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UniProtKB - P15923 (TFE2_HUMAN)

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Protein

Transcription factor E2-alpha

Gene

TCF3

Organism
Homo sapiens (Human)
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.By similarity

GO - Molecular functioni

  • bHLH transcription factor binding Source: BHF-UCL
  • DNA binding Source: UniProtKB
  • DNA binding transcription factor activity Source: BHF-UCL
  • E-box binding Source: UniProtKB
  • enhancer binding Source: BHF-UCL
  • mitogen-activated protein kinase kinase kinase binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • repressing transcription factor binding Source: UniProtKB
  • RNA polymerase II proximal promoter sequence-specific DNA binding Source: NTNU_SB
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: NTNU_SB
  • transcriptional repressor activity, RNA polymerase II proximal promoter sequence-specific DNA binding Source: NTNU_SB
  • transcription coactivator activity Source: UniProtKB
  • transcription factor binding Source: BHF-UCL
  • vitamin D response element binding Source: BHF-UCL
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • B cell differentiation Source: UniProtKB
  • B cell lineage commitment Source: UniProtKB
  • immunoglobulin V(D)J recombination Source: MGI
  • negative regulation of transcription by RNA polymerase II Source: NTNU_SB
  • 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 muscle cell differentiation Source: Reactome
  • 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
  • regulation of G1/S transition of mitotic cell cycle Source: UniProtKB
  • regulation of hematopoietic stem cell differentiation Source: Reactome
  • regulation of transcription, DNA-templated Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB
View the complete GO annotation on QuickGO ...

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-375170 CDO in myogenesis
R-HSA-8939236 RUNX1 regulates transcription of genes involved in differentiation of HSCs
SignaLinkiP15923
SIGNORiP15923

Names & Taxonomyi

Protein namesi
Recommended name:
Transcription factor E2-alpha
Alternative name(s):
Class B basic helix-loop-helix protein 21
Short name:
bHLHb21
Immunoglobulin enhancer-binding factor E12/E47
Immunoglobulin transcription factor 1
Kappa-E2-binding factor
Transcription factor 3
Short name:
TCF-3
Transcription factor ITF-1
Gene namesi
Name:TCF3
Synonyms:BHLHB21, E2A, ITF1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000071564.14
HGNCiHGNC:11633 TCF3
MIMi147141 gene
neXtProtiNX_P15923

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

Involvement in diseasei

Chromosomal aberrations involving TCF3 are cause of forms of pre-B-cell acute lymphoblastic leukemia (B-ALL). Translocation t(1;19)(q23;p13.3) with PBX1. TCF3-PBX1 transforms cells by constitutively activating transcription of genes regulated by PBX1 or by other members of the PBX protein family (PubMed:1967983, PubMed:1671560). Translocation t(17;19)(q22;p13.3) with HLF (PubMed:1386162). Inversion inv(19)(p13;q13) with TFPT (PubMed:10086727).4 Publications
Agammaglobulinemia 8, autosomal dominant (AGM8)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of agammaglobulinemia, a primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B-cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life.
See also OMIM:616941
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Isoform E47 (identifier: P15923-2)
Natural varianti555E → K in AGM8, localizes normally to the nucleus, does not perform proper DNA binding, acts in a dominant-negative manner when coexpressed with wild-type) (Ref.29. Combined sources1 Publication1

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei483 – 484Breakpoint for translocation to form TCF3-PBX1 oncogene2

Keywords - Diseasei

Disease mutation, Proto-oncogene

Organism-specific databases

DisGeNETi6929
MalaCardsiTCF3
MIMi616941 phenotype
OpenTargetsiENSG00000071564
Orphaneti33110 Autosomal agammaglobulinemia
99860 Precursor B-cell acute lymphoblastic leukemia
PharmGKBiPA164742580

Polymorphism and mutation databases

BioMutaiTCF3
DMDMi135655

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001274661 – 654Transcription factor E2-alphaAdd BLAST654

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei134PhosphoserineCombined sources1
Modified residuei139PhosphoserineCombined sources1
Modified residuei355PhosphothreonineBy similarity1
Modified residuei359PhosphoserineCombined sources1
Modified residuei371Omega-N-methylarginineBy similarity1
Modified residuei379PhosphoserineCombined sources1
Cross-linki498Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei529PhosphoserineCombined sources1
Cross-linki625Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Isoform E47 (identifier: P15923-2)
Modified residuei531PhosphothreonineCombined sources1 Publication1

Post-translational modificationi

Phosphorylated following NGF stimulation.By similarity

Keywords - PTMi

Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP15923
MaxQBiP15923
PaxDbiP15923
PeptideAtlasiP15923
PRIDEiP15923
ProteomicsDBi53242
53243 [P15923-2]

PTM databases

iPTMnetiP15923
PhosphoSitePlusiP15923

Expressioni

Gene expression databases

BgeeiENSG00000071564
CleanExiHS_TCF3
ExpressionAtlasiP15923 baseline and differential
GenevisibleiP15923 HS

