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Protein

Transcription factor 7-like 2

Gene

TCF7L2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 5'-CCTTTGATC-3' 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. Necessary for the maintenance of the epithelial stem-cell compartment of the small intestine.5 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi350 – 418HMG boxPROSITE-ProRule annotationAdd BLAST69

GO - Molecular functioni

  • armadillo repeat domain binding Source: BHF-UCL
  • beta-catenin binding Source: BHF-UCL
  • gamma-catenin binding Source: BHF-UCL
  • nuclear hormone receptor binding Source: BHF-UCL
  • protein kinase binding Source: UniProtKB
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: BHF-UCL
  • RNA polymerase II repressing transcription factor binding Source: BHF-UCL
  • sequence-specific DNA binding Source: UniProtKB
  • transcription factor activity, sequence-specific DNA binding Source: BHF-UCL
  • transcription factor binding Source: BHF-UCL
  • transcription regulatory region DNA binding Source: UniProtKB

GO - Biological processi

  • beta-catenin-TCF complex assembly Source: Reactome
  • blood vessel development Source: BHF-UCL
  • canonical Wnt signaling pathway Source: BHF-UCL
  • canonical Wnt signaling pathway involved in positive regulation of epithelial to mesenchymal transition Source: BHF-UCL
  • cell cycle arrest Source: BHF-UCL
  • cell proliferation Source: BHF-UCL
  • fat cell differentiation Source: BHF-UCL
  • glucose homeostasis Source: BHF-UCL
  • maintenance of DNA repeat elements Source: BHF-UCL
  • myoblast fate commitment Source: BHF-UCL
  • negative regulation of canonical Wnt signaling pathway Source: UniProtKB
  • negative regulation of extrinsic apoptotic signaling pathway Source: BHF-UCL
  • negative regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • negative regulation of type B pancreatic cell apoptotic process Source: BHF-UCL
  • pancreas development Source: BHF-UCL
  • positive regulation of heparan sulfate proteoglycan biosynthetic process Source: BHF-UCL
  • positive regulation of insulin secretion Source: BHF-UCL
  • positive regulation of protein binding Source: BHF-UCL
  • positive regulation of protein export from nucleus Source: BHF-UCL
  • positive regulation of protein kinase B signaling Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • regulation of hormone metabolic process Source: BHF-UCL
  • regulation of smooth muscle cell proliferation Source: BHF-UCL
  • regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • response to glucose Source: BHF-UCL
  • transcription, DNA-templated Source: UniProtKB-KW
  • Wnt signaling pathway, calcium modulating pathway Source: Reactome
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:ENSG00000148737-MONOMER.
ReactomeiR-HSA-201722. Formation of the beta-catenin:TCF transactivating complex.
R-HSA-3769402. Deactivation of the beta-catenin transactivating complex.
R-HSA-381771. Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
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.
R-HSA-5339700. TCF7L2 mutants don't bind CTBP.
SignaLinkiQ9NQB0.
SIGNORiQ9NQB0.

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:
hTCF-4
Gene namesi
Name:TCF7L2
Synonyms:TCF4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:11641. TCF7L2.

Subcellular locationi

GO - Cellular componenti

  • beta-catenin-TCF7L2 complex Source: BHF-UCL
  • cytoplasm Source: HPA
  • nuclear chromatin Source: BHF-UCL
  • nucleoplasm Source: BHF-UCL
  • nucleus Source: UniProtKB
  • PML body Source: UniProtKB-SubCell
  • protein-DNA complex Source: BHF-UCL
Complete GO annotation...

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).

Diabetes mellitus, non-insulin-dependent (NIDDM)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
See also OMIM:125853

