P25963 (IKBA_HUMAN) 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
Major histocompatibility complex enhancer-binding protein MAD3

Gene names

Name:	NFKBIA
Synonyms:	IKBA, MAD3, NFKBI

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	317 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 tranlocate to the nucleus and activate transcription. Ref.11
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. Interacts with PRMT2. Interacts with PRKACA in platlets; this interaction is disrupted by thrombin and collagen. Ref.10 Ref.19 Ref.22 Ref.25 Ref.26 Ref.27
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. Ref.16 Ref.23 Ref.24 Ref.26
Induction	Induced in adherent monocytes.
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. Ref.12 Ref.13 Ref.15 Ref.18 Ref.20 Ref.21 Sumoylated; sumoylation requires the presence of the nuclear import signal. Ref.24 Ref.27 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. Deubiquitinated by porcine reproductive and respiratory syndrome virus Nsp2 protein, which thereby interefers with NFKBIA degradation and impairs subsequenbt NF-kappa-B activation.
Involvement in disease	Defects in NFKBIA are the cause of ectodermal dysplasia anhidrotic with T-cell immunodeficiency autosomal dominant (ADEDAID) [MIM:612132]. Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. ADEDAID is an ectodermal dysplasia associated with decreased production of pro-inflammatory cytokines and certain interferons, rendering patients susceptible to infection. Ref.32 Ref.33
Sequence similarities	Belongs to the NF-kappa-B inhibitor family. Contains 5 ANK repeats.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Cytoplasm Nucleus
Disease	Disease mutation Ectodermal dysplasia
Domain	ANK repeat Repeat
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	MyD88-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome MyD88-independent toll-like receptor signaling pathway Traceable author statement. Source: Reactome T cell receptor signaling pathway Traceable author statement. Source: Reactome Toll signaling pathway Traceable author statement. Source: Reactome anti-apoptosis Traceable author statement. Source: Reactome apoptotic process Traceable author statement. Source: ProtInc cellular response to cold Non-traceable author statement. Source: BHF-UCL cytoplasmic sequestering of NF-kappaB Inferred from mutant phenotype. Source: BHF-UCL innate immune response Traceable author statement. Source: Reactome interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of DNA binding Non-traceable author statement. Source: UniProtKB negative regulation of NF-kappaB transcription factor activity Inferred from direct assay. Source: MGI negative regulation of lipid storage Inferred from mutant phenotype. Source: BHF-UCL negative regulation of macrophage derived foam cell differentiation Inferred from mutant phenotype. Source: BHF-UCL nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome positive regulation of NF-kappaB transcription factor activity Traceable author statement. Source: Reactome positive regulation of cellular protein metabolic process Inferred from mutant phenotype. Source: BHF-UCL positive regulation of cholesterol efflux Inferred from mutant phenotype. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype. Source: BHF-UCL 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
Cellular component	I-kappaB/NF-kappaB complex Traceable author statement. Source: BHF-UCL cytosol Traceable author statement. Source: Reactome nucleus Inferred from direct assay Ref.26. Source: UniProtKB plasma membrane Inferred from direct assay. Source: HPA
Molecular function	NF-kappaB binding Inferred from physical interaction. Source: UniProtKB identical protein binding Inferred from physical interaction. Source: IntAct nuclear localization sequence binding Inferred from physical interaction Ref.10. Source: UniProtKB ubiquitin protein ligase binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-307386,EBI-307386
CHUK	O15111	5	EBI-307386,EBI-81249
Chuk	Q60680-2	2	EBI-307386,EBI-646264	From a different organism.
COMMD1	Q8N668	3	EBI-307386,EBI-1550112
IKBKB	O14920	7	EBI-307386,EBI-81266
NFKB1	P19838	2	EBI-307386,EBI-300010
RELA	Q04206	11	EBI-307386,EBI-73886

