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Protein

Transcription factor 7-like 2

Gene

Tcf7l2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Participates in the Wnt signaling pathway and modulates MYC expression by binding to its promoter in a sequence-specific manner. Acts as repressor in the absence of CTNNB1, and as activator in its presence. Activates transcription from promoters with several copies of the Tcf motif CCTTTGATC in the presence of CTNNB1. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7L2/TCF4 and CTNNB1. Expression of dominant-negative mutants results in cell-cycle arrest in G1 (By similarity). Necessary for the maintenance of the epithelial stem-cell compartment of the small intestine.By similarity2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi327 – 395HMG boxPROSITE-ProRule annotationAdd BLAST69

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding, Repressor
Biological processTranscription, Transcription regulation, Wnt signaling pathway

Enzyme and pathway databases

ReactomeiR-MMU-201722 Formation of the beta-catenin:TCF transactivating complex
R-MMU-3769402 Deactivation of the beta-catenin transactivating complex
R-MMU-4086398 Ca2+ pathway
R-MMU-4641265 Repression of WNT target genes
R-MMU-8951430 RUNX3 regulates WNT signaling

Names & Taxonomyi

Protein namesi
Recommended name:
Transcription factor 7-like 2
Alternative name(s):
HMG box transcription factor 4
T-cell-specific transcription factor 4
Short name:
T-cell factor 4
Short name:
TCF-4
Short name:
mTCF-4
Gene namesi
Name:Tcf7l2
Synonyms:Tcf4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:1202879 Tcf7l2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Constitutive activation and subsequent transactivation of target genes may lead to the maintenance of stem-cell characteristics (cycling and longevity) in cells that should normally undergo terminal differentiation and constitute the primary transforming event in colorectal cancer (CRC).

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000486241 – 459Transcription factor 7-like 2Add BLAST459

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki22Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei178Phosphothreonine; by NLKBy similarity1
Modified residuei189Phosphothreonine; by NLKBy similarity1
Cross-linki297Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

Post-translational modificationi

Phosphorylated at Thr-178 and/or Thr-189 by NLK. Phosphorylation by NLK at these sites inhibits DNA-binding by TCF7L2/TCF4, thereby preventing transcriptional activation of target genes of the canonical Wnt/beta-catenin signaling pathway (By similarity).By similarity
Polysumoylated. Sumoylation is enhanced by PIAS family members and desumoylation is enhanced by SENP2. Sumoylation/desumoylation regulates TCF7L2/TCF4 transcription activity in the Wnt/beta-catenin signaling pathway without altering interaction with CTNNB1 nor binding to DNA (By similarity).By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ924A0
PeptideAtlasiQ924A0
PRIDEiQ924A0

PTM databases

iPTMnetiQ924A0
PhosphoSitePlusiQ924A0

Expressioni

Tissue specificityi

Detected in adult brain and liver, and at lower levels in intestine, with a clear increase from the distal colon to the duodenum. Detected at low levels in heart, lung, kidney, pituitary and testis.

Developmental stagei

First detected at E10.5. Highly expressed at E13.5-E16.5 in the central nervous system, in particular in the roof of the mesencephalon, at the ditelencephalic junction and in dorsal thalamus. At E13.5, detected at low levels in gastrointestinal epithelia.

Gene expression databases

BgeeiENSMUSG00000024985 Expressed in 348 organ(s), highest expression level in inferior colliculus
CleanExiMM_TCF4
ExpressionAtlasiQ924A0 baseline and differential
GenevisibleiQ924A0 MM

