UniProt functional annotation for P15923



	UniProt functional annotation for P15923

UniProt code: P15923.

Organism: Homo sapiens (Human).

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

Function: Transcriptional regulator involved in the initiation of neuronal differentiation and mesenchymal to epithelial transition. Heterodimers between TCF3 and tissue-specific basic helix-loop-helix (bHLH) proteins play major roles in determining tissue-specific cell fate during embryogenesis, like muscle or early B-cell differentiation. Together with TCF15, required for the mesenchymal to epithelial transition. Dimers bind DNA on E-box motifs: 5'-CANNTG-3' (By similarity). Binds to the kappa-E2 site in the kappa immunoglobulin gene enhancer (PubMed:2493990). Binds to IEB1 and IEB2, which are short DNA sequences in the insulin gene transcription control region (By similarity). {ECO:0000250|UniProtKB:P15806, ECO:0000269|PubMed:2493990}.

Subunit: Homodimer (PubMed:2112746, PubMed:14752053). Heterodimer; efficient DNA binding requires dimerization with another bHLH protein (By similarity). Forms a heterodimer with ASH1, TWIST1 and TWIST2 (By similarity). Forms a heterodimer with MYOG; heterodimerization enhances MYOG DNA-binding and transcriptional activities (By similarity). Forms a heterodimer with NEUROD1; the heterodimer is inhibited in presence of ID2, but not NR0B2, to E-box element (PubMed:14752053). Forms a heterodimer with TCF15; the heterodimer binds E-box element (By similarity). Forms a heterodimer with ATOH8; repress transcription of TCF3 and TCF3/NEUROG3 dimer-induced transactivation of E box-dependent promoters (By similarity). Component of a nuclear TAL-1 complex composed at least of CBFA2T3, LDB1, TAL1 and TCF3 (By similarity). Interacts with NEUROD2, PTF1A and TGFB1I1 (By similarity). Interacts with EP300 and UBE2I (PubMed:9409784, PubMed:14752053). Interacts with BHLHA9 (PubMed:25466284). {ECO:0000250|UniProtKB:P15806, ECO:0000269|PubMed:14752053, ECO:0000269|PubMed:2112746, ECO:0000269|PubMed:25466284, ECO:0000269|PubMed:9409784}.

Subunit: [Isoform E12]: Interacts with RALGAPA1 and FIGLA. {ECO:0000269|PubMed:15044608}.

Subcellular location: Nucleus {ECO:0000250|UniProtKB:P15806}.

Domain: the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. {ECO:0000269|PubMed:17467953, ECO:0000269|PubMed:2493990}.

Ptm: Phosphorylated following NGF stimulation. {ECO:0000250}.

Disease: Note=Chromosomal aberrations involving TCF3 are cause of forms of pre-B-cell acute lymphoblastic leukemia (B-ALL). Translocation t(1;19)(q23;p13.3) with PBX1. TCF3-PBX1 transforms cells by constitutively activating transcription of genes regulated by PBX1 or by other members of the PBX protein family (PubMed:1967983, PubMed:1671560). Translocation t(17;19)(q22;p13.3) with HLF (PubMed:1386162). Inversion inv(19)(p13;q13) with TFPT (PubMed:10086727). {ECO:0000269|PubMed:10086727, ECO:0000269|PubMed:1386162, ECO:0000269|PubMed:1671560, ECO:0000269|PubMed:1967983}.

Disease: Agammaglobulinemia 8, autosomal dominant (AGM8) [MIM:616941]: A form of agammaglobulinemia, a primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B-cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life. {ECO:0000269|PubMed:24216514}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: [Isoform E47]: The bHLH domain encompassing amino acids 546 to 599 is sufficient to mediate DNA-binding and homodimerization. Combined mutagenesis of Phe-566 and Leu-569 to Asp-566 and Glu-569, mutagenesis of Lys-585 to Ala-585 or combined mutagenesis of Ile-588 and Leu-589 to Asp-588 and Glu-589 prevents DNA-binding and homodimerization. Mutagenesis of Arg-548 to Lys-548, combined mutagenesis of Arg-547 and Arg-548 to Gly-547 and Gly-548, mutagenesis of Arg-556 to Lys-556, mutagenesis of Arg-558 to Lys-558, or combined mutagenesis of Arg-556 and Arg-558 to Gly-556 and Gly-558, alter DNA- binding but not dimerization. {ECO:0000305}.

