TF7L1_HUMAN
ID TF7L1_HUMAN Reviewed; 588 AA.
AC Q9HCS4; Q53R97; Q6PD70; Q9NP00;
DT 25-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Transcription factor 7-like 1;
DE AltName: Full=HMG box transcription factor 3;
DE Short=TCF-3;
GN Name=TCF7L1; Synonyms=TCF3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fetal lung;
RX PubMed=11085512;
RA Sagara N., Katoh M.;
RT "Mitomycin C resistance induced by TCF-3 overexpression in gastric cancer
RT cell line MKN28 is associated with DT-diaphorase down-regulation.";
RL Cancer Res. 60:5959-5962(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-533.
RC TISSUE=Eye;
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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 331-419.
RX PubMed=1741298; DOI=10.1093/nar/20.3.611;
RA Castrop J., van Norren K., Clevers H.C.;
RT "A gene family of HMG-box transcription factors with homology to TCF-1.";
RL Nucleic Acids Res. 20:611-611(1992).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=9916915; DOI=10.1016/s0002-9440(10)65247-9;
RA Barker N., Huls G., Korinek V., Clevers H.;
RT "Restricted high level expression of Tcf-4 protein in intestinal and
RT mammary gland epithelium.";
RL Am. J. Pathol. 154:29-35(1999).
RN [6]
RP VARIANT [LARGE SCALE ANALYSIS] ASN-147.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Participates in the Wnt signaling pathway. Binds to DNA and
CC acts as a repressor in the absence of CTNNB1, and as an activator in
CC its presence. Necessary for the terminal differentiation of epidermal
CC cells, the formation of keratohyalin granules and the development of
CC the barrier function of the epidermis (By similarity). Down-regulates
CC NQO1, leading to increased mitomycin c resistance. {ECO:0000250}.
CC -!- SUBUNIT: Binds the armadillo repeat of CTNNB1 and forms a stable
CC complex. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- TISSUE SPECIFICITY: Detected in hair follicles and skin keratinocytes,
CC and at lower levels in stomach epithelium.
CC {ECO:0000269|PubMed:9916915}.
CC -!- DOMAIN: The putative Groucho interaction domain between the N-terminal
CC CTNNB1 binding domain and the HMG-box is necessary for repression of
CC the transactivation mediated by TCF7L1 and CTNNB1. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the TCF/LEF family. {ECO:0000305}.
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DR EMBL; AB031046; BAB18185.1; -; mRNA.
DR EMBL; AC011236; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC093162; AAY24094.1; -; Genomic_DNA.
DR EMBL; BC058894; AAH58894.1; -; mRNA.
DR EMBL; X62870; CAB91064.1; -; Genomic_DNA.
DR CCDS; CCDS1971.1; -.
DR PIR; S22806; S22806.
DR RefSeq; NP_112573.1; NM_031283.2.
DR AlphaFoldDB; Q9HCS4; -.
DR SMR; Q9HCS4; -.
DR BioGRID; 123642; 10.
DR IntAct; Q9HCS4; 2.
DR STRING; 9606.ENSP00000282111; -.
DR iPTMnet; Q9HCS4; -.
DR PhosphoSitePlus; Q9HCS4; -.
DR BioMuta; TCF7L1; -.
DR DMDM; 29337134; -.
DR EPD; Q9HCS4; -.
DR jPOST; Q9HCS4; -.
DR MassIVE; Q9HCS4; -.
DR MaxQB; Q9HCS4; -.
DR PaxDb; Q9HCS4; -.
DR PeptideAtlas; Q9HCS4; -.
DR PRIDE; Q9HCS4; -.
DR ProteomicsDB; 81794; -.
DR Antibodypedia; 31794; 167 antibodies from 35 providers.
DR DNASU; 83439; -.
DR Ensembl; ENST00000282111.4; ENSP00000282111.3; ENSG00000152284.5.
DR GeneID; 83439; -.
DR KEGG; hsa:83439; -.
DR MANE-Select; ENST00000282111.4; ENSP00000282111.3; NM_031283.3; NP_112573.1.
DR UCSC; uc002soy.4; human.
DR CTD; 83439; -.
DR DisGeNET; 83439; -.
DR GeneCards; TCF7L1; -.
DR HGNC; HGNC:11640; TCF7L1.
DR HPA; ENSG00000152284; Low tissue specificity.
DR MIM; 604652; gene.
DR neXtProt; NX_Q9HCS4; -.
DR OpenTargets; ENSG00000152284; -.
DR PharmGKB; PA36393; -.
DR VEuPathDB; HostDB:ENSG00000152284; -.
DR eggNOG; KOG3248; Eukaryota.
