ID T7L2_MOUSE STANDARD; PRT; 459 AA. AC Q924A0; O70574; Q91XP2; Q91XP3; Q91XP4; Q924A1; Q9Z0V3; Q9Z0V4; DT 10-OCT-2003 (Rel. 42, Created) DT 10-OCT-2003 (Rel. 42, Last sequence update) DT 05-JUL-2004 (Rel. 44, Last annotation update) DE Transcription factor 7-like 2 (HMG box transcription factor 4) (T- DE cell-specific transcription factor 4) (TCF-4) (mTCF-4). GN Name=Tcf7l2; Synonyms=Tcf4; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Rodentia; Sciurognathi; Muridae; Murinae; Mus. OX NCBI_TaxID=10090; RN [1] RP SEQUENCE FROM N.A. (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 SEQUENCE FROM N.A. (ISOFORM 2), AND PARTIAL SEQUENCE FROM N.A. RP (ISOFORMS 1 AND 4). RC STRAIN=ICR; TISSUE=Fetal gut; RX MEDLINE=99098900; PubMed=9880534; 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 SEQUENCE FROM N.A. (ISOFORMS 6 AND 7), AND PARTIAL SEQUENCE FROM N.A. RP (ISOFORMS 1; 3 AND 5). RC STRAIN=C57BL/6J, and CD-1; TISSUE=Pituitary; RX MEDLINE=21833811; PubMed=11845287; 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 SEQUENCE FROM N.A. (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). 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: Binds the armadillo repeat of CTNNB1 and forms a stable CC complex. Binds EP300 (By similarity). CC -!- SUBCELLULAR LOCATION: Nuclear. 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 -!- DISEASE: Constitutive activation and subsequent transactivation of CC target genes may lead to the maintenance of stem-cell CC characteristics (cycling and longevity) in cells that should CC normally undergo terminal differentiation and constitute the CC primary transforming event in colorectal cancer (CRC). CC -!- SIMILARITY: Belongs to the TCF/LEF family. CC -!- SIMILARITY: Contains 1 HMG box 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; -. DR EMBL; AF107298; AAD16967.1; -. DR EMBL; AF107299; AAD16968.1; -. DR EMBL; AF363722; AAK77485.1; -. DR EMBL; AF363722; AAK77486.1; -. DR EMBL; AF363724; AAK77488.1; -. DR EMBL; AF363725; AAK77489.1; -. DR EMBL; AF363726; AAK77490.1; -. DR EMBL; AY072035; AAL58534.1; -. DR HSSP; Q9NQB7; 1JPW. DR TRANSFAC; T02913; -. DR MGD; MGI:1202879; Tcf7l2. DR GO; GO:0005667; C:transcription factor complex; IDA. DR GO; GO:0005515; F:protein binding; IPI. DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IDA. DR InterPro; IPR009071; HMG-box. DR InterPro; IPR000910; HMG_12_box. DR Pfam; PF00505; HMG_box; 1. DR SMART; SM00398; HMG; 1. DR PROSITE; PS50118; HMG_BOX_2; 1. KW Transcription regulation; Activator; Repressor; Trans-acting factor; KW Nuclear protein; DNA-binding; Wnt signaling pathway; KW Alternative splicing. FT DOMAIN 1 53 CTNNB1-BINDING. FT DOMAIN 155 294 Pro-rich. FT DNA_BIND 327 395 HMG box. FT DOMAIN 402 408 Nuclear localization signal (Potential). FT VARSPLIC 127 127 T -> TLHFQSGSTHYSAYKTIEHQIAIQ (in isoform FT 7). FT /FTId=VSP_006973. FT VARSPLIC 161 161 V -> VQSPLPCCTQGHACPHFYTPSDFTVSTQVFRDTKSS FT HSLQKVGEPWYLE (in isoform 5). FT /FTId=VSP_006974. FT VARSPLIC 237 240 Missing (in isoform 3 and isoform 7). FT /FTId=VSP_006975. FT VARSPLIC 268 268 S -> SSFLSS (in isoform 2 and isoform 8). FT /FTId=VSP_006976. FT VARSPLIC 270 459 Missing (in isoform 5, isoform 6 and FT isoform 7). FT /FTId=VSP_006977. FT VARSPLIC 417 433 Missing (in isoform 4). FT /FTId=VSP_006978. FT VARSPLIC 417 459 EHSECFLNPCLSLPPITDLSAPKKCRARFGLDQQNNWCGPC FT SL -> GEKKSAFATYKVKAAASAHPLQMEAY (in FT isoform 2). FT /FTId=VSP_006979. FT VARSPLIC 417 459 EHSECFLNPCLSLPPITDLSAPKKCRARFGLDQQNNWCGPC FT SL -> GERGESGRWRLEDHSYVRLPSGGGRRNPRPGHCGE FT PILGSLFCLCVF (in isoform 8). FT /FTId=VSP_006980. FT VARSPLIC 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 CONFLICT 236 236 W -> R (in Ref. 4). FT CONFLICT 410 410 K -> Q (in Ref. 2; AAD16968). SQ SEQUENCE 459 AA; 51216 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 //