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi10 – 11DD → AA: Reduces CTNNB1 binding. 1 Publication2
Mutagenesisi16D → A: Abolishes CTNNB1 binding. 1 Publication1
Mutagenesisi17E → A: Reduces CTNNB1 binding. 1 Publication1
Mutagenesisi19I → A: Reduces transcription activation. 1 Publication1
Mutagenesisi21F → A: Reduces transcription activation. 1 Publication1
Mutagenesisi23 – 24DE → AA: Reduces CTNNB1 binding. 1 Publication2
Mutagenesisi24E → A: Reduces CTNNB1 binding, and abolishes CTNNB1 binding; when associated with A-26; A-28 and A-29. 1 Publication1
Mutagenesisi26E → A: Abolishes CTNNB1 binding; when associated with A-24; A-28 and A-29. 1 Publication1
Mutagenesisi28E → A: Abolishes CTNNB1 binding; when associated with A-24; A-26 and A-29. 1 Publication1
Mutagenesisi29E → A: Reduces CTNNB1 binding, and abolishes CTNNB1 binding; when associated with A-24; A-26 and A-28. 1 Publication1
Mutagenesisi48L → A: Abolishes CTNNB1 binding. 1 Publication1
Mutagenesisi201T → V: Reduced phosphorylation by NLK and enhanced DNA-binding; when associated with V-212. 1 Publication1
Mutagenesisi212T → V: Reduced phosphorylation by NLK and enhanced DNA-binding; when associated with V-201. 1 Publication1
Mutagenesisi320K → R: Loss of sumoylation. No effect on localization to nuclear bodies. 1 Publication1
Mutagenesisi322E → A: Loss of sumoylation. 1 Publication1

Keywords - Diseasei

Diabetes mellitus

Organism-specific databases

DisGeNETi6934.
MalaCardsiTCF7L2.
MIMi125853. phenotype.
OpenTargetsiENSG00000148737.
PharmGKBiPA36394.

Chemistry databases

ChEMBLiCHEMBL3038511.

Polymorphism and mutation databases

BioMutaiTCF7L2.
DMDMi29337146.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000486231 – 619Transcription factor 7-like 2Add BLAST619

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei201Phosphothreonine; by NLK1 Publication1
Modified residuei212Phosphothreonine; by NLK1 Publication1
Cross-linki320Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication

Post-translational modificationi

In vitro, phosphorylated by TNIK.1 Publication
Phosphorylated at Thr-201 and/or Thr-212 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.1 Publication
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.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ9NQB0.
PaxDbiQ9NQB0.
PeptideAtlasiQ9NQB0.
PRIDEiQ9NQB0.

PTM databases

iPTMnetiQ9NQB0.
PhosphoSitePlusiQ9NQB0.

Expressioni

Tissue specificityi

Detected in epithelium from small intestine, with the highest expression at the top of the crypts and a gradient of expression from crypt to villus. Detected in colon epithelium and colon cancer, and in epithelium from mammary gland and carcinomas derived therefrom.1 Publication

Developmental stagei

Highly expressed in crypt regions and barely detectable in villi in epithelium from fetal small intestine at week 16. At week 22 expression in villi had increased strongly.

Gene expression databases

BgeeiENSG00000148737.
CleanExiHS_TCF4.
ExpressionAtlasiQ9NQB0. baseline and differential.
GenevisibleiQ9NQB0. HS.

Organism-specific databases

HPAiCAB013535.
HPA038800.

Interactioni

Subunit structurei

Interacts with TGFB1I1 (By similarity). Interacts with CTNNB1 (via the armadillo repeat); forms stable transcription complex. Interacts with EP300. Interacts with NLK. Interacts with CCDC85B (probably through the HMG box); prevents interaction with CTNNB1. Interacts with TNIK. 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 SPIN1.By similarity19 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CTNNB1P3522230EBI-924724,EBI-491549
DAXXQ9UER75EBI-924724,EBI-77321
HIC1Q145266EBI-924724,EBI-2507362
JUPP1492313EBI-924724,EBI-702484
RUNX3Q1376114EBI-924724,EBI-925990
TNIKQ9UKE53EBI-924724,EBI-1051794
XRCC6P129569EBI-924724,EBI-353208

GO - Molecular functioni

  • armadillo repeat domain binding Source: BHF-UCL
  • beta-catenin binding Source: BHF-UCL
  • gamma-catenin binding Source: BHF-UCL
  • nuclear hormone receptor binding Source: BHF-UCL
  • protein kinase binding Source: UniProtKB
  • RNA polymerase II repressing transcription factor binding Source: BHF-UCL
  • transcription factor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi112795. 35 interactors.
DIPiDIP-36236N.
IntActiQ9NQB0. 38 interactors.
MINTiMINT-222146.
STRINGi9606.ENSP00000444972.

