BioPAX pathway converted from "beta-catenin is replaced by repression complexes at the promoter" in the Reactome database.beta-catenin is replaced by repression complexes at the promoter

beta-catenin is replaced by repression complexes at the promoter

Displacement of the APC:CTBP:beta-catenin:betaTrCP complex allows subsequent recruitment of TLE:HDAC1 to TCF/LEF, re-establishing a repression complex (Sierra et al, 2006)

Authored: Rothfels, K, 2013-05-29Reviewed: Rajakulendran, Nishani, 2014-01-22Reviewed: van Amerongen, R, 2014-02-14Reviewed: Kikuchi, Akira, 2014-04-22Edited: Gillespie, ME, 2013-10-02

Reactome DB_ID: 3361754

nucleoplasmGO0005654TCF/LEF:CTNNB1:APC:CTBP:BTRC [nucleoplasm]

TCF/LEF:CTNNB1:APC:CTBP:BTRC

Converted from EntitySet in Reactome

Reactome DB_ID: 3299546

TCF/LEF [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityTCF7L2 [nucleoplasm]LEF1 [nucleoplasm]

Reactomehttp://www.reactome.orgHomo sapiens

NCBI Taxonomy9606UniProtQ9NQB0UniProtQ9UJU2

Reactome DB_ID: 3361755

UniProt:P25054 APC

APC

APCDP2.5FUNCTION Tumor suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signaling as a negative regulator. APC activity is correlated with its phosphorylation state. Activates the GEF activity of SPATA13 and ARHGEF4. Plays a role in hepatocyte growth factor (HGF)-induced cell migration. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex. It is required for the localization of MACF1 to the cell membrane and this localization of MACF1 is critical for its function in microtubule stabilization.SUBUNIT Forms homooligomers and heterooligomers with APC2. Interacts with DIAPH1 and DIAPH2 (By similarity). Interacts with PDZ domains of DLG1 and DLG3. Associates with catenins. Binds axin. Interacts with ARHGEF4 (via N-terminus). Interacts with MAPRE1 (via C-terminus); probably required for APC targeting to the growing microtubule plus ends. Interacts with MAPRE2 and MAPRE3 (via C-terminus). Found in a complex consisting of ARHGEF4, APC and CTNNB1. Interacts with SCRIB; may mediate APC targeting to adherens junctions of epithelial cells. Interacts with SPATA13 (via N-terminus and SH3 domain). Interacts with ASAP1 (via SH3 domain). Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B (By similarity). Interacts at the cell membrane with AMER1 and AMER2 (via ARM repeats). Interacts with KHDRBS1. The complex composed, at least, of APC, CTNNB1 and GSK3B interacts with JPT1; the interaction requires the inactive form of GSK3B (phosphorylated at 'Ser-9') (PubMed:25169422).TISSUE SPECIFICITY Expressed in a variety of tissues: brain, small intestine, colon, thymus, skeletal muscle, heart, prostate, lung, spleen, ovary, testis kidney, placenta, blood and liver (PubMed:21643010, PubMed:27217144). Isoform 1A: Very strongly expressed in brain but has relatively low expression levels in other tissues (PubMed:19527921, PubMed:21643010, PubMed:27217144). Isoform 1B: Predominant form in all tissues except for brain, including gastric mucosa and blood (PubMed:19527921, PubMed:21643010, PubMed:27217144).DOMAIN The microtubule tip localization signal (MtLS) motif; mediates interaction with MAPRE1 and targeting to the growing microtubule plus ends.PTM Phosphorylated by GSK3B.PTM Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is facilitated by Axin. Deubiquitinated by ZRANB1/TRABID.MISCELLANEOUS APC mutations have led to some interesting observations. (1) the great majority of the mutations found to date would result in truncation of the APC product. (2) almost all the mutations have occurred within the first half of the coding sequence, and somatic mutations in colorectal tumors are further clustered in a particular region, called MCR (mutation cluster region). (3) most identified point mutations in the APC gene are transitions from cytosine to other nucleotides. (4) the location of germline mutations tends to correlate with the number of colorectal polyps in FAP1 patients. Inactivation of both alleles of the APC gene seems to be required as an early event to develop most adenomas and carcinomas in the colon and rectum as well as some of those in the stomach.SIMILARITY Belongs to the adenomatous polyposis coli (APC) family.