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 317

317

NF-kappa-B inhibitor alpha

PRO_0000066999

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

Motif

110 – 120

11

Nuclear import signal

Amino acid modifications

Modified residue

32

1

Phosphoserine; by IKKA and IKKE Ref.18 Ref.20

Modified residue

36

1

Phosphoserine; by IKKA, IKKB, IKKE and TBK1 Ref.18 Ref.20

Modified residue

42

1

Phosphotyrosine; by Tyr-kinases Ref.12

Modified residue

283

1

Phosphoserine; by CK2 Ref.13 Ref.15

Modified residue

288

1

Phosphoserine; by CK2 Ref.13

Modified residue

291

1

Phosphothreonine; by CK2 Ref.13 Ref.15

Modified residue

293

1

Phosphoserine; by CK2 Ref.13

Modified residue

299

1

Phosphothreonine; by CK2 Ref.15

Cross-link

21

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO or ubiquitin) Ref.11 Ref.24 Ref.28

Cross-link

22

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.11 Ref.28

Natural variations

Natural variant

32

1

S → I in ADEDAID. Ref.32
Corresponds to variant rs28933100 [ dbSNP | Ensembl ].

VAR_034871

Experimental info

Mutagenesis

21

1

K → R: Little change in Tax-stimulated transactivation. No sumoylation. Greatly reduced Tax- or cytokine-stimulated transactivation and decrease in ubiquitination and degradation; when associated with R-22. Ref.11 Ref.14 Ref.24 Ref.27

Mutagenesis

22

1

K → R: Little change in Tax-stimulated transactivation. No sumoylation. Greatly reduced Tax- or cytokine-stimulated transactivation and decrease in ubiquitination and degradation; when associated with R-21. Ref.11 Ref.14 Ref.24 Ref.27

Mutagenesis

31

1

D → A: Loss of phosphorylation; when associated with A-35. Ref.14

Mutagenesis

32

1

S → A: Loss of phosphorylation, ubiquitination and degradation; when associated with A-36. Ref.14 Ref.18

Mutagenesis

32

1

S → T: Decrease in phosphorylation and degradation; when associated with T-36. Ref.14 Ref.18

Mutagenesis

35

1

D → A: Loss in phosphorylation; when associated with A-31. Ref.14

Mutagenesis

35

1

D → G: No change neither in phosphorylation, nor on degradation. Ref.14

Mutagenesis

36

1

S → A: Loss of phosphorylation, ubiquitination, and degradation; when associated with A-32. Ref.14 Ref.18

Mutagenesis

36

1

S → T: Decrease in phosphorylation and degradation; when associated with T-32. Ref.14 Ref.18

Mutagenesis

38

1

K → R: No change in Tax-stimulated transactivation. No change in Tax-stimulated transactivation; when associated with R-47. Ref.11

Mutagenesis

42

1

Y → F: No phosphorylation. Ref.12

Mutagenesis

45 – 52

8

MVKELQEI → AAKEAQEA: No nuclear export. Ref.23

Mutagenesis

47

1

K → R: Little change in Tax-stimulated transactivation. No change in Tax-stimulated transactivation; when associated with R-38. Ref.11

Mutagenesis

115 – 120

6

LHLAVI → AHAAVA: Greatly reduced nuclear localization. Great reduction in its ability to inhibit DNA binding of RELA. Ref.16

Mutagenesis

234

1

S → A: No inducible ubiquitination nor protein degradation. Ref.14

Mutagenesis

262

1

S → A: No inducible ubiquitination nor protein degradation. Ref.14

Mutagenesis

263

1

T → A: No inducible ubiquitination nor protein degradation. Ref.14

Secondary structure

1

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317

Helix Strand Turn

Details...

