TCF15_MOUSE
ID TCF15_MOUSE Reviewed; 195 AA.
AC Q60756; Q60788;
DT 25-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2002, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Transcription factor 15 {ECO:0000303|PubMed:8825648};
DE Short=TCF-15 {ECO:0000303|PubMed:8825648};
DE AltName: Full=Meso1 {ECO:0000303|PubMed:7597044};
DE AltName: Full=Paraxis {ECO:0000303|PubMed:7729571};
DE AltName: Full=Protein bHLH-EC2 {ECO:0000303|PubMed:8825648};
GN Name=Tcf15 {ECO:0000303|PubMed:8825648, ECO:0000312|MGI:MGI:104664};
GN Synonyms=Bhlhec2 {ECO:0000303|PubMed:8825648};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RC STRAIN=NIH Swiss; TISSUE=Embryo;
RX PubMed=7729571; DOI=10.1006/dbio.1995.1081;
RA Burgess R., Cserjesi P., Ligon K.L., Olson E.N.;
RT "Paraxis: a basic helix-loop-helix protein expressed in paraxial mesoderm
RT and developing somites.";
RL Dev. Biol. 168:296-306(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-35.
RC STRAIN=129/SvJ;
RX PubMed=8825648; DOI=10.1006/geno.1995.1282;
RA Hidai H., Quertermous E.E., Espinosa R., Le Beau M.M., Quertermous T.;
RT "Genomic organization and chromosomal localization of the gene TCF15
RT encoding the early mesodermal basic helix-loop-helix factor bHLH-EC2.";
RL Genomics 30:598-601(1995).
RN [4]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=8041747; DOI=10.1073/pnas.91.15.7066;
RA Quertermous E.E., Hidai H., Blanar M.A., Quertermous T.;
RT "Cloning and characterization of a basic helix-loop-helix protein expressed
RT in early mesoderm and the developing somites.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:7066-7070(1994).
RN [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=7597044; DOI=10.1073/pnas.92.13.5870;
RA Blanar M.A., Crossley P.H., Peters K.G., Steingrimsson E., Copeland N.G.,
RA Jenkins N.A., Martin G.R., Rutter W.J.;
RT "Meso1, a basic-helix-loop-helix protein involved in mammalian presomitic
RT mesoderm development.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:5870-5874(1995).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=8955271; DOI=10.1038/384570a0;
RA Burgess R., Rawls A., Brown D., Bradley A., Olson E.N.;
RT "Requirement of the paraxis gene for somite formation and musculoskeletal
RT patterning.";
RL Nature 384:570-573(1996).
RN [7]
RP FUNCTION, DNA-BINDING, INTERACTION WITH TCF3, AND MUTAGENESIS OF
RP 70-ARG-GLN-71; ALA-75 AND PHE-90.
RX PubMed=15226298; DOI=10.1074/jbc.m401319200;
RA Wilson-Rawls J., Rhee J.M., Rawls A.;
RT "Paraxis is a basic helix-loop-helix protein that positively regulates
RT transcription through binding to specific E-box elements.";
RL J. Biol. Chem. 279:37685-37692(2004).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH
RP TCF3.
RX PubMed=23395635; DOI=10.1016/j.celrep.2013.01.017;
RA Davies O.R., Lin C.Y., Radzisheuskaya A., Zhou X., Taube J., Blin G.,
RA Waterhouse A., Smith A.J., Lowell S.;
RT "Tcf15 primes pluripotent cells for differentiation.";
RL Cell Rep. 3:472-484(2013).
RN [10]
RP FUNCTION.
RX PubMed=24038871; DOI=10.1002/dvdy.24033;
RA Rowton M., Ramos P., Anderson D.M., Rhee J.M., Cunliffe H.E., Rawls A.;
RT "Regulation of mesenchymal-to-epithelial transition by PARAXIS during
RT somitogenesis.";
RL Dev. Dyn. 242:1332-1344(2013).
RN [11]
RP FUNCTION, AND INTERACTION WITH MEOX2.
RX PubMed=25561514; DOI=10.1161/circulationaha.114.013721;
RA Coppiello G., Collantes M., Sirerol-Piquer M.S., Vandenwijngaert S.,
RA Schoors S., Swinnen M., Vandersmissen I., Herijgers P., Topal B.,
RA van Loon J., Goffin J., Prosper F., Carmeliet P., Garcia-Verdugo J.M.,
RA Janssens S., Penuelas I., Aranguren X.L., Luttun A.;
RT "Meox2/Tcf15 heterodimers program the heart capillary endothelium for
RT cardiac fatty acid uptake.";
RL Circulation 131:815-826(2015).
RN [12]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=32669716; DOI=10.1038/s41586-020-2503-6;
RA Rodriguez-Fraticelli A.E., Weinreb C., Wang S.W., Migueles R.P.,
RA Jankovic M., Usart M., Klein A.M., Lowell S., Camargo F.D.;
RT "Single-cell lineage tracing unveils a role for TCF15 in haematopoiesis.";
RL Nature 583:585-589(2020).
