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TAX1-BINDING PROTEIN 1; TAX1BP1

TAX1-BINDING PROTEIN 1; TAX1BP1

Alternative titles; symbolsHUMAN T-CELL LEUKEMIA VIRUS TYPE 1-BINDING PROTEINTXBP151TRAF6-INTERACTING PROTEIN; T6BPHGNC Approved Gene Symbol: TAX1BP1Cytogenetic ...

Alternative titles; symbols

  • HUMAN T-CELL LEUKEMIA VIRUS TYPE 1-BINDING PROTEIN
  • TXBP151
  • TRAF6-INTERACTING PROTEIN; T6BP

HGNC Approved Gene Symbol: TAX1BP1

Cytogenetic location: 7p15.2 Genomic coordinates (GRCh38): 7:27,739,372-27,829,766 (from NCBI)

▼ Description
The HTLV-1 Tax protein transcriptionally activates the HTLV-1 promoter. Tax also binds to and stimulates the expression of cellular genes, including transcription factors and other proteins (Gachon et al., 1998).

▼ Cloning and Expression
Using a yeast 2-hybrid screen of a mouse fibrosarcoma library with A20 (see TNFAIP3; 191163) as bait, followed by a screening of a HeLa cell cDNA library, De Valck et al. (1999) isolated a TAX1BP1 cDNA, which the authors termed TXBP151, encoding a 747-amino acid protein. Northern blot analysis revealed expression of 1.9- and 2.4-kb transcripts in various cell lines. Western blot analysis showed that TAX1BP1 is expressed as an 86-kD or a 68-kD protein.

By a yeast 2-hybrid screen of a HeLa cell cDNA library with TRAF6 (602355) as bait, Ling and Goeddel (2000) isolated a TAX1BP1 cDNA, which they termed T6BP. Sequence analysis determined that TAX1BP1 contains 3 coiled-coil domains and 2 helix loop-helix regions.

▼ Gene Function
De Valck et al. (1999) showed that overexpression of TAX1BP1 or A20 leads to apoptosis of NIH 3T3 cell lines, which could be partially blocked by antisense TAX1BP1. Apoptosis induced by tumor necrosis factor (TNF; 191160) or CD95 (134637) leads to TAX1BP1, but not A20, degradation. This degradation could be blocked by CASP3 (600636)-like inhibitors.

By coprecipitation and immunoblot analysis, Ling and Goeddel (2000) showed that TAX1BP1 binds TRAF6 but not TRAFs 1-5; the interaction requires the N-terminal zinc and ring finger domains of TRAF6 and either the N-terminal first coiled-coil region or the 2 coiled-coil regions of the C-terminus of TAX1BP1. Immunoprecipitation and immunoblot analysis determined that stimulation of cells with IL1B (147720), but not with TNF or CD40LG (see 300386), induces independent, mutually exclusive TRAF6/TAX1BP1 complexes as well as TRAF6/IRAK (300283) complexes. Transient expression of TRAF6, but not TAX1BP1, induces NFKB and JNK (MAPK8; 601158) activation.

Shembade et al. (2010) showed that A20 inhibits the E3 ligase activities of TRAF6, TRAF2 (601895), and cIAP1 (601712) by antagonizing interactions with E2 ubiquitin-conjugating enzymes UBC13 (603679) and UBCH5C (602963). A20, together with the regulatory molecule TAX1BP1, interacted with UBC13 and UBCH5C and triggered their ubiquitination and proteasome-dependent degradation. These findings suggested a mechanism of A20 action in the inhibition of inflammatory signaling pathways.

▼ Mapping
The International Radiation Hybrid Mapping Consortium mapped the TAX1BP1 gene to chromosome 7 (WI-11921).

Tags: 7p15.2