TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 (TAB3)

The protein contains 712 amino acids for an estimated molecular weight of 78683 Da.

 

Adapter required to activate the JNK and NF-kappa-B signaling pathways through the specific recognition of 'Lys-63'-linked polyubiquitin chains by its RanBP2-type zinc finger (NZF) (PubMed:14633987, PubMed:14766965, PubMed:15327770, PubMed:22158122). Acts as an adapter linking MAP3K7/TAK1 and TRAF6 to 'Lys-63'-linked polyubiquitin chains (PubMed:14633987, PubMed:14766965, PubMed:15327770, PubMed:22158122). The RanBP2-type zinc finger (NZF) specifically recognizes Lys-63'-linked polyubiquitin chains unanchored or anchored to the substrate proteins such as RIPK1/RIP1: this acts as a scaffold to organize a large signaling complex to promote autophosphorylation of MAP3K7/TAK1, and subsequent activation of I-kappa-B-kinase (IKK) core complex by MAP3K7/TAK1 (PubMed:15327770, PubMed:22158122).May be an oncogenic factor. (updated: June 2, 2021)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology.


Interpro domains
Total structural coverage: 55%
Model score: 0
No model available.

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VariantDescription
dbSNP:rs5927629

The reference OMIM entry for this protein is 300480

Tak1-binding protein 3; tab3

CLONING

By random activation of gene expression (RAGE), Jin et al. (2004) generated a limited protein expression library in a transgenic NF-kappa-B (see 164011) reporter cell line, and the library was selected for cells that constitutively activated NF-kappa-B. By RT-PCR and 3-prime RACE of one of these clones, they obtained full length TAB3 and a splice variant that excludes exon 10. They termed the full length variant TAB3a, and the splice variant TAB3b. TAB3a encodes a deduced 712-amino acid protein that contains an N-terminal CUE domain, a central coiled-coil region, and a C-terminal zinc finger domain. The CUE domain is expected to direct self-monoubiquitylation. TAB3b encodes a deduced 684-amino acid protein that lacks 28 amino acids between the coiled-coil domain and the zinc finger domain. Within their C-terminal zinc finger domains, TAB3 shares 82% identity with TAB2 (605101). Overall, TAB3 shares 67% identity with X. laevis Tab3. PCR analysis detected both transcripts in all tissues examined, which included kidney, brain, prostate, and peripheral blood leukocytes. TAB3b represented 13 to 20% of the total TAB3 transcripts. RNA dot blot analysis detected expression in matched normal and tumor cells of testis, skin, and small intestine, with higher expression in most tumor samples.

GENE FUNCTION

Jin et al. (2004) found that both TAB3a and TAB3b increased expression from an IL8 (146930) promoter. Overexpression of TAB3 activated both NF-kappa-B and AP1 (see 165160) transcription factors. The activation of NF-kappa-B was blocked by an NF-kappa-B inhibitor, and by expression of dominant negative forms of TNF-alpha (TNFA; 191160)-associated factor-6 (AF6; 159559) and TGF-beta (TGFB; 190180)-activated kinase (AK) indicating that TAB3 is a constituent of the NF-kappa-B pathway, functioning upstream of TNFA-AF6 and TGFB-AK. Overexpression of TAB3 resulted in cellular transformation of NIH 3T3 mouse fibroblasts. Zhang et al. (2012) showed that human TAB2 and TAB3, ubiquitin chain sensory proteins involved in NF-kappa-B signaling, are directly inactivated by enteropathogenic E. coli NleE, a conserved bacterial type III-secreted effector responsible for blocking host NF-kappa-B signaling. NleE harbored an unprecedented S-adenosyl-L-methionine-dependent methyltransferase activity that specifically modified a zinc-coordinating cysteine in the Npl4 zinc finger (NZF) domains in TAB2 and TAB3. Cysteine-methylated TAB2-NZF and TAB3-NZF (truncated proteins comprising only the NZF domain) lost the zinc ion as well as the ubiquitin chain binding activity. Ectopically expressed or type III secretion system-delivered NleE methylated TAB2 and TAB3 in host cells and diminished their ubiquitin chain binding activity. Replacement of the NZF domain of TAB3 with the NleE methylation-insensitive Npl4 NZF domain resulted in NleE-resistant NF-kappa-B activation. Zhang et al. (2012) postulated that, given the prevalence of zinc finger motifs and activation of cysteine thiol by zinc binding, methylation of zinc finger cysteine might regulate other eukaryotic pathways in addition to NF-kappa-B signaling.

GENE STRUCTURE

Jin et al. (2004) determined that the TAB3 gene contains at least 12 exons. The open reading frame (ORF) begins in exon 6 and ends in exon 12. They predict the possibility of an additional uncharacterized upstream exon that may contribute to the 5-prime UTR.

MAPPING

Jin et al. (2004) stated that TAB3 map ... More on the omim web site

Subscribe to this protein entry history

July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 25, 2017: Additional information
No protein expression data in P. Mayeux work for TAB3

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 300480 was added.