Reviewed, UniProtKB/Swiss-Prot Q9NQB0 (TF7L2_HUMAN)

Names and origin

Protein names

Recommended name:
    Transcription factor 7-like 2
Alternative name(s):
    HMG box transcription factor 4
    T-cell-specific transcription factor 4
      Short name=TCF-4
      Short name=hTCF-4

Gene names

Name:	TCF7L2
Synonyms:	TCF4

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	619 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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 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. Ref.6 Ref.10 Ref.11
Subunit structure	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.
Subcellular location	Nucleus. Note: Diffuse pattern. Colocalizes with SUMO1 and PIAS4 in a subset of PML (promyelocytic leukemia) nuclear bodies. Ref.11 Ref.7
Tissue specificity	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. Ref.7
Developmental stage	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.
Domain	The promoter-specific activation domain interacts with the transcriptional coactivator EP300.
Post-translational modification	Polysumoylated. Sumoylation is enhanced by PIAS family members and desumoylated by AXAM/SENP2. Sumoylation/desumoylation regulates TCF4 transcription activity in the Wnt signaling pathway without altering interaction with CTNNB1 nor binding DNA. Ref.11
Involvement in disease	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). Genetic variations in TCF7L2 are associated with susceptibility to non-insulin-dependent diabetes mellitus (NIDDM) [MIM:125853]. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance. Ref.17
Sequence similarities	Belongs to the TCF/LEF family. Contains 1 HMG box DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation Wnt signaling pathway
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Diabetes mellitus
Ligand	DNA-binding
Molecular function	Activator Repressor
PTM	Isopeptide bond Ubl conjugation
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	Wnt receptor signaling pathway through beta-catenin Ref.1 Inferred by curator. Source: UniProtKB anti-apoptosis Inferred from direct assay. Source: UniProtKB blood vessel development Inferred from mutant phenotype. Source: UniProtKB cell cycle arrest Ref.10 Inferred from mutant phenotype. Source: UniProtKB cell proliferation Ref.10 Inferred from mutant phenotype. Source: UniProtKB fat cell differentiation Inferred from direct assay. Source: UniProtKB glucose homeostasis Inferred from direct assay. Source: UniProtKB myoblast cell fate commitment Inferred from direct assay. Source: UniProtKB pancreas development Traceable author statement. Source: UniProtKB positive regulation of gene-specific transcription from RNA polymerase II promoter Ref.1 Inferred from direct assay. Source: UniProtKB positive regulation of heparan sulfate proteoglycan biosynthetic process Inferred from mutant phenotype. Source: UniProtKB positive regulation of insulin secretion Inferred from direct assay. Source: UniProtKB regulation of hormone metabolic process Inferred from direct assay. Source: UniProtKB transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	beta-catenin-TCF7L2 complex Ref.1 Inferred from direct assay. Source: UniProtKB nucleus Ref.1 Inferred from direct assay. Source: UniProtKB
Molecular function	RNA polymerase II transcription factor activity Ref.1 Inferred from direct assay. Source: UniProtKB beta-catenin binding Ref.1 Inferred from direct assay. Source: UniProtKB protein kinase binding Ref.13 Inferred from physical interaction. Source: UniProtKB specific transcriptional repressor activity Inferred from direct assay. Source: UniProtKB transcription factor activity Ref.6 Inferred from direct assay. Source: UniProtKB transcription factor binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CTNNB1	P35222	6	EBI-924724,EBI-491549
DAXX	Q9UER7	3	EBI-924724,EBI-77321
JUP	P14923	1	EBI-924724,EBI-702484
RUNX3	Q13761	2	EBI-924724,EBI-925990
XRCC6	P12956	3	EBI-924724,EBI-353208

Alternative products

This entry describes 10 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NQB0-1)

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.

Isoform 2 (identifier: Q9NQB0-2)

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

Isoform 3 (identifier: Q9NQB0-3)

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

Isoform 4 (identifier: Q9NQB0-4)

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

Isoform 5 (identifier: Q9NQB0-5)

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

Isoform 6 (identifier: Q9NQB0-6)

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

Isoform 7 (identifier: Q9NQB0-7)

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

Isoform 8 (identifier: Q9NQB0-8)

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

Isoform 9 (identifier: Q9NQB0-9)

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

Isoform 10 (identifier: Q9NQB0-10)

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.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 619

619

Transcription factor 7-like 2

PRO_0000048623

Regions

DNA binding

350 – 418

69

HMG box

Region

1 – 53

53

CTNNB1-binding By similarity

Region

459 – 505

47

Promoter-specific activation domain

Motif

425 – 430

6

Nuclear localization signal Potential

Compositional bias

178 – 317

140

Pro-rich

Amino acid modifications

Cross-link

320

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.11

Natural variations

Alternative sequence

128 – 150

23

Missing in isoform 8 and isoform 10.

