Reviewed, UniProtKB/Swiss-Prot P15923 (TFE2_HUMAN)

Names and origin

Protein names

Recommended name:
    Transcription factor E2-alpha
Alternative name(s):
    Immunoglobulin enhancer-binding factor E12/E47
    Transcription factor 3
      Short name=TCF-3
    Immunoglobulin transcription factor 1
    Transcription factor ITF-1
    Kappa-E2-binding factor

Gene names

Name:	TCF3
Synonyms:	E2A, ITF1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	654 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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.
Subunit structure	Efficient DNA binding requires dimerization with another bHLH protein. Forms a heterodimer with ASH1 and TWIST2. Isoform E12 interacts with GRIPE and FIGLA By similarity. Interacts with PTF1A and TGFB1I1. Component of a nuclear TAL-1 complex composed at least of CBFA2T3, LDB1, TAL1 and TCF3 By similarity. Interacts with UBE2I.
Subcellular location	Nucleus.
Post-translational modification	Phosphorylated following NGF stimulation By similarity.
Involvement in disease	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; Translocation t(17;19)(q22;p13.3) with HLF. Inversion inv(19)(p13;q13) with TFPT.
Sequence similarities	Contains 1 basic helix-loop-helix (bHLH) domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Disease	Proto-oncogene
Ligand	DNA-binding
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	B cell lineage commitment Non-traceable author statement. Source: UniProtKB positive regulation of transcription, DNA-dependent Ref.8 Inferred from direct assay. Source: UniProtKB transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Ref.5 Non-traceable author statement. Source: UniProtKB
Molecular function	bHLH transcription factor binding Inferred from physical interaction. Source: UniProtKB protein heterodimerization activity Ref.8 Non-traceable author statement. Source: UniProtKB protein homodimerization activity Inferred from direct assay. Source: UniProtKB transcription factor activity Ref.5 Ref.8 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		1	EBI-769645,EBI-769645
ASCL1	P50553	1	EBI-769630,EBI-957042
CCNDBP1	O95273	2	EBI-769645,EBI-748961
ID2	Q02363	2	EBI-769645,EBI-713450
MYOD1	P15172	2	EBI-769645,EBI-488878
Tcf3	P15806-2	1	EBI-769650,EBI-413585	From a different organism.
Ube2i	P63280	2	EBI-769645,EBI-80180	From a different organism.
Ube2i	P63280	1	EBI-769650,EBI-80180	From a different organism.

Alternative products

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

Isoform E12 (identifier: P15923-1)

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.

Isoform E47 (identifier: P15923-2)

Also known as: PAN-1;

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

Note: Phosphorylated on Thr-531.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 654

654

Transcription factor E2-alpha

PRO_0000127466

Regions

Domain

389 – 425

37

Leucine-zipper Potential

Domain

562 – 605

44

Helix-loop-helix motif

DNA binding

546 – 561

16

Basic motif

Motif

170 – 176

7

Nuclear localization signal Potential

Sites

Site

483 – 484

2

Breakpoint for translocation to form TCF3-PBX1 oncogene

Amino acid modifications

Modified residue

379

1

Phosphoserine Ref.15

Natural variations

Alternative sequence

530 – 601

72

PDEDE…SVILN → STDEVLSLEEKDLRDRERRM ANNARERVRVRDINEAFREL GRMCQMHLKSDKAQTKLLIL QQAVQVILG in isoform E47.

VSP_002155

Natural variant

8

1

A → V in a colorectal cancer sample; somatic mutation. Ref.17

VAR_036396

Natural variant

120

1

L → P: dbSNP rs35354874.

VAR_049552

Natural variant

198

1

T → A: dbSNP rs11879402.

VAR_049553

Natural variant

431

1

G → S: dbSNP rs1052692.

VAR_049554

Experimental info

Mutagenesis

550 – 551

2

RR → GG: No DNA-binding.

