TFE2_HUMAN
ID TFE2_HUMAN Reviewed; 654 AA.
AC P15923; P15883; Q14208; Q14635; Q14636; Q2TB39; Q2TB40; Q9UPI9;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 240.
DE RecName: Full=Transcription factor E2-alpha;
DE AltName: Full=Class B basic helix-loop-helix protein 21;
DE Short=bHLHb21;
DE AltName: Full=Immunoglobulin enhancer-binding factor E12/E47;
DE AltName: Full=Immunoglobulin transcription factor 1;
DE AltName: Full=Kappa-E2-binding factor;
DE AltName: Full=Transcription factor 3;
DE Short=TCF-3;
DE AltName: Full=Transcription factor ITF-1;
GN Name=TCF3; Synonyms=BHLHB21, E2A, ITF1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM E12), AND CHROMOSOMAL TRANSLOCATION
RP WITH PBX1.
RX PubMed=1967983; DOI=10.1016/0092-8674(90)90658-2;
RA Kamps M.P., Murre C., Sun X.-H., Baltimore D.;
RT "A new homeobox gene contributes the DNA binding domain of the t(1;19)
RT translocation protein in pre-B ALL.";
RL Cell 60:547-555(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM E12).
RX PubMed=1967982; DOI=10.1016/0092-8674(90)90657-z;
RA Nourse J., Mellentin J.D., Galili N., Wilkinson J., Stanbridge E.,
RA Smith S.D., Cleary M.L.;
RT "Chromosomal translocation t(1;19) results in synthesis of a homeobox
RT fusion mRNA that codes for a potential chimeric transcription factor.";
RL Cell 60:535-545(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS E47 AND 3).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 214-654 (ISOFORMS E12 AND E47), FUNCTION, AND
RP DOMAIN BHLH.
RC TISSUE=Lymphoma;
RX PubMed=2493990; DOI=10.1016/0092-8674(89)90682-x;
RA Murre C., McCaw P.S., Baltimore D.;
RT "A new DNA binding and dimerization motif in immunoglobulin enhancer
RT binding, daughterless, MyoD, and myc proteins.";
RL Cell 56:777-783(1989).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 69-654 (ISOFORM E47).
RX PubMed=2308859; DOI=10.1093/nar/18.3.677;
RA Henthorn P., McCarrick-Walmsley R., Kadesch T.;
RT "Sequence of the cDNA encoding ITF-1, a positive-acting transcription
RT factor.";
RL Nucleic Acids Res. 18:677-677(1990).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 511-654 (ISOFORM E47).
RX PubMed=1818757; DOI=10.3109/10425179109039690;
RA Zhang Y., Bina M.;
RT "Sequence of a HeLa cDNA provides the DNA binding domain and carboxy
RT terminus of HE47: a human helix-loop-helix protein related to the enhancer
RT binding factor E47.";
RL DNA Seq. 2:197-202(1991).
RN [8]
RP DISCUSSION OF SEQUENCE.
RX PubMed=2105528; DOI=10.1126/science.2105528;
RA Henthorn P., Kiledjian M., Kadesch T.;
RT "Two distinct transcription factors that bind the immunoglobulin enhancer
RT microE5/kappa 2 motif.";
RL Science 247:467-470(1990).
RN [9]
RP MUTAGENESIS, DNA-BINDING, AND HOMODIMERIZATION.
RX PubMed=2112746; DOI=10.1073/pnas.87.12.4722;
RA Voronova A., Baltimore D.;
RT "Mutations that disrupt DNA binding and dimer formation in the E47 helix-
RT loop-helix protein map to distinct domains.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:4722-4726(1990).
RN [10]
RP CHROMOSOMAL TRANSLOCATION WITH PBX1.
RX PubMed=1671560;
RA Hunger S.P., Galili N., Carroll A.J., Crist W.M., Link M.P., Cleary M.L.;
RT "The t(1;19)(q23;p13) results in consistent fusion of E2A and PBX1 coding
RT sequences in acute lymphoblastic leukemias.";
RL Blood 77:687-693(1991).
RN [11]
RP CHROMOSOMAL TRANSLOCATION WITH HLF.
RX PubMed=1386162; DOI=10.1126/science.1386162;
RA Inaba T., Roberts W.M., Shapiro L.H., Jolly K.W., Raimondi S.C.,
RA Smith S.D., Look A.T.;
RT "Fusion of the leucine zipper gene HLF to the E2A gene in human acute B-
RT lineage leukemia.";
RL Science 257:531-534(1992).