VSP_006962

Alternative sequence

260 – 263

4

Missing in isoform 10.

VSP_006963

Alternative sequence

440 – 465

26

EHSEC…PKKCR → GEKKSAFATYKVKAAASAHP LQMEAY in isoform 9.

VSP_006965

Alternative sequence

440 – 456

17

Missing in isoform 4, isoform 5 and isoform 7.

VSP_006964

Alternative sequence

457 – 619

163

DLSAP…TKSLE → GEKKSAFATYKVKAAASAHP LQMEAY in isoform 6.

VSP_006967

Alternative sequence

457 – 482

26

DLSAP…GPCRR → GEKKSAFATYKVKAAASAHP LQMEAY in isoform 10.

VSP_006968

Alternative sequence

457 – 478

22

DLSAP…NNWCG → DANTPKKCRALFGLDRQTLW CK in isoform 3 and isoform 7.

VSP_006966

Alternative sequence

466 – 619

154

Missing in isoform 9.

VSP_006969

Alternative sequence

482 – 494

13

RKKKC…IQGEG → CKYSKEVSGTVRA in isoform 2 and isoform 4.

VSP_006970

Alternative sequence

483 – 619

137

Missing in isoform 10.

VSP_006971

Alternative sequence

495 – 619

125

Missing in isoform 2 and isoform 4.

VSP_006972

Natural variant

346

1

K → N: dbSNP rs2757884. Ref.2

VAR_047126

Natural variant

465

1

R → C in a colorectal cancer sample; somatic mutation. Ref.18

VAR_035939

Experimental info

Mutagenesis

10 – 11

2

DD → AA: Reduces CTNNB1 binding.

Mutagenesis

16

1

D → A: Abolishes CTNNB1 binding. Ref.8

Mutagenesis

17

1

E → A: Reduces CTNNB1 binding. Ref.8

Mutagenesis

19

1

I → A: Reduces transcription activation. Ref.16

Mutagenesis

21

1

F → A: Reduces transcription activation. Ref.16

Mutagenesis

23 – 24

2

DE → AA: Reduces CTNNB1 binding. Ref.15

Mutagenesis

24

1

E → A: Reduces CTNNB1 binding, and abolishes CTNNB1 binding; when associated with A-26; A-28 and A-29. Ref.15

Mutagenesis

26

1

E → A: Abolishes CTNNB1 binding; when associated with A-24; A-28 and A-29. Ref.15

Mutagenesis

28

1

E → A: Abolishes CTNNB1 binding; when associated with A-24; A-26 and A-29. Ref.15

Mutagenesis

29

1

E → A: Reduces CTNNB1 binding, and abolishes CTNNB1 binding; when associated with A-24; A-26 and A-28. Ref.15

Mutagenesis

48

1

L → A: Abolishes CTNNB1 binding. Ref.8

Mutagenesis

320

1

K → R: Loss of sumoylation. No effect on localization to nuclear bodies. Ref.11

Mutagenesis

322

1

E → A: Loss of sumoylation. Ref.11

Sequence conflict

118 – 121

4

NGSL → KRSV in CAB97212. Ref.2

Sequence conflict

118 – 121

4

NGSL → KRSV in CAB97213. Ref.2

Sequence conflict

290

1

M → V in CAA72166. Ref.1

Sequence conflict

596

1

S → W in CAA72166. Ref.1

Secondary structure

1

.

.

.

.

.

619

Helix Strand Turn

Details...

