TCF3

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
Inferred from physical interactionⁱ
- 10749989
DNA binding
Source: UniProtKB
Inferred from direct assayⁱ
- 10958665
- 8759016
DNA-binding transcription factor activity
Source: BHF-UCL
Inferred from direct assayⁱ
- 11802795
- 15509787
E-box binding
Source: UniProtKB
Inferred from direct assayⁱ
- 7933101
enhancer binding
Source: BHF-UCL
Inferred by curatorⁱ
- 21828274
mitogen-activated protein kinase kinase kinase binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 19801649
protein heterodimerization activity
Source: UniProtKB
Inferred from direct assayⁱ
- 10775504
- 14752053
protein homodimerization activity
Source: UniProtKB
Inferred from direct assayⁱ
repressing transcription factor binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 12493738
RNA polymerase II proximal promoter sequence-specific DNA binding
Source: NTNU_SB
Inferred from direct assayⁱ
- 14576336
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
Inferred from direct assayⁱ
- 14576336
transcription coactivator activity
Source: UniProtKB
Inferred from direct assayⁱ
- 14752053
transcription factor binding
Source: BHF-UCL
Inferred from physical interactionⁱ
- 21828274
vitamin D response element binding
Source: BHF-UCL
Inferred from direct assayⁱ
- 17426122

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

B cell differentiation
Source: UniProtKB
Non-traceable author statementⁱ
- 12435739
B cell lineage commitment
Source: UniProtKB
Inferred from direct assayⁱ
- 15030778
immunoglobulin V(D)J recombination
Source: MGI
Inferred from direct assayⁱ
- 16428437
negative regulation of transcription by RNA polymerase II
Source: NTNU_SB
Inferred from direct assayⁱ
- 14576336
positive regulation of B cell proliferation
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 11509675
positive regulation of cell cycle
Source: UniProtKB
Inferred from direct assayⁱ
- 11509675
positive regulation of DNA-binding transcription factor activity
Source: UniProtKB
Inferred from direct assayⁱ
- 14752053
positive regulation of muscle cell differentiation Source: Reactome
positive regulation of neuron differentiation Source: UniProtKB
positive regulation of transcription, DNA-templated
Source: BHF-UCL
Inferred from direct assayⁱ
- 15509787
positive regulation of transcription by RNA polymerase II
Source: BHF-UCL
Inferred from direct assayⁱ
- 16043483
regulation of G1/S transition of mitotic cell cycle
Source: UniProtKB
Inferred from direct assayⁱ
- 11509675
regulation of hematopoietic stem cell differentiation Source: Reactome
regulation of transcription, DNA-templated
Source: UniProtKB
Non-traceable author statementⁱ
- 2493990
transcription, DNA-templated
Source: UniProtKB
Inferred from direct assayⁱ
- 10775504

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	DNA-binding
Biological process	Differentiation, Neurogenesis, Transcription, Transcription regulation

Enzyme and pathway databases

Reactomeⁱ	R-HSA-375170 CDO in myogenesis R-HSA-8939236 RUNX1 regulates transcription of genes involved in differentiation of HSCs
SignaLinkⁱ	P15923
SIGNORⁱ	P15923

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
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 19

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000071564.14
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:11633 TCF3
MIMⁱ	147141 gene
neXtProtⁱ	NX_P15923

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.

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Isoform E47 (identifier: P15923-2)
Natural variantⁱ	555	E → 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 Publication		1

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Siteⁱ	483 – 484	Breakpoint for translocation to form TCF3-PBX1 oncogene		2

Keywords - Diseaseⁱ

Disease mutation, Proto-oncogene

Organism-specific databases

DisGeNET More...DisGeNETⁱ	6929
MalaCards human disease database More...MalaCardsⁱ	TCF3
MIMⁱ	616941 phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000071564
Orphanetⁱ	33110 Autosomal agammaglobulinemia 99860 Precursor B-cell acute lymphoblastic leukemia
PharmGKBⁱ	PA164742580

Polymorphism and mutation databases

BioMutaⁱ	TCF3
DMDMⁱ	135655

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000127466	1 – 654	Transcription factor E2-alphaAdd BLAST		654

