ID TF7L2_MOUSE Reviewed; 459 AA. AC Q924A0; O70574; Q91XP2; Q91XP3; Q91XP4; Q924A1; Q9Z0V3; Q9Z0V4; DT 25-MAR-2003, integrated into UniProtKB/Swiss-Prot. DT 25-MAR-2003, sequence version 2. DT 31-MAY-2011, entry version 90. DE RecName: Full=Transcription factor 7-like 2; DE AltName: Full=HMG box transcription factor 4; DE AltName: Full=T-cell-specific transcription factor 4; DE Short=T-cell factor 4; DE Short=TCF-4; DE Short=mTCF-4; GN Name=Tcf7l2; Synonyms=Tcf4; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC STRAIN=C57BL/6; TISSUE=Embryo; RX MEDLINE=98147763; PubMed=9488439; RA Korinek V., Barker N., Willert K., Molenaar M., Roose J., Wagenaar G., RA Markman M., Lamers W., Destree O., Clevers H.; RT "Two members of the Tcf family implicated in Wnt/b-catenin signaling RT during embryogenesis in the mouse."; RL Mol. Cell. Biol. 18:1248-1256(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND PARTIAL NUCLEOTIDE RP SEQUENCE [MRNA] (ISOFORMS 1 AND 4). RC STRAIN=ICR; TISSUE=Fetal intestine; RX MEDLINE=99098900; PubMed=9880534; DOI=10.1074/jbc.274.3.1566; RA Lee Y.J., Swencki B., Shoichet S., Shivdasani R.A.; RT "A possible role for the high mobility group box transcription factor RT Tcf-4 in vertebrate gut epithelial cell differentiation."; RL J. Biol. Chem. 274:1566-1572(1999). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 6 AND 7), AND RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3 AND 5). RC STRAIN=C57BL/6J, and CD-1; TISSUE=Pituitary; RX MEDLINE=21833811; PubMed=11845287; DOI=10.1007/s00335-001-2076-0; RA Douglas K.R., Brinkmeier M.L., Kennell J.A., Eswara P., Harrison T.A., RA Patrianakos A.I., Sprecher B.S., Potok M.A., Lyons R.H. Jr., RA MacDougald O.A., Camper S.A.; RT "Identification of members of the Wnt signaling pathway in the RT embryonic pituitary gland."; RL Mamm. Genome 12:843-851(2001). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 8). RA Bayarsaihan D.; RT "A novel isoform of the HMG transcription factor Tcf4."; RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases. RN [5] RP FUNCTION. RX MEDLINE=98361166; PubMed=9697701; DOI=10.1038/1270; RA Korinek V., Barker N., Moerer P., van Donselaar E., Huls G., RA Peters P.J., Clevers H.; RT "Depletion of epithelial stem-cell compartments in the small intestine RT of mice lacking Tcf-4."; RL Nat. Genet. 19:379-383(1998). RN [6] RP INTERACTION WITH TGFB1I1. RX PubMed=16291758; DOI=10.1074/jbc.M505869200; RA Ghogomu S.M., van Venrooy S., Ritthaler M., Wedlich D., Gradl D.; RT "HIC-5 is a novel repressor of lymphoid enhancer factor/T-cell factor- RT driven transcription."; RL J. Biol. Chem. 281:1755-1764(2006). RN [7] RP INTERACTION WITH TNIK AND CTNNB1. RX PubMed=19816403; DOI=10.1038/emboj.2009.285; RA Mahmoudi T., Li V.S.W., Ng S.S., Taouatas N., Vries R.G.J., RA Mohammed S., Heck A.J., Clevers H.; RT "The kinase TNIK is an essential activator of Wnt target genes."; RL EMBO J. 28:3329-3340(2009). CC -!