Organism-specific databases

HPAiCAB018351
HPA049808
HPA062476

Interactioni

Subunit structurei

Forms a heterodimer with ASH1 and TWIST2. Isoform E12 interacts with RALGAPA1 and FIGLA. Efficient DNA binding requires dimerization with another bHLH protein. Component of a nuclear TAL-1 complex composed at least of CBFA2T3, LDB1, TAL1 and TCF3. Interacts with NEUROD2, PTF1A and TGFB1I1. Forms a heterodimer with MYOG; heterodimerization enhances MYOG DNA-binding and transcriptional activities (By similarity). Homodimer. Heterodimer. Forms a heterodimer with NEUROD1; the heterodimer is inhibited in presence of ID2, but not NR0B2, to E-box element. Interacts with EP300 and UBE2I. Interacts with BHLHA9 (PubMed:25466284). Forms a heterodimer with ATOH8; repress transcription of TCF3 and TCF3/NEUROG3 dimer-induced transactivation of E box-dependent promoters (By similarity).By similarity4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • bHLH transcription factor binding Source: BHF-UCL
  • mitogen-activated protein kinase kinase kinase binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • repressing transcription factor binding Source: UniProtKB
  • transcription factor binding Source: BHF-UCL
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi112791, 159 interactors
CORUMiP15923
DIPiDIP-74N
IntActiP15923, 31 interactors
MINTiP15923
STRINGi9606.ENSP00000262965

Structurei

Secondary structure

1654
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi12 – 25Combined sources14
Helixi563 – 580Combined sources18
Helixi588 – 608Combined sources21

3D structure databases

ProteinModelPortaliP15923
SMRiP15923
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini549 – 602bHLHPROSITE-ProRule annotationAdd BLAST54

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni389 – 425Leucine-zipperAdd BLAST37

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi19 – 279aaTAD9
Motifi170 – 176Nuclear localization signalSequence analysis7

Domaini

the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.2 Publications

Phylogenomic databases

eggNOGiKOG3910 Eukaryota
ENOG410XYUA LUCA
GeneTreeiENSGT00510000046438
HOGENOMiHOG000234180
HOVERGENiHBG003854
InParanoidiP15923
KOiK09063
OMAiKGGSQYY
PhylomeDBiP15923
TreeFamiTF321672

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 (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform E12 (identifier: P15923-1) [UniParc]FASTAAdd to basket
Also known as: PAN-2

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
MNQPQRMAPV GTDKELSDLL DFSMMFPLPV TNGKGRPASL AGAQFGGSGL 
        60         70         80         90        100
EDRPSSGSWG SGDQSSSSFD PSRTFSEGTH FTESHSSLSS STFLGPGLGG 
       110        120        130        140        150
KSGERGAYAS FGRDAGVGGL TQAGFLSGEL ALNSPGPLSP SGMKGTSQYY 
       160        170        180        190        200
PSYSGSSRRR AADGSLDTQP KKVRKVPPGL PSSVYPPSSG EDYGRDATAY 
       210        220        230        240        250
PSAKTPSSTY PAPFYVADGS LHPSAELWSP PGQAGFGPML GGGSSPLPLP 
       260        270        280        290        300
PGSGPVGSSG SSSTFGGLHQ HERMGYQLHG AEVNGGLPSA SSFSSAPGAT 
       310        320        330        340        350
YGGVSSHTPP VSGADSLLGS RGTTAGSSGD ALGKALASIY SPDHSSNNFS 
       360        370        380        390        400
SSPSTPVGSP QGLAGTSQWP RAGAPGALSP SYDGGLHGLQ SKIEDHLDEA 
       410        420        430        440        450
IHVLRSHAVG TAGDMHTLLP GHGALASGFT GPMSLGGRHA GLVGGSHPED 
       460        470        480        490        500
GLAGSTSLMH NHAALPSQPG TLPDLSRPPD SYSGLGRAGA TAAASEIKRE 
       510        520        530        540        550
EKEDEENTSA ADHSEEEKKE LKAPRARTSP DEDEDDLLPP EQKAEREKER 
       560        570        580        590        600
RVANNARERL RVRDINEAFK ELGRMCQLHL NSEKPQTKLL ILHQAVSVIL 
       610        620        630        640        650
NLEQQVRERN LNPKAACLKR REEEKVSGVV GDPQMVLSAP HPGLSEAHNP 

AGHM
Length:654
Mass (Da):67,600
Last modified:April 1, 1990 - v1
Checksum:i52F5E3DE1890AE13
GO
Isoform E47 (identifier: P15923-2) [UniParc]FASTAAdd to basket
Also known as: PAN-1

The sequence of this isoform differs from the canonical sequence as follows:
     530-601: PDEDEDDLLP...LHQAVSVILN → STDEVLSLEE...LQQAVQVILG