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	134	PhosphoserineCombined sources	1
Modified residueⁱ	139	PhosphoserineCombined sources	1
Modified residueⁱ	355	PhosphothreonineBy similarity	1
Modified residueⁱ	359	PhosphoserineCombined sources	1
Modified residueⁱ	371	Omega-N-methylarginineBy similarity	1
Modified residueⁱ	379	PhosphoserineCombined sources	1
Cross-linkⁱ	498	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residueⁱ	529	PhosphoserineCombined sources	1
Cross-linkⁱ	625	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Isoform E47 (identifier: P15923-2)
Modified residueⁱ	531	PhosphothreonineCombined sources1 Publication	1

Post-translational modificationⁱ

Phosphorylated following NGF stimulation.By similarity

Keywords - PTMⁱ

Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDⁱ	P15923
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	P15923
PaxDbⁱ	P15923
PeptideAtlas More...PeptideAtlasⁱ	P15923
PRIDEⁱ	P15923
ProteomicsDBⁱ	53242 53243 [P15923-2]

PTM databases

iPTMnetⁱ	P15923
PhosphoSitePlusⁱ	P15923

Expressionⁱ

Gene expression databases

Bgeeⁱ	ENSG00000071564 Expressed in 232 organ(s), highest expression level in testis
CleanExⁱ	HS_TCF3
ExpressionAtlasⁱ	P15923 baseline and differential
Genevisibleⁱ	P15923 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	CAB018351 HPA049808 HPA062476

HPAⁱ

CAB018351
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

With	Entry	#Exp.	IntAct
ASCL1	P50553	3	EBI-769630,EBI-957042
CCNDBP1	O95273	3	EBI-769645,EBI-748961
FOXH1	O75593	2	EBI-769630,EBI-1759806
ID2	Q02363	3	EBI-769645,EBI-713450
ID3	Q02535	3	EBI-769630,EBI-1387094
MYOD1	P15172	2	EBI-769645,EBI-488878
PSMD9	O00233	2	EBI-769645,EBI-750973
TAL1	P17542	7	EBI-769630,EBI-1753878
TCAF1	Q9Y4C2	3	EBI-769630,EBI-750484

GO - Molecular functionⁱ

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	112791, 159 interactors
CORUMⁱ	P15923
Database of interacting proteins More...DIPⁱ	DIP-74N
IntActⁱ	P15923, 31 interactors
Molecular INTeraction database More...MINTⁱ	P15923
STRINGⁱ	9606.ENSP00000262965

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Helixⁱ	12 – 25	Combined sources	14
Helixⁱ	563 – 580	Combined sources	18
Helixⁱ	588 – 608	Combined sources	21

Show more details

3D structure databases

ProteinModelPortalⁱ	P15923
SMRⁱ	P15923
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	549 – 602	bHLHPROSITE-ProRule annotationAdd BLAST		54

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	389 – 425	Leucine-zipperAdd BLAST		37

Motif

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Motifⁱ	19 – 27	9aaTAD		9
Motifⁱ	170 – 176	Nuclear localization signalSequence analysis		7

Domainⁱ

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

Phylogenomic databases

eggNOGⁱ	KOG3910 Eukaryota ENOG410XYUA LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00510000046438
HOGENOMⁱ	HOG000234180
HOVERGENⁱ	HBG003854
InParanoidⁱ	P15923
KEGG Orthology (KO) More...KOⁱ	K09063
OMAⁱ	KGGSQYY
PhylomeDBⁱ	P15923
TreeFamⁱ	TF321672

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd00083 HLH, 1 hit
Gene3Dⁱ	4.10.280.10, 1 hit
InterProⁱ	View protein in InterPro IPR011598 bHLH_dom IPR036638 HLH_DNA-bd_sf
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00010 HLH, 1 hit
SMARTⁱ	View protein in SMART SM00353 HLH, 1 hit
SUPFAMⁱ	SSF47459 SSF47459, 1 hit
PROSITEⁱ	View protein in PROSITE PS50888 BHLH, 1 hit

Sequences (3+)ⁱ

Sequence statusⁱ: Complete.

