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Protein

Transcription factor 7-like 1

Gene

TCF7L1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Participates in the Wnt signaling pathway. Binds to DNA and acts as a repressor in the absence of CTNNB1, and as an activator in its presence. Necessary for the terminal differentiation of epidermal cells, the formation of keratohyalin granules and the development of the barrier function of the epidermis (By similarity). Down-regulates NQO1, leading to increased mitomycin c resistance.By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi346 – 414HMG boxPROSITE-ProRule annotationAdd BLAST69

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

Transcription, Transcription regulation, Wnt signaling pathway

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000152284-MONOMER.
ReactomeiR-HSA-201722. Formation of the beta-catenin:TCF transactivating complex.
R-HSA-3769402. Deactivation of the beta-catenin transactivating complex.
R-HSA-4086398. Ca2+ pathway.
R-HSA-4411364. Binding of TCF/LEF:CTNNB1 to target gene promoters.
R-HSA-4641265. Repression of WNT target genes.

Names & Taxonomyi

Protein namesi
Recommended name:
Transcription factor 7-like 1
Alternative name(s):
HMG box transcription factor 3
Short name:
TCF-3
Gene namesi
Name:TCF7L1
Synonyms:TCF3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:11640. TCF7L1.

Subcellular locationi

GO - Cellular componenti

  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • transcription factor complex Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi83439.
OpenTargetsiENSG00000152284.
PharmGKBiPA36393.

Polymorphism and mutation databases

BioMutaiTCF7L1.
DMDMi29337134.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000486141 – 588Transcription factor 7-like 1Add BLAST588

Proteomic databases

EPDiQ9HCS4.
MaxQBiQ9HCS4.
PaxDbiQ9HCS4.
PeptideAtlasiQ9HCS4.
PRIDEiQ9HCS4.

PTM databases

iPTMnetiQ9HCS4.
PhosphoSitePlusiQ9HCS4.

Expressioni

Tissue specificityi

Detected in hair follicles and skin keratinocytes, and at lower levels in stomach epithelium.1 Publication

Gene expression databases

BgeeiENSG00000152284.
CleanExiHS_TCF3.
HS_TCF7L1.
ExpressionAtlasiQ9HCS4. baseline and differential.
GenevisibleiQ9HCS4. HS.

Interactioni

Subunit structurei

Binds the armadillo repeat of CTNNB1 and forms a stable complex.By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi123642. 6 interactors.
STRINGi9606.ENSP00000282111.

Structurei

3D structure databases

ProteinModelPortaliQ9HCS4.
SMRiQ9HCS4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 74CTNNB1-bindingBy similarityAdd BLAST74

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi421 – 427Nuclear localization signalSequence analysis7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi5 – 29Gly-richAdd BLAST25
Compositional biasi117 – 326Pro-richAdd BLAST210

Domaini

The putative Groucho interaction domain between the N-terminal CTNNB1 binding domain and the HMG-box is necessary for repression of the transactivation mediated by TCF7L1 and CTNNB1.By similarity

Sequence similaritiesi

Belongs to the TCF/LEF family.Curated
Contains 1 HMG box DNA-binding domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3248. Eukaryota.
ENOG41109RU. LUCA.
GeneTreeiENSGT00390000009964.
HOGENOMiHOG000116032.
HOVERGENiHBG000419.
InParanoidiQ9HCS4.
KOiK04490.
OMAiPEKSCDS.
OrthoDBiEOG091G0705.
PhylomeDBiQ9HCS4.
TreeFamiTF318448.

Family and domain databases

Gene3Di1.10.30.10. 1 hit.
4.10.900.10. 1 hit.
InterProiIPR027397. Catenin_binding_dom.
IPR013558. CTNNB1-bd_N.
IPR009071. HMG_box_dom.
IPR024940. TCF/LEF.
IPR028778. Tcf7l1.
[Graphical view]
PANTHERiPTHR10373. PTHR10373. 2 hits.
PTHR10373:SF25. PTHR10373:SF25. 2 hits.
PfamiPF08347. CTNNB1_binding. 1 hit.
PF00505. HMG_box. 1 hit.
[Graphical view]
SMARTiSM00398. HMG. 1 hit.
[Graphical view]
SUPFAMiSSF47095. SSF47095. 1 hit.
PROSITEiPS50118. HMG_BOX_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9HCS4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPQLGGGGGG GGGGSGGGGG SSAGAAGGGD DLGANDELIP FQDEGGEEQE
60 70 80 90 100
PSSDSASAQR DLDEVKSSLV NESENQSSSS DSEAERRPQP VRDTFQKPRD
110 120 130 140 150
YFAEVRRPQD SAFFKGPPYP GYPFLMIPDL SSPYLSNGPL SPGGARTYLQ
160 170 180 190 200
MKWPLLDVPS SATVKDTRSP SPAHLSNKVP VVQHPHHMHP LTPLITYSND
210 220 230 240 250
HFSPGSPPTH LSPEIDPKTG IPRPPHPSEL SPYYPLSPGA VGQIPHPLGW
260 270 280 290 300
LVPQQGQPMY SLPPGGFRHP YPALAMNASM SSLVSSRFSP HMVAPAHPGL
310 320 330 340 350
PTSGIPHPAI VSPIVKQEPA PPSLSPAVSV KSPVTVKKEE EKKPHVKKPL
360 370 380 390 400
NAFMLYMKEM RAKVVAECTL KESAAINQIL GRKWHNLSRE EQAKYYELAR
410 420 430 440 450
KERQLHSQLY PTWSARDNYG KKKKRKREKQ LSQTQSQQQV QEAEGALASK
460 470 480 490 500
SKKPCVQYLP PEKPCDSPAS SHGSMLDSPA TPSAALASPA APAATHSEQA
510 520 530 540 550
QPLSLTTKPE TRAQLALHSA AFLSAKAAAS SSGQMGSQPP LLSRPLPLGS
560 570 580
MPTALLASPP SFPATLHAHQ ALPVLQAQPL SLVTKSAH
Length:588
Mass (Da):62,631
Last modified:March 1, 2001 - v1
Checksum:i82FB0C9300482A02
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti14Missing in AAH58894 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_035938147T → N in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_049561533G → R.1 PublicationCorresponds to variant rs11547160dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB031046 mRNA. Translation: BAB18185.1.
AC011236 Genomic DNA. No translation available.
AC093162 Genomic DNA. Translation: AAY24094.1.
BC058894 mRNA. Translation: AAH58894.1.
X62870 Genomic DNA. Translation: CAB91064.1.
CCDSiCCDS1971.1.
PIRiS22806.
RefSeqiNP_112573.1. NM_031283.2.
UniGeneiHs.516297.