Mutagenesis

551

1

R → K: No DNA-binding.

Mutagenesis

561 – 563

3

RVR → GVG: No DNA-binding.

Mutagenesis

561

1

R → K: No DNA-binding.

Mutagenesis

563

1

R → K: No DNA-binding.

Mutagenesis

588

1

K → A: No DNA-binding and no dimerization.

Mutagenesis

591 – 592

2

IL → DE: No DNA-binding and no dimerization.

Mutagenesis

595

1

A → D: No change in DNA-binding or dimerization.

Sequence conflict

69 – 99

31

FDPSR…GPGLG → GGGECLAWCGPSAVHRCADV GLGMVSARTAP in CAA36297. Ref.6

Sequence conflict

214 – 216

3

FYV → EFR in AAA56830. Ref.5

Sequence conflict

390

1

Missing in AAA56830. Ref.5

Secondary structure

1

.

.

.

.

.

654

Helix Strand Turn

Details...

Helix

549 – 575

27

Helix

585 – 607

23

Sequences

	Sequence		Length	Mass (Da)
	Isoform E12 (PAN-2) [UniParc]. Last modified April 1, 1990. Version 1. Checksum: 52F5E3DE1890AE13	FASTA	654	67,600
	10 20 30 40 50 60 MNQPQRMAPV GTDKELSDLL DFSMMFPLPV TNGKGRPASL AGAQFGGSGL EDRPSSGSWG 70 80 90 100 110 120 SGDQSSSSFD PSRTFSEGTH FTESHSSLSS STFLGPGLGG KSGERGAYAS FGRDAGVGGL 130 140 150 160 170 180 TQAGFLSGEL ALNSPGPLSP SGMKGTSQYY PSYSGSSRRR AADGSLDTQP KKVRKVPPGL 190 200 210 220 230 240 PSSVYPPSSG EDYGRDATAY PSAKTPSSTY PAPFYVADGS LHPSAELWSP PGQAGFGPML 250 260 270 280 290 300 GGGSSPLPLP PGSGPVGSSG SSSTFGGLHQ HERMGYQLHG AEVNGGLPSA SSFSSAPGAT 310 320 330 340 350 360 YGGVSSHTPP VSGADSLLGS RGTTAGSSGD ALGKALASIY SPDHSSNNFS SSPSTPVGSP 370 380 390 400 410 420 QGLAGTSQWP RAGAPGALSP SYDGGLHGLQ SKIEDHLDEA IHVLRSHAVG TAGDMHTLLP 430 440 450 460 470 480 GHGALASGFT GPMSLGGRHA GLVGGSHPED GLAGSTSLMH NHAALPSQPG TLPDLSRPPD 490 500 510 520 530 540 SYSGLGRAGA TAAASEIKRE EKEDEENTSA ADHSEEEKKE LKAPRARTSP DEDEDDLLPP 550 560 570 580 590 600 EQKAEREKER RVANNARERL RVRDINEAFK ELGRMCQLHL NSEKPQTKLL ILHQAVSVIL 610 620 630 640 650 NLEQQVRERN LNPKAACLKR REEEKVSGVV GDPQMVLSAP HPGLSEAHNP AGHM
	Isoform E47 (PAN-1). Checksum: F5F11C462351FFD6	FASTA	651	67,265
	10 20 30 40 50 60 MNQPQRMAPV GTDKELSDLL DFSMMFPLPV TNGKGRPASL AGAQFGGSGL EDRPSSGSWG 70 80 90 100 110 120 SGDQSSSSFD PSRTFSEGTH FTESHSSLSS STFLGPGLGG KSGERGAYAS FGRDAGVGGL 130 140 150 160 170 180 TQAGFLSGEL ALNSPGPLSP SGMKGTSQYY PSYSGSSRRR AADGSLDTQP KKVRKVPPGL 190 200 210 220 230 240 PSSVYPPSSG EDYGRDATAY PSAKTPSSTY PAPFYVADGS LHPSAELWSP PGQAGFGPML 250 260 270 280 290 300 GGGSSPLPLP PGSGPVGSSG SSSTFGGLHQ HERMGYQLHG AEVNGGLPSA SSFSSAPGAT 310 320 330 340 350 360 YGGVSSHTPP VSGADSLLGS RGTTAGSSGD ALGKALASIY SPDHSSNNFS SSPSTPVGSP 370 380 390 400 410 420 QGLAGTSQWP RAGAPGALSP SYDGGLHGLQ SKIEDHLDEA IHVLRSHAVG TAGDMHTLLP 430 440 450 460 470 480 GHGALASGFT GPMSLGGRHA GLVGGSHPED GLAGSTSLMH NHAALPSQPG TLPDLSRPPD 490 500 510 520 530 540 SYSGLGRAGA TAAASEIKRE EKEDEENTSA ADHSEEEKKE LKAPRARTSS TDEVLSLEEK 550 560 570 580 590 600 DLRDRERRMA NNARERVRVR DINEAFRELG RMCQMHLKSD KAQTKLLILQ QAVQVILGLE 610 620 630 640 650 QQVRERNLNP KAACLKRREE EKVSGVVGDP QMVLSAPHPG LSEAHNPAGH M