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

This entry has 3 described isoforms and 13 potential isoforms that are computationally mapped.Show all Align All

Isoform E12 (identifier: P15923-1) [UniParc]FASTA Add 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]FASTA Add 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

« 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 LKAPRARTSS TDEVLSLEEK DLRDRERRMA 
       560        570        580        590        600
NNARERVRVR DINEAFRELG RMCQMHLKSD KAQTKLLILQ QAVQVILGLE 
       610        620        630        640        650
QQVRERNLNP KAACLKRREE EKVSGVVGDP QMVLSAPHPG LSEAHNPAGH 

M

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]FASTA Add to basket

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

« Hide

        10         20         30         40         50
MNQPQRMAPV GTDKELSDLL DFSMMFPLPV TNGKGRPASL AGAQFGGSGK 
        60         70         80         90        100
SGERGAYASF GRDAGVGGLT QAGFLSGELA LNSPGPLSPS GMKGTSQYYP 
       110        120        130        140        150
SYSGSSRRRA ADGSLDTQPK KVRKVPPGLP SSVYPPSSGE DYGRDATAYP 
       160        170        180        190        200
SAKTPSSTYP APFYVADGSL HPSAELWSPP GQAGFGPMLG GGSSPLPLPP 
       210        220        230        240        250
GSGPVGSSGS SSTFGGLHQH ERMGYQLHGA EVNGGLPSAS SFSSAPGATY 
       260        270        280        290        300
GGVSSHTPPV SGADSLLGSR GTTAGSSGDA LGKALASIYS PDHSSNNFSS 
       310        320        330        340        350
SPSTPVGSPQ GLAGTSQWPR AGAPGALSPS YDGGLHGLQS KIEDHLDEAI 
       360        370        380        390        400
HVLRSHAVGT AGDMHTLLPG HGALASGFTG PMSLGGRHAG LVGGSHPEDG 
       410        420        430        440        450
LAGSTSLMHN HAALPSQPGT LPDLSRPPDS YSGLGRAGAT AAASEIKREE 
       460        470        480        490        500
KEDEENTSAA DHSEEEKKEL KAPRARTRCQ PTPRHSPPSP HQDAHVHRPH 
       510        520        530        540        550
AHRTHTGRPS AGPTLFPQPH CLPLAPSRRP PHSPDEDEDD LLPPEQKAER 
       560        570        580        590        600
EKERRVANNA RERLRVRDIN EAFKELGRMC QLHLNSEKPQ TKLLILHQAV 
       610        620        630        640        650
SVILNLEQQV RERNLNPKAA CLKRREEEKV SGVVGDPQMV LSAPHPGLSE 

AHNPAGHM

Note: No experimental confirmation available.

Show »

Length:658

Mass (Da):68,510

Checksum:ⁱ3CAD1F1EB5AD39EA

GO

Computationally mapped potential isoform sequencesⁱ

There are 13 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

	Entry	Entry name	Protein names	Gene names	Length	Annotation

	K7ELF3	K7ELF3_HUMAN	Transcription factor E2-alpha Transcription factor E2-alpha	TCF3	213	Annotation score:
	X6REB3	X6REB3_HUMAN	Transcription factor E2-alpha Transcription factor E2-alpha	TCF3	679	Annotation score:
	A0A0A0MRB7	A0A0A0MRB7_HUMAN	Transcription factor E2-alpha Transcription factor E2-alpha	TCF3	600	Annotation score:
	K7EKB9	K7EKB9_HUMAN	Transcription factor E2-alpha Transcription factor E2-alpha	TCF3	179	Annotation score:
	K7ERZ7	K7ERZ7_HUMAN	Transcription factor E2-alpha Transcription factor E2-alpha	TCF3	204	Annotation score:
	K7EMM4	K7EMM4_HUMAN	Transcription factor E2-alpha Transcription factor E2-alpha	TCF3	220	Annotation score:
	K7EPS2	K7EPS2_HUMAN	Transcription factor E2-alpha Transcription factor E2-alpha	TCF3	165	Annotation score:
	A0A0A0MTS0	A0A0A0MTS0_HUMAN	Transcription factor E2-alpha Transcription factor E2-alpha	TCF3	159	Annotation score:
	K7ENH8	K7ENH8_HUMAN	Transcription factor E2-alpha Transcription factor E2-alpha	TCF3	314	Annotation score:
	K7EK65	K7EK65_HUMAN	Transcription factor E2-alpha Transcription factor E2-alpha	TCF3	82	Annotation score:
There are more potential isoformsShow all

