UniProt functional annotation for Q06455



	UniProt functional annotation for Q06455

UniProt code: Q06455.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Transcriptional corepressor which facilitates transcriptional repression via its association with DNA-binding transcription factors and recruitment of other corepressors and histone-modifying enzymes (PubMed:12559562, PubMed:15203199, PubMed:10688654). Can repress the expression of MMP7 in a ZBTB33-dependent manner (PubMed:23251453). Can repress transactivation mediated by TCF12 (PubMed:16803958). Acts as a negative regulator of adipogenesis (By similarity). The AML1-MTG8/ETO fusion protein frequently found in leukemic cells is involved in leukemogenesis and contributes to hematopoietic stem/progenitor cell self-renewal (PubMed:23812588). {ECO:0000250|UniProtKB:Q61909, ECO:0000269|PubMed:10688654, ECO:0000269|PubMed:10973986, ECO:0000269|PubMed:16803958, ECO:0000269|PubMed:23251453, ECO:0000269|PubMed:23812588, ECO:0000303|PubMed:12559562, ECO:0000303|PubMed:15203199}.

Subunit: Homooligomer. Homotetramerization is mediated by nervy homology region 2 (NRH2). Can interact with CBFA2T2 and CBFA2T3; heterotetramerization between members of the CBFA2T family is proposed. Interacts with TCF12, SIN3A, HDAC1, HDAC2, HDAC3, NCOR1, NCOR2. Interacts with ATN1 (via its N-terminus); the interaction enhances the transcriptional repression. Interacts (via its N-terminus) with ZBTB16; the interaction increases the transcription repression activity of ZBTB16 (PubMed:10688654). AML1-MTG8/ETO fusion protein interacts with CBFB. AML1-MTG8/ETO is part of a stable transcription factor complex AETFC in leukemic cells; AETFC formation seems to be involved in recruitment of EP300. AML1-MTG8/ETO nervy homology region 2-mediated oligomerization is proposed to be homotypic, required for AML1- MTG8/ETO-mediated transformation of primary hematopoietic cells and is required for AML1-MTG8/ETO interaction with TCF12. {ECO:0000269|PubMed:10688654, ECO:0000269|PubMed:10973986, ECO:0000269|PubMed:12242670, ECO:0000269|PubMed:16616331, ECO:0000269|PubMed:16803958, ECO:0000269|PubMed:17560331, ECO:0000269|PubMed:17572682, ECO:0000269|PubMed:19202074, ECO:0000269|PubMed:23812588}.

Subcellular location: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00440, ECO:0000269|PubMed:10973986}. Note=Colocalizes with ATN1 in discrete nuclear dots.

Tissue specificity: Most abundantly expressed in brain. Lower levels in lung, heart, testis and ovary.

Domain: The TAFH domain mediates interaction with transcription regulators. {ECO:0000269|PubMed:17572682}.

Domain: Nervy homology region 2 (NHR2) mediates homo- and possibly heterotypic oligomerization by forming a four-helix bundle tetrameric structure. {ECO:0000269|PubMed:16616331}.

Disease: Note=A chromosomal aberration involving RUNX1T1 is a cause of acute myeloid leukemia (AML-M2). Translocation t(8;21)(q22;q22) with RUNX1/AML1. {ECO:0000269|PubMed:1423235, ECO:0000269|PubMed:7541640, ECO:0000269|PubMed:8334990, ECO:0000269|PubMed:8353289}.

Similarity: Belongs to the CBFA2T family. {ECO:0000305}.

Sequence caution: Sequence=AAH05850.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAA03247.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Transcriptional corepressor which facilitates transcriptional repression via its association with DNA-binding transcription factors and recruitment of other corepressors and histone-modifying enzymes (PubMed:12559562, PubMed:15203199, PubMed:10688654). Can repress the expression of MMP7 in a ZBTB33-dependent manner (PubMed:23251453). Can repress transactivation mediated by TCF12 (PubMed:16803958). Acts as a negative regulator of adipogenesis (By similarity). The AML1-MTG8/ETO fusion protein frequently found in leukemic cells is involved in leukemogenesis and contributes to hematopoietic stem/progenitor cell self-renewal (PubMed:23812588). {ECO:0000250\|UniProtKB:Q61909, ECO:0000269\|PubMed:10688654, ECO:0000269\|PubMed:10973986, ECO:0000269\|PubMed:16803958, ECO:0000269\|PubMed:23251453, ECO:0000269\|PubMed:23812588, ECO:0000303\|PubMed:12559562, ECO:0000303\|PubMed:15203199}.


Subunit:		Homooligomer. Homotetramerization is mediated by nervy homology region 2 (NRH2). Can interact with CBFA2T2 and CBFA2T3; heterotetramerization between members of the CBFA2T family is proposed. Interacts with TCF12, SIN3A, HDAC1, HDAC2, HDAC3, NCOR1, NCOR2. Interacts with ATN1 (via its N-terminus); the interaction enhances the transcriptional repression. Interacts (via its N-terminus) with ZBTB16; the interaction increases the transcription repression activity of ZBTB16 (PubMed:10688654). AML1-MTG8/ETO fusion protein interacts with CBFB. AML1-MTG8/ETO is part of a stable transcription factor complex AETFC in leukemic cells; AETFC formation seems to be involved in recruitment of EP300. AML1-MTG8/ETO nervy homology region 2-mediated oligomerization is proposed to be homotypic, required for AML1- MTG8/ETO-mediated transformation of primary hematopoietic cells and is required for AML1-MTG8/ETO interaction with TCF12. {ECO:0000269\|PubMed:10688654, ECO:0000269\|PubMed:10973986, ECO:0000269\|PubMed:12242670, ECO:0000269\|PubMed:16616331, ECO:0000269\|PubMed:16803958, ECO:0000269\|PubMed:17560331, ECO:0000269\|PubMed:17572682, ECO:0000269\|PubMed:19202074, ECO:0000269\|PubMed:23812588}.
Subcellular location:		Nucleus {ECO:0000255\|PROSITE-ProRule:PRU00440, ECO:0000269\|PubMed:10973986}. Note=Colocalizes with ATN1 in discrete nuclear dots.
Tissue specificity:		Most abundantly expressed in brain. Lower levels in lung, heart, testis and ovary.
Domain:		The TAFH domain mediates interaction with transcription regulators. {ECO:0000269\|PubMed:17572682}.
Domain:		Nervy homology region 2 (NHR2) mediates homo- and possibly heterotypic oligomerization by forming a four-helix bundle tetrameric structure. {ECO:0000269\|PubMed:16616331}.
Disease:		Note=A chromosomal aberration involving RUNX1T1 is a cause of acute myeloid leukemia (AML-M2). Translocation t(8;21)(q22;q22) with RUNX1/AML1. {ECO:0000269\|PubMed:1423235, ECO:0000269\|PubMed:7541640, ECO:0000269\|PubMed:8334990, ECO:0000269\|PubMed:8353289}.
Similarity:		Belongs to the CBFA2T family. {ECO:0000305}.
Sequence caution:		Sequence=AAH05850.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAA03247.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};