TFE2_MESAU
ID TFE2_MESAU Reviewed; 649 AA.
AC P98180;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 25-MAY-2022, entry version 121.
DE RecName: Full=Transcription factor E2-alpha;
DE AltName: Full=Immunoglobulin-enhancer-binding factor E12/E47;
DE AltName: Full=Transcription factor 3;
DE Short=TCF-3;
DE AltName: Full=Transcription regulator Pan;
GN Name=TCF3; Synonyms=PAN;
OS Mesocricetus auratus (Golden hamster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Mesocricetus.
OX NCBI_TaxID=10036;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS E12 AND E47), AND FUNCTION.
RC TISSUE=Insulinoma;
RX PubMed=1710033; DOI=10.1210/mend-5-2-292;
RA German M.S., Blanar M.A., Nelson C., Moss L.G., Rutter W.J.;
RT "Two related helix-loop-helix proteins participate in separate cell-
RT specific complexes that bind the insulin enhancer.";
RL Mol. Endocrinol. 5:292-299(1991).
CC -!- FUNCTION: Transcriptional regulator (PubMed:1710033). Involved in the
CC initiation of neuronal differentiation and mesenchymal to epithelial
CC transition (By similarity). Heterodimers between TCF3 and tissue-
CC specific basic helix-loop-helix (bHLH) proteins play major roles in
CC determining tissue-specific cell fate during embryogenesis, like muscle
CC or early B-cell differentiation (By similarity). Together with TCF15,
CC required for the mesenchymal to epithelial transition (By similarity).
CC Dimers bind DNA on E-box motifs: 5'-CANNTG-3' (By similarity). Binds to
CC the kappa-E2 site in the kappa immunoglobulin gene enhancer (By
CC similarity). Binds to IEB1 and IEB2, which are short DNA sequences in
CC the insulin gene transcription control region (By similarity).
CC {ECO:0000250|UniProtKB:P15806, ECO:0000250|UniProtKB:P15923}.
CC -!- FUNCTION: [Isoform E47]: Facilitates ATOH7 binding to DNA at the
CC consensus sequence 5'-CAGGTG-3', and positively regulates
CC transcriptional activity. {ECO:0000250|UniProtKB:P15923}.
CC -!- SUBUNIT: Homodimer. Heterodimer; efficient DNA binding requires
CC dimerization with another bHLH protein. Forms a heterodimer with TWIST1
CC and TWIST2. Forms a heterodimer with NEUROD1; the heterodimer is
CC inhibited in presence of ID2, but not NR0B2, to E-box element. Forms a
CC heterodimer with TCF15; the heterodimer binds E-box element. Forms a
CC heterodimer with MYOG; heterodimerization enhances MYOG DNA-binding and
CC transcriptional activities. Forms a heterodimer with ATOH8; repress
CC transcription of TCF3 and TCF3-NEUROG3 dimer-induced transactivation of
CC E box-dependent promoters. Component of a nuclear TAL-1 complex
CC composed at least of CBFA2T3, LDB1, TAL1 and TCF3. Interacts with
CC NEUROD2 (By similarity). Interacts with EP300 (By similarity).
CC Interacts with PTF1A, TGFB1I1 and UBE2I (By similarity). Interacts with
CC BHLHA9 (By similarity). Interacts with ASB2; the interaction is
CC mediated by SKP2 and targets TCF3 for Notch-induced proteasomal
CC degradation (By similarity). {ECO:0000250|UniProtKB:P15806,
CC ECO:0000250|UniProtKB:P15923}.
CC -!- SUBUNIT: [Isoform E12]: Interacts with RALGAPA1 (By similarity).
CC Interacts with FIGLA (By similarity). {ECO:0000250|UniProtKB:P15806,
CC ECO:0000250|UniProtKB:P15923}.
CC -!- SUBUNIT: [Isoform E47]: Forms a heterodimer with ATOH7; required for
CC ATOH7 DNA-binding. {ECO:0000250|UniProtKB:P15923}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P15806}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=E12; Synonyms=PAN-2;
CC IsoId=P98180-1; Sequence=Displayed;
CC Name=E47; Synonyms=PAN-1;
CC IsoId=P98180-2; Sequence=VSP_002156;
CC -!- PTM: Phosphorylated following NGF stimulation. {ECO:0000250}.
