TCF7_MOUSE
ID TCF7_MOUSE Reviewed; 419 AA.
AC Q00417;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 25-MAR-2003, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Transcription factor 7;
DE Short=TCF-7;
DE AltName: Full=T-cell-specific transcription factor 1;
DE Short=T-cell factor 1;
DE Short=TCF-1;
GN Name=Tcf7; Synonyms=Tcf-1, Tcf1;
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] (ISOFORM 1).
RC TISSUE=Thymus;
RX PubMed=1827138; DOI=10.1084/jem.173.5.1133;
RA Oosterwegel M.A., Clevers H.;
RT "Cloning of murine TCF-1, a T cell-specific transcription factor
RT interacting with functional motifs in the CD3-epsilon and T cell receptor
RT alpha enhancers.";
RL J. Exp. Med. 173:1133-1142(1991).
RN [2]
RP UTILIZATION OF AN UPSTREAM PROMOTER, AND IDENTIFICATION OF ISOFORM 2.
RX PubMed=8622675; DOI=10.1128/mcb.16.3.745;
RA Van de Wetering M., Castrop J., Korinek V., Clevers H.;
RT "Extensive alternative splicing and dual promoter usage generate Tcf-1
RT protein isoforms with differential transcription control properties.";
RL Mol. Cell. Biol. 16:745-752(1996).
RN [3]
RP DISEASE.
RX PubMed=10489374; DOI=10.1126/science.285.5435.1923;
RA Roose J., Huls G., van Beest M., Moerer P., van der Horn K.,
RA Goldschmeding R., Logtenberg T., Clevers H.;
RT "Synergy between tumor suppressor APC and the beta-catenin-Tcf4 target
RT Tcf1.";
RL Science 285:1923-1926(1999).
RN [4]
RP FUNCTION.
RX PubMed=11477404; DOI=10.1038/90623;
RA Ioannidis V., Beermann F., Clevers H., Held W.;
RT "The beta-catenin-TCF-1 pathway ensures CD4(+)CD8(+) thymocyte survival.";
RL Nat. Immunol. 2:691-697(2001).
RN [5]
RP FUNCTION, INTERACTION WITH SOX13, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=17218525; DOI=10.1126/science.1135344;
RA Melichar H.J., Narayan K., Der S.D., Hiraoka Y., Gardiol N., Jeannet G.,
RA Held W., Chambers C.A., Kang J.;
RT "Regulation of gammadelta versus alphabeta T lymphocyte differentiation by
RT the transcription factor SOX13.";
RL Science 315:230-233(2007).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=23562159; DOI=10.1016/j.immuni.2013.01.010;
RG Immunological Genome Project Consortium;
RA Malhotra N., Narayan K., Cho O.H., Sylvia K.E., Yin C., Melichar H.,
RA Rashighi M., Lefebvre V., Harris J.E., Berg L.J., Kang J.;
RT "A network of high-mobility group box transcription factors programs innate
RT interleukin-17 production.";
RL Immunity 38:681-693(2013).
RN [7]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=30413363; DOI=10.1016/j.immuni.2018.09.010;
RA Spidale N.A., Sylvia K., Narayan K., Miu B., Frascoli M., Melichar H.J.,
RA Zhihao W., Kisielow J., Palin A., Serwold T., Love P., Kobayashi M.,
RA Yoshimoto M., Jain N., Kang J.;
RT "Interleukin-17-Producing gammadelta T Cells Originate from SOX13+
RT Progenitors that Are Independent of gammadeltaTCR Signaling.";
RL Immunity 49:857-872.E5(2018).
CC -!- FUNCTION: Transcriptional activator involved in T-cell lymphocyte
CC differentiation. Necessary for the survival of CD4(+) CD8(+) immature
CC thymocytes. Isoforms lacking the N-terminal CTNNB1 binding domain
CC cannot fulfill this role. Binds to the T-lymphocyte-specific enhancer
CC element (5'-WWCAAAG-3') found in the promoter of the CD3E gene.
CC Represses expression of the T-cell receptor gamma gene in alpha-beta T-
CC cell lineages (PubMed:17218525). Inhibits the developmental program of
CC IL17A effector gamma-delta T-cell subsets via regulating the
CC transcription of T-cell lineage effector proteins (PubMed:23562159,
CC PubMed:30413363). Required for the development of natural killer
CC receptor-positive lymphoid tissue inducer T-cells (PubMed:23562159).
CC TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7 and
CC CTNNB1 (By similarity). May also act as feedback transcriptional
CC repressor of CTNNB1 and TCF7L2 target genes. {ECO:0000250,
CC ECO:0000269|PubMed:11477404, ECO:0000269|PubMed:17218525,
CC ECO:0000269|PubMed:23562159, ECO:0000269|PubMed:30413363}.