CC -!- FUNCTION: Early transcription factor that plays a key role in
CC somitogenesis, paraxial mesoderm development and regulation of stem
CC cell pluripotency (PubMed:7597044, PubMed:8955271, PubMed:23395635,
CC PubMed:32669716, PubMed:24038871). Essential for the mesenchymal to
CC epithelial transition associated with somite formation (PubMed:7597044,
CC PubMed:8955271, PubMed:24038871). Required for somite morphogenesis,
CC thereby regulating patterning of the axial skeleton and skeletal
CC muscles (PubMed:8955271). Required for proper localization of somite
CC epithelium markers during the mesenchymal to epithelial transition
CC (PubMed:24038871). Also plays a key role in regulation of stem cell
CC pluripotency (PubMed:23395635, PubMed:32669716). Promotes pluripotency
CC exit of embryonic stem cells (ESCs) by priming ESCs for differentiation
CC (PubMed:23395635). Acts as a key regulator of self-renewal of
CC hematopoietic stem cells (HSCs) by mediating HSCs quiescence and long-
CC term self-renewal (PubMed:32669716). Together with MEOX2, regulates
CC transcription in heart endothelial cells to regulate fatty acid
CC transport across heart endothelial cells (PubMed:25561514). Acts by
CC forming a heterodimer with another helix-loop-helix (bHLH) protein,
CC such as TCF3/E12, that binds DNA on E-box motifs (5'-CANNTG-3') and
CC activates transcription of target genes (PubMed:15226298,
CC PubMed:23395635). {ECO:0000269|PubMed:15226298,
CC ECO:0000269|PubMed:23395635, ECO:0000269|PubMed:24038871,
CC ECO:0000269|PubMed:25561514, ECO:0000269|PubMed:32669716,
CC ECO:0000269|PubMed:7597044, ECO:0000269|PubMed:8955271}.
CC -!- SUBUNIT: Heterodimer; efficient DNA binding requires dimerization with
CC another bHLH protein, such as TCF3/E12 (PubMed:15226298,
CC PubMed:23395635). Interacts with MEOX2 (PubMed:25561514).
CC {ECO:0000269|PubMed:15226298, ECO:0000269|PubMed:23395635,
CC ECO:0000269|PubMed:25561514}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981,
CC ECO:0000269|PubMed:23395635}.
CC -!- TISSUE SPECIFICITY: Expressed in heart and skeletal muscle
CC (PubMed:8041747, PubMed:7597044). Specifically expressed in a
CC subpopulation of embryonic stem cells (ESCs), that are still
CC undifferentiated but primed for ifferentiation (PubMed:23395635).
CC Expressed in hematopoietic stem cells (HSCs) (PubMed:32669716).
CC {ECO:0000269|PubMed:23395635, ECO:0000269|PubMed:32669716,
CC ECO:0000269|PubMed:7597044, ECO:0000269|PubMed:8041747}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the embryonic day 4.5 embryo
CC (PubMed:23395635). Expressed in paraxial mesoderm and developing
CC somites (PubMed:7729571). At 7.5 dpc, low expression is detected in a
CC subdomain of the primitive mesoderm (PubMed:8041747). At 8.5 dpc,
CC expressed at high levels throughout the uncompartmentalized epithelial
CC somites and in the rostral paraxial mesoderm (PubMed:8041747). By 9.5
CC dpc, expression is confined to the somite and is most prominent in the
CC myotome and dermatome (PubMed:8041747). At 10 dpc, expression in somite
CC declines in the myotome but persists at high level in the dermatome
CC (PubMed:8041747). At 10.5 dpc, expression is seen only in the somites
CC in the caudal portion of the embryo (PubMed:8041747).
CC {ECO:0000269|PubMed:23395635, ECO:0000269|PubMed:7729571,
CC ECO:0000269|PubMed:8041747}.
CC -!- DISRUPTION PHENOTYPE: Lethality within an hour of birth, possibly
CC caused by rib defects that lead to respiratory distress
CC (PubMed:8955271). At birth, neonates display obvious caudal agenesis
CC with tails that are shortened and curled (PubMed:8955271). They also
CC lack the normal cervical flexure of the vertebral column, and their
CC hindlimbs are curved towards the midline (PubMed:8955271). Neonates
CC also display low-set ears, a thickened neck and loose skin
CC (PubMed:8955271). Defects are caused by impaired formation of somites:
CC cells from the paraxial mesoderm are unable to form epithelia,
CC preventing formation of somites (PubMed:8955271). In the absence of
CC normal somites, the axial skeleton and skeletal muscle form but are
CC improperly patterned (PubMed:8955271). Hematopoietic stem cells (HSCs)
CC show a specific loss of quiescent stem cells (PubMed:32669716).
CC {ECO:0000269|PubMed:32669716, ECO:0000269|PubMed:8955271}.
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DR EMBL; U18658; AAA86825.1; -; mRNA.