Chemistry databases

BindingDBiQ9NQB0.

Structurei

Secondary structure

1619
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi22 – 31Combined sources10
Helixi38 – 48Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JDHX-ray1.90B12-49[»]
1JPWX-ray2.50D/E/F6-54[»]
2GL7X-ray2.60B/E1-53[»]
DisProtiDP00175.
ProteinModelPortaliQ9NQB0.
SMRiQ9NQB0.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9NQB0.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 53CTNNB1-bindingBy similarityAdd BLAST53
Regioni201 – 395Mediates interaction with MAD2L21 PublicationAdd BLAST195
Regioni459 – 505Promoter-specific activation domainAdd BLAST47

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi425 – 430Nuclear localization signalSequence analysis6

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi178 – 317Pro-richAdd BLAST140

Domaini

The promoter-specific activation domain interacts with the transcriptional coactivator EP300.

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.
HOVERGENiHBG000419.
InParanoidiQ9NQB0.
KOiK04491.
OMAiEPWCLES.
OrthoDBiEOG091G0705.
PhylomeDBiQ9NQB0.
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.
IPR028773. TCF7L2.
[Graphical view]
PANTHERiPTHR10373. PTHR10373. 3 hits.
PTHR10373:SF32. PTHR10373:SF32. 3 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]

Sequences (17)i

Sequence statusi: Complete.

This entry describes 17 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NQB0-1) [UniParc]FASTAAdd to basket
Also known as: TCF-4M

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 SSENSSAERD LADVKSSLVN
60 70 80 90 100
ESETNQNSSS DSEAERRPPP RSESFRDKSR ESLEEAAKRQ DGGLFKGPPY
110 120 130 140 150
PGYPFIMIPD LTSPYLPNGS LSPTARTLHF QSGSTHYSAY KTIEHQIAVQ
160 170 180 190 200
YLQMKWPLLD VQAGSLQSRQ ALKDARSPSP AHIVSNKVPV VQHPHHVHPL
210 220 230 240 250
TPLITYSNEH FTPGNPPPHL PADVDPKTGI PRPPHPPDIS PYYPLSPGTV
260 270 280 290 300
GQIPHPLGWL VPQQGQPVYP ITTGGFRHPY PTALTVNASM SRFPPHMVPP
310 320 330 340 350
HHTLHTTGIP HPAIVTPTVK QESSQSDVGS LHSSKHQDSK KEEEKKKPHI
360 370 380 390 400
KKPLNAFMLY MKEMRAKVVA ECTLKESAAI NQILGRRWHA LSREEQAKYY
410 420 430 440 450
ELARKERQLH MQLYPGWSAR DNYGKKKKRK RDKQPGETNE HSECFLNPCL
460 470 480 490 500
SLPPITDLSA PKKCRARFGL DQQNNWCGPC RRKKKCVRYI QGEGSCLSPP
510 520 530 540 550
SSDGSLLDSP PPSPNLLGSP PRDAKSQTEQ TQPLSLSLKP DPLAHLSMMP
560 570 580 590 600
PPPALLLAEA THKASALCPN GALDLPPAAL QPAAPSSSIA QPSTSSLHSH
610
SSLAGTQPQP LSLVTKSLE
Length:619
Mass (Da):67,919
Last modified:March 25, 2003 - v2
Checksum:i4DD2D3CC814AE16E
GO
Isoform 2 (identifier: Q9NQB0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     482-494: RKKKCVRYIQGEG → CKYSKEVSGTVRA
     495-619: Missing.

Show »
Length:494
Mass (Da):55,152
Checksum:iAC0B8049DF6F4498
GO
Isoform 3 (identifier: Q9NQB0-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     457-478: DLSAPKKCRARFGLDQQNNWCG → DANTPKKCRALFGLDRQTLWCK

Show »
Length:619
Mass (Da):67,976
Checksum:i6F0250E096854CC0
GO
Isoform 4 (identifier: Q9NQB0-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     440-456: Missing.
     482-494: RKKKCVRYIQGEG → CKYSKEVSGTVRA
     495-619: Missing.

Show »
Length:477
Mass (Da):53,270
Checksum:i380199CA672A41A8
GO
Isoform 5 (identifier: Q9NQB0-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     440-456: Missing.