CC -!- SUBUNIT: Binds the armadillo repeat of CTNNB1 and forms a stable
CC complex (By similarity). Binds TLE5, TLE1, TLE2, TLE3 and TLE4 (By
CC similarity). Interacts with MLLT11 (By similarity).
CC {ECO:0000250|UniProtKB:P36402}.
CC -!- SUBUNIT: [Isoform 2]: Interacts (via N-terminus) with SOX13; inhibits
CC WNT-mediated transcriptional activity. {ECO:0000269|PubMed:17218525}.
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=2;
CC Comment=Additional isoforms seem to exist.;
CC Name=2;
CC IsoId=Q00417-1; Sequence=Displayed;
CC Name=1;
CC IsoId=Q00417-2; Sequence=VSP_014963;
CC -!- TISSUE SPECIFICITY: T-cell specific. Expressed in triple negative 2
CC subpopulations of T-cells and both the gamma-delta and alpha-beta T-
CC cell lineages (PubMed:17218525). Expressed in Il7 receptor positive
CC innate-like T-cells in the mesenteric lymph nodes and spleen (at
CC protein level) (PubMed:23562159). {ECO:0000269|PubMed:17218525,
CC ECO:0000269|PubMed:23562159}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the yolk sac.
CC {ECO:0000269|PubMed:30413363}.
CC -!- DISEASE: Note=Defects in Tcf7 may allow the formation of epithelial
CC tumors. {ECO:0000269|PubMed:10489374}.
CC -!- DISRUPTION PHENOTYPE: Aberrant expression of Vgamma2 T-cell receptor in
CC alpha-beta T-cells (PubMed:17218525). Reduced frequency of DN1d cells,
CC a subset of DN1 precursor thymocytes (PubMed:30413363). Decreased
CC number of natural killer receptor-positive lymphoid tissue inducer T-
CC cells (PubMed:23562159). Increased expression of Il17 in Vgamma1.1 and
CC Vgamma2 gamma-delta T-cells (PubMed:23562159). Loss of Lef1 expression
CC in Vgamma1.1 and Vgamma2 gamma-delta T-cells (PubMed:23562159). Loss of
CC Cd27 expression in Il17a expressing gamma-delta T-cells
CC (PubMed:23562159). Double knockout of Sox13 and Tcf7/Tcf1 show a
CC reduced number of DN1d cells (PubMed:30413363).
CC {ECO:0000269|PubMed:17218525, ECO:0000269|PubMed:23562159,
CC ECO:0000269|PubMed:30413363}.
CC -!- SIMILARITY: Belongs to the TCF/LEF family. {ECO:0000305}.
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DR EMBL; X61385; CAA43658.1; -; mRNA.
DR CCDS; CCDS24670.1; -. [Q00417-2]
DR PIR; JH0401; JH0401.
DR RefSeq; NP_001300910.1; NM_001313981.1. [Q00417-2]
DR RefSeq; NP_033357.1; NM_009331.4. [Q00417-2]
DR AlphaFoldDB; Q00417; -.
DR SMR; Q00417; -.
DR BioGRID; 204007; 1.
DR IntAct; Q00417; 2.
DR MINT; Q00417; -.
DR STRING; 10090.ENSMUSP00000084055; -.
DR PhosphoSitePlus; Q00417; -.
DR EPD; Q00417; -.
DR MaxQB; Q00417; -.
DR PaxDb; Q00417; -.
DR PeptideAtlas; Q00417; -.
DR PRIDE; Q00417; -.
DR ProteomicsDB; 262970; -. [Q00417-1]
DR ProteomicsDB; 262971; -. [Q00417-2]
DR Antibodypedia; 14629; 490 antibodies from 37 providers.
DR DNASU; 21414; -.
DR Ensembl; ENSMUST00000086844; ENSMUSP00000084055; ENSMUSG00000000782. [Q00417-2]
DR GeneID; 21414; -.
DR KEGG; mmu:21414; -.
DR UCSC; uc007ivj.2; mouse. [Q00417-1]
DR CTD; 6932; -.
DR MGI; MGI:98507; Tcf7.
DR VEuPathDB; HostDB:ENSMUSG00000000782; -.
DR eggNOG; KOG3248; Eukaryota.
DR GeneTree; ENSGT00940000159831; -.
DR HOGENOM; CLU_013229_1_1_1; -.
DR InParanoid; Q00417; -.
DR PhylomeDB; Q00417; -.
DR TreeFam; TF318448; -.
DR Reactome; R-MMU-201722; Formation of the beta-catenin:TCF transactivating complex.