UniProtP25054

Chain Coordinates

EQUAL

2843

EQUAL

Reactome DB_ID: 3361753

UniProt:Q9Y297 BTRC

BTRC

FBW1ABTRCPFBXW1ABTRCFUNCTION Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognizes and binds to phosphorylated target proteins (PubMed:10066435, PubMed:10497169, PubMed:10644755, PubMed:10835356, PubMed:11238952, PubMed:11359933, PubMed:11994270, PubMed:12791267, PubMed:12902344, PubMed:14603323, PubMed:14681206, PubMed:14988407, PubMed:15448698, PubMed:15917222, PubMed:16371461, PubMed:25503564, PubMed:25704143, PubMed:9859996, PubMed:22087322). SCF(BTRC) mediates the ubiquitination of CTNNB1 and participates in Wnt signaling (PubMed:12077367, PubMed:12820959). SCF(BTRC) mediates the ubiquitination of phosphorylated NFKB1, ATF4, CDC25A, DLG1, FBXO5, PER1, SMAD3, SMAD4, SNAI1 and probably NFKB2 (PubMed:10835356, PubMed:11238952, PubMed:14681206, PubMed:14603323). SCF(BTRC) mediates the ubiquitination of NFKBIA, NFKBIB and NFKBIE; the degradation frees the associated NFKB1 to translocate into the nucleus and to activate transcription (PubMed:10066435, PubMed:10497169, PubMed:10644755). Ubiquitination of NFKBIA occurs at 'Lys-21' and 'Lys-22' (PubMed:10066435). SCF(BTRC) mediates the ubiquitination of CEP68; this is required for centriole separation during mitosis (PubMed:25704143, PubMed:25503564). SCF(BTRC) mediates the ubiquitination and subsequent degradation of nuclear NFE2L1 (By similarity). Has an essential role in the control of the clock-dependent transcription via degradation of phosphorylated PER1 and PER2 (PubMed:15917222). May be involved in ubiquitination and subsequent proteasomal degradation through a DBB1-CUL4 E3 ubiquitin-protein ligase. Required for activation of NFKB-mediated transcription by IL1B, MAP3K14, MAP3K1, IKBKB and TNF. Required for proteolytic processing of GLI3 (PubMed:16371461). Mediates ubiquitination of REST, thereby leading to its proteasomal degradation (PubMed:21258371, PubMed:18354482).PATHWAY Protein modification; protein ubiquitination.SUBUNIT Homodimer. Self-associates. Component of the SCF(BTRC) complex formed of CUL1, SKP1, RBX1 and a BTRC dimer. Direct interaction with SKP1 occurs via the F-box domain. Interacts with phosphorylated ubiquitination substrates SMAD3 and SMAD4. Interacts with phosphorylated ubiquitination substrates CTNNB1, NFKBIA, NFKBIB, NFKBIE, NFKB1/nuclear factor NF-kappa-B p105 subunit, ATF4, CDC25A, DLG1, FBXO5 and SNAI1; the interaction requires the phosphorylation of the 2 serine residues in the substrate destruction motif D-S-G-X(2,3,4)-S. Binds UBQLN1. Interacts with CDC34 and UBE2R2. Interacts with FBXW11. Interacts with CUL4A and DDB1. Part of a SCF(BTRC)-like complex lacking CUL1, which is associated with phosphorylated NKBIA and RELA; RELA interacts directly with NFKBIA. Interacts with the phosphorylated form of GLI3. Interacts with CLU. Interacts with PER1 (phosphorylated), PER2 (phosphorylated) and PER3. Interacts with phosphorylated ubiquitination substrate CEP68 (PubMed:25704143, PubMed:25503564). Interacts with ZC3H12A; this interaction occurs when ZC3H12A is phosphorylated in a IKBKB/IKKB-dependent manner (By similarity). Interacts with HSF1; this interaction occurs during mitosis and induces HSF1 ubiquitin-dependent degradation, a process inhibited by CDC20 (PubMed:18794143). Interacts with NFE2L1 (By similarity). Interacts with INAVA (PubMed:29420262). Interacts with IL10RA; this interaction leads to IL10RA ubiquitination and subsequent degradation (PubMed:22087322). Interacts with REST (PubMed:18354482).SUBUNIT (Microbial infection) Interacts with vaccinia virus A49; this interaction inhibits NF-kappa-B activation.SUBUNIT (Microbial infection) Interacts with HIV-1 Vpu.TISSUE SPECIFICITY Expressed in epididymis (at protein level).DOMAIN The N-terminal D domain mediates homodimerization.