- FUNCTION: Participates in the Wnt signaling pathway and modulates CC MYC expression by binding to its promoter in a sequence-specific CC manner. Acts as repressor in the absence of CTNNB1, and as CC activator in its presence. Activates transcription from promoters CC with several copies of the Tcf motif CCTTTGATC in the presence of CC CTNNB1. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated CC by TCF7L2 and CTNNB1. Expression of dominant-negative mutants CC results in cell-cycle arrest in G1 (By similarity). Necessary for CC the maintenance of the epithelial stem-cell compartment of the CC small intestine. CC -!- SUBUNIT: Interacts with TGFB1I1. Interacts with CTNNB1 (via the CC armadillo repeat); forms stable transcription complex. Interacts CC with EP300. Interacts with NLK. Interacts with CCDC85B (probably CC through the HMG box); prevents interaction with CTNNB1. Interacts CC with MAD2L2; prevents TCF7L2 binding to promoters, negatively CC modulating its transcriptional activity (By similarity). Interacts CC with TNIK. CC -!- INTERACTION: CC Q8CE28:Traf1; NbExp=3; IntAct=EBI-646713, EBI-646694; CC -!- SUBCELLULAR LOCATION: Nucleus, PML body. Note=Diffuse pattern. CC Colocalizes with SUMO1 and PIAS4 in a subset of PML (promyelocytic CC leukemia) nuclear bodies (By similarity). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=8; CC Name=1; CC IsoId=Q924A0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q924A0-2; Sequence=VSP_006976, VSP_006979; CC Name=3; CC IsoId=Q924A0-3; Sequence=VSP_006975; CC Name=4; CC IsoId=Q924A0-4; Sequence=VSP_006978, VSP_006981; CC Name=5; CC IsoId=Q924A0-5; Sequence=VSP_006974, VSP_006977; CC Name=6; CC IsoId=Q924A0-6; Sequence=VSP_006977; CC Name=7; CC IsoId=Q924A0-7; Sequence=VSP_006973, VSP_006975, VSP_006977; CC Name=8; CC IsoId=Q924A0-8; Sequence=VSP_006976, VSP_006980; CC Note=May result from the retention of an intron in the cDNA; CC -!- TISSUE SPECIFICITY: Detected in adult brain and liver, and at CC lower levels in intestine, with a clear increase from the distal CC colon to the duodenum. Detected at low levels in heart, lung, CC kidney, pituitary and testis. CC -!- DEVELOPMENTAL STAGE: First detected at E10.5. Highly expressed at CC E13.5-E16.5 in the central nervous system, in particular in the CC roof of the mesencephalon, at the ditelencephalic junction and in CC dorsal thalamus. At E13.5, detected at low levels in CC gastrointestinal epithelia. CC -!- PTM: Polysumoylated. Sumoylation is enhanced by PIAS family CC members and desumoylated by AXAM/SENP2. Sumoylation/desumoylation CC regulates TCF4 transcription activity in the Wnt signaling pathway CC without altering interaction with CTNNB1 nor binding DNA (By CC similarity). CC -!- DISEASE: Note=Constitutive activation and subsequent CC transactivation of target genes may lead to the maintenance of CC stem-cell characteristics (cycling and longevity) in cells that CC should normally undergo terminal differentiation and constitute CC the primary transforming event in colorectal cancer (CRC). CC -!- SIMILARITY: Belongs to the TCF/LEF family. CC -!- SIMILARITY: Contains 1 HMG box DNA-binding domain. 