DR Reactome; R-MMU-3769402; Deactivation of the beta-catenin transactivating complex.
DR Reactome; R-MMU-4086398; Ca2+ pathway.
DR Reactome; R-MMU-4641265; Repression of WNT target genes.
DR Reactome; R-MMU-8853884; Transcriptional Regulation by VENTX.
DR Reactome; R-MMU-8951430; RUNX3 regulates WNT signaling.
DR BioGRID-ORCS; 21414; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Tcf7; mouse.
DR PRO; PR:Q00417; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q00417; protein.
DR Bgee; ENSMUSG00000000782; Expressed in thymus and 282 other tissues.
DR ExpressionAtlas; Q00417; baseline and differential.
DR Genevisible; Q00417; MM.
DR GO; GO:1990907; C:beta-catenin-TCF complex; IBA:GO_Central.
DR GO; GO:0000791; C:euchromatin; IDA:BHF-UCL.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0008013; F:beta-catenin binding; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0001217; F:DNA-binding transcription repressor activity; IMP:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IMP:BHF-UCL.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR GO; GO:0046632; P:alpha-beta T cell differentiation; IGI:MGI.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:MGI.
DR GO; GO:0044336; P:canonical Wnt signaling pathway involved in negative regulation of apoptotic process; IDA:MGI.
DR GO; GO:0071353; P:cellular response to interleukin-4; ISO:MGI.
DR GO; GO:0048557; P:embryonic digestive tract morphogenesis; IGI:MGI.
DR GO; GO:0030538; P:embryonic genitalia morphogenesis; IGI:MGI.
DR GO; GO:0048619; P:embryonic hindgut morphogenesis; IGI:MGI.
DR GO; GO:0042492; P:gamma-delta T cell differentiation; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0021915; P:neural tube development; IGI:MGI.
DR GO; GO:0042127; P:regulation of cell population proliferation; IDA:MGI.
DR GO; GO:0045586; P:regulation of gamma-delta T cell differentiation; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0033153; P:T cell receptor V(D)J recombination; IGI:MGI.
DR Gene3D; 1.10.30.10; -; 1.
DR Gene3D; 4.10.900.10; -; 1.
DR InterPro; IPR027397; Catenin-bd_sf.
DR InterPro; IPR013558; CTNNB1-bd_N.
DR InterPro; IPR009071; HMG_box_dom.
DR InterPro; IPR036910; HMG_box_dom_sf.
DR InterPro; IPR024940; TCF/LEF.
DR InterPro; IPR028785; Tcf7.
DR PANTHER; PTHR10373; PTHR10373; 1.
DR PANTHER; PTHR10373:SF33; PTHR10373:SF33; 1.
DR Pfam; PF08347; CTNNB1_binding; 1.
DR Pfam; PF00505; HMG_box; 1.
DR SMART; SM00398; HMG; 1.
DR SUPFAM; SSF47095; SSF47095; 1.
DR PROSITE; PS50118; HMG_BOX_2; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative promoter usage; DNA-binding; Nucleus;
KW Reference proteome; Repressor; Transcription; Transcription regulation;
KW Wnt signaling pathway.
FT CHAIN 1..419
FT /note="Transcription factor 7"
FT /id="PRO_0000048613"
FT DNA_BIND 304..372
FT /note="HMG box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267"
FT REGION 1..111
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..60
FT /note="CTNNB1-binding"
FT /evidence="ECO:0000250"
FT REGION 134..200
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 374..406
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 379..385
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 30..46
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 81..106
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 137..159
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 186..200
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..116
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:1827138"
FT /id="VSP_014963"
SQ SEQUENCE 419 AA; 45465 MW; C49C39AE8871C2C0 CRC64;
MPQLDSGGGG AGRGDDLGAP DELLAFQDEG EEQDDKNRDS PVGPERDLAE LKSSLVNESE
GAAAGAGVPG PGVRVHGEAE GAPEALGREH TSQRLFPDKL PESLEDGLKA PECTSGMYKE
TVYSAFNLLM PYPPASGAGQ HPQPQPPLHN KPGQPPHGVP QLSPLYEHFS SPHPTPAPAD
ISQKQGVHRP LQTPDLSGFY SLTSGSMGQL PHTVSWPSPP LYPLSPSCGY RQHFPAPTAA
PGAPYPRFTH PSLMLGSGVP GHPAAIPHPA IVPSSGKQEL QPYDRNLKTQ AEPKAEKEAK
KPVIKKPLNA FMLYMKEMRA KVIAECTLKE SAAINQILGR RWHALSREEQ AKYYELARKE
RQLHMQLYPG WSARDNYGKK KRRSREKHQE STTGGKRNAF GTYPEKAAAP APFLPMTVL
