Transcription factor E2-alpha - Mus musculus (Mouse)

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

Alternative products

Sequence annotation (Features)

Sequences

References

Cross-references

Entry information

Relevant documents

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

Alternative products

Sequence annotation (Features)

Sequences

References

Cross-references

Entry information

Relevant documents

Preferred order of sections

Molecule processing

Regions

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Preferred order of sections

With

Entry

#Exp.

IntAct

Notes

Molecule processing

Regions

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Protein names

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 names

Name:	Tcf3
Synonyms:	Alf2, Me2, Tcfe2a

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Sequence length	651 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

Function	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. Ref.13
Subunit structure	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. 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. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14
Subcellular location	Nucleus.
Developmental stage	Expressed during the development of the nervous system. Ref.13
Post-translational modification	Phosphorylated following NGF stimulation By similarity.
Disruption phenotype	Mice are smaller than their wild-type littermates and fail to thrive 14 days after birth. Ref.13
Sequence similarities	Contains 1 bHLH (basic helix-loop-helix) domain.

Keywords
Biological process	Differentiation Neurogenesis Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	DNA-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell lineage commitment Inferred from sequence or structural similarity. Source: UniProtKB G1 phase of mitotic cell cycle Inferred from sequence or structural similarity. Source: UniProtKB Peyer's patch development Inferred from genetic interaction PubMed 17452521. Source: MGI T cell differentiation in thymus Inferred from mutant phenotype PubMed 18958875. Source: MGI cell development Inferred from genetic interaction PubMed 17452521. Source: MGI histone H3 acetylation Inferred from mutant phenotype PubMed 16428437. Source: MGI histone H4 acetylation Inferred from mutant phenotype PubMed 16428437. Source: MGI immunoglobulin V(D)J recombination Inferred from mutant phenotype PubMed 16428437. Source: MGI natural killer cell differentiation Inferred from genetic interaction PubMed 17452521. Source: MGI positive regulation of B cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell cycle Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of neuron differentiation Inferred from direct assay Ref.13. Source: UniProtKB positive regulation of sequence-specific DNA binding transcription factor activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 11812799. Source: BHF-UCL positive regulation of transcription, DNA-dependent Inferred from sequence or structural similarity. Source: UniProtKB protein stabilization Inferred from direct assay PubMed 15322112. Source: MGI response to drug Inferred from mutant phenotype PubMed 2160325. Source: MGI response to lipopolysaccharide Inferred from mutant phenotype PubMed 16428437. Source: MGI transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB nuclear nucleosome Inferred from direct assay PubMed 16428437. Source: MGI nucleus Inferred from sequence or structural similarity. Source: UniProtKB protein complex Inferred from sequence or structural similarity. Source: UniProtKB transcription factor complex Inferred from direct assay PubMed 11812799. Source: BHF-UCL
Molecular_function	DNA binding Inferred from sequence or structural similarity. Source: UniProtKB E-box binding Inferred from direct assay Ref.13. Source: UniProtKB chromatin binding Inferred from direct assay PubMed 18550854 PubMed 19011221. Source: MGI protein heterodimerization activity Inferred from direct assay Ref.13. Source: UniProtKB protein homodimerization activity Inferred from sequence or structural similarity. Source: UniProtKB sequence-specific DNA binding Inferred from direct assay PubMed 16428437 PubMed 17938243 PubMed 18388149. Source: MGI sequence-specific DNA binding transcription factor activity Inferred from sequence or structural similarity. Source: UniProtKB transcription coactivator activity Inferred from sequence or structural similarity. Source: UniProtKB transcription factor binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

With	Entry	#Exp.	IntAct	Notes
Hand1	Q64279	2	EBI-81370,EBI-81361
Hand2	Q61039	2	EBI-81370,EBI-81388

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Chain

1 – 651

651

Transcription factor E2-alpha

PRO_0000127468

Domain

546 – 599

54

bHLH

Region

387 – 422

36

Leucine-zipper

Modified residue

135

1

Phosphoserine By similarity

Modified residue

140

1

Phosphoserine By similarity

Modified residue

357

1

Phosphoserine By similarity

Alternative sequence

527 – 598

72

PDEDE…AVILS → STDEVLSLEEKDLRDRERRM ANNARERVRVRDINEAFREL GRMCQLHLKSDKAQTKLLIL QQAVQVILG in isoform E47.