Helix

22 – 31

10

Helix

38 – 48

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 25, 2003. Version 2. Checksum: 4DD2D3CC814AE16E	FASTA	619	67,919
	10 20 30 40 50 60 MPQLNGGGGD DLGANDELIS FKDEGEQEEK SSENSSAERD LADVKSSLVN ESETNQNSSS 70 80 90 100 110 120 DSEAERRPPP RSESFRDKSR ESLEEAAKRQ DGGLFKGPPY PGYPFIMIPD LTSPYLPNGS 130 140 150 160 170 180 LSPTARTLHF QSGSTHYSAY KTIEHQIAVQ YLQMKWPLLD VQAGSLQSRQ ALKDARSPSP 190 200 210 220 230 240 AHIVSNKVPV VQHPHHVHPL TPLITYSNEH FTPGNPPPHL PADVDPKTGI PRPPHPPDIS 250 260 270 280 290 300 PYYPLSPGTV GQIPHPLGWL VPQQGQPVYP ITTGGFRHPY PTALTVNASM SRFPPHMVPP 310 320 330 340 350 360 HHTLHTTGIP HPAIVTPTVK QESSQSDVGS LHSSKHQDSK KEEEKKKPHI KKPLNAFMLY 370 380 390 400 410 420 MKEMRAKVVA ECTLKESAAI NQILGRRWHA LSREEQAKYY ELARKERQLH MQLYPGWSAR 430 440 450 460 470 480 DNYGKKKKRK RDKQPGETNE HSECFLNPCL SLPPITDLSA PKKCRARFGL DQQNNWCGPC 490 500 510 520 530 540 RRKKKCVRYI QGEGSCLSPP SSDGSLLDSP PPSPNLLGSP PRDAKSQTEQ TQPLSLSLKP 550 560 570 580 590 600 DPLAHLSMMP PPPALLLAEA THKASALCPN GALDLPPAAL QPAAPSSSIA QPSTSSLHSH 610 SSLAGTQPQP LSLVTKSLE
	Isoform 2. Checksum: AC0B8049DF6F4498	FASTA	494	55,152
	10 20 30 40 50 60 MPQLNGGGGD DLGANDELIS FKDEGEQEEK SSENSSAERD LADVKSSLVN ESETNQNSSS 70 80 90 100 110 120 DSEAERRPPP RSESFRDKSR ESLEEAAKRQ DGGLFKGPPY PGYPFIMIPD LTSPYLPNGS 130 140 150 160 170 180 LSPTARTLHF QSGSTHYSAY KTIEHQIAVQ YLQMKWPLLD VQAGSLQSRQ ALKDARSPSP 190 200 210 220 230 240 AHIVSNKVPV VQHPHHVHPL TPLITYSNEH FTPGNPPPHL PADVDPKTGI PRPPHPPDIS 250 260 270 280 290 300 PYYPLSPGTV GQIPHPLGWL VPQQGQPVYP ITTGGFRHPY PTALTVNASM SRFPPHMVPP 310 320 330 340 350 360 HHTLHTTGIP HPAIVTPTVK QESSQSDVGS LHSSKHQDSK KEEEKKKPHI KKPLNAFMLY 370 380 390 400 410 420 MKEMRAKVVA ECTLKESAAI NQILGRRWHA LSREEQAKYY ELARKERQLH MQLYPGWSAR 430 440 450 460 470 480 DNYGKKKKRK RDKQPGETNE HSECFLNPCL SLPPITDLSA PKKCRARFGL DQQNNWCGPC 490 RCKYSKEVSG TVRA
	Isoform 3. Checksum: 6F0250E096854CC0	FASTA	619	67,976
	10 20 30 40 50 60 MPQLNGGGGD DLGANDELIS FKDEGEQEEK SSENSSAERD LADVKSSLVN ESETNQNSSS 70 80 90 100 110 120 DSEAERRPPP RSESFRDKSR ESLEEAAKRQ DGGLFKGPPY PGYPFIMIPD LTSPYLPNGS 130 140 150 160 170 180 LSPTARTLHF QSGSTHYSAY KTIEHQIAVQ YLQMKWPLLD VQAGSLQSRQ ALKDARSPSP 190 200 210 220 230 240 AHIVSNKVPV VQHPHHVHPL TPLITYSNEH FTPGNPPPHL PADVDPKTGI PRPPHPPDIS 250 260 270 280 290 300 PYYPLSPGTV GQIPHPLGWL VPQQGQPVYP ITTGGFRHPY PTALTVNASM SRFPPHMVPP 310 320 330 340 350 360 HHTLHTTGIP HPAIVTPTVK QESSQSDVGS LHSSKHQDSK KEEEKKKPHI KKPLNAFMLY 370 380 390 400 410 420 MKEMRAKVVA ECTLKESAAI NQILGRRWHA LSREEQAKYY ELARKERQLH MQLYPGWSAR 430 440 450 460 470 480 DNYGKKKKRK RDKQPGETNE HSECFLNPCL SLPPITDANT PKKCRALFGL DRQTLWCKPC 490 500 510 520 530 540 RRKKKCVRYI QGEGSCLSPP SSDGSLLDSP PPSPNLLGSP PRDAKSQTEQ TQPLSLSLKP 550 560 570 580 590 600 DPLAHLSMMP PPPALLLAEA THKASALCPN GALDLPPAAL QPAAPSSSIA QPSTSSLHSH 610 SSLAGTQPQP LSLVTKSLE
