DP00468: NF-kappa-B inhibitor alphaFASTA viewXML view

General information
DisProt:DP00468
Name:NF-kappa-B inhibitor alpha
Synonym(s):IKBA_HUMAN
I-kappa-B-alpha
IkappaBalpha
IkB-alpha
Major histocompatibility complex enhancer-binding protein MAD3
First appeared in release:Release 3.1 (03/31/2006)
UniProt:P25963
UniGene:Hs.81328
SwissProt: IKBA_HUMAN
TrEMBL:  
NCBI (GI): 126682
Source organism:Homo sapiens (Human)
Sequence length:317
Percent disordered:34%
Homologues: 


Native sequence

        10         20         30         40         50         60
         |          |          |          |          |          |
MFQAAERPQE WAMEGPRDGL KKERLLDDRH DSGLDSMKDE EYEQMVKELQ EIRLEPQEVP - 60
RGSEPWKQQL TEDGDSFLHL AIIHEEKALT MEVIRQVKGD LAFLNFQNNL QQTPLHLAVI - 120
TNQPEIAEAL LGAGCDPELR DFRGNTPLHL ACEQGCLASV GVLTQSCTTP HLHSILKATN - 180
YNGHTCLHLA SIHGYLGIVE LLVSLGADVN AQEPCNGRTA LHLAVDLQNP DLVSLLLKCG - 240
ADVNRVTYQG YSPYQLTWGR PSTRIQQQLG QLTLENLQML PESEDEESYD TESEFTEFTE - 300
DELPYDDCVF GGQRLTL



Functional narrative    

The transcription factor NF-kB DNA-binding activity and nuclear/cytoplasmic distribution are controlled by the IkB inhibitor proteins. In unstimulated cells, NF-kB is held in the cytoplasm, in a form that is unable to bind DNA, by the inhibitory IkB proteins. Exposure of cells to a wide variety of stimuli results in release of the transcription factor from the IkB proteins, allowing the active DNA-binding form of the transcription factor to translocate to the nucleus, where it binds to its recognition sites in the upstream regions of a wide variety of genes that respond to immune and inflammatory signals, including human immunodeficiency virus type 1. IkBa may be involved in regulation of transcriptional responses to NF-kappa-B, including cell adhesion, immune and proinflammatory responses, apoptosis, differentiation and growth. It is controlled by sequential serine-phosphorylation, ubiquitination and degradation. Tyrosine-phosphorylation could only lead to dissociation from NF-kappa-B. 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.

Region 1: 1-66 Region 2: 276-317

Map of ordered and disordered regions







Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.


Region 1
Type:Disordered
Name:N-terminal region
Location:1 - 66
Length:66
Region sequence:

MFQAAERPQEWAMEGPRDGLKKERLLDDRHDSGLDSMKDEEYEQMVKELQEIRLEPQEVP
RGSEPW

Modification type: Native
PDB:  
Structural/functional type: Relationship to function unknown
Functional classes:  
Functional subclasses:  
Detection methods:
  1. Nuclear magnetic resonance (NMR) (309 K; pH: 7.1; 0.1 mM protein; 90% H2O/10% D2O, 10 mM sodium phosphate, 25 mM glycerol; TOCSY, one-dimensional 1H-NMR and 13C-HSQC spectrum)

  2. Sensitivity to proteolysis (293 K; pH: 8; 25 microM protein; 50 mM Tris HCl, 0.45M NaCl; chymotrypsin or V8 protease)
References:
  1. Jaffray E, Wood KM, Hay RT. "Domain organization of I kappa B alpha and sites of interaction with NF-kappa B p65." Mol Cell Biol. 1995; 15(4): 2166-72. PubMed: 7891711

  2. Leonchiks A, Liepinsh E, Barishev M, Sharipo A, Masucci MG, Otting G. "Random coil conformation of a Gly/Ala-rich insert in IkappaB alpha excludes structural stabilization as the mechanism for protection against proteasomal degradation." FEBS Lett. 1998; 440(3): 365-9. PubMed: 9872404
Comments:
 



Region 2
Type:Disordered
Name:C-terminal region
Location:276 - 317
Length:42
Region sequence:

NLQMLPESEDEESYDTESEFTEFTEDELPYDDCVFGGQRLTL

Modification type: Native
PDB:  
Structural/functional type: Function arises via a disorder to order transition
Functional classes:  
Functional subclasses: Protein-protein binding
Detection methods:
  1. Nuclear magnetic resonance (NMR) (309 K; pH: 7.1; 0.1 mM protein; 90% H2O/10% D2O, 10 mM sodium phosphate, 25 mM glycerol; TOCSY, one-dimensional 1H-NMR and 13C-HSQC spectrum)

  2. Sensitivity to proteolysis (293 K; pH: 8; 25 microM protein; 50 mM Tris HCl, 0.45M NaCl; chymotrypsin or V8 protease)
References:
  1. Jaffray E, Wood KM, Hay RT. "Domain organization of I kappa B alpha and sites of interaction with NF-kappa B p65." Mol Cell Biol. 1995; 15(4): 2166-72. PubMed: 7891711

  2. Leonchiks A, Liepinsh E, Barishev M, Sharipo A, Masucci MG, Otting G. "Random coil conformation of a Gly/Ala-rich insert in IkappaB alpha excludes structural stabilization as the mechanism for protection against proteasomal degradation." FEBS Lett. 1998; 440(3): 365-9. PubMed: 9872404
Comments:
 



References

  1. Li Q, Verma IM. "NF-kappaB regulation in the immune system." Nat Rev Immunol. 2002; 2(10): 725-34. PubMed: 12360211


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