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 24-JAN-2024, entry version 181. DE RecName: Full=Transcription factor 7 {ECO:0000312|MGI:MGI:98507}; DE Short=TCF-7 {ECO:0000305}; DE AltName: Full=T-cell-specific transcription factor 1 {ECO:0000303|PubMed:1827138}; DE Short=T-cell factor 1 {ECO:0000303|PubMed:1827138}; GN Name=Tcf7 {ECO:0000312|MGI:MGI:98507}; GN Synonyms=Tcf-1 {ECO:0000303|PubMed:1827138}, Tcf1 GN {ECO:0000303|PubMed:10489374}; 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 DEVELOPMENTAL STAGE. RX PubMed=27713059; DOI=10.1016/j.ydbio.2016.10.001; RA Jia S., Kwon H.E., Lan Y., Zhou J., Liu H., Jiang R.; RT "Bmp4-Msx1 signaling and Osr2 control tooth organogenesis through RT antagonistic regulation of secreted Wnt antagonists."; RL Dev. Biol. 420:110-119(2016). RN [8] 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). Interacts with CC DAZAP2 (By similarity). {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 (at protein level) CC (PubMed:30413363). Expressed in the mandibular molar tooth mesenchyme CC at 13.5 dpc (PubMed:27713059). {ECO:0000269|PubMed:27713059, 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 10090-ENSMUSP00000084055; -. DR PeptideAtlas; Q00417; -. DR ProteomicsDB; 262970; -. [Q00417-1] DR ProteomicsDB; 262971; -. [Q00417-2] DR Antibodypedia; 14629; 521 antibodies from 37 providers. DR DNASU; 21414; -. DR Ensembl; ENSMUST00000086844.10; ENSMUSP00000084055.4; ENSMUSG00000000782.17. [Q00417-2] DR GeneID; 21414; -. DR KEGG; mmu:21414; -. DR UCSC; uc007ivj.2; mouse. [Q00417-1] DR AGR; MGI:98507; -. 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 OrthoDB; 5351131at2759; -. 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-4641265; Repression of WNT target genes. DR Reactome; R-MMU-8951430; RUNX3 regulates WNT signaling. DR BioGRID-ORCS; 21414; 2 hits in 79 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 285 other cell types or tissues. DR ExpressionAtlas; Q00417; baseline and differential. 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:0043066; P:negative regulation of apoptotic process; IDA:MGI. 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:0006355; P:regulation of DNA-templated transcription; IMP:UniProtKB. 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:0033153; P:T cell receptor V(D)J recombination; IGI:MGI. DR CDD; cd21996; HMG-box_TCF7-like; 1. DR Gene3D; 1.10.30.10; High mobility group box domain; 1. DR Gene3D; 4.10.900.10; TCF3-CBD (Catenin binding domain); 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 PANTHER; PTHR10373:SF33; TRANSCRIPTION FACTOR 7; 1. DR PANTHER; PTHR10373; TRANSCRIPTION FACTOR 7 FAMILY MEMBER; 1. DR Pfam; PF08347; CTNNB1_binding; 1. DR Pfam; PF00505; HMG_box; 1. DR SMART; SM00398; HMG; 1. DR SUPFAM; SSF47095; HMG-box; 1. DR PROSITE; PS50118; HMG_BOX_2; 1. DR Genevisible; Q00417; MM. 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 //