RN [12]
RP INTERACTION WITH UBE2I.
RX PubMed=9409784; DOI=10.1016/s0378-1119(97)00444-7;
RA Loveys D.A., Streiff M.B., Schaefer T.S., Kato G.J.;
RT "The mUBC9 murine ubiquitin conjugating enzyme interacts with the E2A
RT transcription factors.";
RL Gene 201:169-177(1997).
RN [13]
RP CHROMOSOMAL TRANSLOCATION WITH TFPT.
RX PubMed=10086727; DOI=10.1038/sj.leu.2401338;
RA Brambillasca F., Mosna G., Colombo M., Rivolta A., Caslini C., Minuzzo M.,
RA Giudici G., Mizzi L., Biondi A., Privitera E.;
RT "Identification of a novel molecular partner of the E2A gene in childhood
RT leukemia.";
RL Leukemia 13:369-375(1999).
RN [14]
RP INTERACTION WITH NEUROD1 AND EP300, HOMODIMERIZATION, AND
RP HETERODIMERIZATION.
RX PubMed=14752053; DOI=10.1210/me.2003-0311;
RA Kim J.Y., Chu K., Kim H.J., Seong H.A., Park K.C., Sanyal S., Takeda J.,
RA Ha H., Shong M., Tsai M.J., Choi H.S.;
RT "Orphan nuclear receptor small heterodimer partner, a novel corepressor for
RT a basic helix-loop-helix transcription factor BETA2/neuroD.";
RL Mol. Endocrinol. 18:776-790(2004).
RN [15]
RP INTERACTION WITH FIGLA.
RX PubMed=15044608; DOI=10.1093/molehr/gah056;
RA Bayne R.A.L., Martins da Silva S.J., Anderson R.A.;
RT "Increased expression of the FIGLA transcription factor is associated with
RT primordial follicle formation in the human fetal ovary.";
RL Mol. Hum. Reprod. 10:373-381(2004).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-531 (ISOFORM E47), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-139 AND SER-359, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-134, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [20]
RP INTERACTION WITH ASB2, AND PROTEASOMAL DEGRADATION.
RX PubMed=21119685; DOI=10.1038/cr.2010.165;
RA Nie L., Zhao Y., Wu W., Yang Y.Z., Wang H.C., Sun X.H.;
RT "Notch-induced Asb2 expression promotes protein ubiquitination by forming
RT non-canonical E3 ligase complexes.";
RL Cell Res. 21:754-769(2011).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-379 AND SER-529, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [23]
RP INTERACTION WITH BHLHA9.
RX PubMed=25466284; DOI=10.1016/j.ajhg.2014.10.012;
RA Malik S., Percin F.E., Bornholdt D., Albrecht B., Percesepe A., Koch M.C.,
RA Landi A., Fritz B., Khan R., Mumtaz S., Akarsu N.A., Grzeschik K.H.;
RT "Mutations affecting the BHLHA9 DNA-binding domain cause MSSD, mesoaxial
RT synostotic syndactyly with phalangeal reduction, Malik-Percin type.";
RL Am. J. Hum. Genet. 95:649-659(2014).
RN [24]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-498, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [25]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-498, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [26]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-498 AND LYS-625, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [27]
RP FUNCTION, INTERACTION WITH ATOH7, AND SUBCELLULAR LOCATION.
RX PubMed=31696227; DOI=10.1093/hmg/ddz268;
RA Atac D., Koller S., Hanson J.V.M., Feil S., Tiwari A., Bahr A., Baehr L.,
RA Magyar I., Kottke R., Gerth-Kahlert C., Berger W.;
RT "Atonal homolog 7 (ATOH7) loss-of-function mutations in predominant
RT bilateral optic nerve hypoplasia.";
RL Hum. Mol. Genet. 29:132-148(2020).
RN [28]
RP 3D-STRUCTURE MODELING OF 549-610.
RX PubMed=8433970; DOI=10.1093/protein/6.1.41;
RA Gibson T.J., Thompson J.D., Abagyan R.A.;
RT "Proposed structure for the DNA-binding domain of the helix-loop-helix
RT family of eukaryotic gene regulatory proteins.";
RL Protein Eng. 6:41-50(1993).