Show »
Length:602
Mass (Da):66,037
Checksum:iA52CA392A33AB61C
GO
Isoform 6 (identifier: Q9NQB0-6) [UniParc]FASTAAdd to basket
Also known as: TCF-4I

The sequence of this isoform differs from the canonical sequence as follows:
     457-619: DLSAPKKCRA...PLSLVTKSLE → GEKKSAFATYKVKAAASAHPLQMEAY

Show »
Length:482
Mass (Da):53,676
Checksum:iB68AD303BF9F3E25
GO
Isoform 7 (identifier: Q9NQB0-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     440-456: Missing.
     457-478: DLSAPKKCRARFGLDQQNNWCG → DANTPKKCRALFGLDRQTLWCK

Show »
Length:602
Mass (Da):66,094
Checksum:i87FC20BEB4F51BB2
GO
Isoform 8 (identifier: Q9NQB0-8) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     128-150: Missing.

Show »
Length:596
Mass (Da):65,291
Checksum:iA022284FEC164B09
GO
Isoform 9 (identifier: Q9NQB0-9) [UniParc]FASTAAdd to basket
Also known as: TCF-4G

The sequence of this isoform differs from the canonical sequence as follows:
     440-465: EHSECFLNPCLSLPPITDLSAPKKCR → GEKKSAFATYKVKAAASAHPLQMEAY
     466-619: Missing.

Show »
Length:465
Mass (Da):51,794
Checksum:i5E1E47B5DCB132BE
GO
Isoform 10 (identifier: Q9NQB0-10) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     128-150: Missing.
     260-263: Missing.
     457-482: DLSAPKKCRARFGLDQQNNWCGPCRR → GEKKSAFATYKVKAAASAHPLQMEAY
     483-619: Missing.

Show »
Length:455
Mass (Da):50,611
Checksum:i2775B43A2E392581
GO
Isoform 11 (identifier: Q9NQB0-11) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     128-150: Missing.
     184-184: V → VSPLPCCTQGHDCQHFYPPSDFTVSTQVFRDMKRSHSLQKVGEPWCIE
     440-465: EHSECFLNPCLSLPPITDLSAPKKCR → GEKKSAFATYKVKAAASAHPLQMEAY
     466-619: Missing.

Show »
Length:489
Mass (Da):54,572
Checksum:i9817D6DB995CBCD2
GO
Isoform 12 (identifier: Q9NQB0-12) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     128-150: Missing.
     481-619: RRKKKCVRYI...PLSLVTKSLE → SL

Note: Low expression in pancreas and colon.
Show »
Length:459
Mass (Da):51,159
Checksum:i59C37C6D178BD813
GO
Isoform 13 (identifier: Q9NQB0-13) [UniParc]FASTAAdd to basket
Also known as: TCF-4J

The sequence of this isoform differs from the canonical sequence as follows:
     128-150: Missing.
     440-456: Missing.
     457-478: DLSAPKKCRARFGLDQQNNWCG → DANTPKKCRALFGLDRQTLWCK

Note: Common splicing form, lowest expression in skeletal muscle.
Show »
Length:579
Mass (Da):63,466
Checksum:iB2DEA916F03B0F63
GO
Isoform 14 (identifier: Q9NQB0-14) [UniParc]FASTAAdd to basket
Also known as: TCF-4B, short

The sequence of this isoform differs from the canonical sequence as follows:
     128-150: Missing.
     440-465: EHSECFLNPCLSLPPITDLSAPKKCR → GEKKSAFATYKVKAAASAHPLQMEAY
     466-619: Missing.

Note: High transcriptional activity. Major isoform in liver.
Show »
Length:442
Mass (Da):49,166
Checksum:i57D7E679A87FF4C3
GO
Isoform 15 (identifier: Q9NQB0-15) [UniParc]FASTAAdd to basket
Also known as: TCF-4A

The sequence of this isoform differs from the canonical sequence as follows:
     128-150: Missing.
     290-290: M → MSSFLS
     440-465: EHSECFLNPCLSLPPITDLSAPKKCR → GEKKSAFATYKVKAAASAHPLQMEAY
     466-619: Missing.