UniProtQ9Y297

EQUAL

605

EQUAL

Reactome DB_ID: 3451168

UniProt:P35222 CTNNB1

CTNNB1

CTNNBOK/SW-cl.35CTNNB1PRO2286FUNCTION Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). Involved in the regulation of cell adhesion, as component of an E-cadherin:catenin adhesion complex (By similarity). Acts as a negative regulator of centrosome cohesion (PubMed:18086858). Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization (PubMed:21262353). Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2 (PubMed:18957423). Disrupts PML function and PML-NB formation by inhibiting RANBP2-mediated sumoylation of PML (PubMed:22155184). Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle (By similarity). Involved in chondrocyte differentiation via interaction with SOX9: SOX9-binding competes with the binding sites of TCF/LEF within CTNNB1, thereby inhibiting the Wnt signaling (By similarity).SUBUNIT Two separate complex-associated pools are found in the cytoplasm. The majority is present as component of an E-cadherin:catenin adhesion complex composed of at least E-cadherin/CDH1 and beta-catenin/CTNNB1, and possibly alpha-catenin/CTNNA1; the complex is located to adherens junctions. The stable association of CTNNA1 is controversial as CTNNA1 was shown not to bind to F-actin when assembled in the complex. Alternatively, the CTNNA1-containing complex may be linked to F-actin by other proteins such as LIMA1. Another cytoplasmic pool is part of a large complex containing AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. Wnt-dependent activation of DVL antagonizes the action of GSK3B. When GSK3B activity is inhibited the complex dissociates, CTNNB1 is dephosphorylated and is no longer targeted for destruction. The stabilized protein translocates to the nucleus, where it binds TCF/LEF-1 family members, TBP, BCL9, BCL9L and possibly also RUVBL1 and CHD8. Binds CTNNBIP and EP300. CTNNB1 forms a ternary complex with LEF1 and EP300 that is disrupted by CTNNBIP1 binding. Interacts with TAX1BP3 (via the PDZ domain); this interaction inhibits the transcriptional activity of CTNNB1. Interacts with AJAP1, BAIAP1, CARM1, CTNNA3, CXADR and PCDH11Y. Binds SLC9A3R1. Interacts with GLIS2 and MUC1. Interacts with SLC30A9. Interacts with XIRP1. Interacts directly with AXIN1; the interaction is regulated by CDK2 phosphorylation of AXIN1. Interacts with SCRIB. Interacts with RAPGEF2. Interacts with PTPRU (via the cytoplasmic juxtamembrane domain). Interacts with EMD. Interacts with TNIK and TCF7L2. Interacts with SESTD1 and TRPC4. Interacts with CAV1. Interacts with TRPV4. The TRPV4 and CTNNB1 complex can interact with CDH1. Interacts with VCL. Interacts with PTPRJ. Interacts with PKT7 and CDK2. Interacts with FAT1 (via the cytoplasmic domain). Interacts with NANOS1 and NDRG2. Interacts with isoform 1 of NEK2. Interacts with both isoform 1 and isoform 2 of CDK5. Interacts with PTK6. Interacts with SOX7; this interaction may lead to proteasomal degradation of active CTNNB1 and thus inhibition of Wnt/beta-catenin-stimulated transcription. Identified in a complex with HINT1 and MITF. Interacts with FHIT. The CTNNB1 and TCF7L2/TCF4 complex interacts with PML (isoform PML-4). Interacts with FERMT2. Identified in a complex with TCF7L2/TCF4 and FERMT2 (PubMed:29739711, PubMed:22699938). Interacts with RORA. May interact with P-cadherin/CDH3. Interacts with RNF220 (PubMed:25266658). Interacts with CTNND2 (PubMed:25807484). Interacts (via the C-terminal region) with CBY1 (PubMed:12712206, PubMed:16424001). The complex composed, at least, of APC, CTNNB1 and GSK3B interacts with JPT1; the interaction requires the inactive form of GSK3B (phosphorylated