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Protein

Transcription factor E2-alpha

Gene

Tcf3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 from RNA polymerase II promoter 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 gene expression Source: MGI
  • positive regulation of muscle cell differentiation Source: Reactome
  • positive regulation of neuron differentiation Source: UniProtKB
  • positive regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter 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 from RNA polymerase II promoter Source: MGI
  • response to drug Source: MGI
  • response to lipopolysaccharide Source: MGI
  • T cell differentiation in thymus Source: MGI
  • transcription, DNA-templated Source: MGI
Complete GO annotation...

Keywords - Biological processi

Differentiation, Neurogenesis, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiR-MMU-375170. CDO in myogenesis.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:98510. Tcf3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • nuclear chromatin Source: MGI
  • nuclear nucleosome Source: MGI
  • nucleoplasm Source: Reactome
  • nucleus Source: MGI
  • protein complex Source: UniProtKB
  • RNA polymerase II transcription factor complex Source: MGI
  • transcription factor complex Source: BHF-UCL
Complete GO annotation...

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
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

WithEntry#Exp.IntActNotes
Hand1Q642792EBI-81370,EBI-81361
Hand2Q610392EBI-81370,EBI-81388
Id2P411366EBI-413585,EBI-309167
Tal1P220914EBI-81370,EBI-8006437

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204015. 105 interactors.
DIPiDIP-30940N.
IntActiP15806. 14 interactors.
MINTiMINT-218641.
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

Sequence similaritiesi

Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3910. Eukaryota.
ENOG410XYUA. LUCA.
GeneTreeiENSGT00510000046438.
HOVERGENiHBG003854.
InParanoidiP15806.
KOiK09063.
PhylomeDBiP15806.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
[Graphical view]
PfamiPF00010. HLH. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
[Graphical view]

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 → LQ.1 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

Cross-referencesi

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.

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...

Protein-protein interaction databases

BioGridi204015. 105 interactors.
DIPiDIP-30940N.
IntActiP15806. 14 interactors.
MINTiMINT-218641.
STRINGi10090.ENSMUSP00000100979.

PTM databases

iPTMnetiP15806.
PhosphoSitePlusiP15806.

Proteomic databases

MaxQBiP15806.
PaxDbiP15806.
PRIDEiP15806.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi6929.
MGIiMGI:98510. Tcf3.

Phylogenomic databases

eggNOGiKOG3910. Eukaryota.
ENOG410XYUA. LUCA.
GeneTreeiENSGT00510000046438.
HOVERGENiHBG003854.
InParanoidiP15806.
KOiK09063.
PhylomeDBiP15806.

Enzyme and pathway databases

ReactomeiR-MMU-375170. CDO in myogenesis.

Miscellaneous databases

ChiTaRSiTcf3. mouse.
EvolutionaryTraceiP15806.
PROiP15806.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020167.
CleanExiMM_ME2.
MM_TCF3.
MM_TCFE2A.
ExpressionAtlasiP15806. baseline and differential.
GenevisibleiP15806. MM.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
[Graphical view]
PfamiPF00010. HLH. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTFE2_MOUSE
AccessioniPrimary (citable) accession number: P15806
Secondary accession number(s): Q3U153
, Q8CAH9, Q8VCY4, Q922S2, Q99MB8, Q9CYJ4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: August 16, 2004
Last modified: November 2, 2016
This is version 169 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.