VSP_011354

Natural variant

387

1

L → LQ. Ref.5

Sequence conflict

156

1

S → N in AAK18618. Ref.1

Sequence conflict

164

1

D → N in AAK18618. Ref.1

Sequence conflict

167

1

L → LA in AAH18260. Ref.3

Sequence conflict

294

1

P → T in BAB30842. Ref.2

Sequence conflict

633

1

A → P in AAH06860. Ref.3

1

.

651

Helix Strand Turn

Details...

Sequence		Length	Mass (Da)
Isoform E12 [UniParc]. Last modified August 16, 2004. Version 2. Checksum: 7904ABB37B8D39CB Show »	FASTA	651	67,701
10 20 30 40 50 60 MMNQSQRMAP VGSDKELSDL LDFSMMFPLP VANGKSRPAS LGGTQFAGSG LEDRPSSGSW 70 80 90 100 110 120 GSSDQNSSSF DPSRTYSEGA HFSDSHSSLP PSTFLGAGLG GKGSERNAYA TFGRDTSVGT 130 140 150 160 170 180 LSQAGFLPGE LSLSSPGPLS PSGIKSSSQY YPSFPSNPRR RAADGGLDTQ PKKVRKVPPG 190 200 210 220 230 240 LPSSVYPPSS GDSYSRDAAA YPSAKTPSSA YPSPFYVADG SLHPSAELWS TPSQVGFGPM 250 260 270 280 290 300 LGDGSSPLPL APGSSSVGSG TFGGLQQQDR MGYQLHGSEV NGSLPAVSSF SAAPGTYSGT 310 320 330 340 350 360 SGHTPPVSGA AAESLLGTRG TTASSSGDAL GKALASIYSP DHSSNNFSPS PSTPVGSPQG 370 380 390 400 410 420 LPGTSQWPRA GAPSALSPNY DAGLHGLSKM EDRLDEAIHV LRSHAVGTAS DLHGLLPGHG 430 440 450 460 470 480 ALTTSFTGPM SLGGRHAGLV GGSHPEEGLT SGASLLHNHA SLPSQPSSLP DLSQRPPDSY 490 500 510 520 530 540 SGLGRAGTTA GASEIKREEK EDEEIASVAD AEEDKKDLKV PRTRTSPDED EDDLLPPEQK 550 560 570 580 590 600 AEREKERRVA NNARERLRVR DINEAFKELG RMCQLHLSSE KPQTKLLILH QAVAVILSLE 610 620 630 640 650 QQVRERNLNP KAACLKRREE EKVSGVVGDP QLALSAAHPG LGEAHNPAGH L « Hide
Isoform E47 [UniParc]. Checksum: 5C1B68DDBF29A93B Show »	FASTA	648	67,417
10 20 30 40 50 60 MMNQSQRMAP VGSDKELSDL LDFSMMFPLP VANGKSRPAS LGGTQFAGSG LEDRPSSGSW 70 80 90 100 110 120 GSSDQNSSSF DPSRTYSEGA HFSDSHSSLP PSTFLGAGLG GKGSERNAYA TFGRDTSVGT 130 140 150 160 170 180 LSQAGFLPGE LSLSSPGPLS PSGIKSSSQY YPSFPSNPRR RAADGGLDTQ PKKVRKVPPG 190 200 210 220 230 240 LPSSVYPPSS GDSYSRDAAA YPSAKTPSSA YPSPFYVADG SLHPSAELWS TPSQVGFGPM 250 260 270 280 290 300 LGDGSSPLPL APGSSSVGSG TFGGLQQQDR MGYQLHGSEV NGSLPAVSSF SAAPGTYSGT 310 320 330 340 350 360 SGHTPPVSGA AAESLLGTRG TTASSSGDAL GKALASIYSP DHSSNNFSPS PSTPVGSPQG 370 380 390 400 410 420 LPGTSQWPRA GAPSALSPNY DAGLHGLSKM EDRLDEAIHV LRSHAVGTAS DLHGLLPGHG 430 440 450 460 470 480 ALTTSFTGPM SLGGRHAGLV GGSHPEEGLT SGASLLHNHA SLPSQPSSLP DLSQRPPDSY 490 500 510 520 530 540 SGLGRAGTTA GASEIKREEK EDEEIASVAD AEEDKKDLKV PRTRTSSTDE VLSLEEKDLR 550 560 570 580 590 600 DRERRMANNA RERVRVRDIN EAFRELGRMC QLHLKSDKAQ TKLLILQQAV QVILGLEQQV 610 620 630 640 RERNLNPKAA CLKRREEEKV SGVVGDPQLA LSAAHPGLGE AHNPAGHL « Hide