Helix

79 – 83

5

Beta strand

87 – 91

5

Helix

114 – 120

7

Helix

124 – 128

5

Helix

147 – 154

8

Helix

157 – 165

9

Turn

167 – 170

4

Beta strand

171 – 173

3

Helix

175 – 177

3

Helix

186 – 192

7

Helix

196 – 205

10

Turn

214 – 216

3

Helix

220 – 226

7

Helix

230 – 237

8

Turn

238 – 240

3

Helix

253 – 256

4

Helix

263 – 270

8

Helix

275 – 277

3

Turn

285 – 287

3

Sequences

	Sequence		Length	Mass (Da)
	P25963 [UniParc]. Last modified May 1, 1992. Version 1. Checksum: 088B313226786395	FASTA	317	35,609
	10 20 30 40 50 60 MFQAAERPQE WAMEGPRDGL KKERLLDDRH DSGLDSMKDE EYEQMVKELQ EIRLEPQEVP 70 80 90 100 110 120 RGSEPWKQQL TEDGDSFLHL AIIHEEKALT MEVIRQVKGD LAFLNFQNNL QQTPLHLAVI 130 140 150 160 170 180 TNQPEIAEAL LGAGCDPELR DFRGNTPLHL ACEQGCLASV GVLTQSCTTP HLHSILKATN 190 200 210 220 230 240 YNGHTCLHLA SIHGYLGIVE LLVSLGADVN AQEPCNGRTA LHLAVDLQNP DLVSLLLKCG 250 260 270 280 290 300 ADVNRVTYQG YSPYQLTWGR PSTRIQQQLG QLTLENLQML PESEDEESYD TESEFTEFTE 310 DELPYDDCVF GGQRLTL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of an immediate-early gene induced in adherent monocytes that encodes I kappa B-like activity." Haskill S., Beg A.A., Tompkins S.M., Morris J.S., Yurochko A.D., Sampson-Johannes A., Mondal K., Ralph P., Baldwin A.S. Jr. Cell 65:1281-1289(1991) [PubMed: 1829648] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Monocyte.
[2]	"Clonal deleterious mutations in the IkappaB alpha gene in the malignant cells in Hodgkin's lymphoma." Jungnickel B., Staratschek-Jox A., Braeuninger A., Spieker T., Wolf J., Diehl V., Hansmann M.-L., Rajewsky K., Kueppers R. J. Exp. Med. 191:395-402(2000) [PubMed: 10637284] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Lymph node.
[3]	"Homo sapiens IkBa mRNA." Liu B., Huang A. Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"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 (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	SeattleSNPs variation discovery resource Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cerebellum.
[7]	"The DNA sequence and analysis of human chromosome 14." Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J. Nature 421:601-607(2003) [PubMed: 12508121] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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]. Tissue: Brain and Kidney.
[10]	"I kappa B/MAD-3 masks the nuclear localization signal of NF-kappa B p65 and requires the transactivation domain to inhibit NF-kappa B p65 DNA binding." Ganchi P.A., Sun S.C., Greene W.C., Ballard D.W. Mol. Biol. Cell 3:1339-1352(1992) [PubMed: 1493333] [Abstract] Cited for: INTERACTION WITH RELA.
[11]	"Signal-induced degradation of IkappaB alpha requires site-specific ubiquitination." Scherer D.C., Brockman J.A., Chen Z., Maniatis T., Ballard D.W. Proc. Natl. Acad. Sci. U.S.A. 92:11259-11263(1995) [PubMed: 7479976] [Abstract] Cited for: UBIQUITINATION AT LYS-21 AND LYS-22, FUNCTION, MUTAGENESIS OF LYS-21; LYS-22; LYS-38 AND LYS-47.
[12]	"Tyrosine phosphorylation of IkappaB-alpha activates NF-kappaB without proteolytic degradation of IkappaB-alpha." Imbert V., Rupec R.A., Livolsi A., Pahl H.L., Traenckner E.B.-M., Mueller-Dieckmann C., Farahifar D., Rossi B., Auberger P., Baeuerle P.A., Peyron J.-F. Cell 86:787-798(1996) [PubMed: 8797825] [Abstract] Cited for: PHOSPHORYLATION AT TYR-42, MUTAGENESIS OF TYR-42.