at 'Ser-9') (PubMed:25169422). Interacts with DLG5 (By similarity). Interacts with FAM53B; promoting translocation to the nucleus (PubMed:25183871). Interacts with TMEM170B (PubMed:29367600). Interacts with AHI1 (PubMed:21623382). Interacts with GID8 (PubMed:28829046). Component of an cadherin:catenin adhesion complex composed of at least of CDH26, beta-catenin/CTNNB1, alpha-catenin/CTNNA1 and p120 catenin/CTNND1 (PubMed:28051089). Forms a complex comprising APPL1, RUVBL2, APPL2, HDAC1 and HDAC2 (PubMed:19433865). Interacts with IRF2BPL; mediates the ubiquitination and degradation of CTNNB1 (PubMed:29374064). Interacts with AMFR (By similarity). Interacts with LMBR1L (PubMed:31073040). Interacts with SOX30; prevents interaction of CTNNB1 with TCF7L2/TCF4 and leads to inhibition of Wnt signaling (PubMed:29739711). Interacts with SOX9; inhibiting CTNNB1 activity by competing with the binding sites of TCF/LEF within CTNNB1, thereby inhibiting the Wnt signaling (By similarity).SUBUNIT (Microbial infection) Interacts with herpes virus 8 protein vPK; this interaction inhibits the Wnt signaling pathway.TISSUE SPECIFICITY Expressed in several hair follicle cell types: basal and peripheral matrix cells, and cells of the outer and inner root sheaths. Expressed in colon. Present in cortical neurons (at protein level). Expressed in breast cancer tissues (at protein level) (PubMed:29367600).PTM Phosphorylation at Ser-552 by AMPK promotes stabilizion of the protein, enhancing TCF/LEF-mediated transcription (By similarity). Phosphorylation by GSK3B requires prior phosphorylation of Ser-45 by another kinase. Phosphorylation proceeds then from Thr-41 to Ser-37 and Ser-33. Phosphorylated by NEK2. EGF stimulates tyrosine phosphorylation. Phosphorylation on Tyr-654 decreases CDH1 binding and enhances TBP binding. Phosphorylated on Ser-33 and Ser-37 by HIPK2 and GSK3B, this phosphorylation triggers proteasomal degradation (PubMed:25169422). Phosphorylation on Ser-191 and Ser-246 by CDK5. Phosphorylation by CDK2 regulates insulin internalization. Phosphorylation by PTK6 at Tyr-64, Tyr-142, Tyr-331 and/or Tyr-333 with the predominant site at Tyr-64 is not essential for inhibition of transcriptional activity.PTM Ubiquitinated by the SCF(BTRC) E3 ligase complex when phosphorylated by GSK3B, leading to its degradation (PubMed:12077367). Ubiquitinated by a E3 ubiquitin ligase complex containing UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X, leading to its subsequent proteasomal degradation (PubMed:11389839, PubMed:11389840, PubMed:20307497). Ubiquitinated and degraded following interaction with SOX9 (By similarity).PTM S-nitrosylation at Cys-619 within adherens junctions promotes VEGF-induced, NO-dependent endothelial cell permeability by disrupting interaction with E-cadherin, thus mediating disassembly adherens junctions.PTM O-glycosylation at Ser-23 decreases nuclear localization and transcriptional activity, and increases localization to the plasma membrane and interaction with E-cadherin CDH1.PTM Deacetylated at Lys-49 by SIRT1.DISEASE Activating mutations in CTNNB1 have oncogenic activity resulting in tumor development. Somatic mutations are found in various tumor types, including colon cancers, ovarian and prostate carcinomas, hepatoblastoma (HB), hepatocellular carcinoma (HCC). HBs are malignant embryonal tumors mainly affecting young children in the first three years of life.DISEASE A chromosomal aberration involving CTNNB1 is found in salivary gland pleiomorphic adenomas, the most common benign epithelial tumors of the salivary gland. Translocation t(3;8)(p21;q12) with PLAG1.SIMILARITY Belongs to the beta-catenin family.