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; AJ223070; CAA11071.1; -; mRNA. DR EMBL; AF107298; AAD16967.1; -; mRNA. DR EMBL; AF107299; AAD16968.1; -; mRNA. DR EMBL; AF363722; AAK77485.1; -; Genomic_DNA. DR EMBL; AF363722; AAK77486.1; -; Genomic_DNA. DR EMBL; AF363724; AAK77488.1; -; mRNA. DR EMBL; AF363725; AAK77489.1; -; mRNA. DR EMBL; AF363726; AAK77490.1; -; mRNA. DR EMBL; AY072035; AAL58534.1; -; mRNA. DR IPI; IPI00129307; -. DR IPI; IPI00224936; -. DR IPI; IPI00224938; -. DR IPI; IPI00224939; -. DR IPI; IPI00224941; -. DR IPI; IPI00831494; -. DR IPI; IPI00831648; -. DR IPI; IPI00918384; -. DR RefSeq; NP_001136390.1; NM_001142918.1. DR RefSeq; NP_001136393.1; NM_001142921.1. DR UniGene; Mm.139815; -. DR ProteinModelPortal; Q924A0; -. DR SMR; Q924A0; 12-49, 326-401. DR IntAct; Q924A0; 6. DR MINT; MINT-421706; -. DR STRING; Q924A0; -. DR PhosphoSite; Q924A0; -. DR PRIDE; Q924A0; -. DR Ensembl; ENSMUST00000111649; ENSMUSP00000107276; ENSMUSG00000024985. DR Ensembl; ENSMUST00000111651; ENSMUSP00000107278; ENSMUSG00000024985. DR Ensembl; ENSMUST00000111652; ENSMUSP00000107279; ENSMUSG00000024985. DR Ensembl; ENSMUST00000111659; ENSMUSP00000107287; ENSMUSG00000024985. DR GeneID; 21416; -. DR KEGG; mmu:21416; -. DR UCSC; uc008hyb.1; mouse. DR UCSC; uc008hyc.1; mouse. DR UCSC; uc008hyd.1; mouse. DR UCSC; uc008hyf.1; mouse. DR UCSC; uc008hyh.1; mouse. DR UCSC; uc008hyk.1; mouse. DR CTD; 21416; -. DR MGI; MGI:1202879; Tcf7l2. DR eggNOG; roNOG13396; -. DR GeneTree; ENSGT00390000009964; -. DR HOVERGEN; HBG000419; -. DR OrthoDB; EOG43XV3J; -. DR ArrayExpress; Q924A0; -. DR Bgee; Q924A0; -. DR CleanEx; MM_TCF4; -. DR Genevestigator; Q924A0; -. DR GermOnline; ENSMUSG00000024985; Mus musculus. DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell. DR GO; GO:0005667; C:transcription factor complex; IDA:MGI. DR GO; GO:0008013; F:beta-catenin binding; IDA:MGI. DR GO; GO:0003682; F:chromatin binding; IDA:MGI. DR GO; GO:0030282; P:bone mineralization; IGI:MGI. DR GO; GO:0035411; P:catenin import into nucleus; IDA: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:0060325; P:face morphogenesis; IGI:MGI. DR GO; GO:0048625; P:myoblast cell fate commitment; IMP:MGI. DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IMP:MGI. DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IMP:MGI. DR GO; GO:0040037; P:negative regulation of fibroblast growth factor receptor signaling pathway; IMP:MGI. DR GO; GO:0046621; P:negative regulation of organ growth; IMP:MGI. DR GO; GO:0021915; P:neural tube development; IGI:MGI. DR GO; GO:0042475; P:odontogenesis of dentine-containing tooth; IGI:MGI. DR GO; GO:0014003; P:oligodendrocyte development; IMP:MGI. DR GO; GO:0021983; P:pituitary gland development; IMP:MGI. DR GO; GO:0043065; P:positive regulation of apoptosis; IMP:MGI. DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:MGI. DR GO; GO:0032024; P:positive regulation of insulin secretion; IMP:BHF-UCL. DR GO; GO:0061178; P:regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:MGI. DR GO; GO:0031641; P:regulation