Sequence cautionⁱ

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

Experimental Info

Feature key	Position(s)	DescriptionActions	Length
Sequence conflictⁱ	69 – 99	FDPSR…GPGLG → GGGECLAWCGPSAVHRCADV GLGMVSARTAP in CAA36297 (PubMed:2308859).CuratedAdd BLAST	31
Sequence conflictⁱ	214 – 216	FYV → EFR in AAA56830 (PubMed:2493990).Curated	3
Sequence conflictⁱ	302	Missing in AAA36764 (PubMed:1967983).Curated	1
Sequence conflictⁱ	390	Missing in AAA56830 (PubMed:2493990).Curated	1

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_036396	8	A → V in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs376780559Ensembl.	1
Natural variantⁱVAR_049552	120	L → P. Corresponds to variant dbSNP:rs35354874Ensembl.	1
Natural variantⁱVAR_049553	198	T → A. Corresponds to variant dbSNP:rs11879402Ensembl.	1
Natural variantⁱVAR_049554	431	G → S. Corresponds to variant dbSNP:rs1052692Ensembl.	1
Isoform E47 (identifier: P15923-2)
Natural variantⁱ	555	E → 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 Publication	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Length
Alternative sequenceⁱVSP_057277	49 – 99	Missing in isoform 3. 1 PublicationAdd BLAST	51
Alternative sequenceⁱVSP_057278	528	T → TRCQPTPRHSPPSPHQDAHV HRPHAHRTHTGRPSAGPTLF PQPHCLPLAPSRRPPH in isoform 3. 1 Publication	1
Alternative sequenceⁱVSP_002155	530 – 601	PDEDE…SVILN → STDEVLSLEEKDLRDRERRM ANNARERVRVRDINEAFREL GRMCQMHLKSDKAQTKLLIL QQAVQVILG in isoform E47. 4 PublicationsAdd BLAST	72

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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS12074.1 [P15923-1] CCDS45899.1 [P15923-2]
PIRⁱ	A34734 S10099
NCBI Reference Sequences More...RefSeqⁱ	NP_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]
UniGeneⁱ	Hs.371282 Hs.657044

Genome annotation databases

Ensemblⁱ	ENST00000262965; ENSP00000262965; ENSG00000071564 [P15923-1] ENST00000395423; ENSP00000378813; ENSG00000071564 [P15923-3] ENST00000588136; ENSP00000468487; ENSG00000071564 [P15923-2] ENST00000611869; ENSP00000480564; ENSG00000071564 [P15923-1]
GeneIDⁱ	6929
KEGGⁱ	hsa:6929
UCSC genome browser More...UCSCⁱ	uc002ltr.3 human [P15923-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing, Chromosomal rearrangement, Polymorphism

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
P15923	TCF3 protein (Fragment)		HUMAN		591	UniRef100_P15923

Protein	Similar proteins		Species	Score	Length	Source
P15923	TCF3 protein (Fragment)		HUMAN		591	UniRef90_P15923
Transcription factor 3		SAIBB		668
Transcription factor E2-alpha isoform E12		CALJA		655
Uncharacterized protein		RHIRO		655
Uncharacterized protein		AOTNA		655
+70
P15923-2	Uncharacterized protein		NOMLE		654	UniRef90_P15923-2
Uncharacterized protein		COLAP		648
Uncharacterized protein		PANPA		642
Transcription factor 3		PANTR		636
Transcription factor 3		GORGO		636
+5
P15923-3	Uncharacterized protein		NOMLE		667	UniRef90_P15923-3
Uncharacterized protein		CALJA		659
Uncharacterized protein		AOTNA		659
TCF3 isoform 2		PANTR		658
Transcription factor 3		SAIBB		658
+6

Protein	Similar proteins		Species	Score	Length	Source
P15923	TCF3 protein (Fragment)		HUMAN		591	UniRef50_P15923
Transcription factor 3		SAIBB		668
Uncharacterized protein		RHIRO		655
Uncharacterized protein		AOTNA		655
Transcription factor E2-alpha isoform E12		CALJA		655
+146
P15923-2	Transcription factor E2-alpha	)	MOUSE		651	UniRef50_P15806
Transcription factor E2-alpha		MESAU		649
Transcription factor E2-alpha		RAT		649
Transcription factor-like protein (Fragment)		Daphnia magna		148
Transcription factor E2-alpha		CRIGR		643
+358

Cross-referencesⁱ

Web resourcesⁱ

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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
CCDSⁱ	CCDS12074.1 [P15923-1] CCDS45899.1 [P15923-2]
PIRⁱ	A34734 S10099
RefSeqⁱ	NP_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]
UniGeneⁱ	Hs.371282 Hs.657044