[13]	"Casein kinase II phosphorylates I kappa B alpha at S-283, S-289, S-293, and T-291 and is required for its degradation." McElhinny J.A., Trushin S.A., Bren G.D., Chester N., Paya C.V. Mol. Cell. Biol. 16:899-906(1996) [PubMed: 8622692] [Abstract] Cited for: PHOSPHORYLATION AT SER-283; SER-288; SER-293 AND THR-291.
[14]	"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: 8657102] [Abstract] Cited for: MUTAGENESIS OF LYS-21; LYS-22; ASP-31; SER-32; ASP-35; SER-36; SER-234; SER-262 AND THR-263.
[15]	"Phosphorylation of IkappaBalpha in the C-terminal PEST domain by casein kinase II affects intrinsic protein stability." Lin R., Beauparlant P., Makris C., Meloche S., Hiscott J. Mol. Cell. Biol. 16:1401-1409(1996) [PubMed: 8657113] [Abstract] Cited for: PHOSPHORYLATION AT THR-291; SER-283 AND THR-299.
[16]	"Nuclear localization of IkappaB alpha is mediated by the second ankyrin repeat: the IkappaB alpha ankyrin repeats define a novel class of cis-acting nuclear import sequences." Sachdev S., Hoffmann A., Hannink M. Mol. Cell. Biol. 18:2524-2534(1998) [PubMed: 9566872] [Abstract] Cited for: SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL, MUTAGENESIS OF 115-LEU--ILE-120.
[17]	"A complex containing betaTrCP recruits Cdc34 to catalyse ubiquitination of IkappaBalpha." Vuillard L., Nicholson J., Hay R.T. FEBS Lett. 455:311-314(1999) [PubMed: 10437795] [Abstract] Cited for: UBIQUITINATION BY THE SCF(FBXW11) COMPLEX.
[18]	"Identification of the ubiquitin carrier proteins, E2s, involved in signal-induced conjugation and subsequent degradation of IkappaBalpha." Gonen H., Bercovich B., Orian A., Carrano A., Takizawa C., Yamanaka K., Pagano M., Iwai K., Ciechanover A. J. Biol. Chem. 274:14823-14830(1999) [PubMed: 10329681] [Abstract] Cited for: PHOSPHORYLATION AT SER-32 AND SER-36, MUTAGENESIS OF SER-32 AND SER-36, UBIQUITINATION BY UBE2D2 AND UBE2D3.
[19]	"Direct association and nuclear import of the hepatitis B virus X protein with the NF-kappaB inhibitor IkappaBalpha." Weil R., Sirma H., Giannini C., Kremsdorf D., Bessia C., Dargemont C., Brechot C., Israel A. Mol. Cell. Biol. 19:6345-6354(1999) [PubMed: 10454581] [Abstract] Cited for: INTERACTION WITH HBV PROTEIN X.
[20]	"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: PHOSPHORYLATION AT SER-32 AND SER-36.
[21]	"NAK is an IkappaB kinase-activating kinase." Tojima Y., Fujimoto A., Delhase M., Chen Y., Hatakeyama S., Nakayama K., Kaneko Y., Nimura Y., Motoyama N., Ikeda K., Karin M., Nakanishi M. Nature 404:778-782(2000) [PubMed: 10783893] [Abstract] Cited for: PHOSPHORYLATION BY TBK1.
[22]	"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: 10657303] [Abstract] Cited for: INTERACTION WITH NKIRAS1 AND NKIRAS2.
[23]	"A nuclear export signal in the N-terminal regulatory domain of IkappaBalpha controls cytoplasmic localization of inactive NF-kappaB/IkappaBalpha complexes." Huang T.T., Kudo N., Yoshida M., Miyamoto S. Proc. Natl. Acad. Sci. U.S.A. 97:1014-1019(2000) [PubMed: 10655476] [Abstract] Cited for: SUBCELLULAR LOCATION, NUCLEAR EXPORT SIGNAL, MUTAGENESIS OF 45-MET--ILE-52.