RN [29]
RP VARIANT [LARGE SCALE ANALYSIS] VAL-8.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [30]
RP DOMAIN.
RX PubMed=17467953; DOI=10.1016/j.ygeno.2007.02.003;
RA Piskacek S., Gregor M., Nemethova M., Grabner M., Kovarik P., Piskacek M.;
RT "Nine-amino-acid transactivation domain: establishment and prediction
RT utilities.";
RL Genomics 89:756-768(2007).
RN [31]
RP INVOLVEMENT IN AGM8, VARIANT AGM8 LYS-555 (ISOFORM E47), AND
RP CHARACTERIZATION OF VARIANT AGM8 (ISOFORM E47) LYS-555.
RX PubMed=24216514; DOI=10.1172/jci71927;
RA Boisson B., Wang Y.D., Bosompem A., Ma C.S., Lim A., Kochetkov T.,
RA Tangye S.G., Casanova J.L., Conley M.E.;
RT "A recurrent dominant negative E47 mutation causes agammaglobulinemia and
RT BCR(-) B cells.";
RL J. Clin. Invest. 123:4781-4786(2013).
CC -!- FUNCTION: Transcriptional regulator involved in the initiation of
CC neuronal differentiation and mesenchymal to epithelial transition (By
CC similarity). Heterodimers between TCF3 and tissue-specific basic helix-
CC loop-helix (bHLH) proteins play major roles in determining tissue-
CC specific cell fate during embryogenesis, like muscle or early B-cell
CC differentiation (By similarity). Together with TCF15, required for the
CC mesenchymal to epithelial transition (By similarity). Dimers bind DNA
CC on E-box motifs: 5'-CANNTG-3' (By similarity). Binds to the kappa-E2
CC site in the kappa immunoglobulin gene enhancer (PubMed:2493990). Binds
CC to IEB1 and IEB2, which are short DNA sequences in the insulin gene
CC transcription control region (By similarity).
CC {ECO:0000250|UniProtKB:P15806, ECO:0000269|PubMed:2493990}.
CC -!- FUNCTION: [Isoform E47]: Facilitates ATOH7 binding to DNA at the
CC consensus sequence 5'-CAGGTG-3', and positively regulates
CC transcriptional activity. {ECO:0000269|PubMed:31696227}.
CC -!- SUBUNIT: Homodimer (PubMed:2112746, PubMed:14752053). Heterodimer;
CC efficient DNA binding requires dimerization with another bHLH protein
CC (By similarity). Forms a heterodimer with ASH1, TWIST1 and TWIST2 (By
CC similarity). Forms a heterodimer with MYOG; heterodimerization enhances
CC MYOG DNA-binding and transcriptional activities (By similarity). Forms
CC a heterodimer with NEUROD1; the heterodimer is inhibited in presence of
CC ID2, but not NR0B2, to E-box element (PubMed:14752053). Forms a
CC heterodimer with TCF15; the heterodimer binds E-box element (By
CC similarity). Forms a heterodimer with ATOH8; repress transcription of
CC TCF3 and TCF3/NEUROG3 dimer-induced transactivation of E box-dependent
CC promoters (By similarity). Component of a nuclear TAL-1 complex
CC composed at least of CBFA2T3, LDB1, TAL1 and TCF3 (By similarity).
CC Interacts with NEUROD2, PTF1A and TGFB1I1 (By similarity). Interacts
CC with EP300 and UBE2I (PubMed:9409784, PubMed:14752053). Interacts with
CC BHLHA9 (PubMed:25466284). Interacts with ASB2; the interaction is
CC mediated by SKP2 and targets TCF3 for Notch-induced proteasomal
CC degradation (PubMed:21119685). {ECO:0000250|UniProtKB:P15806,
CC ECO:0000269|PubMed:14752053, ECO:0000269|PubMed:21119685,
CC ECO:0000269|PubMed:2112746, ECO:0000269|PubMed:25466284,
CC ECO:0000269|PubMed:9409784}.
CC -!- SUBUNIT: [Isoform E47]: Forms a heterodimer with ATOH7; required for
CC ATOH7 DNA-binding. {ECO:0000269|PubMed:31696227}.
CC -!- SUBUNIT: [Isoform E12]: Interacts with RALGAPA1 and FIGLA.
CC {ECO:0000269|PubMed:15044608}.