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B ALL." Kamps M.P., Murre C., Sun X.-H., Baltimore D. Cell 60:547-555(1990) [PubMed: 1967983] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM E12), CHROMOSOMAL TRANSLOCATION WITH PBX1.
[2]	"Chromosomal translocation t(1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor." Nourse J., Mellentin J.D., Galili N., Wilkinson J., Stanbridge E., Smith S.D., Cleary M.L. Cell 60:535-545(1990) [PubMed: 1967982] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM E12).
[3]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed: 15057824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM E47).
[5]	"A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins." Murre C., McCaw P.S., Baltimore D. Cell 56:777-783(1989) [PubMed: 2493990] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 214-654 (ISOFORMS E12 AND E47), DOMAIN BHLH. Tissue: Lymphoma.
[6]	"Sequence of the cDNA encoding ITF-1, a positive-acting transcription factor." Henthorn P., McCarrick-Walmsley R., Kadesch T. Nucleic Acids Res. 18:677-677(1990) [PubMed: 2308859] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 69-654 (ISOFORM E47).
[7]	"Sequence of a HeLa cDNA provides the DNA binding domain and carboxy terminus of HE47: a human helix-loop-helix protein related to the enhancer binding factor E47." Zhang Y., Bina M. DNA Seq. 2:197-202(1991) [PubMed: 1818757] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 511-654 (ISOFORM E47).
[8]	"Two distinct transcription factors that bind the immunoglobulin enhancer microE5/kappa 2 motif." Henthorn P., Kiledjian M., Kadesch T. Science 247:467-470(1990) [PubMed: 2105528] [Abstract] Cited for: DISCUSSION OF SEQUENCE.
[9]	"Mutations that disrupt DNA binding and dimer formation in the E47 helix-loop-helix protein map to distinct domains." Voronova A., Baltimore D. Proc. Natl. Acad. Sci. U.S.A. 87:4722-4726(1990) [PubMed: 2112746] [Abstract] Cited for: MUTAGENESIS.
[10]	"The t(1;19)(q23;p13) results in consistent fusion of E2A and PBX1 coding sequences in acute lymphoblastic leukemias." Hunger S.P., Galili N., Carroll A.J., Crist W.M., Link M.P., Cleary M.L. Blood 77:687-693(1991) [PubMed: 1671560] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION WITH PBX1.
[11]	"Fusion of the leucine zipper gene HLF to the E2A gene in human acute B-lineage leukemia." Inaba T., Roberts W.M., Shapiro L.H., Jolly K.W., Raimondi S.C., Smith S.D., Look A.T. Science 257:531-534(1992) [PubMed: 1386162] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION WITH HLF.
[12]	"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: 9409784] [Abstract] Cited for: INTERACTION WITH UBE2I.
[13]	"Identification of a novel molecular partner of the E2A gene in childhood leukemia." Brambillasca F., Mosna G., Colombo M., Rivolta A., Caslini C., Minuzzo M., Giudici G., Mizzi L., Biondi A., Privitera E. Leukemia 13:369-375(1999) [PubMed: 10086727] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION WITH TFPT.
[14]	"Increased expression of the FIGLA transcription factor is associated with primordial follicle formation in the human fetal ovary." Bayne R.A.L., Martins da Silva S.J., Anderson R.A. Mol. Hum. Reprod. 10:373-381(2004) [PubMed: 15044608] [Abstract] Cited for: INTERACTION WITH FIGLA.
[15]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-379, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-531 (ISOFORM 2), MASS SPECTROMETRY.
[16]	"Proposed structure for the DNA-binding domain of the helix-loop-helix family of eukaryotic gene regulatory proteins." Gibson T.J., Thompson J.D., Abagyan R.A. Protein Eng. 6:41-50(1993) [PubMed: 8433970] [Abstract] Cited for: 3D-STRUCTURE MODELING OF 549-610.
[17]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-8.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