DR GeneTree; ENSGT00940000157038; -.
DR HOGENOM; CLU_013229_4_1_1; -.
DR InParanoid; Q9HCS4; -.
DR OMA; HPLSWLV; -.
DR OrthoDB; 807716at2759; -.
DR PhylomeDB; Q9HCS4; -.
DR TreeFam; TF318448; -.
DR PathwayCommons; Q9HCS4; -.
DR Reactome; R-HSA-201722; Formation of the beta-catenin:TCF transactivating complex.
DR Reactome; R-HSA-3769402; Deactivation of the beta-catenin transactivating complex.
DR Reactome; R-HSA-4086398; Ca2+ pathway.
DR Reactome; R-HSA-4411364; Binding of TCF/LEF:CTNNB1 to target gene promoters.
DR Reactome; R-HSA-4641265; Repression of WNT target genes.
DR Reactome; R-HSA-8951430; RUNX3 regulates WNT signaling.
DR SignaLink; Q9HCS4; -.
DR SIGNOR; Q9HCS4; -.
DR BioGRID-ORCS; 83439; 20 hits in 1094 CRISPR screens.
DR ChiTaRS; TCF7L1; human.
DR GeneWiki; TCF7L1; -.
DR GenomeRNAi; 83439; -.
DR Pharos; Q9HCS4; Tbio.
DR PRO; PR:Q9HCS4; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9HCS4; protein.
DR Bgee; ENSG00000152284; Expressed in popliteal artery and 152 other tissues.
DR ExpressionAtlas; Q9HCS4; baseline and differential.
DR Genevisible; Q9HCS4; HS.
DR GO; GO:1990907; C:beta-catenin-TCF complex; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; NAS:UniProtKB.
DR GO; GO:0008013; F:beta-catenin binding; IEA:InterPro.
DR GO; GO:0003677; F:DNA binding; NAS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; NAS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IBA:GO_Central.
DR GO; GO:0006325; P:chromatin organization; NAS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; NAS:UniProtKB.
DR GO; GO:0030111; P:regulation of Wnt signaling pathway; NAS:UniProtKB.
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; IPR028778; Tcf7l1.
DR PANTHER; PTHR10373; PTHR10373; 1.
DR PANTHER; PTHR10373:SF25; PTHR10373:SF25; 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 2: Evidence at transcript level;
KW Activator; DNA-binding; Nucleus; Reference proteome; Repressor;
KW Transcription; Transcription regulation; Wnt signaling pathway.
FT CHAIN 1..588
FT /note="Transcription factor 7-like 1"
FT /id="PRO_0000048614"
FT DNA_BIND 346..414
FT /note="HMG box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267"
FT REGION 1..101
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..74
FT /note="CTNNB1-binding"
FT /evidence="ECO:0000250"
FT REGION 203..234
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 409..506
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 421..427
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 79..101
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 218..232
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 147
FT /note="T -> N (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035938"
FT VARIANT 533
FT /note="G -> R (in dbSNP:rs11547160)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_049561"
FT CONFLICT 14
FT /note="Missing (in Ref. 3; AAH58894)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 588 AA; 62631 MW; 82FB0C9300482A02 CRC64;
MPQLGGGGGG GGGGSGGGGG SSAGAAGGGD DLGANDELIP FQDEGGEEQE PSSDSASAQR
DLDEVKSSLV NESENQSSSS DSEAERRPQP VRDTFQKPRD YFAEVRRPQD SAFFKGPPYP
GYPFLMIPDL SSPYLSNGPL SPGGARTYLQ MKWPLLDVPS SATVKDTRSP SPAHLSNKVP
VVQHPHHMHP LTPLITYSND HFSPGSPPTH LSPEIDPKTG IPRPPHPSEL SPYYPLSPGA
VGQIPHPLGW LVPQQGQPMY SLPPGGFRHP YPALAMNASM SSLVSSRFSP HMVAPAHPGL
PTSGIPHPAI VSPIVKQEPA PPSLSPAVSV KSPVTVKKEE EKKPHVKKPL NAFMLYMKEM
RAKVVAECTL KESAAINQIL GRKWHNLSRE EQAKYYELAR KERQLHSQLY PTWSARDNYG
KKKKRKREKQ LSQTQSQQQV QEAEGALASK SKKPCVQYLP PEKPCDSPAS SHGSMLDSPA
TPSAALASPA APAATHSEQA QPLSLTTKPE TRAQLALHSA AFLSAKAAAS SSGQMGSQPP
LLSRPLPLGS MPTALLASPP SFPATLHAHQ ALPVLQAQPL SLVTKSAH