[24]	"SUMO-1 conjugation in vivo requires both a consensus modification motif and nuclear targeting." Rodriguez M.S., Dargemont C., Hay R.T. J. Biol. Chem. 276:12654-12659(2001) [PubMed: 11124955] [Abstract] Cited for: SUMOYLATION AT LYS-21, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-21 AND LYS-22.
[25]	"Thrombin and collagen induce a feedback inhibitory signaling pathway in platelets involving dissociation of the catalytic subunit of protein kinase A from an NFkappaB-IkappaB complex." Gambaryan S., Kobsar A., Rukoyatkina N., Herterich S., Geiger J., Smolenski A., Lohmann S.M., Walter U. J. Biol. Chem. 285:18352-18363(2010) [PubMed: 20356841] [Abstract] Cited for: INTERACTION WITH PRKACA.
[26]	"Protein methyltransferase 2 inhibits NF-kappaB function and promotes apoptosis." Ganesh L., Yoshimoto T., Moorthy N.C., Akahata W., Boehm M., Nabel E.G., Nabel G.J. Mol. Cell. Biol. 26:3864-3874(2006) [PubMed: 16648481] [Abstract] Cited for: INTERACTION WITH PRMT2, SUBCELLULAR LOCATION.
[27]	"RSUME, a small RWD-containing protein, enhances SUMO conjugation and stabilizes HIF-1alpha during hypoxia." Carbia-Nagashima A., Gerez J., Perez-Castro C., Paez-Pereda M., Silberstein S., Stalla G.K., Holsboer F., Arzt E. Cell 131:309-323(2007) [PubMed: 17956732] [Abstract] Cited for: INTERACTION WITH RWDD3, SUMOYLATION, MUTAGENESIS OF LYS-21 AND LSY-22.
[28]	"Priming and extending: a UbcH5/Cdc34 E2 handoff mechanism for polyubiquitination on a SCF substrate." Wu K., Kovacev J., Pan Z.Q. Mol. Cell 37:784-796(2010) [PubMed: 20347421] [Abstract] Cited for: UBIQUITINATION AT LYS-21 AND LYS-22.
[29]	"The cysteine protease domain of porcine reproductive and respiratory syndrome virus nonstructural protein 2 possesses deubiquitinating and interferon antagonism functions." Sun Z., Chen Z., Lawson S.R., Fang Y. J. Virol. 84:7832-7846(2010) [PubMed: 20504922] [Abstract] Cited for: DEUBIQUITINATION BY PORCINE REPRODUCTIVE AND RESPIRATORY SYNDROME VIRUS NSP2 PROTEIN.
[30]	"Structure of an IkappaBalpha/NF-kappaB complex." Jacobs M.D., Harrison S.C. Cell 95:749-758(1998) [PubMed: 9865693] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 70-282.
[31]	"The crystal structure of the IkappaBalpha/NF-kappaB complex reveals mechanisms of NF-kappaB inactivation." Huxford T., Huang D.B., Malek S., Ghosh G. Cell 95:759-770(1998) [PubMed: 9865694] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 73-302.
[32]	"A hypermorphic IkappaBalpha mutation is associated with autosomal dominant anhidrotic ectodermal dysplasia and T cell immunodeficiency." Courtois G., Smahi A., Reichenbach J., Doffinger R., Cancrini C., Bonnet M., Puel A., Chable-Bessia C., Yamaoka S., Feinberg J., Dupuis-Girod S., Bodemer C., Livadiotti S., Novelli F., Rossi P., Fischer A., Israel A., Munnich A., Le Deist F., Casanova J.L. J. Clin. Invest. 112:1108-1115(2003) [PubMed: 14523047] [Abstract] Cited for: VARIANT ADEDAID ILE-32.
[33]	"A novel mutation in NFKBIA/IKBA results in a degradation-resistant N-truncated protein and is associated with ectodermal dysplasia with immunodeficiency." Lopez-Granados E., Keenan J.E., Kinney M.C., Leo H., Jain N., Ma C.A., Quinones R., Gelfand E.W., Jain A. Hum. Mutat. 29:861-868(2008) [PubMed: 18412279] [Abstract] Cited for: INVOLVEMENT IN ADEDAID.
+	Additional computationally mapped references.