Sequence caution: Sequence=AAA52331.1; 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 regulator involved in the initiation of neuronal differentiation and mesenchymal to epithelial transition. Heterodimers between TCF3 and tissue-specific basic helix-loop-helix (bHLH) proteins play major roles in determining tissue-specific cell fate during embryogenesis, like muscle or early B-cell differentiation. Together with TCF15, required for the mesenchymal to epithelial transition. Dimers bind DNA on E-box motifs: 5'-CANNTG-3' (By similarity). Binds to the kappa-E2 site in the kappa immunoglobulin gene enhancer (PubMed:2493990). Binds to IEB1 and IEB2, which are short DNA sequences in the insulin gene transcription control region (By similarity). {ECO:0000250\|UniProtKB:P15806, ECO:0000269\|PubMed:2493990}.


Subunit:		Homodimer (PubMed:2112746, PubMed:14752053). Heterodimer; efficient DNA binding requires dimerization with another bHLH protein (By similarity). Forms a heterodimer with ASH1, TWIST1 and TWIST2 (By similarity). Forms a heterodimer with MYOG; heterodimerization enhances MYOG DNA-binding and transcriptional activities (By similarity). Forms a heterodimer with NEUROD1; the heterodimer is inhibited in presence of ID2, but not NR0B2, to E-box element (PubMed:14752053). Forms a heterodimer with TCF15; the heterodimer binds E-box element (By similarity). Forms a heterodimer with ATOH8; repress transcription of TCF3 and TCF3/NEUROG3 dimer-induced transactivation of E box-dependent promoters (By similarity). Component of a nuclear TAL-1 complex composed at least of CBFA2T3, LDB1, TAL1 and TCF3 (By similarity). Interacts with NEUROD2, PTF1A and TGFB1I1 (By similarity). Interacts with EP300 and UBE2I (PubMed:9409784, PubMed:14752053). Interacts with BHLHA9 (PubMed:25466284). {ECO:0000250\|UniProtKB:P15806, ECO:0000269\|PubMed:14752053, ECO:0000269\|PubMed:2112746, ECO:0000269\|PubMed:25466284, ECO:0000269\|PubMed:9409784}.
Subunit:		[Isoform E12]: Interacts with RALGAPA1 and FIGLA. {ECO:0000269\|PubMed:15044608}.
Subcellular location:		Nucleus {ECO:0000250\|UniProtKB:P15806}.
Domain:		the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. {ECO:0000269\|PubMed:17467953, ECO:0000269\|PubMed:2493990}.
Ptm:		Phosphorylated following NGF stimulation. {ECO:0000250}.
Disease:		Note=Chromosomal aberrations involving TCF3 are cause of forms of pre-B-cell acute lymphoblastic leukemia (B-ALL). Translocation t(1;19)(q23;p13.3) with PBX1. TCF3-PBX1 transforms cells by constitutively activating transcription of genes regulated by PBX1 or by other members of the PBX protein family (PubMed:1967983, PubMed:1671560). Translocation t(17;19)(q22;p13.3) with HLF (PubMed:1386162). Inversion inv(19)(p13;q13) with TFPT (PubMed:10086727). {ECO:0000269\|PubMed:10086727, ECO:0000269\|PubMed:1386162, ECO:0000269\|PubMed:1671560, ECO:0000269\|PubMed:1967983}.
Disease:		Agammaglobulinemia 8, autosomal dominant (AGM8) [MIM:616941]: A form of agammaglobulinemia, a primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B-cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life. {ECO:0000269\|PubMed:24216514}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		[Isoform E47]: The bHLH domain encompassing amino acids 546 to 599 is sufficient to mediate DNA-binding and homodimerization. Combined mutagenesis of Phe-566 and Leu-569 to Asp-566 and Glu-569, mutagenesis of Lys-585 to Ala-585 or combined mutagenesis of Ile-588 and Leu-589 to Asp-588 and Glu-589 prevents DNA-binding and homodimerization. Mutagenesis of Arg-548 to Lys-548, combined mutagenesis of Arg-547 and Arg-548 to Gly-547 and Gly-548, mutagenesis of Arg-556 to Lys-556, mutagenesis of Arg-558 to Lys-558, or combined mutagenesis of Arg-556 and Arg-558 to Gly-556 and Gly-558, alter DNA- binding but not dimerization. {ECO:0000305}.
Sequence caution:		Sequence=AAA52331.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};