Show »
Length:447
Mass (Da):49,688
Checksum:i1363601E57F2AA39
GO
Isoform 16 (identifier: Q9NQB0-16) [UniParc]FASTAAdd to basket
Also known as: TCF-4K

The sequence of this isoform differs from the canonical sequence as follows:
     128-150: Missing.
     290-290: M → MSSFLS
     440-456: Missing.

Show »
Length:584
Mass (Da):63,930
Checksum:i7AA2B6E62420108B
GO
Isoform 17 (identifier: Q9NQB0-17) [UniParc]FASTAAdd to basket
Also known as: TCF-4X2

The sequence of this isoform differs from the canonical sequence as follows:
     1-6: MPQLNG → MSSFLS
     7-290: Missing.

Show »
Length:335
Mass (Da):36,884
Checksum:i6085EDAAE3D893A5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti118 – 121NGSL → KRSV in CAB97212 (PubMed:10919662).Curated4
Sequence conflicti118 – 121NGSL → KRSV in CAB97213 (PubMed:10919662).Curated4
Sequence conflicti167Q → R in ADK35180 (PubMed:21256126).Curated1
Sequence conflicti226P → L in ADK35180 (PubMed:21256126).Curated1
Sequence conflicti290M → V in CAA72166 (PubMed:9065401).Curated1
Sequence conflicti331L → H in ACI28527 (PubMed:19602480).Curated1
Sequence conflicti596S → W in CAA72166 (PubMed:9065401).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_047126346K → N.1 PublicationCorresponds to variant rs2757884dbSNPEnsembl.1
Natural variantiVAR_035939465R → C in a colorectal cancer sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0537481 – 6MPQLNG → MSSFLS in isoform 17. 1 Publication6
Alternative sequenceiVSP_0537497 – 290Missing in isoform 17. 1 PublicationAdd BLAST284
Alternative sequenceiVSP_006962128 – 150Missing in isoform 8, isoform 10, isoform 11, isoform 12, isoform 13, isoform 14, isoform 15 and isoform 16. 5 PublicationsAdd BLAST23
Alternative sequenceiVSP_045821184V → VSPLPCCTQGHDCQHFYPPS DFTVSTQVFRDMKRSHSLQK VGEPWCIE in isoform 11. Curated1
Alternative sequenceiVSP_006963260 – 263Missing in isoform 10. 1 Publication4
Alternative sequenceiVSP_053750290M → MSSFLS in isoform 15 and isoform 16. 1 Publication1
Alternative sequenceiVSP_006965440 – 465EHSEC…PKKCR → GEKKSAFATYKVKAAASAHP LQMEAY in isoform 9, isoform 11, isoform 14 and isoform 15. 5 PublicationsAdd BLAST26
Alternative sequenceiVSP_006964440 – 456Missing in isoform 4, isoform 5, isoform 7, isoform 13 and isoform 16. 2 PublicationsAdd BLAST17
Alternative sequenceiVSP_006967457 – 619DLSAP…TKSLE → GEKKSAFATYKVKAAASAHP LQMEAY in isoform 6. 1 PublicationAdd BLAST163
Alternative sequenceiVSP_006968457 – 482DLSAP…GPCRR → GEKKSAFATYKVKAAASAHP LQMEAY in isoform 10. 1 PublicationAdd BLAST26
Alternative sequenceiVSP_006966457 – 478DLSAP…NNWCG → DANTPKKCRALFGLDRQTLW CK in isoform 3, isoform 7 and isoform 13. 2 PublicationsAdd BLAST22
Alternative sequenceiVSP_006969466 – 619Missing in isoform 9, isoform 11, isoform 14 and isoform 15. 5 PublicationsAdd BLAST154
Alternative sequenceiVSP_045822481 – 619RRKKK…TKSLE → SL in isoform 12. 1 PublicationAdd BLAST139
Alternative sequenceiVSP_006970482 – 494RKKKC…IQGEG → CKYSKEVSGTVRA in isoform 2 and isoform 4. CuratedAdd BLAST13
Alternative sequenceiVSP_006971483 – 619Missing in isoform 10. 1 PublicationAdd BLAST137
Alternative sequenceiVSP_006972495 – 619Missing in isoform 2 and isoform 4. CuratedAdd BLAST125