CC -!- INTERACTION:
CC P15923; P50553: ASCL1; NbExp=3; IntAct=EBI-769630, EBI-957042;
CC P15923; O75593: FOXH1; NbExp=2; IntAct=EBI-769630, EBI-1759806;
CC P15923; Q02535: ID3; NbExp=3; IntAct=EBI-769630, EBI-1387094;
CC P15923; P17542: TAL1; NbExp=9; IntAct=EBI-769630, EBI-1753878;
CC P15923; Q9Y4C2: TCAF1; NbExp=3; IntAct=EBI-769630, EBI-750484;
CC P15923-1; O95273: CCNDBP1; NbExp=3; IntAct=EBI-769645, EBI-748961;
CC P15923-1; Q02363: ID2; NbExp=3; IntAct=EBI-769645, EBI-713450;
CC P15923-1; P15172: MYOD1; NbExp=2; IntAct=EBI-769645, EBI-488878;
CC P15923-1; O00233: PSMD9; NbExp=2; IntAct=EBI-769645, EBI-750973;
CC P15923-1; Q15672: TWIST1; NbExp=6; IntAct=EBI-769645, EBI-1797287;
CC P15923-3; Q9NQ33: ASCL3; NbExp=3; IntAct=EBI-12000326, EBI-12108222;
CC P15923-3; P13637: ATP1A3; NbExp=3; IntAct=EBI-12000326, EBI-948169;
CC P15923-3; O96004: HAND1; NbExp=3; IntAct=EBI-12000326, EBI-11320290;
CC P15923-3; P41134: ID1; NbExp=3; IntAct=EBI-12000326, EBI-1215527;
CC P15923-3; Q02535: ID3; NbExp=3; IntAct=EBI-12000326, EBI-1387094;
CC P15923-3; P16284: PECAM1; NbExp=3; IntAct=EBI-12000326, EBI-716404;
CC P15923-3; Q13393: PLD1; NbExp=3; IntAct=EBI-12000326, EBI-2827556;
CC P15923-3; P20339: RAB5A; NbExp=3; IntAct=EBI-12000326, EBI-399437;
CC P15923-3; Q9Y4C2-2: TCAF1; NbExp=3; IntAct=EBI-12000326, EBI-11974855;
CC P15923-3; Q8WVJ9: TWIST2; NbExp=3; IntAct=EBI-12000326, EBI-1797313;
CC P15923-3; P08670: VIM; NbExp=3; IntAct=EBI-12000326, EBI-353844;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:31696227}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=E12; Synonyms=PAN-2;
CC IsoId=P15923-1; Sequence=Displayed;
CC Name=E47; Synonyms=PAN-1;
CC IsoId=P15923-2; Sequence=VSP_002155;
CC Name=3;
CC IsoId=P15923-3; Sequence=VSP_057277, VSP_057278;
CC -!- DOMAIN: the 9aaTAD motif is a transactivation domain present in a large
CC number of yeast and animal transcription factors.
CC {ECO:0000269|PubMed:17467953, ECO:0000269|PubMed:2493990}.
CC -!- PTM: Phosphorylated following NGF stimulation. {ECO:0000250}.
CC -!- PTM: Undergoes Notch-induced ubiquitination and subsequent proteasomal
CC degradation which is mediated by ASB1 or ASB2, the substrate-
CC recognition components of probable ECS E3 ubiquitin-protein ligase
CC complexes. {ECO:0000269|PubMed:21119685}.
CC -!- DISEASE: Note=Chromosomal aberrations involving TCF3 are cause of forms
CC of pre-B-cell acute lymphoblastic leukemia (B-ALL). Translocation
CC t(1;19)(q23;p13.3) with PBX1. TCF3-PBX1 transforms cells by
CC constitutively activating transcription of genes regulated by PBX1 or
CC by other members of the PBX protein family (PubMed:1967983,
CC PubMed:1671560). Translocation t(17;19)(q22;p13.3) with HLF
CC (PubMed:1386162). Inversion inv(19)(p13;q13) with TFPT
CC (PubMed:10086727). {ECO:0000269|PubMed:10086727,
CC ECO:0000269|PubMed:1386162, ECO:0000269|PubMed:1671560,
CC ECO:0000269|PubMed:1967983}.