Note: The bHLH domain encompassing amino acids 546 to 599 is sufficient to mediate DNA-binding and homodimerization. Combined mutagenesis of Phe-566 and Leu-569 to Asp-566 and Glu-569, mutagenesis of Lys-585 to Ala-585 or combined mutagenesis of Ile-588 and Leu-589 to Asp-588 and Glu-589 prevents DNA-binding and homodimerization. Mutagenesis of Arg-548 to Lys-548, combined mutagenesis of Arg-547 and Arg-548 to Gly-547 and Gly-548, mutagenesis of Arg-556 to Lys-556, mutagenesis of Arg-558 to Lys-558, or combined mutagenesis of Arg-556 and Arg-558 to Gly-556 and Gly-558, alter DNA-binding but not dimerization.Combined sources1 Publication
Show »
Length:651
Mass (Da):67,265
Checksum:iF5F11C462351FFD6
GO
Isoform 3 (identifier: P15923-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     49-99: Missing.
     528-528: T → TRCQPTPRHSPPSPHQDAHVHRPHAHRTHTGRPSAGPTLFPQPHCLPLAPSRRPPH

Note: No experimental confirmation available.
Show »
Length:658
Mass (Da):68,510
Checksum:i3CAD1F1EB5AD39EA
GO

Sequence cautioni

The sequence AAA52331 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti69 – 99FDPSR…GPGLG → GGGECLAWCGPSAVHRCADV GLGMVSARTAP in CAA36297 (PubMed:2308859).CuratedAdd BLAST31
Sequence conflicti214 – 216FYV → EFR in AAA56830 (PubMed:2493990).Curated3
Sequence conflicti302Missing in AAA36764 (PubMed:1967983).Curated1
Sequence conflicti390Missing in AAA56830 (PubMed:2493990).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0363968A → V in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs376780559Ensembl.1
Natural variantiVAR_049552120L → P. Corresponds to variant dbSNP:rs35354874Ensembl.1
Natural variantiVAR_049553198T → A. Corresponds to variant dbSNP:rs11879402Ensembl.1
Natural variantiVAR_049554431G → S. Corresponds to variant dbSNP:rs1052692Ensembl.1
Isoform E47 (identifier: P15923-2)
Natural varianti555E → K in AGM8, localizes normally to the nucleus, does not perform proper DNA binding, acts in a dominant-negative manner when coexpressed with wild-type) (Ref.29. Combined sources1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05727749 – 99Missing in isoform 3. 1 PublicationAdd BLAST51
Alternative sequenceiVSP_057278528T → TRCQPTPRHSPPSPHQDAHV HRPHAHRTHTGRPSAGPTLF PQPHCLPLAPSRRPPH in isoform 3. 1 Publication1
Alternative sequenceiVSP_002155530 – 601PDEDE…SVILN → STDEVLSLEEKDLRDRERRM ANNARERVRVRDINEAFREL GRMCQMHLKSDKAQTKLLIL QQAVQVILG in isoform E47. 4 PublicationsAdd BLAST72

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M31523 mRNA Translation: AAA61146.1
M31522 mRNA Translation: AAA36764.1 Different termination.
M31222 mRNA Translation: AAA52331.1 Different initiation.
AC006274 Genomic DNA Translation: AAC99797.1
AC005321 Genomic DNA Translation: AAC27373.1
KC877695 Genomic DNA No translation available.
BC110579 mRNA Translation: AAI10580.1
BC110580 mRNA Translation: AAI10581.1
M24404 mRNA Translation: AAA56829.1
M24405 mRNA Translation: AAA56830.1
X52078 mRNA Translation: CAA36297.1
M65214 mRNA Translation: AAC41693.1
CCDSiCCDS12074.1 [P15923-1]
CCDS45899.1 [P15923-2]
PIRiA34734
S10099
RefSeqiNP_001129611.1, NM_001136139.2 [P15923-2]
NP_003191.1, NM_003200.3 [P15923-1]
XP_016882669.1, XM_017027180.1 [P15923-3]
XP_016882670.1, XM_017027181.1 [P15923-1]
XP_016882671.1, XM_017027182.1 [P15923-2]
UniGeneiHs.371282
Hs.657044

Genome annotation databases

EnsembliENST00000262965; ENSP00000262965; ENSG00000071564 [P15923-1]
ENST00000395423; ENSP00000378813; ENSG00000071564 [P15923-3]
ENST00000588136; ENSP00000468487; ENSG00000071564 [P15923-2]
ENST00000611869; ENSP00000480564; ENSG00000071564 [P15923-1]
GeneIDi6929
KEGGihsa:6929
UCSCiuc002ltr.3 human [P15923-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTFE2_HUMAN
AccessioniPrimary (citable) accession number: P15923
Secondary accession number(s): P15883
, Q14208, Q14635, Q14636, Q2TB39, Q2TB40, Q9UPI9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: July 18, 2018
This is version 215 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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