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Protein

Transcription factor E2-alpha

Gene

Tcf3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Transcriptional regulator. Involved in the initiation of neuronal differentiation. 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. Dimers bind DNA on E-box motifs: 5'-CANNTG-3'. Binds to the kappa-E2 site in the kappa immunoglobulin gene enhancer. Binds to IEB1 and IEB2, which are short DNA sequences in the insulin gene transcription control region.1 Publication

GO - Molecular functioni

GO - Biological processi

  • B cell lineage commitment Source: UniProtKB
  • cell development Source: MGI
  • gastrulation Source: BHF-UCL
  • histone H3 acetylation Source: MGI
  • histone H4 acetylation Source: MGI
  • immunoglobulin V(D)J recombination Source: MGI
  • lymphocyte differentiation Source: MGI
  • natural killer cell differentiation Source: MGI
  • negative regulation of transcription by RNA polymerase II Source: MGI
  • Peyer's patch development Source: MGI
  • positive regulation of B cell proliferation Source: UniProtKB
  • positive regulation of cell cycle Source: UniProtKB
  • positive regulation of DNA binding transcription factor activity Source: UniProtKB
  • positive regulation of gene expression Source: MGI
  • positive regulation of neuron differentiation Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: BHF-UCL
  • positive regulation of transcription by RNA polymerase II Source: BHF-UCL
  • protein stabilization Source: MGI
  • regulation of G1/S transition of mitotic cell cycle Source: UniProtKB
  • regulation of transcription, DNA-templated Source: MGI
  • regulation of transcription by RNA polymerase II Source: MGI
  • response to drug Source: MGI
  • response to lipopolysaccharide Source: MGI
  • T cell differentiation in thymus Source: MGI
  • transcription, DNA-templated Source: MGI

Keywordsi

Molecular functionDNA-binding
Biological processDifferentiation, Neurogenesis, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-MMU-375170 CDO in myogenesis
R-MMU-8939236 RUNX1 regulates transcription of genes involved in differentiation of HSCs

Names & Taxonomyi

Protein namesi
Recommended name:
Transcription factor E2-alpha
Alternative name(s):
Immunoglobulin enhancer-binding factor E12/E47
Transcription factor 3
Short name:
TCF-3
Transcription factor A1
Gene namesi
Name:Tcf3
Synonyms:Alf2, Me2, Tcfe2a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:98510 Tcf3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice are smaller than their wild-type littermates and fail to thrive 14 days after birth.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001274681 – 651Transcription factor E2-alphaAdd BLAST651

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei135PhosphoserineBy similarity1
Modified residuei140PhosphoserineBy similarity1
Modified residuei353PhosphothreonineCombined sources1
Modified residuei357PhosphoserineCombined sources1
Modified residuei369Omega-N-methylarginineCombined sources1
Modified residuei377PhosphoserineBy similarity1
Cross-linki496Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei526PhosphoserineBy similarity1
Cross-linki622Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Isoform E47 (identifier: P15806-2)
Modified residuei528PhosphothreonineCombined sources1
Modified residuei533PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated following NGF stimulation.By similarity

Keywords - PTMi

Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP15806
PaxDbiP15806
PRIDEiP15806

PTM databases

iPTMnetiP15806
PhosphoSitePlusiP15806

Expressioni

Developmental stagei

Expressed during the development of the nervous system.1 Publication

Gene expression databases

BgeeiENSMUSG00000020167
CleanExiMM_ME2
MM_TCF3
MM_TCFE2A
ExpressionAtlasiP15806 baseline and differential
GenevisibleiP15806 MM

Interactioni

Subunit structurei

Forms a heterodimer with TWIST2. Forms a heterodimer with NEUROD1; the heterodimer is inhibited in presence of ID2, but not NR0B2, to E-box element. Isoform E12 interacts with RALGAPA1 and FIGLA. Interacts with EP300. Efficient DNA binding requires dimerization with another bHLH protein (By similarity). Homodimer. Heterodimer. Forms a heterodimer with MYOG; heterodimerization enhances MYOG DNA-binding and transcriptional activities. Interacts with PTF1A, TGFB1I1 and UBE2I. Component of a nuclear TAL-1 complex composed at least of CBFA2T3, LDB1, TAL1 and TCF3. Interacts with NEUROD2. Interacts with BHLHA9. Forms a heterodimer with ATOH8; repress transcription of TCF3 and TCF3/NEUROG3 dimer-induced transactivation of E box-dependent promoters.By similarity10 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • bHLH transcription factor binding Source: MGI
  • mitogen-activated protein kinase kinase kinase binding Source: MGI
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: MGI
  • repressing transcription factor binding Source: MGI
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi204015, 103 interactors
CORUMiP15806
DIPiDIP-30940N
IntActiP15806, 15 interactors
MINTiP15806
STRINGi10090.ENSMUSP00000100979

Structurei

Secondary structure

1651
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi548 – 574Combined sources27
Helixi585 – 602Combined sources18

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2QL2X-ray2.50A/C547-606[»]
ProteinModelPortaliP15806
SMRiP15806
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP15806

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini546 – 599bHLHPROSITE-ProRule annotationAdd BLAST54

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni387 – 422Leucine-zipperAdd BLAST36

Phylogenomic databases

eggNOGiKOG3910 Eukaryota
ENOG410XYUA LUCA
GeneTreeiENSGT00510000046438
HOVERGENiHBG003854
InParanoidiP15806
KOiK09063
PhylomeDBiP15806