CC -!- PTM: Undergoes Notch-induced ubiquitination and subsequent proteasomal
CC degradation which is mediated by ASB1 or ASB2, the substrate-
CC recognition components of probable ECS E3 ubiquitin-protein ligase
CC complexes. {ECO:0000250|UniProtKB:P15923}.
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DR PIR; A37953; A37953.
DR PIR; B37953; B37953.
DR AlphaFoldDB; P98180; -.
DR SMR; P98180; -.
DR eggNOG; KOG3910; Eukaryota.
DR Proteomes; UP000189706; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:GO_Central.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISS:UniProtKB.
DR GO; GO:0070888; F:E-box binding; IDA:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0002326; P:B cell lineage commitment; ISS:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; ISS:UniProtKB.
DR GO; GO:0045787; P:positive regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:GO_Central.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; ISS:UniProtKB.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Differentiation; DNA-binding; Isopeptide bond;
KW Methylation; Neurogenesis; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..649
FT /note="Transcription factor E2-alpha"
FT /id="PRO_0000127467"
FT DOMAIN 544..597
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 34..107
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 127..206
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 222..267
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 291..325
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 339..382
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 385..420
FT /note="Leucine-zipper"
FT REGION 431..547
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 171..177
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 50..98
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 139..155
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 249..267
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 339..362
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 449..472
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 490..547
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 135
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15923"
FT MOD_RES 140
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15923"
FT MOD_RES 351
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P15806"
FT MOD_RES 355
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15923"
FT MOD_RES 367
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P15806"
FT MOD_RES 375
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15923"
FT MOD_RES 524
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15923"
FT CROSSLNK 494
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P15923"
FT CROSSLNK 620
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P15923"
FT VAR_SEQ 528..596
FT /note="DEDDLLPPEQKAEREKERRVANNARERLRVRDINEAFKELGRMCQLHLSSEK
FT PQTKLLILHQAVAVILS -> STDEVLSLEEKDLRDRERRMANNARERVRVRDINEAFR
FT ELGRICQLHLKSDKAQTKLLILQQAVQVILG (in isoform E47)"
FT /evidence="ECO:0000305"
FT /id="VSP_002156"
FT MOD_RES P98180-2:529
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P15806"
SQ SEQUENCE 649 AA; 67323 MW; 3C35F296316EB34D CRC64;
MMNQSQRMAP VGSDKELSDL LDFSMMFPLP VANGKGRPAS LAGTQFAGSG LEDRPSSGSW
GNSDQNSSSF DPSRTYSEGA HFSESHNSLP SSTFLGPGLG GKSSERSAYA TFGRDTSVSA
LTQAGFLPGE LGLSSPGPLS PSGVKSGSQY YPSYPSNPRR RAADSGLDTQ SKKVRKVPPG
LPSSVYPSSS GDSYGRDAAA YPSAKTPGSA YPSPFYVADG SLHPSAELWS PPSQAGFGPM
LGDGSSPLPL APGSSSVGSG TFGGLQQQER MSYQLHGSEV NGTLPAVSSF SAAPGTYGGA
SGHTPPVSGA DSLMGTRGTT ASSSGDALGK ALASIYSPDH SSNNFSPSPS TPVGSPQGLP
GTSQWPRAGA PSALSPTYDG GLHGLSKMED RLDEAIHVLR SHAVGTASDL HGLLPGHGAL
TTSFPGPVPL GGRHAGLVGG GHPEDGLTSG TSLLHTHASL PSQASSLPDL SQRPPDSYGG
LGRAGAPAGA SEIKREEKDD EESTSVADAE EDKKDLKAPR TRTSPDEDED DLLPPEQKAE
REKERRVANN ARERLRVRDI NEAFKELGRM CQLHLSSEKP QTKLLILHQA VAVILSLEQQ
VRERNLNPKA ACLKRREEEK VSGVVGDPQL ALSAAHPGLG EAHNPPGHL
