TCF3

Protein identityUniProt · HPA

UniProt accession

P15923

Gene

TCF3

Ensembl

ENSG00000071564

Chromosome

19

Canonical length

654 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Transcription factors

Subcellular location

Nucleoplasm

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a member of the E protein (class I) family of helix-loop-helix transcription factors. E proteins activate transcription by binding to regulatory E-box sequences on target genes as heterodimers or homodimers, and are inhibited by heterodimerization with inhibitor of DNA-binding (class IV) helix-loop-helix proteins. E proteins play a critical role in lymphopoiesis, and the encoded protein is required for B and T lymphocyte development. Deletion of this gene or diminished activity of the encoded protein may play a role in lymphoid malignancies. This gene is also involved in several chromosomal translocations that are associated with lymphoid malignancies including pre-B-cell acute lymphoblastic leukemia (t(1;19), with PBX1), childhood leukemia (t(19;19), with TFPT) and acute leukemia (t(12;19), with ZNF384). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the short arm of chromosome 9. [provided by RefSeq, Sep 2011]

Canonical amino-acid sequenceUniProt

654 residues, UniProt reviewed canonical sequence.

>P15923|TCF3
     1  MNQPQRMAPV GTDKELSDLL DFSMMFPLPV TNGKGRPASL AGAQFGGSGL EDRPSSGSWG
    61  SGDQSSSSFD PSRTFSEGTH FTESHSSLSS STFLGPGLGG KSGERGAYAS FGRDAGVGGL
   121  TQAGFLSGEL ALNSPGPLSP SGMKGTSQYY PSYSGSSRRR AADGSLDTQP KKVRKVPPGL
   181  PSSVYPPSSG EDYGRDATAY PSAKTPSSTY PAPFYVADGS LHPSAELWSP PGQAGFGPML
   241  GGGSSPLPLP PGSGPVGSSG SSSTFGGLHQ HERMGYQLHG AEVNGGLPSA SSFSSAPGAT
   301  YGGVSSHTPP VSGADSLLGS RGTTAGSSGD ALGKALASIY SPDHSSNNFS SSPSTPVGSP
   361  QGLAGTSQWP RAGAPGALSP SYDGGLHGLQ SKIEDHLDEA IHVLRSHAVG TAGDMHTLLP
   421  GHGALASGFT GPMSLGGRHA GLVGGSHPED GLAGSTSLMH NHAALPSQPG TLPDLSRPPD
   481  SYSGLGRAGA TAAASEIKRE EKEDEENTSA ADHSEEEKKE LKAPRARTSP DEDEDDLLPP
   541  EQKAEREKER RVANNARERL RVRDINEAFK ELGRMCQLHL NSEKPQTKLL ILHQAVSVIL
   601  NLEQQVRERN LNPKAACLKR REEEKVSGVV GDPQMVLSAP HPGLSEAHNP AGHM

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TCF3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.68

Highest tissue expression

78 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TCF3.

Disease | AllUniProt

Conditions TCF3 is implicated in, by any mechanism.

• Agammaglobulinemia 8A, autosomal dominant (AGM8A) MIM:616941
• Agammaglobulinemia 8B, autosomal recessive (AGM8B) MIM:619824

Disease | GeneticClinVar

33 pathogenic / likely-pathogenic of 1,207 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Agammaglobulinemia 8, autosomal dominant
• Agammaglobulinemia 8b, autosomal recessive
• Inborn genetic diseases
• Multiple myeloma

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.5

gnomAD pLI

0.03

gnomAD missense Z

-0.23

DepMap mean gene effect

-0.07

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• B cell differentiation
• B cell lineage commitment
• immunoglobulin V(D)J recombination
• negative regulation of transcription by RNA polymerase II
• nervous system development
• positive regulation of B cell proliferation
• positive regulation of cell cycle
• positive regulation of DNA-binding transcription factor activity
• positive regulation of DNA-templated transcription
• positive regulation of neuron differentiation
• positive regulation of transcription by RNA polymerase II
• regulation of DNA-templated transcription
• regulation of G1/S transition of mitotic cell cycle
• regulation of transcription by RNA polymerase II

Molecular functions

• bHLH transcription factor binding
• cis-regulatory region sequence-specific DNA binding
• DNA binding
• DNA-binding transcription activator activity, RNA polymerase II-specific
• DNA-binding transcription factor activity
• DNA-binding transcription factor activity, RNA polymerase II-specific
• DNA-binding transcription factor binding
• DNA-binding transcription repressor activity, RNA polymerase II-specific
• E-box binding
• mitogen-activated protein kinase kinase kinase binding
• protein heterodimerization activity
• protein homodimerization activity
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• RNA polymerase II-specific DNA-binding transcription factor binding
• vitamin D response element binding

Cellular components

• chromatin
• cytoplasm
• euchromatin
• nucleoplasm
• nucleus
• protein-containing complex
• RNA polymerase II transcription regulator complex
• transcription regulator complex

Protein domainsUniProt · Pfam · InterPro

• Myc-type, basic helix-loop-helix (bHLH) domain
• Helix-loop-helix DNA-binding domain superfamily
• Neuronal Differentiation E-box Binding Transcription Factors
• Helix-loop-helix DNA-binding domain

KeywordsUniProt

• Chromosomal rearrangement
• Differentiation
• DNA-binding
• Isopeptide bond
• Methylation
• Neurogenesis
• Nucleus
• Phosphoprotein
• Proto-oncogene
• Transcription
• Transcription regulation
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of TCF3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ASB2
• BHLHA9
• EP300
• FIGLA
• NEUROD2
• PTF1A
• RALGAPA1
• TGFB1I1
• UBE2I
• MAPKAPK3
• ASCL1
• ID2
• ID3
• TAL1