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	1HLH	model	-	A/B	549-610	[»]
	2MH0	NMR	-	A	1-37	[»]
	2YPA	X-ray	2.80	B	546-616	[»]
	2YPB	X-ray	2.87	B	546-616	[»]
	3U5V	X-ray	1.70	A	563-613	[»]
ProteinModelPortalⁱ	P15923
SMRⁱ	P15923
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	112791, 159 interactors
CORUMⁱ	P15923
DIPⁱ	DIP-74N
IntActⁱ	P15923, 31 interactors
MINTⁱ	P15923
STRINGⁱ	9606.ENSP00000262965

PTM databases

iPTMnetⁱ	P15923
PhosphoSitePlusⁱ	P15923

Polymorphism and mutation databases

BioMutaⁱ	TCF3
DMDMⁱ	135655

Proteomic databases

EPDⁱ	P15923
MaxQBⁱ	P15923
PaxDbⁱ	P15923
PeptideAtlasⁱ	P15923
PRIDEⁱ	P15923
ProteomicsDBⁱ	53242 53243 [P15923-2]

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENST00000262965; ENSP00000262965; ENSG00000071564 [P15923-1] ENST00000395423; ENSP00000378813; ENSG00000071564 [P15923-3] ENST00000588136; ENSP00000468487; ENSG00000071564 [P15923-2] ENST00000611869; ENSP00000480564; ENSG00000071564 [P15923-1]
GeneIDⁱ	6929
KEGGⁱ	hsa:6929
UCSCⁱ	uc002ltr.3 human [P15923-1]

Organism-specific databases

CTDⁱ	6929
DisGeNETⁱ	6929
EuPathDBⁱ	HostDB:ENSG00000071564.14
GeneCardsⁱ	TCF3
HGNCⁱ	HGNC:11633 TCF3
HPAⁱ	CAB018351 HPA049808 HPA062476
MalaCardsⁱ	TCF3
MIMⁱ	147141 gene 616941 phenotype
neXtProtⁱ	NX_P15923
OpenTargetsⁱ	ENSG00000071564
Orphanetⁱ	33110 Autosomal agammaglobulinemia 99860 Precursor B-cell acute lymphoblastic leukemia
PharmGKBⁱ	PA164742580
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG3910 Eukaryota ENOG410XYUA LUCA
GeneTreeⁱ	ENSGT00510000046438
HOGENOMⁱ	HOG000234180
HOVERGENⁱ	HBG003854
InParanoidⁱ	P15923
KOⁱ	K09063
OMAⁱ	KGGSQYY
PhylomeDBⁱ	P15923
TreeFamⁱ	TF321672

Enzyme and pathway databases

Reactomeⁱ	R-HSA-375170 CDO in myogenesis R-HSA-8939236 RUNX1 regulates transcription of genes involved in differentiation of HSCs
SignaLinkⁱ	P15923
SIGNORⁱ	P15923

Miscellaneous databases

ChiTaRSⁱ	TCF3 human
GeneWikiⁱ	TCF3
GenomeRNAiⁱ	6929
Protein Ontology More...PROⁱ	PR:P15923
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000071564 Expressed in 232 organ(s), highest expression level in testis
CleanExⁱ	HS_TCF3
ExpressionAtlasⁱ	P15923 baseline and differential
Genevisibleⁱ	P15923 HS

Family and domain databases

CDDⁱ	cd00083 HLH, 1 hit
Gene3Dⁱ	4.10.280.10, 1 hit
InterProⁱ	View protein in InterPro IPR011598 bHLH_dom IPR036638 HLH_DNA-bd_sf
Pfamⁱ	View protein in Pfam PF00010 HLH, 1 hit
SMARTⁱ	View protein in SMART SM00353 HLH, 1 hit
SUPFAMⁱ	SSF47459 SSF47459, 1 hit
PROSITEⁱ	View protein in PROSITE PS50888 BHLH, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	TFE2_HUMAN
Accessionⁱ	P15923Primary (citable) accession number: P15923 Secondary accession number(s): P15883 Q9UPI9
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
	Last sequence update:	April 1, 1990
	Last modified:	September 12, 2018
	This is version 216 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any 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

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

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UniProtKB - P15923 (TFE2_HUMAN)

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Transcription factor E2-alpha

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

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<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence cautionⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Web resourcesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