Interactioni

Subunit structurei

Interacts with TGFB1I1 (PubMed:16291758). Interacts with SPIN1 (By similarity). Interacts with CTNNB1 (via the armadillo repeat); forms stable transcription complex (PubMed:19816403). Interacts with EP300. Interacts with NLK. Interacts with CCDC85B (probably through the HMG box); prevents interaction with CTNNB1 (By similarity). Interacts with TNIK (PubMed:19816403). Interacts with MAD2L2; prevents TCF7L2/TCF4 binding to promZIPK/DAPK3oters, negatively modulating its transcriptional activity. Interacts with ZIPK/DAPK3. Interacts with XIAP/BIRC4 and TLE3. Interacts with DDIT3/CHOP. The CTNNB1 and TCF7L2/TCF4 complex interacts with PML (isoform PML-4). Identified in a complex with CTNNB1 and FERMT2. Interacts with C11orf84/SPINDOC in a SPIN1-dependent manner (By similarity).By similarity2 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204009, 10 interactors
DIPiDIP-40920N
IntActiQ924A0, 5 interactors
MINTiQ924A0
STRINGi10090.ENSMUSP00000107284

Structurei

3D structure databases

ProteinModelPortaliQ924A0
SMRiQ924A0
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 53CTNNB1-bindingAdd BLAST53
Regioni178 – 372Mediates interaction with MAD2L2By similarityAdd BLAST195

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi402 – 408Nuclear localization signalSequence analysis7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi155 – 294Pro-richAdd BLAST140

Sequence similaritiesi

Belongs to the TCF/LEF family.Curated

Phylogenomic databases

eggNOGiKOG3248 Eukaryota
ENOG41109RU LUCA
GeneTreeiENSGT00390000009964
HOGENOMiHOG000116032
HOVERGENiHBG000419
InParanoidiQ924A0
KOiK04491

Family and domain databases

Gene3Di1.10.30.10, 1 hit
4.10.900.10, 1 hit
InterProiView protein in InterPro
IPR027397 Catenin_binding_dom_sf
IPR013558 CTNNB1-bd_N
IPR009071 HMG_box_dom
IPR036910 HMG_box_dom_sf
IPR024940 TCF/LEF
IPR028773 TCF7L
PANTHERiPTHR10373 PTHR10373, 1 hit
PTHR10373:SF25 PTHR10373:SF25, 1 hit
PfamiView protein in Pfam
PF08347 CTNNB1_binding, 1 hit
PF00505 HMG_box, 1 hit
SMARTiView protein in SMART
SM00398 HMG, 1 hit
SUPFAMiSSF47095 SSF47095, 1 hit
PROSITEiView protein in PROSITE
PS50118 HMG_BOX_2, 1 hit

Sequences (9+)i

Sequence statusi: Complete.

This entry describes 9 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 9 described isoforms and 16 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q924A0-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MPQLNGGGGD DLGANDELIS FKDEGEQEEK NSENSSAERD LADVKSSLVN
60 70 80 90 100
ESETNQDSSS DSEAERRPPP RSESFRDKSR ESLEEAAKRQ DGGLFKGPPY
110 120 130 140 150
PGYPFIMIPD LTSPYLPNGS LSPTARTYLQ MKWPLLDVQA GSLQSRQTLK
160 170 180 190 200
DARSPSPAHI VSNKVPVVQH PHHVHPLTPL ITYSNEHFTP GNPPPHLPAD
210 220 230 240 250
VDPKTGIPRP PHPPDISPYY PLSPGTVGQI PHPLGWLVPQ QGQPVYPITT
260 270 280 290 300
GGFRHPYPTA LTVNASMSRF PPHMVPPHHT LHTTGIPHPA IVTPTVKQES
310 320 330 340 350
SQSDVGSLHS SKHQDSKKEE EKKKPHIKKP LNAFMLYMKE MRAKVVAECT
360 370 380 390 400
LKESAAINQI LGRRWHALSR EEQAKYYELA RKERQLHMQL YPGWSARDNY
410 420 430 440 450
GKKKKRKRDK QPGETNEHSE CFLNPCLSLP PITDLSAPKK CRARFGLDQQ

NNWCGPCSL
Length:459
Mass (Da):51,217
Last modified:March 25, 2003 - v2
Checksum:i43BC307DC258E83F
GO
Isoform 2 (identifier: Q924A0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     268-268: S → SSFLSS
     417-459: EHSECFLNPCLSLPPITDLSAPKKCRARFGLDQQNNWCGPCSL → GEKKSAFATYKVKAAASAHPLQMEAY

Show »
Length:447
Mass (Da):49,746
Checksum:iEDD7D6F4E01EBF2D
GO
Isoform 3 (identifier: Q924A0-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     237-240: Missing.