UniProtP35222

EQUAL

781

EQUAL

Reactome DB_ID: 212372

UniProt:Q13363 CTBP1

CTBP1

CTBPCTBP1FUNCTION Corepressor targeting diverse transcription regulators such as GLIS2 or BCL6. Has dehydrogenase activity. Involved in controlling the equilibrium between tubular and stacked structures in the Golgi complex. Functions in brown adipose tissue (BAT) differentiation.SUBUNIT Homo- or heterodimer. Heterodimer with CTBP2. Interacts with PRDM16; the interaction represses white adipose tissue (WAT)-specific genes expression. Interacts with GLIS2, FOXP2, HDAC4, HDAC5, HDAC9 and ZNF217. Interacts with ELK3 (via its PXDLS motif). Interacts with RBBP8 (via its PXDLS motif); the interaction is disrupted by binding to adenovirus E1A. Interacts with FOXP1, HIPK2, PNN, NRIP1, MECOM, ZFHX1B and WIZ. Interacts with ZNF366 (via PXDLS motif) (PubMed:16393996, PubMed:17085477). Interaction with SATB1 (non-acetylated form); the interaction stabilizes its attachment to DNA and promotes transcription repression. Interacts with BCL6; the interaction is required for BCL6 transcriptional autoinhibition and inhibition of some BCL6 target genes. Interacts with IKZF4 (By similarity). Interacts with MCRIP1 (unphosphorylated form, via the PXDLS motif); competitively inhibiting CTBP-ZEB1 interaction (PubMed:25728771). Interacts with Bassoon/BSN; this interaction targets and anchors CTBP1 to presynapses (By similarity).SUBUNIT (Microbial infection) Interacts with Epstein-Barr virus EBNA3 and EBNA6.SUBUNIT (Microbial infection) Interacts with adenovirus E1A protein (via its C-terminus); the interaction disrupts the interaction of CTBP1 with RBBP8.SUBUNIT (Microbial infection) Interacts with human adenovirus 5 E1A protein; this interaction seems to potentiate viral replication.TISSUE SPECIFICITY Expressed in germinal center B-cells.PTM The level of phosphorylation appears to be regulated during the cell cycle. Phosphorylation by HIPK2 on Ser-422 induces proteasomal degradation.PTM ADP-ribosylated; when cells are exposed to brefeldin A.PTM Sumoylation on Lys-428 is promoted by the E3 SUMO-protein ligase CBX4.SIMILARITY Belongs to the D-isomer specific 2-hydroxyacid dehydrogenase family.

UniProtQ13363

EQUAL

440

EQUAL

Reactome Database ID Release 753361754Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3361754ReactomeR-HSA-3361754

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-3361754.1

Reactome DB_ID: 3299553

TLE1:HDAC1 [nucleoplasm]