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A new role for E12/E47 in the repression of E-cadherin expression and epithelial-mesenchymal transitions." Perez-Moreno M.A., Locascio A., Rodrigo I., Dhondt G., Portillo F., Nieto M.A., Cano A. J. Biol. Chem. 276:27424-27431(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM E47). Strain: NIH Swiss.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS E12 AND E47). Strain: C57BL/6J and NOD. Tissue: Hypothalamus and Spleen.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS E12 AND E47). Strain: FVB/N. Tissue: Mammary tumor and Salivary gland.
[4]	"A cDNA from a mouse pancreatic beta cell encoding a putative transcription factor of the insulin gene." Walker M.D., Park C.W., Rosen A., Aronheim A. Nucleic Acids Res. 18:1159-1166(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 369-651 (ISOFORM E47). Tissue: Pancreas.
[5]	"Identification of amino-acid polymorphism within the leucine zipper motif of mouse transcription factor A1." Kajimoto Y., Kawamori R., Umayahara Y., Watada H., Iwama N., Morishima T., Yamasaki Y., Kamada T. Gene 139:247-249(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 386-493, VARIANT GLN-387 INS. Tissue: Adipocyte.
[6]	"Ubiquitous, but variable, expression of two alternatively spliced mRNAs encoding mouse homologues of transcription factors E47 and E12." Watada H., Kajimoto Y., Umayahara Y., Matsuoka T., Morishima T., Yamasaki Y., Kawamori R., Kamada T. Gene 153:255-259(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 485-651 (ISOFORM E12). Strain: C57BL/6.
[7]	"Dermo-1: a novel twist-related bHLH protein expressed in the developing dermis." Li L., Cserjesi P., Olson E.N. Dev. Biol. 172:280-292(1995) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TWIST2. Strain: Swiss. Tissue: Brain and Embryonic head.
[8]	"The mUBC9 murine ubiquitin conjugating enzyme interacts with the E2A transcription factors." Loveys D.A., Streiff M.B., Schaefer T.S., Kato G.J. Gene 201:169-177(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH UBE2I.
[9]	"p48 subunit of mouse PTF1 binds to RBP-Jkappa/CBF-1, the intracellular mediator of Notch signalling, and is expressed in the neural tube of early stage embryos." Obata J., Yano M., Mimura H., Goto T., Nakayama R., Mibu Y., Oka C., Kawaichi M. Genes Cells 6:345-360(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PTF1A.
[10]	"Cloning and characterization of GRIPE, a novel interacting partner of the transcription factor E12 in developing mouse forebrain." Heng J.I.T., Tan S.-S. J. Biol. Chem. 277:43152-43159(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RALGAPA1.
[11]	"ETO2 coordinates cellular proliferation and differentiation during erythropoiesis." Goardon N., Lambert J.A., Rodriguez P., Nissaire P., Herblot S., Thibault P., Dumenil D., Strouboulis J., Romeo P.-H., Hoang T. EMBO J. 25:357-366(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A NUCLEAR TAL-1 COMPLEX.
[12]	"HIC-5 is a novel repressor of lymphoid enhancer factor/T-cell factor-driven transcription." Ghogomu S.M., van Venrooy S., Ritthaler M., Wedlich D., Gradl D. J. Biol. Chem. 281:1755-1764(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TGFB1I1.
[13]	"E protein dosage influences brain development more than family member identity." Ravanpay A.C., Olson J.M. J. Neurosci. Res. 86:1472-1481(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH NEUROD2, DNA-BINDING, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE.
[14]	"Crystal structure of E47-NeuroD1/beta2 bHLH domain-DNA complex: heterodimer selectivity and DNA recognition." Longo A., Guanga G.P., Rose R.B. Biochemistry 47:218-229(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 547-606 IN COMPLEX WITH NEUROD1 AND PROMOTER E-BOX DNA SEQUENCE, SUBUNIT.
+	Additional computationally mapped references.