Show »
Length:455
Mass (Da):50,779
Checksum:iCAAC8E5E0E20C558
GO
Isoform 4 (identifier: Q924A0-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     417-433: Missing.
     457-459: CSL → ADANTPKKCR...PLSLVTKSLE

Show »
Length:605
Mass (Da):66,406
Checksum:i5E99A68C93632464
GO
Isoform 5 (identifier: Q924A0-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     161-161: V → VQSPLPCCTQGHACPHFYTPSDFTVSTQVFRDTKSSHSLQKVGEPWYLE
     270-459: Missing.

Show »
Length:317
Mass (Da):34,803
Checksum:i37F33F08CAF073EF
GO
Isoform 6 (identifier: Q924A0-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     270-459: Missing.

Show »
Length:269
Mass (Da):29,379
Checksum:i2D77D77415FF4833
GO
Isoform 7 (identifier: Q924A0-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     127-127: T → TLHFQSGSTHYSAYKTIEHQIAIQ
     237-240: Missing.
     270-459: Missing.

Show »
Length:288
Mass (Da):31,583
Checksum:i62778EB672DF0785
GO
Isoform 8 (identifier: Q924A0-8) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     268-268: S → SSFLSS
     417-459: EHSECFLNPC...QNNWCGPCSL → GERGESGRWR...LGSLFCLCVF

Note: May result from the retention of an intron in the cDNA.
Show »
Length:468
Mass (Da):52,160
Checksum:iA0E7D915D2EC4D0B
GO
Isoform 9 (identifier: Q924A0-9) [UniParc]FASTAAdd to basket
Also known as: dnTcf7l2 exon1b/c

The sequence of this isoform differs from the canonical sequence as follows:
     1-161: MPQLNGGGGD...ARSPSPAHIV → M

Note: Dominant negative form which cannot bind CTNNB1. Expression is VAX2-dependent.
Show »
Length:299
Mass (Da):33,726
Checksum:iE046B2B2BBB11219
GO

Computationally mapped potential isoform sequencesi

There are 16 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9QQ90E9QQ90_MOUSE
Transcription factor 7-like 2
Tcf7l2
598Annotation score:
D3YWT3D3YWT3_MOUSE
Transcription factor 7-like 2
Tcf7l2
442Annotation score:
E9QQ91E9QQ91_MOUSE
Transcription factor 7-like 2
Tcf7l2
459Annotation score:
E9Q990E9Q990_MOUSE
Transcription factor 7-like 2
Tcf7l2
435Annotation score:
F6WBK9F6WBK9_MOUSE
Transcription factor 7-like 2
Tcf7l2
459Annotation score:
D3Z2K5D3Z2K5_MOUSE
Transcription factor 7-like 2
Tcf7l2
468Annotation score:
A0A0R4J1G0A0A0R4J1G0_MOUSE
Transcription factor 7-like 2
Tcf7l2
447Annotation score:
Q3V1G9Q3V1G9_MOUSE
Transcription factor 7-like 2
Tcf7l2
482Annotation score:
E9QQ89E9QQ89_MOUSE
Transcription factor 7-like 2
Tcf7l2
606Annotation score:
D3Z1L0D3Z1L0_MOUSE
Transcription factor 7-like 2
Tcf7l2
265Annotation score:
There are more potential isoformsShow all