	Isoform 4. Checksum: 380199CA672A41A8	FASTA	477	53,270
	10 20 30 40 50 60 MPQLNGGGGD DLGANDELIS FKDEGEQEEK SSENSSAERD LADVKSSLVN ESETNQNSSS 70 80 90 100 110 120 DSEAERRPPP RSESFRDKSR ESLEEAAKRQ DGGLFKGPPY PGYPFIMIPD LTSPYLPNGS 130 140 150 160 170 180 LSPTARTLHF QSGSTHYSAY KTIEHQIAVQ YLQMKWPLLD VQAGSLQSRQ ALKDARSPSP 190 200 210 220 230 240 AHIVSNKVPV VQHPHHVHPL TPLITYSNEH FTPGNPPPHL PADVDPKTGI PRPPHPPDIS 250 260 270 280 290 300 PYYPLSPGTV GQIPHPLGWL VPQQGQPVYP ITTGGFRHPY PTALTVNASM SRFPPHMVPP 310 320 330 340 350 360 HHTLHTTGIP HPAIVTPTVK QESSQSDVGS LHSSKHQDSK KEEEKKKPHI KKPLNAFMLY 370 380 390 400 410 420 MKEMRAKVVA ECTLKESAAI NQILGRRWHA LSREEQAKYY ELARKERQLH MQLYPGWSAR 430 440 450 460 470 DNYGKKKKRK RDKQPGETND LSAPKKCRAR FGLDQQNNWC GPCRCKYSKE VSGTVRA
	Isoform 5. Checksum: A52CA392A33AB61C	FASTA	602	66,037
	10 20 30 40 50 60 MPQLNGGGGD DLGANDELIS FKDEGEQEEK SSENSSAERD LADVKSSLVN ESETNQNSSS 70 80 90 100 110 120 DSEAERRPPP RSESFRDKSR ESLEEAAKRQ DGGLFKGPPY PGYPFIMIPD LTSPYLPNGS 130 140 150 160 170 180 LSPTARTLHF QSGSTHYSAY KTIEHQIAVQ YLQMKWPLLD VQAGSLQSRQ ALKDARSPSP 190 200 210 220 230 240 AHIVSNKVPV VQHPHHVHPL TPLITYSNEH FTPGNPPPHL PADVDPKTGI PRPPHPPDIS 250 260 270 280 290 300 PYYPLSPGTV GQIPHPLGWL VPQQGQPVYP ITTGGFRHPY PTALTVNASM SRFPPHMVPP 310 320 330 340 350 360 HHTLHTTGIP HPAIVTPTVK QESSQSDVGS LHSSKHQDSK KEEEKKKPHI KKPLNAFMLY 370 380 390 400 410 420 MKEMRAKVVA ECTLKESAAI NQILGRRWHA LSREEQAKYY ELARKERQLH MQLYPGWSAR 430 440 450 460 470 480 DNYGKKKKRK RDKQPGETND LSAPKKCRAR FGLDQQNNWC GPCRRKKKCV RYIQGEGSCL 490 500 510 520 530 540 SPPSSDGSLL DSPPPSPNLL GSPPRDAKSQ TEQTQPLSLS LKPDPLAHLS MMPPPPALLL 550 560 570 580 590 600 AEATHKASAL CPNGALDLPP AALQPAAPSS SIAQPSTSSL HSHSSLAGTQ PQPLSLVTKS LE
	Isoform 6. Checksum: B68AD303BF9F3E25	FASTA	482	53,676
	10 20 30 40 50 60 MPQLNGGGGD DLGANDELIS FKDEGEQEEK SSENSSAERD LADVKSSLVN ESETNQNSSS 70 80 90 100 110 120 DSEAERRPPP RSESFRDKSR ESLEEAAKRQ DGGLFKGPPY PGYPFIMIPD LTSPYLPNGS 130 140 150 160 170 180 LSPTARTLHF QSGSTHYSAY KTIEHQIAVQ YLQMKWPLLD VQAGSLQSRQ ALKDARSPSP 190 200 210 220 230 240 AHIVSNKVPV VQHPHHVHPL TPLITYSNEH FTPGNPPPHL PADVDPKTGI PRPPHPPDIS 250 260 270 280 290 300 PYYPLSPGTV GQIPHPLGWL VPQQGQPVYP ITTGGFRHPY PTALTVNASM SRFPPHMVPP 310 320 330 340 350 360 HHTLHTTGIP HPAIVTPTVK QESSQSDVGS LHSSKHQDSK KEEEKKKPHI KKPLNAFMLY 370 380 390 400 410 420 MKEMRAKVVA ECTLKESAAI NQILGRRWHA LSREEQAKYY ELARKERQLH MQLYPGWSAR 430 440 450 460 470 480 DNYGKKKKRK RDKQPGETNE HSECFLNPCL SLPPITGEKK SAFATYKVKA AASAHPLQME AY
	Isoform 7. Checksum: 87FC20BEB4F51BB2	FASTA	602	66,094