EMBL
GenBank
DDBJ

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.

IPI

IPI00122714.
IPI00461050.

PIR

S08410.

RefSeq

NP_001157620.1. NM_001164148.1.
NP_001157621.1. NM_001164149.1.
NP_001157623.1. NM_001164151.1.
NP_035678.3. NM_011548.4.

UniGene

Mm.3406.

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2QL2	X-ray	2.50	A/C	547-606	[»]

ProteinModelPortal

P15806.

SMR

P15806. Positions 547-606.

ModBase

Search...

DIP

DIP-30940N.

IntAct

P15806. 11 interactions.

MINT

MINT-218641.

PhosphoSite

P15806.

PaxDb

P15806.

PRIDE

P15806.

StructuralBiologyKnowledgebase

Search...

Ensembl

ENSMUST00000020377; ENSMUSP00000020377; ENSMUSG00000020167.
ENSMUST00000020379; ENSMUSP00000020379; ENSMUSG00000020167.
ENSMUST00000105345; ENSMUSP00000100982; ENSMUSG00000020167.
ENSMUST00000105346; ENSMUSP00000100983; ENSMUSG00000020167.

GeneID

21423.

KEGG

mmu:21423.

UCSC

uc007gdf.2. mouse.
uc007gdg.2. mouse.

CTD

6929.

MGI

MGI:98510. Tcf3.

eggNOG

NOG282899.

GeneTree

ENSGT00510000046438.

HOVERGEN

HBG003854.

KO

K09063.

OrthoDB

EOG4HX50S.

Reactome

REACT_127416. Developmental Biology.

ArrayExpress

P15806.

Bgee

P15806.

CleanEx

MM_ME2.
MM_TCF3.
MM_TCFE2A.

Genevestigator

P15806.

GermOnline

ENSMUSG00000020167. Mus musculus.

Gene3D

4.10.280.10. 1 hit.

InterPro

IPR011598. bHLH_dom.
[Graphical view]

Pfam

PF00010. HLH. 1 hit.
[Graphical view]

SMART

SM00353. HLH. 1 hit.
[Graphical view]

SUPFAM

SSF47459. HLH_basic. 1 hit.

PROSITE

PS50888. BHLH. 1 hit.
[Graphical view]

ProtoNet

Search...

ChiTaRS

TCF3. mouse.

EvolutionaryTrace

P15806.

NextBio

300742.

SOURCE

Search...

Entry name

TFE2_MOUSE

Accession

Primary (citable) accession number: P15806
Secondary accession number(s): Q3U153

Q9CYJ4

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	August 16, 2004
Last modified:	May 1, 2013
This is version 135 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform E12 (identifier: P15806-1)

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.

Isoform E47 (identifier: P15806-2)

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

Note: Contains a phosphothreonine at position 528 (By similarity).