DR EMBL; BC027533; AAH27533.1; -; mRNA.
DR EMBL; U20164; AAB48215.1; -; Genomic_DNA.
DR CCDS; CCDS16878.1; -.
DR RefSeq; NP_033354.2; NM_009328.2.
DR AlphaFoldDB; Q60756; -.
DR SMR; Q60756; -.
DR BioGRID; 204001; 2.
DR STRING; 10090.ENSMUSP00000086511; -.
DR iPTMnet; Q60756; -.
DR PhosphoSitePlus; Q60756; -.
DR jPOST; Q60756; -.
DR PaxDb; Q60756; -.
DR PRIDE; Q60756; -.
DR ProteomicsDB; 263145; -.
DR Antibodypedia; 6289; 108 antibodies from 21 providers.
DR DNASU; 21407; -.
DR Ensembl; ENSMUST00000089112; ENSMUSP00000086511; ENSMUSG00000068079.
DR GeneID; 21407; -.
DR KEGG; mmu:21407; -.
DR UCSC; uc008nex.1; mouse.
DR CTD; 6939; -.
DR MGI; MGI:104664; Tcf15.
DR VEuPathDB; HostDB:ENSMUSG00000068079; -.
DR eggNOG; KOG4029; Eukaryota.
DR GeneTree; ENSGT00940000161320; -.
DR HOGENOM; CLU_115077_0_0_1; -.
DR InParanoid; Q60756; -.
DR OMA; HPFSYPA; -.
DR OrthoDB; 1511100at2759; -.
DR PhylomeDB; Q60756; -.
DR TreeFam; TF315153; -.
DR BioGRID-ORCS; 21407; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Tcf15; mouse.
DR PRO; PR:Q60756; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q60756; protein.
DR Bgee; ENSMUSG00000068079; Expressed in head paraxial mesoderm and 132 other tissues.
DR Genevisible; Q60756; MM.
DR GO; GO:0005634; C:nucleus; IMP:UniProtKB.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IDA:NTNU_SB.
DR GO; GO:0043425; F:bHLH transcription factor binding; IPI:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0070888; F:E-box binding; IDA:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IMP:MGI.
DR GO; GO:0032502; P:developmental process; IBA:GO_Central.
DR GO; GO:0043583; P:ear development; IMP:MGI.
DR GO; GO:0045198; P:establishment of epithelial cell apical/basal polarity; IMP:MGI.
DR GO; GO:0060231; P:mesenchymal to epithelial transition; IMP:MGI.
DR GO; GO:0007517; P:muscle organ development; IMP:MGI.
DR GO; GO:0048644; P:muscle organ morphogenesis; IMP:MGI.
DR GO; GO:1902037; P:negative regulation of hematopoietic stem cell differentiation; IDA:UniProtKB.
DR GO; GO:0050884; P:neuromuscular process controlling posture; IMP:MGI.
DR GO; GO:0048339; P:paraxial mesoderm development; IMP:MGI.
DR GO; GO:2000738; P:positive regulation of stem cell differentiation; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0036342; P:post-anal tail morphogenesis; IMP:MGI.
DR GO; GO:1903053; P:regulation of extracellular matrix organization; IMP:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0003016; P:respiratory system process; IMP:MGI.
DR GO; GO:0048705; P:skeletal system morphogenesis; IMP:MGI.
DR GO; GO:0001756; P:somitogenesis; IMP:MGI.
DR GO; GO:0019827; P:stem cell population maintenance; IDA:UniProtKB.
DR Gene3D; 4.10.280.10; -; 1.
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 Activator; Developmental protein; Differentiation; DNA-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..195
FT /note="Transcription factor 15"
FT /id="PRO_0000127462"
FT DOMAIN 70..122
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 44..65
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 60
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MUTAGEN 70..71
FT /note="RQ->KK: Does not affect formation of a heterodimer
FT with TCF3 and ability to bind DNA."
FT /evidence="ECO:0000269|PubMed:15226298"
FT MUTAGEN 75
FT /note="A->N: Does not affect formation of a heterodimer
FT with TCF3 and ability to bind DNA."
FT /evidence="ECO:0000269|PubMed:15226298"
FT MUTAGEN 90
FT /note="F->P: Impaired formation of a heterodimer with TCF3
FT and decreased ability to bind DNA."
FT /evidence="ECO:0000269|PubMed:15226298"
FT CONFLICT 130..131
FT /note="DA -> ELT (in Ref. 1; AAA86825)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 195 AA; 20721 MW; F659B94C5F125E56 CRC64;
MAFALLRPVG AHVLYPDVRL LSEDEENRSE SDASDQSFGC CEGLEAARRG PGPGSGRRAS
NGAGPVVVVR QRQAANARER DRTQSVNTAF TALRTLIPTE PVDRKLSKIE TLRLASSYIA
HLANVLLLGD AADDGQPCFR AAGGGKSAVP AADGRQPRSI CTFCLSNQRK GGSRRDLGGS
CLKVRGVAPL RGPRR