	10 20 30 40 50 60 MPQLNGGGGD DLGANDELIS FKDEGEQEEK SSENSSAERD LADVKSSLVN ESETNQNSSS 70 80 90 100 110 120 DSEAERRPPP RSESFRDKSR ESLEEAAKRQ DGGLFKGPPY PGYPFIMIPD LTSPYLPNGS 130 140 150 160 170 180 LSPTARTLHF QSGSTHYSAY KTIEHQIAVQ YLQMKWPLLD VQAGSLQSRQ ALKDARSPSP 190 200 210 220 230 240 AHIVSNKVPV VQHPHHVHPL TPLITYSNEH FTPGNPPPHL PADVDPKTGI PRPPHPPDIS 250 260 270 280 290 300 PYYPLSPGTV GQIPHPLGWL VPQQGQPVYP ITTGGFRHPY PTALTVNASM SRFPPHMVPP 310 320 330 340 350 360 HHTLHTTGIP HPAIVTPTVK QESSQSDVGS LHSSKHQDSK KEEEKKKPHI KKPLNAFMLY 370 380 390 400 410 420 MKEMRAKVVA ECTLKESAAI NQILGRRWHA LSREEQAKYY ELARKERQLH MQLYPGWSAR 430 440 450 460 470 480 DNYGKKKKRK RDKQPGETND ANTPKKCRAL FGLDRQTLWC KPCRRKKKCV RYIQGEGSCL 490 500 510 520 530 540 SPPSSDGSLL DSPPPSPNLL GSPPRDAKSQ TEQTQPLSLS LKPDPLAHLS MMPPPPALLL 550 560 570 580 590 600 AEATHKASAL CPNGALDLPP AALQPAAPSS SIAQPSTSSL HSHSSLAGTQ PQPLSLVTKS LE
	Isoform 8. Checksum: A022284FEC164B09	FASTA	596	65,291
	10 20 30 40 50 60 MPQLNGGGGD DLGANDELIS FKDEGEQEEK SSENSSAERD LADVKSSLVN ESETNQNSSS 70 80 90 100 110 120 DSEAERRPPP RSESFRDKSR ESLEEAAKRQ DGGLFKGPPY PGYPFIMIPD LTSPYLPNGS 130 140 150 160 170 180 LSPTARTYLQ MKWPLLDVQA GSLQSRQALK DARSPSPAHI VSNKVPVVQH PHHVHPLTPL 190 200 210 220 230 240 ITYSNEHFTP GNPPPHLPAD VDPKTGIPRP PHPPDISPYY PLSPGTVGQI PHPLGWLVPQ 250 260 270 280 290 300 QGQPVYPITT GGFRHPYPTA LTVNASMSRF PPHMVPPHHT LHTTGIPHPA IVTPTVKQES 310 320 330 340 350 360 SQSDVGSLHS SKHQDSKKEE EKKKPHIKKP LNAFMLYMKE MRAKVVAECT LKESAAINQI 370 380 390 400 410 420 LGRRWHALSR EEQAKYYELA RKERQLHMQL YPGWSARDNY GKKKKRKRDK QPGETNEHSE 430 440 450 460 470 480 CFLNPCLSLP PITDLSAPKK CRARFGLDQQ NNWCGPCRRK KKCVRYIQGE GSCLSPPSSD 490 500 510 520 530 540 GSLLDSPPPS PNLLGSPPRD AKSQTEQTQP LSLSLKPDPL AHLSMMPPPP ALLLAEATHK 550 560 570 580 590 ASALCPNGAL DLPPAALQPA APSSSIAQPS TSSLHSHSSL AGTQPQPLSL VTKSLE
	Isoform 9. Checksum: 5E1E47B5DCB132BE	FASTA	465	51,794
	10 20 30 40 50 60 MPQLNGGGGD DLGANDELIS FKDEGEQEEK SSENSSAERD LADVKSSLVN ESETNQNSSS 70 80 90 100 110 120 DSEAERRPPP RSESFRDKSR ESLEEAAKRQ DGGLFKGPPY PGYPFIMIPD LTSPYLPNGS 130 140 150 160 170 180 LSPTARTLHF QSGSTHYSAY KTIEHQIAVQ YLQMKWPLLD VQAGSLQSRQ ALKDARSPSP 190 200 210 220 230 240 AHIVSNKVPV VQHPHHVHPL TPLITYSNEH FTPGNPPPHL PADVDPKTGI PRPPHPPDIS 250 260 270 280 290 300 PYYPLSPGTV GQIPHPLGWL VPQQGQPVYP ITTGGFRHPY PTALTVNASM SRFPPHMVPP 310 320 330 340 350 360 HHTLHTTGIP HPAIVTPTVK QESSQSDVGS LHSSKHQDSK KEEEKKKPHI KKPLNAFMLY 370 380 390 400 410 420 MKEMRAKVVA ECTLKESAAI NQILGRRWHA LSREEQAKYY ELARKERQLH MQLYPGWSAR 430 440 450 460 DNYGKKKKRK RDKQPGETNG EKKSAFATYK VKAAASAHPL QMEAY
	Isoform 10. Checksum: 2775B43A2E392581	FASTA	455	50,611