of myelination; IMP:MGI. DR GO; GO:0048713; P:regulation of oligodendrocyte differentiation; IMP:MGI. DR GO; GO:0048641; P:regulation of skeletal muscle tissue development; IMP:MGI. DR GO; GO:0009749; P:response to glucose stimulus; IMP:BHF-UCL. DR GO; GO:0032252; P:secretory granule localization; IMP:MGI. DR GO; GO:0043588; P:skin development; IGI:MGI. DR GO; GO:0035019; P:somatic stem cell maintenance; IMP:MGI. DR InterPro; IPR013558; CTNNB1-bd_N. DR InterPro; IPR000910; HMG_HMG1/HMG2. DR InterPro; IPR009071; HMG_superfamily. DR Gene3D; G3DSA:1.10.30.10; HMG-box; 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. PE 1: Evidence at protein level; KW Activator; Alternative splicing; Complete proteome; DNA-binding; KW Isopeptide bond; Nucleus; Repressor; Transcription; KW Transcription regulation; Ubl conjugation; Wnt signaling pathway. FT CHAIN 1 459 Transcription factor 7-like 2. FT /FTId=PRO_0000048624. FT DNA_BIND 327 395 HMG box. FT REGION 1 53 CTNNB1-binding. FT REGION 178 372 Mediates interaction with MAD2L2 (By FT similarity). FT MOTIF 402 408 Nuclear localization signal (Potential). FT COMPBIAS 155 294 Pro-rich. FT CROSSLNK 297 297 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO) (By FT similarity). FT VAR_SEQ 127 127 T -> TLHFQSGSTHYSAYKTIEHQIAIQ (in isoform FT 7). FT /FTId=VSP_006973. FT VAR_SEQ 161 161 V -> VQSPLPCCTQGHACPHFYTPSDFTVSTQVFRDTKSS FT HSLQKVGEPWYLE (in isoform 5). FT /FTId=VSP_006974. FT VAR_SEQ 237 240 Missing (in isoform 3 and isoform 7). FT /FTId=VSP_006975. FT VAR_SEQ 268 268 S -> SSFLSS (in isoform 2 and isoform 8). FT /FTId=VSP_006976. FT VAR_SEQ 270 459 Missing (in isoform 5, isoform 6 and FT isoform 7). FT /FTId=VSP_006977. FT VAR_SEQ 417 459 EHSECFLNPCLSLPPITDLSAPKKCRARFGLDQQNNWCGPC FT SL -> GEKKSAFATYKVKAAASAHPLQMEAY (in FT isoform 2). FT /FTId=VSP_006979. FT VAR_SEQ 417 459 EHSECFLNPCLSLPPITDLSAPKKCRARFGLDQQNNWCGPC FT SL -> GERGESGRWRLEDHSYVRLPSGGGRRNPRPGHCGE FT PILGSLFCLCVF (in isoform 8). FT /FTId=VSP_006980. FT VAR_SEQ 417 433 Missing (in isoform 4). FT /FTId=VSP_006978. FT VAR_SEQ 457 459 CSL -> ADANTPKKCRALFGLDRQTLWCKPCRRKKKCVRY FT IQGEGSCLSPPSSDGSLLDSPPPSPHLLGSPPQDAKSQTEQ FT TQPLSLSLKPDPLAHLSMMPPPPALLLAEAAHGKASALCPN FT GALDLPPAALQPSMVPSSSLAQPSTSSLHSHNSLAGTQPQP FT LSLVTKSLE (in isoform 4). FT /FTId=VSP_006981. FT CONFLICT 57 57 D -> N (in Ref. 2; AAD16967 and 3; FT AAK77488/AAK77489/AAK77490). FT CONFLICT 236 236 W -> R (in Ref. 4; AAL58534). FT CONFLICT 410 410 K -> Q (in Ref. 2; AAD16968). SQ SEQUENCE 459 AA; 51217 MW; 43BC307DC258E83F CRC64; MPQLNGGGGD DLGANDELIS FKDEGEQEEK NSENSSAERD LADVKSSLVN ESETNQDSSS DSEAERRPPP RSESFRDKSR ESLEEAAKRQ DGGLFKGPPY PGYPFIMIPD LTSPYLPNGS LSPTARTYLQ MKWPLLDVQA GSLQSRQTLK DARSPSPAHI VSNKVPVVQH PHHVHPLTPL ITYSNEHFTP GNPPPHLPAD VDPKTGIPRP PHPPDISPYY PLSPGTVGQI PHPLGWLVPQ QGQPVYPITT GGFRHPYPTA LTVNASMSRF PPHMVPPHHT LHTTGIPHPA IVTPTVKQES SQSDVGSLHS SKHQDSKKEE EKKKPHIKKP LNAFMLYMKE MRAKVVAECT LKESAAINQI LGRRWHALSR EEQAKYYELA RKERQLHMQL YPGWSARDNY GKKKKRKRDK QPGETNEHSE CFLNPCLSLP PITDLSAPKK CRARFGLDQQ NNWCGPCSL //