CC -!- DISEASE: Agammaglobulinemia 8, autosomal dominant (AGM8) [MIM:616941]:
CC A form of agammaglobulinemia, a primary immunodeficiency characterized
CC by profoundly low or absent serum antibodies and low or absent
CC circulating B-cells due to an early block of B-cell development.
CC Affected individuals develop severe infections in the first years of
CC life. {ECO:0000269|PubMed:24216514}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform E47]: The bHLH domain encompassing amino acids
CC 546 to 599 is sufficient to mediate DNA-binding and homodimerization.
CC Combined mutagenesis of Phe-566 and Leu-569 to Asp-566 and Glu-569,
CC mutagenesis of Lys-585 to Ala-585 or combined mutagenesis of Ile-588
CC and Leu-589 to Asp-588 and Glu-589 prevents DNA-binding and
CC homodimerization. Mutagenesis of Arg-548 to Lys-548, combined
CC mutagenesis of Arg-547 and Arg-548 to Gly-547 and Gly-548, mutagenesis
CC of Arg-556 to Lys-556, mutagenesis of Arg-558 to Lys-558, or combined
CC mutagenesis of Arg-556 and Arg-558 to Gly-556 and Gly-558, alter DNA-
CC binding but not dimerization. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA52331.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/E2AID50.html";
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DR EMBL; M31523; AAA61146.1; -; mRNA.
DR EMBL; M31522; AAA36764.1; ALT_TERM; mRNA.
DR EMBL; M31222; AAA52331.1; ALT_INIT; mRNA.
DR EMBL; AC006274; AAC99797.1; -; Genomic_DNA.
DR EMBL; AC005321; AAC27373.1; -; Genomic_DNA.
DR EMBL; KC877695; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC110579; AAI10580.1; -; mRNA.
DR EMBL; BC110580; AAI10581.1; -; mRNA.
DR EMBL; M24404; AAA56829.1; -; mRNA.
DR EMBL; M24405; AAA56830.1; -; mRNA.
DR EMBL; X52078; CAA36297.1; -; mRNA.
DR EMBL; M65214; AAC41693.1; -; mRNA.
DR CCDS; CCDS12074.1; -. [P15923-1]
DR CCDS; CCDS45899.1; -. [P15923-2]
DR PIR; A34734; A34734.
DR PIR; S10099; S10099.
DR RefSeq; NP_001129611.1; NM_001136139.2. [P15923-2]
DR RefSeq; NP_003191.1; NM_003200.3. [P15923-1]
DR RefSeq; XP_016882669.1; XM_017027180.1. [P15923-3]
DR RefSeq; XP_016882670.1; XM_017027181.1. [P15923-1]
DR RefSeq; XP_016882671.1; XM_017027182.1.
DR PDB; 2MH0; NMR; -; A=1-37.
DR PDB; 2YPA; X-ray; 2.80 A; B=546-616.
DR PDB; 2YPB; X-ray; 2.87 A; B=546-616.
DR PDB; 3U5V; X-ray; 1.70 A; A=563-613.
DR PDB; 6MGN; X-ray; 1.90 A; A=561-612.
DR PDBsum; 2MH0; -.
DR PDBsum; 2YPA; -.
DR PDBsum; 2YPB; -.
DR PDBsum; 3U5V; -.
DR PDBsum; 6MGN; -.
DR AlphaFoldDB; P15923; -.
DR SMR; P15923; -.
DR BioGRID; 112791; 216.
DR CORUM; P15923; -.
DR DIP; DIP-74N; -.
DR IntAct; P15923; 50.
DR MINT; P15923; -.
DR STRING; 9606.ENSP00000262965; -.
DR iPTMnet; P15923; -.
DR PhosphoSitePlus; P15923; -.
DR BioMuta; TCF3; -.
DR DMDM; 135655; -.
DR EPD; P15923; -.
DR jPOST; P15923; -.
DR MassIVE; P15923; -.
DR MaxQB; P15923; -.
DR PaxDb; P15923; -.
DR PeptideAtlas; P15923; -.
DR PRIDE; P15923; -.
DR ProteomicsDB; 53242; -. [P15923-1]
DR ProteomicsDB; 53243; -. [P15923-2]
DR ProteomicsDB; 61481; -.
DR Antibodypedia; 4332; 594 antibodies from 46 providers.
DR DNASU; 6929; -.