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti57D → N in AAD16967 (PubMed:9880534).Curated1
Sequence conflicti57D → N in AAK77488 (PubMed:11845287).Curated1
Sequence conflicti57D → N in AAK77489 (PubMed:11845287).Curated1
Sequence conflicti57D → N in AAK77490 (PubMed:11845287).Curated1
Sequence conflicti236W → R in AAL58534 (Ref. 4) Curated1
Sequence conflicti410K → Q in AAD16968 (PubMed:9880534).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0432051 – 161MPQLN…PAHIV → M in isoform 9. 1 PublicationAdd BLAST161
Alternative sequenceiVSP_006973127T → TLHFQSGSTHYSAYKTIEHQ IAIQ in isoform 7. 1 Publication1
Alternative sequenceiVSP_006974161V → VQSPLPCCTQGHACPHFYTP SDFTVSTQVFRDTKSSHSLQ KVGEPWYLE in isoform 5. Curated1
Alternative sequenceiVSP_006975237 – 240Missing in isoform 3 and isoform 7. 1 Publication4
Alternative sequenceiVSP_006976268S → SSFLSS in isoform 2 and isoform 8. 2 Publications1
Alternative sequenceiVSP_006977270 – 459Missing in isoform 5, isoform 6 and isoform 7. 1 PublicationAdd BLAST190
Alternative sequenceiVSP_006979417 – 459EHSEC…GPCSL → GEKKSAFATYKVKAAASAHP LQMEAY in isoform 2. 1 PublicationAdd BLAST43
Alternative sequenceiVSP_006980417 – 459EHSEC…GPCSL → GERGESGRWRLEDHSYVRLP SGGGRRNPRPGHCGEPILGS LFCLCVF in isoform 8. 1 PublicationAdd BLAST43
Alternative sequenceiVSP_006978417 – 433Missing in isoform 4. CuratedAdd BLAST17
Alternative sequenceiVSP_006981457 – 459CSL → ADANTPKKCRALFGLDRQTL WCKPCRRKKKCVRYIQGEGS CLSPPSSDGSLLDSPPPSPH LLGSPPQDAKSQTEQTQPLS LSLKPDPLAHLSMMPPPPAL LLAEAAHGKASALCPNGALD LPPAALQPSMVPSSSLAQPS TSSLHSHNSLAGTQPQPLSL VTKSLE in isoform 4. Curated3

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ223070 mRNA Translation: CAA11071.1
AF107298 mRNA Translation: AAD16967.1
AF107299 mRNA Translation: AAD16968.1
AF363722 Genomic DNA Translation: AAK77485.1
AF363722 Genomic DNA Translation: AAK77486.1
AF363724 mRNA Translation: AAK77488.1
AF363725 mRNA Translation: AAK77489.1
AF363726 mRNA Translation: AAK77490.1
AY072035 mRNA Translation: AAL58534.1
AK048536 mRNA Translation: BAC33366.1
AC118695 Genomic DNA No translation available.
AC137148 Genomic DNA No translation available.
AC157916 Genomic DNA No translation available.
CCDSiCCDS50470.1 [Q924A0-2]
CCDS50471.1 [Q924A0-1]
CCDS50474.1 [Q924A0-9]
RefSeqiNP_001136390.1, NM_001142918.2
NP_001136393.1, NM_001142921.2
NP_001136396.1, NM_001142924.2 [Q924A0-9]
UniGeneiMm.139815