Web resources

NFKBIAbase

NFKBIA mutation db

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M69043 mRNA. Translation: AAA16489.1.
AJ249294 , AJ249295, AJ249283, AJ249284, AJ249285, AJ249286 Genomic DNA. Translation: CAB65556.2.
AY033600 mRNA. Translation: AAK51149.1.
BT007091 mRNA. Translation: AAP35754.1.
AY496422 Genomic DNA. Translation: AAR29599.1.
AK313421 mRNA. Translation: BAG36213.1.
AL133163 Genomic DNA. No translation available.
CH471078 Genomic DNA. Translation: EAW65875.1.
BC002601 mRNA. Translation: AAH02601.1.
BC004983 mRNA. Translation: AAH04983.1.

IPI

IPI00018330.

PIR

A39935.

RefSeq

NP_065390.1. NM_020529.2.

UniGene

Hs.81328.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IKN	X-ray	2.30	D	67-302	[»]
1NFI	X-ray	2.70	E/F	70-282	[»]

ProteinModelPortal

P25963.

SMR

P25963. Positions 4-314.

DisProt

DP00468.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-139N.

IntAct

P25963. 31 interactions.

MINT

MINT-120458.

STRING

P25963.

PTM databases

PhosphoSite

P25963.

Polymorphism databases

DMDM

126682.

Proteomic databases

PeptideAtlas

P25963.

PRIDE

P25963.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000216797; ENSP00000216797; ENSG00000100906.

GeneID

4792.

KEGG

hsa:4792.

UCSC

uc001wtf.2. human.

Organism-specific databases

CTD

4792.

GeneCards

GC14M035870.

H-InvDB

HIX0011599.

HGNC

HGNC:7797. NFKBIA.

HPA

CAB003815.
HPA029207.

MIM

164008. gene.
612132. phenotype.

neXtProt

NX_P25963.

Orphanet

98813. Hypohidrotic ectodermal dysplasia with immunodeficiency.

PharmGKB

PA31601.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG14773.

HOGENOM

HBG713075.

HOVERGEN

HBG018875.

InParanoid

P25963.

OMA

HGYLAIV.

OrthoDB

EOG40CHHR.

PhylomeDB

P25963.

Enzyme and pathway databases

Pathway_Interaction_DB

nfkappabatypicalpathway. Atypical NF-kappaB pathway.
aurora_a_pathway. Aurora A signaling.
bcr_5pathway. BCR signaling pathway.
nfkappabcanonicalpathway. Canonical NF-kappaB pathway.
ceramidepathway. Ceramide signaling pathway.
hivnefpathway. HIV-1 Nef: Negative effector of Fas and TNF-alpha.
il23pathway. IL23-mediated signaling events.
lysophospholipid_pathway. LPA receptor mediated events.
avb3_opn_pathway. Osteopontin-mediated events.
hdac_classi_pathway. Signaling events mediated by HDAC Class I.

Reactome

REACT_111102. Signal Transduction.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P25963.

Bgee

P25963.

CleanEx

HS_NFKBIA.

Genevestigator

P25963.

GermOnline

ENSG00000100906. Homo sapiens.

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

PF00023. Ank. 3 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

18466.

PMAP-CutDB

P25963.

SOURCE

Search...

Entry information

Entry name

IKBA_HUMAN

Accession

Primary (citable) accession number: P25963
Secondary accession number(s): B2R8L6

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1992
Last sequence update:	May 1, 1992
Last modified:	January 25, 2012
This is version 137 of the entry and version 1 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.