DR Ensembl; ENST00000262965.12; ENSP00000262965.5; ENSG00000071564.17. [P15923-1]
DR Ensembl; ENST00000395423.7; ENSP00000378813.3; ENSG00000071564.17. [P15923-3]
DR Ensembl; ENST00000588136.7; ENSP00000468487.1; ENSG00000071564.17. [P15923-2]
DR Ensembl; ENST00000611869.5; ENSP00000480564.2; ENSG00000071564.17. [P15923-2]
DR GeneID; 6929; -.
DR KEGG; hsa:6929; -.
DR MANE-Select; ENST00000262965.12; ENSP00000262965.5; NM_003200.5; NP_003191.1.
DR UCSC; uc002ltr.3; human. [P15923-1]
DR CTD; 6929; -.
DR DisGeNET; 6929; -.
DR GeneCards; TCF3; -.
DR HGNC; HGNC:11633; TCF3.
DR HPA; ENSG00000071564; Low tissue specificity.
DR MalaCards; TCF3; -.
DR MIM; 147141; gene.
DR MIM; 616941; phenotype.
DR neXtProt; NX_P15923; -.
DR OpenTargets; ENSG00000071564; -.
DR Orphanet; 33110; Autosomal agammaglobulinemia.
DR Orphanet; 585877; B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormality.
DR PharmGKB; PA164742580; -.
DR VEuPathDB; HostDB:ENSG00000071564; -.
DR eggNOG; KOG3910; Eukaryota.
DR GeneTree; ENSGT00940000157036; -.
DR HOGENOM; CLU_021099_2_1_1; -.
DR InParanoid; P15923; -.
DR OMA; AHVHRPH; -.
DR OrthoDB; 571132at2759; -.
DR PhylomeDB; P15923; -.
DR TreeFam; TF321672; -.
DR PathwayCommons; P15923; -.
DR Reactome; R-HSA-525793; Myogenesis.
DR Reactome; R-HSA-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs.
DR SignaLink; P15923; -.
DR SIGNOR; P15923; -.
DR BioGRID-ORCS; 6929; 52 hits in 1104 CRISPR screens.
DR ChiTaRS; TCF3; human.
DR GeneWiki; TCF3; -.
DR GenomeRNAi; 6929; -.
DR Pharos; P15923; Tbio.
DR PRO; PR:P15923; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P15923; protein.
DR Bgee; ENSG00000071564; Expressed in ganglionic eminence and 205 other tissues.
DR ExpressionAtlas; P15923; baseline and differential.
DR Genevisible; P15923; HS.
DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0000791; C:euchromatin; IDA:ARUK-UCL.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IDA:BHF-UCL.
DR GO; GO:0005667; C:transcription regulator complex; IDA:UniProtKB.
DR GO; GO:0043425; F:bHLH transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IC:BHF-UCL.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:BHF-UCL.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0070888; F:E-box binding; IDA:UniProtKB.
DR GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; IPI:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:ARUK-UCL.
DR GO; GO:0070644; F:vitamin D response element binding; IDA:BHF-UCL.
DR GO; GO:0030183; P:B cell differentiation; NAS:UniProtKB.
DR GO; GO:0002326; P:B cell lineage commitment; IDA:UniProtKB.
DR GO; GO:0033152; P:immunoglobulin V(D)J recombination; IDA:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IMP:UniProtKB.
DR GO; GO:0045787; P:positive regulation of cell cycle; IDA:UniProtKB.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; NAS:UniProtKB.
DR Gene3D; 4.10.280.10; -; 1.