	10 20 30 40 50 60 MPQLNGGGGD DLGANDELIS FKDEGEQEEK SSENSSAERD LADVKSSLVN ESETNQNSSS 70 80 90 100 110 120 DSEAERRPPP RSESFRDKSR ESLEEAAKRQ DGGLFKGPPY PGYPFIMIPD LTSPYLPNGS 130 140 150 160 170 180 LSPTARTYLQ MKWPLLDVQA GSLQSRQALK DARSPSPAHI VSNKVPVVQH PHHVHPLTPL 190 200 210 220 230 240 ITYSNEHFTP GNPPPHLPAD VDPKTGIPRP PHPPDISPYY PLSPGTVGQI PHPLGWQGQP 250 260 270 280 290 300 VYPITTGGFR HPYPTALTVN ASMSRFPPHM VPPHHTLHTT GIPHPAIVTP TVKQESSQSD 310 320 330 340 350 360 VGSLHSSKHQ DSKKEEEKKK PHIKKPLNAF MLYMKEMRAK VVAECTLKES AAINQILGRR 370 380 390 400 410 420 WHALSREEQA KYYELARKER QLHMQLYPGW SARDNYGKKK KRKRDKQPGE TNEHSECFLN 430 440 450 PCLSLPPITG EKKSAFATYK VKAAASAHPL QMEAY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma." Korinek V., Barker N., Morin P.J., van Wichen D., de Weger R., Kinzler K.W., Vogelstein B., Clevers H. Science 275:1784-1787(1997) [PubMed: 9065401] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 8 AND 9), INTERACTION WITH CTNNB1. Tissue: Fetus.
[2]	"The human T cell transcription factor-4 gene: structure, extensive characterization of alternative splicings, and mutational analysis in colorectal cancer cell lines." Duval A., Rolland S., Tubacher E., Bui H., Thomas G., Hamelin R. Cancer Res. 60:3872-3879(2000) [PubMed: 10919662] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1; 2; 3; 4; 5; 6; 7 AND 9), VARIANT ASN-346.
[3]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 10). Tissue: Uterus.
[5]	"Human TCF-4 splice form B." Saeki H., Tanaka S., Sugimachi K. Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 449-494. Tissue: Gastric carcinoma.
[6]	"Identification of c-MYC as a target of the APC pathway." He T.-C., Sparks A.B., Rago C., Hermeking H., Zawel L., da Costa L.T., Morin P.J., Vogelstein B., Kinzler K.W. Science 281:1509-1512(1998) [PubMed: 9727977] [Abstract] Cited for: FUNCTION.
[7]	"Restricted high level expression of Tcf-4 protein in intestinal and mammary gland epithelium." Barker N., Huls G., Korinek V., Clevers H. Am. J. Pathol. 154:29-35(1999) [PubMed: 9916915] [Abstract] Cited for: TISSUE SPECIFICITY, INTERACTION WITH CTNNB1, SUBCELLULAR LOCATION.
[8]	"Identification of Tcf4 residues involved in high-affinity beta-catenin binding." Omer C.A., Miller P.J., Diehl R.E., Kral A.M. Biochem. Biophys. Res. Commun. 256:584-590(1999) [PubMed: 10080941] [Abstract] Cited for: INTERACTION WITH CTNNB1, MUTAGENESIS OF 10-ASP-ASP-11; ASP-16; GLU-17; 23-ASP-GLU-24 AND LEU-48.
[9]	"All Tcf HMG box transcription factors interact with Groucho-related co-repressors." Brantjes H., Roose J., van De Wetering M., Clevers H. Nucleic Acids Res. 29:1410-1419(2001) [PubMed: 11266540] [Abstract] Cited for: INTERACTION WITH TLE1; TLE2; TLE3 AND TLE4.
[10]	"The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells." van de Wetering M., Sancho E., Verweij C., de Lau W., Oving I., Hurlstone A., van der Horn K., Batlle E., Coudreuse D., Haramis A.-P., Tjon-Pon-Fong M., Moerer P., van den Born M., Soete G., Pals S., Eilers M., Medema R., Clevers H. Cell 111:241-250(2002) [PubMed: 12408868] [Abstract] Cited for: FUNCTION.