M31523 mRNA. Translation: AAA61146.1.
M31522 mRNA. Translation: AAA36764.1. Sequence problems.
M31222 mRNA. Translation: AAA52331.1. Different initiation.
AC006274 Genomic DNA. Translation: AAC99797.1.
AC005321 Genomic DNA. Translation: AAC27373.1.
BC110579 mRNA. Translation: AAI10580.1.
M24404 mRNA. Translation: AAA56829.1.
M24405 mRNA. Translation: AAA56830.1.
X52078 mRNA. Translation: CAA36297.1.
M65214 mRNA. Translation: AAC41693.1.

IPI

IPI00013929.
IPI00216911.

PIR

A34734.
S10099.

RefSeq

NP_001129611.1.
NP_003191.1.

UniGene

Hs.371282

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HLH	model	-	A/B	549-610	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:74N.

IntAct

P15923. 15 interactions.

PTM databases

PhosphoSite

P15923.

Proteomic databases

PRIDE

P15923.

Genome annotation databases

Ensembl

ENSG00000071564. Homo sapiens. [Contig view]

GeneID

6929.

Organism-specific databases

GeneCards

GC19M001560.

H-InvDB

HIX0014593.

HGNC

HGNC:11633. TCF3.

HPA

CAB018351.

MIM

147141. gene.

Orphanet

513. Leukemia, lymphoblastic, acute.

PharmGKB

PA36388.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P15923.

HOVERGEN

P15923.

OMA

P15923. DRERRMA.

Enzyme and pathway databases

Pathway_Interaction_DB

wnt_canonical_pathway. Canonical Wnt signaling pathway.
p38_mk2pathway. p38 signaling mediated by MAPKAP kinases.
smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.

Gene expression databases

ArrayExpress

P15923.

Bgee

P15923.

CleanEx

HS_TCF3.

GermOnline

ENSG00000071564. Homo sapiens.

Family and domain databases

InterPro

IPR001092. HLH_basic.
IPR011598. HLH_DNA_bd.
[Graphical view]

Gene3D

G3DSA:4.10.280.10. HLH_DNA_bd. 1 hit.

Pfam

PF00010. HLH. 1 hit.
[Graphical view]

SMART

SM00353. HLH. 1 hit.
[Graphical view]

PROSITE

PS50888. HLH. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

27113.

SOURCE

Search...

Entry information

Entry name

TFE2_HUMAN

Accession

Primary (citable) accession number: P15923
Secondary accession number(s): P15883 , Q14208, Q14635, Q14636, Q2TB40, Q9UPI9

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	April 1, 1990
Last modified:	June 16, 2009
This is version 116 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)