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y11306 mRNA. Translation: CAA72166.2.
AJ270770
, AJ270771, AJ270772, AJ270773, AJ270774, AJ270775, AJ270776, AJ270778 Genomic DNA. Translation: CAB97212.1.
AJ270770
, AJ270771, AJ270772, AJ270773, AJ270774, AJ270775, AJ270776, AJ270778 Genomic DNA. Translation: CAB97213.1.
AJ270770
, AJ270771, AJ270772, AJ270773, AJ270774, AJ270775, AJ270777, AJ270778 Genomic DNA. Translation: CAB97214.1.
AJ270770
, AJ270771, AJ270772, AJ270773, AJ270774, AJ270775, AJ270777, AJ270778 Genomic DNA. Translation: CAB97215.1.
AJ270770
, AJ270771, AJ270772, AJ270773, AJ270774, AJ270775, AJ270778 Genomic DNA. Translation: CAB97216.1.
AJ270770
, AJ270771, AJ270772, AJ270773, AJ270774, AJ270775, AJ270778 Genomic DNA. Translation: CAB97217.1.
AJ270770
, AJ270771, AJ270772, AJ270773, AJ270774, AJ270775, AJ270776, AJ270777 Genomic DNA. Translation: CAB97218.1.
AJ270770
, AJ270771, AJ270772, AJ270773, AJ270774, AJ270775, AJ270776, AJ270777 Genomic DNA. Translation: CAB97219.1.
FJ010167 mRNA. Translation: ACI28525.1.
FJ010169 mRNA. Translation: ACI28527.1.
FJ010172 mRNA. Translation: ACI28530.1.
HM352839 mRNA. Translation: ADK35175.1.
HM352842 mRNA. Translation: ADK35178.1.
HM352844 mRNA. Translation: ADK35180.1.
HM352845 mRNA. Translation: ADK35187.1.
HM352846 mRNA. Translation: ADK35181.1.
HM352847 mRNA. Translation: ADK35182.1.
HM352849 mRNA. Translation: ADK35184.1.
HM352850 mRNA. Translation: ADK35185.1.
AB440195 mRNA. Translation: BAH24004.1.
AK299295 mRNA. Translation: BAG61310.1.
AL135792 Genomic DNA. No translation available.
AL158212 Genomic DNA. No translation available.
AL445486 Genomic DNA. No translation available.
AL451084 Genomic DNA. No translation available.
CH471066 Genomic DNA. Translation: EAW49513.1.
CH471066 Genomic DNA. Translation: EAW49515.1.
CH471066 Genomic DNA. Translation: EAW49516.1.
BC032656 mRNA. Translation: AAH32656.1.
AB034691 mRNA. Translation: BAA86225.1.
CCDSiCCDS53577.1. [Q9NQB0-7]
CCDS53578.1. [Q9NQB0-11]
CCDS55729.1. [Q9NQB0-12]
CCDS7576.1. [Q9NQB0-8]
PIRiS22807.
RefSeqiNP_001139746.1. NM_001146274.1. [Q9NQB0-7]
NP_001139755.1. NM_001146283.1. [Q9NQB0-11]
NP_001139756.1. NM_001146284.1. [Q9NQB0-10]
NP_001139758.1. NM_001146286.1. [Q9NQB0-14]
NP_001185455.1. NM_001198526.1. [Q9NQB0-13]
NP_001185457.1. NM_001198528.1. [Q9NQB0-12]
NP_001185460.1. NM_001198531.1. [Q9NQB0-9]
XP_005270141.1. XM_005270084.1. [Q9NQB0-1]
XP_005270146.1. XM_005270089.1.
XP_005270153.1. XM_005270096.2. [Q9NQB0-6]
XP_005270160.1. XM_005270103.1. [Q9NQB0-15]
XP_016872081.1. XM_017016592.1. [Q9NQB0-3]
XP_016872082.1. XM_017016593.1. [Q9NQB0-5]
UniGeneiHs.593995.