[11]	"Sumoylation is involved in beta-catenin-dependent activation of Tcf-4." Yamamoto H., Ihara M., Matsuura Y., Kikuchi A. EMBO J. 22:2047-2059(2003) [PubMed: 12727872] [Abstract] Cited for: SUMOYLATION AT LYS-320, INTERACTION WITH PIAS4, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-320 AND GLU-322.
[12]	"Identification of a promoter-specific transcriptional activation domain at the C-terminus of the Wnt effector protein T-cell factor 4." Hecht A., Stemmler M.P. J. Biol. Chem. 278:3776-3785(2003) [PubMed: 12446687] [Abstract] Cited for: INTERACTION WITH EP300.
[13]	"NARF, an nemo-like kinase (NLK)-associated ring finger protein regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (TCF/LEF)." Yamada M., Ohnishi J., Ohkawara B., Iemura S., Satoh K., Hyodo-Miura J., Kawachi K., Natsume T., Shibuya H. J. Biol. Chem. 281:20749-20760(2006) [PubMed: 16714285] [Abstract] Cited for: INTERACTION WITH NLK.
[14]	"Coiled-coil domain containing 85B suppresses the beta-catenin activity in a p53-dependent manner." Iwai A., Hijikata M., Hishiki T., Isono O., Chiba T., Shimotohno K. Oncogene 27:1520-1526(2008) [PubMed: 17873903] [Abstract] Cited for: INTERACTION WITH CCDC85B.
[15]	"Tcf4 can specifically recognize beta-catenin using alternative conformations." Graham T.A., Ferkey D.M., Mao F., Kimelman D., Xu W. Nat. Struct. Biol. 8:1048-1052(2001) [PubMed: 11713475] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 12-49 IN COMPLEX WITH THE ARMADILLO REPEAT REGION OF CTNNB1, MUTAGENESIS OF GLU-24; GLU-26; GLU-28 AND GLU-29.
[16]	"Structure of a human Tcf4-beta-catenin complex." Poy F., Lepourcelet M., Shivdasani R.A., Eck M.J. Nat. Struct. Biol. 8:1053-1057(2001) [PubMed: 11713476] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 8-54 IN COMPLEX WITH THE ARMADILLO REPEAT REGION OF CTNNB1, MUTAGENESIS OF ILE-19 AND PHE-21.
[17]	"Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes." Grant S.F.A., Thorleifsson G., Reynisdottir I., Benediktsson R., Manolescu A., Sainz J., Helgason A., Stefansson H., Emilsson V., Helgadottir A., Styrkarsdottir U., Magnusson K.P., Walters G.B., Palsdottir E., Jonsdottir T., Gudmundsdottir T., Gylfason A., Saemundsdottir J. , Wilensky R.L., Reilly M.P., Rader D.J., Bagger Y., Christiansen C., Gudnason V., Sigurdsson G., Thorsteinsdottir U., Gulcher J.R., Kong A., Stefansson K. Nat. Genet. 38:320-323(2006) [PubMed: 16415884] [Abstract] Cited for: INVOLVEMENT IN NIDDM.
[18]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] CYS-465.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.
AL135792 Genomic DNA. No translation available.
AL158212 Genomic DNA. No translation available.
AL445486 Genomic DNA. No translation available.
AL451084 Genomic DNA. No translation available.
BC032656 mRNA. Translation: AAH32656.1.
AB034691 mRNA. Translation: BAA86225.1.

