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P15806 (TFE2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length651 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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.14

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. 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. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15

Subcellular location

Nucleus.

Developmental stage

Expressed during the development of the nervous system. Ref.14

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.14

Sequence similarities

Contains 1 bHLH (basic helix-loop-helix) domain.

Ontologies

Keywords
   Biological processDifferentiation
Neurogenesis
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandDNA-binding
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell lineage commitment

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

lymphocyte differentiation

Inferred from mutant phenotype PubMed 18958875. 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 gene expression

Inferred from mutant phenotype PubMed 18958875. Source: MGI

positive regulation of neuron differentiation

Inferred from direct assay Ref.14. 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-templated

Inferred from direct assay PubMed 11812799. Source: BHF-UCL

protein stabilization

Inferred from direct assay PubMed 15322112. Source: MGI

regulation of G1/S transition of mitotic cell cycle

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 19796622. Source: MGI

regulation of transcription, DNA-templated

Inferred from direct assay Ref.11PubMed 15351717PubMed 15520228. 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-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

nuclear nucleosome

Inferred from direct assay PubMed 16428437. Source: MGI

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.11PubMed 14573534PubMed 15322112PubMed 19011221PubMed 19796622. Source: MGI

protein complex

Inferred from sequence or structural similarity. Source: UniProtKB

transcription factor complex

Inferred from direct assay PubMed 11812799. Source: BHF-UCL

   Molecular_functionDNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

E-box binding

Inferred from direct assay Ref.14. Source: UniProtKB

chromatin binding

Inferred from direct assay PubMed 18550854PubMed 19011221. Source: MGI

protein heterodimerization activity

Inferred from direct assay Ref.14. Source: UniProtKB

protein homodimerization activity

Inferred from sequence or structural similarity. Source: UniProtKB

sequence-specific DNA binding

Inferred from direct assay PubMed 16428437PubMed 17938243PubMed 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 physical interaction PubMed 9545521. Source: UniProtKB

Complete GO annotation...

Binary interactions

Alternative products

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).

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 651651Transcription factor E2-alpha
PRO_0000127468

Regions

Domain546 – 59954bHLH
Region387 – 42236Leucine-zipper

Amino acid modifications

Modified residue1351Phosphoserine By similarity
Modified residue1401Phosphoserine By similarity
Modified residue3571Phosphoserine By similarity

Natural variations

Alternative sequence527 – 59872PDEDE…AVILS → STDEVLSLEEKDLRDRERRM ANNARERVRVRDINEAFREL GRMCQLHLKSDKAQTKLLIL QQAVQVILG in isoform E47.
VSP_011354
Natural variant3871L → LQ. Ref.5

Experimental info

Sequence conflict1561S → N in AAK18618. Ref.1
Sequence conflict1641D → N in AAK18618. Ref.1
Sequence conflict1671L → LA in AAH18260. Ref.3
Sequence conflict2941P → T in BAB30842. Ref.2
Sequence conflict6331A → P in AAH06860. Ref.3

Secondary structure

..... 651
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform E12 [UniParc].

Last modified August 16, 2004. Version 2.
Checksum: 7904ABB37B8D39CB

FASTA65167,701
        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 »

FASTA64867,417

References

« Hide '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. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai 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]"Analysis of the DNA-binding properties of MyoD, myogenin, and E12 by fluorescence anisotropy."
Maleki S.J., Royer C.A., Hurlburt B.K.
Biochemistry 41:10888-10894(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[11]"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.
[12]"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.
[13]"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.
[14]"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.
[15]"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.

Cross-references

Sequence databases

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.
PIRS08410.
RefSeqNP_001157620.1. NM_001164148.1.
NP_001157621.1. NM_001164149.1.
NP_001157623.1. NM_001164151.1.
NP_035678.3. NM_011548.4.
UniGeneMm.3406.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2QL2X-ray2.50A/C547-606[»]
ProteinModelPortalP15806.
SMRP15806. Positions 547-606.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204015. 99 interactions.
DIPDIP-30940N.
IntActP15806. 13 interactions.
MINTMINT-218641.

PTM databases

PhosphoSiteP15806.

Proteomic databases

PaxDbP15806.
PRIDEP15806.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000020377; ENSMUSP00000020377; ENSMUSG00000020167.
ENSMUST00000020379; ENSMUSP00000020379; ENSMUSG00000020167.
ENSMUST00000105345; ENSMUSP00000100982; ENSMUSG00000020167. [P15806-2]
ENSMUST00000105346; ENSMUSP00000100983; ENSMUSG00000020167. [P15806-1]
GeneID21423.
KEGGmmu:21423.
UCSCuc007gdg.2. mouse. [P15806-2]
uc007gdi.2. mouse. [P15806-1]

Organism-specific databases

CTD6929.
MGIMGI:98510. Tcf3.

Phylogenomic databases

eggNOGNOG282899.
GeneTreeENSGT00510000046438.
HOVERGENHBG003854.
KOK09063.
PhylomeDBP15806.

Enzyme and pathway databases

ReactomeREACT_188576. Developmental Biology.

Gene expression databases

ArrayExpressP15806.
BgeeP15806.
CleanExMM_ME2.
MM_TCF3.
MM_TCFE2A.
GenevestigatorP15806.

Family and domain databases

Gene3D4.10.280.10. 1 hit.
InterProIPR011598. bHLH_dom.
[Graphical view]
PfamPF00010. HLH. 1 hit.
[Graphical view]
SMARTSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMSSF47459. SSF47459. 1 hit.
PROSITEPS50888. BHLH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTCF3. mouse.
EvolutionaryTraceP15806.
NextBio300742.
PROP15806.
SOURCESearch...

Entry information

Entry nameTFE2_MOUSE
AccessionPrimary (citable) accession number: P15806
Secondary accession number(s): Q3U153 expand/collapse secondary AC list , Q8CAH9, Q8VCY4, Q922S2, Q99MB8, Q9CYJ4
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: August 16, 2004
Last modified: April 16, 2014
This is version 144 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

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