TFE2_RAT
ID TFE2_RAT Reviewed; 649 AA.
AC P21677; P21676; Q08440; Q4VY47;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 1.
DT 25-MAY-2022, entry version 182.
DE RecName: Full=Transcription factor E2-alpha;
DE AltName: Full=Immunoglobulin enhancer-binding factor E12/E47;
DE AltName: Full=Pancreas specific transcription factor 1c;
DE AltName: Full=Transcription factor 3;
DE Short=TCF-3;
DE AltName: Full=Transcription regulator Pan;
GN Name=Tcf3; Synonyms=Pan {ECO:0000303|PubMed:2200736}, Ptf1c, Tcfe2a;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS E12 AND E47), AND FUNCTION.
RX PubMed=2200736; DOI=10.1101/gad.4.6.1035;
RA Nelson C., Shen L.-P., Meister A., Fodor E., Rutter W.J.;
RT "Pan: a transcriptional regulator that binds chymotrypsin, insulin, and AP-
RT 4 enhancer motifs.";
RL Genes Dev. 4:1035-1043(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM E12).
RC STRAIN=Sprague-Dawley;
RA Wellauer P.K.;
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 427-649 (ISOFORM E12).
RX PubMed=1766666;
RA Metz R., Ziff E.;
RT "The helix-loop-helix protein rE12 and the C/EBP-related factor rNFIL-6
RT bind to neighboring sites within the c-fos serum response element.";
RL Oncogene 6:2165-2178(1991).
RN [4]
RP INTERACTION WITH UBE2I.
RC STRAIN=CD Charles River; TISSUE=Aorta;
RX PubMed=9013644; DOI=10.1074/jbc.272.6.3845;
RA Kho C.-J., Huggins G.S., Endege W.O., Hsieh C.-M., Lee M.-E., Haber E.;
RT "Degradation of E2A proteins through a ubiquitin-conjugating enzyme,
RT UbcE2A.";
RL J. Biol. Chem. 272:3845-3851(1997).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Transcriptional regulator involved in the initiation of
CC neuronal differentiation and mesenchymal to epithelial transition (By
CC similarity). Heterodimers between TCF3 and tissue-specific basic helix-
CC loop-helix (bHLH) proteins play major roles in determining tissue-
CC specific cell fate during embryogenesis, like muscle or early B-cell
CC differentiation (By similarity). Together with TCF15, required for the
CC mesenchymal to epithelial transition (By similarity). Dimers bind DNA
CC on E-box motifs: 5'-CANNTG-3' (By similarity). Binds to the kappa-E2
CC site in the kappa immunoglobulin gene enhancer (By similarity). Binds
CC to the consensus sequence CAC/GCTGT/C present, in the chymotrypsin,
CC insulin, AP-4, and several other gene enhancer motifs (PubMed:2200736).
CC {ECO:0000250|UniProtKB:P15806, ECO:0000250|UniProtKB:P15923,
CC ECO:0000269|PubMed:2200736}.
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 (By similarity). Interacts with UBE2I
CC (PubMed:9013644). Interacts with BHLHA9 (By similarity). Interacts with
CC ASB2; the interaction is mediated by SKP2 and targets TCF3 for Notch-
CC induced proteasomal degradation (By similarity).
CC {ECO:0000250|UniProtKB:P15806, ECO:0000250|UniProtKB:P15923,
CC ECO:0000269|PubMed:9013644}.
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=P21677-1; Sequence=Displayed;
CC Name=E47; Synonyms=PAN-1;
CC IsoId=P21677-2; Sequence=VSP_002157;
CC -!- PTM: Phosphorylated following NGF stimulation.
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 EMBL; X54549; CAA38421.1; -; mRNA.
DR EMBL; X62323; CAA44199.1; -; mRNA.
DR EMBL; AJ973227; CAJ00426.1; -; mRNA.
DR EMBL; S77532; AAB21103.1; -; mRNA.
DR PIR; A35816; A35816.
DR PIR; B35816; B35816.
DR PIR; I78853; I78853.
DR RefSeq; NP_001030314.1; NM_001035237.1.
DR RefSeq; NP_598208.2; NM_133524.2.
DR AlphaFoldDB; P21677; -.
DR SMR; P21677; -.
DR BioGRID; 251063; 4.
DR CORUM; P21677; -.
DR STRING; 10116.ENSRNOP00000023473; -.
DR iPTMnet; P21677; -.
DR PhosphoSitePlus; P21677; -.
DR PaxDb; P21677; -.
DR GeneID; 171046; -.
DR KEGG; rno:171046; -.
DR UCSC; RGD:620914; rat. [P21677-1]
DR CTD; 6929; -.
DR RGD; 620914; Tcf3.
DR eggNOG; KOG3910; Eukaryota.
DR InParanoid; P21677; -.
DR OrthoDB; 571132at2759; -.
DR PhylomeDB; P21677; -.
DR Reactome; R-RNO-525793; Myogenesis.
DR Reactome; R-RNO-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs.