IPI

IPI00164708.
IPI00221004.
IPI00221005.
IPI00221006.
IPI00221007.
IPI00221008.
IPI00221009.
IPI00221010.
IPI00221011.
IPI00335587.

PIR

S22807.

RefSeq

NP_001139746.1.
NP_001139756.1.

UniGene

Hs.593995

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JDH	X-ray	1.90	B	12-49	[»]
1JPW	X-ray	2.50	D/E/F	8-54	[»]
2GL7	X-ray	2.60	B/E	1-53	[»]

SMR

Q9NQB0. Positions 349-424.

DisProt

DP00175.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9NQB0. 12 interactions.

STRING

Q9NQB0.

PTM databases

PhosphoSite

Q9NQB0.

Proteomic databases

PRIDE

Q9NQB0.

Genome annotation databases

Ensembl

ENST00000277945; ENSP00000277945; ENSG00000148737; Homo sapiens. [Genome view]
ENST00000346198; ENSP00000345640; ENSG00000148737; Homo sapiens. [Genome view]
ENST00000349937; ENSP00000298692; ENSG00000148737; Homo sapiens. [Genome view]
ENST00000352065; ENSP00000344823; ENSG00000148737; Homo sapiens. [Genome view]
ENST00000355717; ENSP00000347949; ENSG00000148737; Homo sapiens. [Genome view]
ENST00000355995; ENSP00000348274; ENSG00000148737; Homo sapiens. [Genome view]
ENST00000369386; ENSP00000358393; ENSG00000148737; Homo sapiens. [Genome view]
ENST00000369389; ENSP00000358396; ENSG00000148737; Homo sapiens. [Genome view]
ENST00000369395; ENSP00000358402; ENSG00000148737; Homo sapiens. [Genome view]
ENST00000369397; ENSP00000358404; ENSG00000148737; Homo sapiens. [Genome view]

GeneID

6934.

UCSC

uc001lac.2. human.
uc001lad.2. human.
uc001lae.2. human.

Organism-specific databases

CTD

6934.

GeneCards

GC10P114700.

H-InvDB

HIX0009211.

HGNC

HGNC:11641. TCF7L2.

HPA

CAB013535.

MIM

125853. phenotype.
602228. gene.

PharmGKB

PA36394.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q9NQB0.

Gene expression databases

ArrayExpress

Q9NQB0.

Bgee

Q9NQB0.

CleanEx

HS_TCF4.

Genevestigator

Q9NQB0.

GermOnline

ENSG00000148737. Homo sapiens.

Family and domain databases

InterPro

IPR013558. CTNNB1_bd_N.
IPR000910. HMG_HMG1/HMG2.
[Graphical view]

Gene3D

G3DSA:1.10.30.10. HMG-box. 1 hit.

Pfam

PF08347. CTNNB1_binding. 1 hit.
PF00505. HMG_box. 1 hit.
[Graphical view]

SMART

SM00398. HMG. 1 hit.
[Graphical view]

PROSITE

PS50118. HMG_BOX_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

27133.

SOURCE

Search...

Entry information

Entry name

TF7L2_HUMAN

Accession

Primary (citable) accession number: Q9NQB0
Secondary accession number(s): O00185 , Q9NQB1, Q9NQB2, Q9NQB3, Q9NQB4, Q9NQB5, Q9NQB6, Q9NQB7, Q9ULC2

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 25, 2003
Last sequence update:	March 25, 2003
Last modified:	November 3, 2009
This is version 92 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.