Genome annotation databases

EnsembliENST00000352065; ENSP00000344823; ENSG00000148737. [Q9NQB0-12]
ENST00000355717; ENSP00000347949; ENSG00000148737. [Q9NQB0-11]
ENST00000355995; ENSP00000348274; ENSG00000148737. [Q9NQB0-1]
ENST00000369397; ENSP00000358404; ENSG00000148737. [Q9NQB0-8]
ENST00000538897; ENSP00000446172; ENSG00000148737. [Q9NQB0-6]
ENST00000627217; ENSP00000486891; ENSG00000148737. [Q9NQB0-7]
GeneIDi6934.
KEGGihsa:6934.
UCSCiuc001lac.5. human. [Q9NQB0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y11306 mRNA. Translation: CAA72166.2.
AJ270770
, AJ270771, AJ270772, AJ270773, AJ270774, AJ270775, AJ270776, AJ270778 Genomic DNA. Translation: CAB97212.1.
AJ270770
, AJ270771, AJ270772, AJ270773, AJ270774, AJ270775, AJ270776, AJ270778 Genomic DNA. Translation: CAB97213.1.
AJ270770
, AJ270771, AJ270772, AJ270773, AJ270774, AJ270775, AJ270777, AJ270778 Genomic DNA. Translation: CAB97214.1.
AJ270770
, AJ270771, AJ270772, AJ270773, AJ270774, AJ270775, AJ270777, AJ270778 Genomic DNA. Translation: CAB97215.1.
AJ270770
, AJ270771, AJ270772, AJ270773, AJ270774, AJ270775, AJ270778 Genomic DNA. Translation: CAB97216.1.
AJ270770
, AJ270771, AJ270772, AJ270773, AJ270774, AJ270775, AJ270778 Genomic DNA. Translation: CAB97217.1.
AJ270770
, AJ270771, AJ270772, AJ270773, AJ270774, AJ270775, AJ270776, AJ270777 Genomic DNA. Translation: CAB97218.1.
AJ270770
, AJ270771, AJ270772, AJ270773, AJ270774, AJ270775, AJ270776, AJ270777 Genomic DNA. Translation: CAB97219.1.
FJ010167 mRNA. Translation: ACI28525.1.
FJ010169 mRNA. Translation: ACI28527.1.
FJ010172 mRNA. Translation: ACI28530.1.
HM352839 mRNA. Translation: ADK35175.1.
HM352842 mRNA. Translation: ADK35178.1.
HM352844 mRNA. Translation: ADK35180.1.
HM352845 mRNA. Translation: ADK35187.1.
HM352846 mRNA. Translation: ADK35181.1.
HM352847 mRNA. Translation: ADK35182.1.
HM352849 mRNA. Translation: ADK35184.1.
HM352850 mRNA. Translation: ADK35185.1.
AB440195 mRNA. Translation: BAH24004.1.
AK299295 mRNA. Translation: BAG61310.1.
AL135792 Genomic DNA. No translation available.
AL158212 Genomic DNA. No translation available.
AL445486 Genomic DNA. No translation available.
AL451084 Genomic DNA. No translation available.
CH471066 Genomic DNA. Translation: EAW49513.1.
CH471066 Genomic DNA. Translation: EAW49515.1.
CH471066 Genomic DNA. Translation: EAW49516.1.
BC032656 mRNA. Translation: AAH32656.1.
AB034691 mRNA. Translation: BAA86225.1.
CCDSiCCDS53577.1. [Q9NQB0-7]
CCDS53578.1. [Q9NQB0-11]
CCDS55729.1. [Q9NQB0-12]
CCDS7576.1. [Q9NQB0-8]
PIRiS22807.
RefSeqiNP_001139746.1. NM_001146274.1. [Q9NQB0-7]
NP_001139755.1. NM_001146283.1. [Q9NQB0-11]
NP_001139756.1. NM_001146284.1. [Q9NQB0-10]
NP_001139758.1. NM_001146286.1. [Q9NQB0-14]
NP_001185455.1. NM_001198526.1. [Q9NQB0-13]
NP_001185457.1. NM_001198528.1. [Q9NQB0-12]
NP_001185460.1. NM_001198531.1. [Q9NQB0-9]
XP_005270141.1. XM_005270084.1. [Q9NQB0-1]
XP_005270146.1. XM_005270089.1.
XP_005270153.1. XM_005270096.2. [Q9NQB0-6]
XP_005270160.1. XM_005270103.1. [Q9NQB0-15]
XP_016872081.1. XM_017016592.1. [Q9NQB0-3]
XP_016872082.1. XM_017016593.1. [Q9NQB0-5]
UniGeneiHs.593995.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JDHX-ray1.90B12-49[»]
1JPWX-ray2.50D/E/F6-54[»]
2GL7X-ray2.60B/E1-53[»]
DisProtiDP00175.
ProteinModelPortaliQ9NQB0.
SMRiQ9NQB0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112795. 35 interactors.
DIPiDIP-36236N.
IntActiQ9NQB0. 38 interactors.
MINTiMINT-222146.
STRINGi9606.ENSP00000444972.