Genome annotation databases

EnsembliENSMUST00000111646; ENSMUSP00000107273; ENSMUSG00000024985 [Q924A0-9]
GeneIDi21416
KEGGimmu:21416
UCSCiuc008hya.2 mouse [Q924A0-6]
uc008hyb.2 mouse [Q924A0-5]
uc008hyk.2 mouse [Q924A0-2]
uc008hyn.2 mouse [Q924A0-9]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ223070 mRNA Translation: CAA11071.1
AF107298 mRNA Translation: AAD16967.1
AF107299 mRNA Translation: AAD16968.1
AF363722 Genomic DNA Translation: AAK77485.1
AF363722 Genomic DNA Translation: AAK77486.1
AF363724 mRNA Translation: AAK77488.1
AF363725 mRNA Translation: AAK77489.1
AF363726 mRNA Translation: AAK77490.1
AY072035 mRNA Translation: AAL58534.1
AK048536 mRNA Translation: BAC33366.1
AC118695 Genomic DNA No translation available.
AC137148 Genomic DNA No translation available.
AC157916 Genomic DNA No translation available.
CCDSiCCDS50470.1 [Q924A0-2]
CCDS50471.1 [Q924A0-1]
CCDS50474.1 [Q924A0-9]
RefSeqiNP_001136390.1, NM_001142918.2
NP_001136393.1, NM_001142921.2
NP_001136396.1, NM_001142924.2 [Q924A0-9]
UniGeneiMm.139815

3D structure databases

ProteinModelPortaliQ924A0
SMRiQ924A0
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204009, 10 interactors
DIPiDIP-40920N
IntActiQ924A0, 5 interactors
MINTiQ924A0
STRINGi10090.ENSMUSP00000107284

PTM databases

iPTMnetiQ924A0
PhosphoSitePlusiQ924A0

Proteomic databases

PaxDbiQ924A0
PeptideAtlasiQ924A0
PRIDEiQ924A0

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000111646; ENSMUSP00000107273; ENSMUSG00000024985 [Q924A0-9]
GeneIDi21416
KEGGimmu:21416
UCSCiuc008hya.2 mouse [Q924A0-6]
uc008hyb.2 mouse [Q924A0-5]
uc008hyk.2 mouse [Q924A0-2]
uc008hyn.2 mouse [Q924A0-9]

Organism-specific databases

CTDi6934
MGIiMGI:1202879 Tcf7l2

Phylogenomic databases

eggNOGiKOG3248 Eukaryota
ENOG41109RU LUCA
GeneTreeiENSGT00390000009964
HOGENOMiHOG000116032
HOVERGENiHBG000419
InParanoidiQ924A0
KOiK04491

Enzyme and pathway databases

ReactomeiR-MMU-201722 Formation of the beta-catenin:TCF transactivating complex
R-MMU-3769402 Deactivation of the beta-catenin transactivating complex
R-MMU-4086398 Ca2+ pathway
R-MMU-4641265 Repression of WNT target genes
R-MMU-8951430 RUNX3 regulates WNT signaling

Miscellaneous databases

ChiTaRSiTcf7l2 mouse
PROiPR:Q924A0
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000024985 Expressed in 348 organ(s), highest expression level in inferior colliculus
CleanExiMM_TCF4
ExpressionAtlasiQ924A0 baseline and differential
GenevisibleiQ924A0 MM

Family and domain databases

Gene3Di1.10.30.10, 1 hit
4.10.900.10, 1 hit
InterProiView protein in InterPro
IPR027397 Catenin_binding_dom_sf
IPR013558 CTNNB1-bd_N
IPR009071 HMG_box_dom
IPR036910 HMG_box_dom_sf
IPR024940 TCF/LEF
IPR028773 TCF7L
PANTHERiPTHR10373 PTHR10373, 1 hit
PTHR10373:SF25 PTHR10373:SF25, 1 hit
PfamiView protein in Pfam
PF08347 CTNNB1_binding, 1 hit
PF00505 HMG_box, 1 hit
SMARTiView protein in SMART
SM00398 HMG, 1 hit
SUPFAMiSSF47095 SSF47095, 1 hit
PROSITEiView protein in PROSITE
PS50118 HMG_BOX_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTF7L2_MOUSE
AccessioniPrimary (citable) accession number: Q924A0
Secondary accession number(s): O70574
, Q8C834, Q91XP2, Q91XP3, Q91XP4, Q924A1, Q9Z0V3, Q9Z0V4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 25, 2003
Last sequence update: March 25, 2003
Last modified: November 7, 2018
This is version 164 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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