DR PRO; PR:P21677; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0000785; C:chromatin; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0000791; C:euchromatin; ISO:RGD.
DR GO; GO:0000786; C:nucleosome; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:RGD.
DR GO; GO:0005667; C:transcription regulator complex; IDA:UniProtKB.
DR GO; GO:0043425; F:bHLH transcription factor binding; IPI:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISS:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0070888; F:E-box binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; ISO:RGD.
DR GO; GO:0030165; F:PDZ domain binding; IPI:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0030297; F:transmembrane receptor protein tyrosine kinase activator activity; ISO:RGD.
DR GO; GO:0070644; F:vitamin D response element binding; ISO:RGD.
DR GO; GO:0002326; P:B cell lineage commitment; ISS:UniProtKB.
DR GO; GO:0048468; P:cell development; ISO:RGD.
DR GO; GO:0007369; P:gastrulation; ISO:RGD.
DR GO; GO:0043966; P:histone H3 acetylation; ISO:RGD.
DR GO; GO:0043967; P:histone H4 acetylation; ISO:RGD.
DR GO; GO:0033152; P:immunoglobulin V(D)J recombination; ISO:RGD.
DR GO; GO:0030098; P:lymphocyte differentiation; ISO:RGD.
DR GO; GO:0001779; P:natural killer cell differentiation; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0048541; P:Peyer's patch development; ISO:RGD.
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:0010628; P:positive regulation of gene expression; IDA: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; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISO:RGD.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISO:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:RGD.
DR GO; GO:0033077; P:T cell differentiation in thymus; ISO:RGD.
DR GO; GO:0006366; P:transcription by RNA polymerase II; ISO:RGD.
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 1: Evidence at protein level;
KW Alternative splicing; DNA-binding; Isopeptide bond; Methylation; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..649
FT /note="Transcription factor E2-alpha"
FT /id="PRO_0000127469"
FT DOMAIN 544..597
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 37..107
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 132..207
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 296..325
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 339..376
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 385..420
FT /note="Leucine-zipper"
FT REGION 435..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..92
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 139..156
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 183..207
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 452..473
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 525..596
FT /note="PDEDEDDLLPPEQKAEREKERRVANNARERLRVRDINEAFKELGRMCQLHLS
FT TEKPQTKLLILHQAVAVILS -> STDEVLSLEEKDLRDRERRMANNARERVRVRDINE
FT AFRELGRMCQLHLKSDKAQTKLLILQQAVQVILG (in isoform E47)"
FT /evidence="ECO:0000303|PubMed:2200736"
FT /id="VSP_002157"
FT CONFLICT 167
FT /note="L -> LA (in Ref. 1; CAA44199)"
FT /evidence="ECO:0000305"
FT CONFLICT 427
FT /note="P -> A (in Ref. 3; AAB21103)"
FT /evidence="ECO:0000305"
FT CONFLICT 508
FT /note="D -> DH (in Ref. 3; AAB21103)"
FT /evidence="ECO:0000305"
FT CONFLICT 576..577
FT /note="ST -> NS (in Ref. 3; AAB21103)"
FT /evidence="ECO:0000305"
FT CONFLICT 637
FT /note="P -> T (in Ref. 3; AAB21103)"
FT /evidence="ECO:0000305"
FT MOD_RES P21677-2:526
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250"
SQ SEQUENCE 649 AA; 67655 MW; 882F19EDB47D14EA CRC64;
MMNQSQRMAP VGSDKELSDL LDFSMMFPLP VANGKGRPAS LAGTQFAGSG LEDRPSSESW
GNSEQNSSSF DPSRAYSEGA HFSDSHSSLP PSTFLGAGLG GKGSERNAYA TFGRDTSVGT
LSQAGFLPGE LGLSSPGPLS PSGVKSSSQY YTSFPSNPRR RAADGGLDTQ PKKVRKVPPG
LPSSVYPSSS GDNYSRDATA YPSAKTPSSA YPSPFYVADG SLHPSAELWS PPGQVGFGPM
LGDGSAPLPL APGSSSVSSG AFGGLQQQDR MGYQLHGSEV NGTLPAVSSF SAAPGTYSGT
SGHTPPVSGA DSLLGTRGTT ASSSGDALGK ALASIYSPDH SSNNFSPSPS TPVGSPQGLP
GTSQWPRAGA PSALSPNYDA GLHGLSKMED RLDEAIHVLR SHAVGTASEL HGLLPGHSTL
TTSFAGPMSL GGRHAGLVSG SHPEDGLTSG ASLLHNHASL PSQPSSLPDL SQRPPDSFSG
LGRAGVTAGA SEIKREEKED EEVTSVADAE EDKKDLKVPR TRTSPDEDED DLLPPEQKAE
REKERRVANN ARERLRVRDI NEAFKELGRM CQLHLSTEKP QTKLLILHQA VAVILSLEQQ
VRERNLNPKA ACLKRREEEK VSGVVGDPQL ALSAAHPGLG EAHNPAGHL
