|Institutional Source||Beutler Lab|
|Gene Name||apoptosis antagonizing transcription factor|
|Synonyms||Trb, 4933415H02Rik, 5830465M17Rik, Che-1|
|Is this an essential gene?||Essential (E-score: 1.000)|
|Stock #||R0324 (G1)|
|Chromosomal Location||84422855-84513522 bp(-) (GRCm38)|
|Type of Mutation||critical splice donor site (2 bp from exon)|
|DNA Base Change (assembly)||A to G at 84512139 bp|
|Amino Acid Change|
|Ref Sequence||ENSEMBL: ENSMUSP00000018841 (fasta)|
|Gene Model||predicted gene model for transcript(s): [ENSMUST00000018841]|
|Predicted Effect||probably null
|Predicted Effect||noncoding transcript
|Coding Region Coverage||
|MGI Phenotype||Strain: 2176283
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene was identified on the basis of its interaction with MAP3K12/DLK, a protein kinase known to be involved in the induction of cell apoptosis. This gene product contains a leucine zipper, which is a characteristic motif of transcription factors, and was shown to exhibit strong transactivation activity when fused to Gal4 DNA binding domain. Overexpression of this gene interfered with MAP3K12 induced apoptosis. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous embryos do not develop past the compacted morula stage, and after failing to maintain compaction. Mutant embryos show abnormal morphology at E3.5, with most not forming a blastocoel cavity. Severely reduced cell proliferation is observed before blastocyst formation. [provided by MGI curators]
|Allele List at MGI|
|Other mutations in this stock||
|Other mutations in Aatf||
(F):5'- ACCAGGCCACATCTTTCATTCCAG -3'
(R):5'- GCCACTAGAGCCAGAGTGATTGAC -3'
(F):5'- agccatctctccagccc -3'
(R):5'- CCAGAGTGATTGACAGGTTTGATG -3'
|Protein Function and Prediction|
Aatf encodes apoptosis-antagonizing transcription factor (AATF; alternatively Che-1 or Traube (Trb)), a nuclear protein that regulates gene transcription and cell proliferation. AATF has a leucine zipper motif, three nuclear receptor-binding LxxLL consensus sequences, and two N-terminal acidic domains (1;2). AATF is essential for preimplantation development.
AATF is expressed at high levels in the heart, skeletal muscle, and testis, and at lower levels in all other tissues analyzed (1-3). In the mouse Aatf is ubiquitously expressed early in development; expression is restricted to the liver and central nervous system from embryonic day (E)11.5 onward (4). The AATF protein is localized to the nucleus and the nucleoli (4).
AATF is an interacting protein for RNA polymerase II. In addition, AATF counteracts Rb repression to facilitate E2F-dependent transactivation during G1-S transition. AATF also functions in the DNA damage response and cell-cycle checkpoint control. AATF is an adaptor that connects transcriptional regulation, cell-cycle progression, checkpoint control, and apoptosis [reviewed in (5)].
Genetic background: either: (involves: 129/Sv * C57BL/6) or (involves: 129/Sv * NMRI)
1. Lindfors, K., Halttunen, T., Huotari, P., Nupponen, N., Vihinen, M., Visakorpi, T., Maki, M., and Kainulainen, H. (2000) Identification of Novel Transcription Factor-Like Gene from Human Intestinal Cells. Biochem Biophys Res Commun. 276, 660-666.
2. Fanciulli, M., Bruno, T., Di Padova, M., De Angelis, R., Iezzi, S., Iacobini, C., Floridi, A., and Passananti, C. (2000) Identification of a Novel Partner of RNA Polymerase II Subunit 11, Che-1, which Interacts with and Affects the Growth Suppression Function of Rb. FASEB J. 14, 904-912.
3. Monaco, L., Passananti, C., and Fanciulli, M. (2003) Genomic Structure and Transcriptional Regulation of Che-1, a Novel Partner of Rb. Gene. 321, 57-63.
4. Thomas, T., Voss, A. K., Petrou, P., and Gruss, P. (2000) The Murine Gene, Traube, is Essential for the Growth of Preimplantation Embryos. Dev Biol. 227, 324-342.
|Science Writer||Anne Murray|