Chemistry databases

BindingDBiQ9NQB0.
ChEMBLiCHEMBL3038511.

PTM databases

iPTMnetiQ9NQB0.
PhosphoSitePlusiQ9NQB0.

Polymorphism and mutation databases

BioMutaiTCF7L2.
DMDMi29337146.

Proteomic databases

MaxQBiQ9NQB0.
PaxDbiQ9NQB0.
PeptideAtlasiQ9NQB0.
PRIDEiQ9NQB0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000352065; ENSP00000344823; ENSG00000148737. [Q9NQB0-12]
ENST00000355717; ENSP00000347949; ENSG00000148737. [Q9NQB0-11]
ENST00000355995; ENSP00000348274; ENSG00000148737. [Q9NQB0-1]
ENST00000369397; ENSP00000358404; ENSG00000148737. [Q9NQB0-8]
ENST00000538897; ENSP00000446172; ENSG00000148737. [Q9NQB0-6]
ENST00000627217; ENSP00000486891; ENSG00000148737. [Q9NQB0-7]
GeneIDi6934.
KEGGihsa:6934.
UCSCiuc001lac.5. human. [Q9NQB0-1]

Organism-specific databases

CTDi6934.
DisGeNETi6934.
GeneCardsiTCF7L2.
HGNCiHGNC:11641. TCF7L2.
HPAiCAB013535.
HPA038800.
MalaCardsiTCF7L2.
MIMi125853. phenotype.
602228. gene.
neXtProtiNX_Q9NQB0.
OpenTargetsiENSG00000148737.
PharmGKBiPA36394.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3248. Eukaryota.
ENOG41109RU. LUCA.
GeneTreeiENSGT00390000009964.
HOVERGENiHBG000419.
InParanoidiQ9NQB0.
KOiK04491.
OMAiEPWCLES.
OrthoDBiEOG091G0705.
PhylomeDBiQ9NQB0.
TreeFamiTF318448.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000148737-MONOMER.
ReactomeiR-HSA-201722. Formation of the beta-catenin:TCF transactivating complex.
R-HSA-3769402. Deactivation of the beta-catenin transactivating complex.
R-HSA-381771. Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
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.
R-HSA-5339700. TCF7L2 mutants don't bind CTBP.
SignaLinkiQ9NQB0.
SIGNORiQ9NQB0.

Miscellaneous databases

ChiTaRSiTCF7L2. human.
EvolutionaryTraceiQ9NQB0.
GeneWikiiTCF7L2.
GenomeRNAii6934.
PROiQ9NQB0.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000148737.
CleanExiHS_TCF4.
ExpressionAtlasiQ9NQB0. baseline and differential.
GenevisibleiQ9NQB0. 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.
IPR028773. TCF7L2.
[Graphical view]
PANTHERiPTHR10373. PTHR10373. 3 hits.
PTHR10373:SF32. PTHR10373:SF32. 3 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 nameiTF7L2_HUMAN
AccessioniPrimary (citable) accession number: Q9NQB0
Secondary accession number(s): B4DRJ8
, B9X074, C6ZRJ8, C6ZRK0, E2GH14, E2GH19, E2GH20, E2GH24, E2GH25, E9PFH9, F8W742, F8W7T5, O00185, Q9NQB1, Q9NQB2, Q9NQB3, Q9NQB4, Q9NQB5, Q9NQB6, Q9NQB7, Q9ULC2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 25, 2003
Last sequence update: March 25, 2003
Last modified: November 30, 2016
This is version 174 of the entry and version 2 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.