CTD	4792.
RGD	3171. Nfkbia.
Phylogenomic databases
eggNOG	roNOG10336.
GeneTree	ENSGT00550000074527.
HOVERGEN	HBG018875.
InParanoid	Q63746.
OMA	HGYLAIV.
OrthoDB	EOG40CHHR.
PhylomeDB	Q63746.
Gene expression databases
ArrayExpress	Q63746.
Genevestigator	Q63746.
GermOnline	ENSRNOG00000007390. Rattus norvegicus.
Family and domain databases
InterPro	IPR002110. Ankyrin_rpt. IPR020683. Ankyrin_rpt-contain_dom. [Graphical view]
Gene3D	G3DSA:1.25.40.20. ANK. 1 hit.
KO	K04734.
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
NextBio	606869.

Entry information

Entry name

IKBA_RAT

Accession

Primary (citable) accession number: Q63746

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2001
Last sequence update:	November 1, 1996
Last modified:	January 25, 2012
This is version 94 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program