DR IDEAL; IID00541; -.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromosomal rearrangement;
KW Differentiation; Disease variant; DNA-binding; Isopeptide bond;
KW Methylation; Neurogenesis; Nucleus; Phosphoprotein; Proto-oncogene;
KW Reference proteome; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..654
FT /note="Transcription factor E2-alpha"
FT /id="PRO_0000127466"
FT DOMAIN 549..602
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 31..103
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 135..205
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 239..268
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 292..329
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 343..385
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 389..425
FT /note="Leucine-zipper"
FT REGION 461..552
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 633..654
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 19..27
FT /note="9aaTAD"
FT MOTIF 170..176
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 54..96
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 139..163
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 292..327
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 343..366
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 494..552
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 483..484
FT /note="Breakpoint for translocation to form TCF3-PBX1
FT oncogene"
FT MOD_RES 134
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 139
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 355
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P15806"
FT MOD_RES 359
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 371
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P15806"
FT MOD_RES 379
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 529
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 498
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:28112733"
FT CROSSLNK 625
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 49..99
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_057277"
FT VAR_SEQ 528
FT /note="T -> TRCQPTPRHSPPSPHQDAHVHRPHAHRTHTGRPSAGPTLFPQPHCLP
FT LAPSRRPPH (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_057278"
FT VAR_SEQ 530..601
FT /note="PDEDEDDLLPPEQKAEREKERRVANNARERLRVRDINEAFKELGRMCQLHLN
FT SEKPQTKLLILHQAVSVILN -> STDEVLSLEEKDLRDRERRMANNARERVRVRDINE
FT AFRELGRMCQMHLKSDKAQTKLLILQQAVQVILG (in isoform E47)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:1818757, ECO:0000303|PubMed:2308859,
FT ECO:0000303|PubMed:2493990"
FT /id="VSP_002155"
FT VARIANT 8
FT /note="A -> V (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs376780559)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036396"
FT VARIANT 120
FT /note="L -> P (in dbSNP:rs35354874)"
FT /id="VAR_049552"
FT VARIANT 198
FT /note="T -> A (in dbSNP:rs11879402)"
FT /id="VAR_049553"
FT VARIANT 431
FT /note="G -> S (in dbSNP:rs1052692)"
FT /id="VAR_049554"
FT CONFLICT 69..99
FT /note="FDPSRTFSEGTHFTESHSSLSSSTFLGPGLG -> GGGECLAWCGPSAVHRC
FT ADVGLGMVSARTAP (in Ref. 6; CAA36297)"
FT /evidence="ECO:0000305"
FT CONFLICT 214..216
FT /note="FYV -> EFR (in Ref. 5; AAA56830)"
FT /evidence="ECO:0000305"
FT CONFLICT 302
FT /note="Missing (in Ref. 1; AAA36764)"
FT /evidence="ECO:0000305"
FT CONFLICT 390
FT /note="Missing (in Ref. 5; AAA56830)"
FT /evidence="ECO:0000305"
FT HELIX 12..25
FT /evidence="ECO:0007829|PDB:2MH0"
FT HELIX 563..580
FT /evidence="ECO:0007829|PDB:3U5V"
FT HELIX 588..608
FT /evidence="ECO:0007829|PDB:3U5V"
FT MOD_RES P15923-2:531
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VARIANT P15923-2:555
FT /note="E -> K (in AGM8, localizes normally to the nucleus,
FT does not perform proper DNA binding, acts in a dominant-
FT negative manner when coexpressed with wild-type) (Ref.29)"
FT /evidence="ECO:0000269|PubMed:24216514"
FT /id="VAR_082832"
SQ SEQUENCE 654 AA; 67600 MW; 52F5E3DE1890AE13 CRC64;
MNQPQRMAPV GTDKELSDLL DFSMMFPLPV TNGKGRPASL AGAQFGGSGL EDRPSSGSWG
SGDQSSSSFD PSRTFSEGTH FTESHSSLSS STFLGPGLGG KSGERGAYAS FGRDAGVGGL
TQAGFLSGEL ALNSPGPLSP SGMKGTSQYY PSYSGSSRRR AADGSLDTQP KKVRKVPPGL
PSSVYPPSSG EDYGRDATAY PSAKTPSSTY PAPFYVADGS LHPSAELWSP PGQAGFGPML
GGGSSPLPLP PGSGPVGSSG SSSTFGGLHQ HERMGYQLHG AEVNGGLPSA SSFSSAPGAT
YGGVSSHTPP VSGADSLLGS RGTTAGSSGD ALGKALASIY SPDHSSNNFS SSPSTPVGSP
QGLAGTSQWP RAGAPGALSP SYDGGLHGLQ SKIEDHLDEA IHVLRSHAVG TAGDMHTLLP
GHGALASGFT GPMSLGGRHA GLVGGSHPED GLAGSTSLMH NHAALPSQPG TLPDLSRPPD
SYSGLGRAGA TAAASEIKRE EKEDEENTSA ADHSEEEKKE LKAPRARTSP DEDEDDLLPP
EQKAEREKER RVANNARERL RVRDINEAFK ELGRMCQLHL NSEKPQTKLL ILHQAVSVIL
NLEQQVRERN LNPKAACLKR REEEKVSGVV GDPQMVLSAP HPGLSEAHNP AGHM