Genome annotation databases

EnsembliENST00000282111; ENSP00000282111; ENSG00000152284.
GeneIDi83439.
KEGGihsa:83439.
UCSCiuc002soy.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB031046 mRNA. Translation: BAB18185.1.
AC011236 Genomic DNA. No translation available.
AC093162 Genomic DNA. Translation: AAY24094.1.
BC058894 mRNA. Translation: AAH58894.1.
X62870 Genomic DNA. Translation: CAB91064.1.
CCDSiCCDS1971.1.
PIRiS22806.
RefSeqiNP_112573.1. NM_031283.2.
UniGeneiHs.516297.

3D structure databases

ProteinModelPortaliQ9HCS4.
SMRiQ9HCS4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123642. 6 interactors.
STRINGi9606.ENSP00000282111.

PTM databases

iPTMnetiQ9HCS4.
PhosphoSitePlusiQ9HCS4.

Polymorphism and mutation databases

BioMutaiTCF7L1.
DMDMi29337134.

Proteomic databases

EPDiQ9HCS4.
MaxQBiQ9HCS4.
PaxDbiQ9HCS4.
PeptideAtlasiQ9HCS4.
PRIDEiQ9HCS4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000282111; ENSP00000282111; ENSG00000152284.
GeneIDi83439.
KEGGihsa:83439.
UCSCiuc002soy.4. human.

Organism-specific databases

CTDi83439.
DisGeNETi83439.
GeneCardsiTCF7L1.
HGNCiHGNC:11640. TCF7L1.
MIMi604652. gene.
neXtProtiNX_Q9HCS4.
OpenTargetsiENSG00000152284.
PharmGKBiPA36393.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3248. Eukaryota.
ENOG41109RU. LUCA.
GeneTreeiENSGT00390000009964.
HOGENOMiHOG000116032.
HOVERGENiHBG000419.
InParanoidiQ9HCS4.
KOiK04490.
OMAiPEKSCDS.
OrthoDBiEOG091G0705.
PhylomeDBiQ9HCS4.
TreeFamiTF318448.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000152284-MONOMER.
ReactomeiR-HSA-201722. Formation of the beta-catenin:TCF transactivating complex.
R-HSA-3769402. Deactivation of the beta-catenin transactivating complex.
R-HSA-4086398. Ca2+ pathway.
R-HSA-4411364. Binding of TCF/LEF:CTNNB1 to target gene promoters.
R-HSA-4641265. Repression of WNT target genes.

Miscellaneous databases

ChiTaRSiTCF7L1. human.
GeneWikiiTCF7L1.
GenomeRNAii83439.
PROiQ9HCS4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000152284.
CleanExiHS_TCF3.
HS_TCF7L1.
ExpressionAtlasiQ9HCS4. baseline and differential.
GenevisibleiQ9HCS4. HS.

Family and domain databases

Gene3Di1.10.30.10. 1 hit.
4.10.900.10. 1 hit.
InterProiIPR027397. Catenin_binding_dom.
IPR013558. CTNNB1-bd_N.
IPR009071. HMG_box_dom.
IPR024940. TCF/LEF.
IPR028778. Tcf7l1.
[Graphical view]
PANTHERiPTHR10373. PTHR10373. 2 hits.
PTHR10373:SF25. PTHR10373:SF25. 2 hits.
PfamiPF08347. CTNNB1_binding. 1 hit.
PF00505. HMG_box. 1 hit.
[Graphical view]
SMARTiSM00398. HMG. 1 hit.
[Graphical view]
SUPFAMiSSF47095. SSF47095. 1 hit.
PROSITEiPS50118. HMG_BOX_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTF7L1_HUMAN
AccessioniPrimary (citable) accession number: Q9HCS4
Secondary accession number(s): Q53R97, Q6PD70, Q9NP00
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 25, 2003
Last sequence update: March 1, 2001
Last modified: November 2, 2016
This is version 135 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.