Family and domain databases

CDDicd00083 HLH, 1 hit
Gene3Di4.10.280.10, 1 hit
InterProiView protein in InterPro
IPR011598 bHLH_dom
IPR036638 HLH_DNA-bd_sf
PfamiView protein in Pfam
PF00010 HLH, 1 hit
SMARTiView protein in SMART
SM00353 HLH, 1 hit
SUPFAMiSSF47459 SSF47459, 1 hit
PROSITEiView protein in PROSITE
PS50888 BHLH, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform E12 (identifier: P15806-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MMNQSQRMAP VGSDKELSDL LDFSMMFPLP VANGKSRPAS LGGTQFAGSG
60 70 80 90 100
LEDRPSSGSW GSSDQNSSSF DPSRTYSEGA HFSDSHSSLP PSTFLGAGLG
110 120 130 140 150
GKGSERNAYA TFGRDTSVGT LSQAGFLPGE LSLSSPGPLS PSGIKSSSQY
160 170 180 190 200
YPSFPSNPRR RAADGGLDTQ PKKVRKVPPG LPSSVYPPSS GDSYSRDAAA
210 220 230 240 250
YPSAKTPSSA YPSPFYVADG SLHPSAELWS TPSQVGFGPM LGDGSSPLPL
260 270 280 290 300
APGSSSVGSG TFGGLQQQDR MGYQLHGSEV NGSLPAVSSF SAAPGTYSGT
310 320 330 340 350
SGHTPPVSGA AAESLLGTRG TTASSSGDAL GKALASIYSP DHSSNNFSPS
360 370 380 390 400
PSTPVGSPQG LPGTSQWPRA GAPSALSPNY DAGLHGLSKM EDRLDEAIHV
410 420 430 440 450
LRSHAVGTAS DLHGLLPGHG ALTTSFTGPM SLGGRHAGLV GGSHPEEGLT
460 470 480 490 500
SGASLLHNHA SLPSQPSSLP DLSQRPPDSY SGLGRAGTTA GASEIKREEK
510 520 530 540 550
EDEEIASVAD AEEDKKDLKV PRTRTSPDED EDDLLPPEQK AEREKERRVA
560 570 580 590 600
NNARERLRVR DINEAFKELG RMCQLHLSSE KPQTKLLILH QAVAVILSLE
610 620 630 640 650
QQVRERNLNP KAACLKRREE EKVSGVVGDP QLALSAAHPG LGEAHNPAGH

L
Length:651
Mass (Da):67,701
Last modified:August 16, 2004 - v2
Checksum:i7904ABB37B8D39CB
GO
Isoform E47 (identifier: P15806-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     527-598: PDEDEDDLLP...LHQAVAVILS → STDEVLSLEE...LQQAVQVILG

Show »
Length:648
Mass (Da):67,417
Checksum:i5C1B68DDBF29A93B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti156S → N in AAK18618 (PubMed:11309385).Curated1
Sequence conflicti164D → N in AAK18618 (PubMed:11309385).Curated1
Sequence conflicti167L → LA in AAH18260 (PubMed:15489334).Curated1
Sequence conflicti294P → T in BAB30842 (PubMed:16141072).Curated1
Sequence conflicti633A → P in AAH06860 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti387L → LQ1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_011354527 – 598PDEDE…AVILS → STDEVLSLEEKDLRDRERRM ANNARERVRVRDINEAFREL GRMCQLHLKSDKAQTKLLIL QQAVQVILG in isoform E47. 4 PublicationsAdd BLAST72

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF352579 mRNA Translation: AAK18618.1
AK017617 mRNA Translation: BAB30842.1
AK038738 mRNA Translation: BAC30118.1
AK156265 mRNA Translation: BAE33647.1
BC006860 mRNA Translation: AAH06860.1
BC018260 mRNA Translation: AAH18260.1
X17500 mRNA Translation: CAA35541.1
D16631 mRNA Translation: BAA04057.1
D16632 mRNA Translation: BAA04058.1
D16633 mRNA Translation: BAA04059.1
D16634 mRNA Translation: BAA04060.1
D16635 mRNA Translation: BAA04061.1
D16636 mRNA Translation: BAA04062.1
D16637 mRNA Translation: BAA04063.1
D16638 mRNA Translation: BAA04064.1
D29919 mRNA Translation: BAA06218.1
CCDSiCCDS24022.1 [P15806-2]
CCDS48630.1 [P15806-1]
PIRiS08410
RefSeqiNP_001157620.1, NM_001164148.1
NP_001157621.1, NM_001164149.1 [P15806-1]
NP_001157623.1, NM_001164151.1
NP_035678.3, NM_011548.4 [P15806-2]
UniGeneiMm.3406

Genome annotation databases

EnsembliENSMUST00000105345; ENSMUSP00000100982; ENSMUSG00000020167 [P15806-2]
ENSMUST00000105346; ENSMUSP00000100983; ENSMUSG00000020167 [P15806-1]
GeneIDi21423
KEGGimmu:21423
UCSCiuc007gdg.2 mouse [P15806-2]
uc007gdi.2 mouse [P15806-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTFE2_MOUSE
AccessioniPrimary (citable) accession number: P15806
Secondary accession number(s): Q3U153
, Q8CAH9, Q8VCY4, Q922S2, Q99MB8, Q9CYJ4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: August 16, 2004
Last modified: May 23, 2018
This is version 182 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health