phospho-IkBa (Tyr-305) Peptide | NFKBIA peptide

phospho-?-kappa-B alpha (Tyr-305) Blocking Peptide

Cat. Num. AAA474038

• Gene Names: NFKBIA; IKBA; MAD-3; NFKBI
• Synonyms: phospho-IkBa (Tyr-305) Peptide; phospho-?-kappa-B alpha (Tyr-305) Blocking Peptide; NFKBIA peptide

• Specificity: The peptide is specifically recognized by I-kappa-B-alpha (Tyr-305) phospho-specific antibody (IP1041) in ELISA, and has been shown to block the reactivity of IP1041 during Western blot. In addition, the peptide is recommended for use in blocking IP1041 reactivity in immunocytochemistry.
• Form/Format: Blocking Peptide is supplied in 50ul phosphate-buffered saline and 0.05% sodium azide.
• Sequence: Peptide Sequence: Phospho-I-kappa-B-alpha (Tyr-305) synthetic peptide corresponds to amino acid residues around tyrosine 305 of human I-kappa-B-alpha. This peptide sequence has low homology to other I-kappa-B proteins.

• Application Notes: Antibody Blocking: 1 ug/ml; ELISA: 10-100 ng/well
• Preparation and Storage: Store at -20 degree C. Stable for 1 year.

Testing Data

Related Product Information for NFKBIA peptide

The NF-kB/Rel transcription factors are present in the cytosol in an inactive state complexed with the inhibitory IkB proteins. Activation of IkBa ?occurs through both serine and tyrosine phosphorylation events. Activation through phosphorylation at Ser-32 and Ser-36 is followed by proteasome-mediated degradation, resulting in the release and nuclear translocation of active NF-kB. This pathway of IkBa regulation occurs in response to various NF-kB-activating agents, such as TNF-alpha, interleukins, LPS, and irradiation. An alternative pathway for IkBa regulation occurs through tyrosine phosphorylation of Tyr-42 and Tyr-305. Tyr-42 is phosphorylated in response to oxidative stress and growth factors. This phosphorylation can lead to degradation of IkB-alpha and NF-kB-activation. In contrast, Tyr-305 phosphorylation by c-Abl has been implicated in IkB-alpha nuclear translocation and inhibition of NF-kB-activation. Thus, tyrosine phosphorylation of IkB-alpha may be an important regulatory mechanism in NF-kB signaling.

References

• Bui, N.T. et al. (2001) J Cell Biol 152(4):753.
• Finco, T.S. et al. (1994) Proc. Natl. Acad. Sci. USA 91:11884.
• Waris et al. (2003) J Biol Chem 278(42):40778.

NCBI and Uniprot Product Information

• NCBI GI #: 6706211
• NCBI GeneID: 4792
• UniProt Accession #: P25963; B2R8L6; Q9UGJ5
• Molecular Weight: 35,609 Da
• NCBI Official Full Name: IkBa
• NCBI Official Synonym Full Names: nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
• NCBI Official Symbol: NFKBIA
• NCBI Official Synonym Symbols: IKBA; MAD-3; NFKBI
• NCBI Protein Information: NF-kappa-B inhibitor alpha; ikB-alpha; IkappaBalpha; I-kappa-B-alpha; OTTHUMP00000178842; nuclear factor of kappa light chain gene enhancer in B-cells; major histocompatibility complex enhancer-binding protein MAD3
• UniProt Protein Name: NF-kappa-B inhibitor alpha
• Protein Family: NF-kappa-B inhibitor
• UniProt Gene Name: NFKBIA
• UniProt Synonym Gene Names: IKBA; MAD3; NFKBI
• UniProt Entry Name: IKBA_HUMAN

NCBI Description

NFKB1 (MIM 164011) or NFKB2 (MIM 164012) is bound to REL (MIM 164910), RELA (MIM 164014), or RELB (MIM 604758) to form the NFKB complex. The NFKB complex is inhibited by I-kappa-B proteins (NFKBIA or NFKBIB, MIM 604495), which inactivate NF-kappa-B by trapping it in the cytoplasm. Phosphorylation of serine residues on the I-kappa-B proteins by kinases (IKBKA, MIM 600664, or IKBKB, MIM 603258) marks them for destruction via the ubiquitination pathway, thereby allowing activation of the NF-kappa-B complex. Activated NFKB complex translocates into the nucleus and binds DNA at kappa-B-binding motifs such as 5-prime GGGRNNYYCC 3-prime or 5-prime HGGARNYYCC 3-prime (where H is A, C, or T; R is an A or G purine; and Y is a C or T pyrimidine).[supplied by OMIM]

Uniprot Description

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. Ref.10 Ref.19 Ref.21 Ref.24 Ref.25

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.22 Ref.23 Ref.24

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.20Sumoylated; sumoylation requires the presence of the nuclear import signal. Ref.23 Ref.25Monoubiquitinated 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.30 Ref.31

Sequence similarities: Belongs to the NF-kappa-B inhibitor family.Contains 5 ANK repeats.