TLE1:HDAC1

Reactome DB_ID: 205021

UniProt:Q13547 HDAC1

HDAC1

HDAC1RPD3L1FUNCTION Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Deacetylates SP proteins, SP1 and SP3, and regulates their function. Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons. Upon calcium stimulation, HDAC1 is released from the complex and CREBBP is recruited, which facilitates transcriptional activation. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Deacetylates 'Lys-310' in RELA and thereby inhibits the transcriptional activity of NF-kappa-B. Deacetylates NR1D2 and abrogates the effect of KAT5-mediated relieving of NR1D2 transcription repression activity. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Involved in CIART-mediated transcriptional repression of the circadian transcriptional activator: CLOCK-ARNTL/BMAL1 heterodimer. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex or CRY1 through histone deacetylation.SUBUNIT Part of the core histone deacetylase (HDAC) complex composed of HDAC1, HDAC2, RBBP4 and RBBP7. The core complex associates with MTA2, MBD2, MBD3, MTA1L1, CHD3 and CHD4 to form the nucleosome remodeling and histone deacetylation (NuRD) complex, or with SIN3, SAP18 and SAP30 to form the SIN3 HDAC complex. Component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B/BRAF35, KDM1A, RCOR1/CoREST and PHF21A/BHC80. The BHC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I. Component of a mSin3A corepressor complex that contains SIN3A, SAP130, SUDS3/SAP45, ARID4B/SAP180, HDAC1 and HDAC2. Found in a trimeric complex with APBB1 and TSHZ3; the interaction between HDAC1 and APBB1 is mediated by TSHZ3. Component of a RCOR/GFI/KDM1A/HDAC complex. Part of a complex composed of TRIM28, HDAC1, HDAC2 and EHMT2. Part of a complex containing at least CDYL, MIER1, MIER2, HDAC1 and HDAC2. The large PER complex involved in the histone deacetylation is composed of at least HDAC1, PER2, SFPQ and SIN3A. Associates with the 9-1-1 complex; interacts with HUS1. Found in a complex with DNMT3A and HDAC7. Interacts with the non-histone region of MACROH2A1. Interacts with TRIM28; the interaction recruits HDAC1 to E2F1 and inhibits its acetylation. Interacts with SP1; the interaction deacetylates SP1 and regulates its transcriptional activity. Interacts with SP3; the interaction deacetylates SP3 and regulates its transcriptional activity. In vitro, C(18) ceramides increase this interaction and the subsequent SP3 deacetylation and SP3-mediated repression of the TERT promoter. Interacts with TSHZ3 (via N-terminus); the interaction is direct. Interacts with APEX1; the interaction is not dependent on the acetylated status of APEX1. Interacts with C10orf90/FATS (via its N-terminal); the interaction prevents binding of HDAC1 to CDKN1A/p21 and facilitates the acetylation and stabilization of CDKN1A/p21. Interacts with CDKN1A/p21. Interacts with CDK5 complexed to CDK5R1 (p25). Interacts directly with GFI1 and GFI1B. Interacts with NR1D2 (via C-terminus). Interacts with TSC22D3 isoform 1; this interaction affects HDAC1 activity on MYOG promoter and thus inhibits MYOD1 transcriptional activity. Interacts with BAZ2A/TIP5, BANP, BCL6, BCOR, BHLHE40/DEC1, BRMS1, BRMS1L, CBFA2T3, CHFR, CIART, CRY1, DAXX, DDIT3/CHOP, DDX5, DNMT1, E4F1, EP300, HCFC1, HDAC9, INSM1, NFE4, NR4A2/NURR1, MIER1, KDM4A, KDM5B, KLF1, MINT, NRIP1, PCAF, PHB2, PRDM6, PRDM16, RB1, RERE, SAMSN1, SAP30L, SETDB1, SMAD3, SMARCA4/BRG1, SMYD2, SUV39H1, TGIF, TGIF2, TRAF6, UHRF1, UHRF2, ZMYND15, ZNF431 and ZNF541. Interacts with KDM5A (By similarity). Interacts with DNTTIP1 (PubMed:25653165). Identified in a histone deacetylase complex that contains DNTTIP1, HDAC1 and MIDEAS; this complex assembles into a tetramer that contains four copies of each protein chain (PubMed:25653165). Interacts with CCAR2 (PubMed:21030595). Interacts with PPHLN1 (PubMed:17963697). Found in a complex with YY1, SIN3A and GON4L (By similarity). Interacts with CHD4 (PubMed:27616479). Found in a complex composed of at least SINHCAF, SIN3A, HDAC1, SAP30, RBBP4, OGT and TET1. Interacts with SIN3A (By similarity). Interacts with DHX36; this interaction occurs in a RNA-dependent manner (PubMed:18279852). Interacts with ZBTB7A (PubMed:25514493). Interacts with SMAD4; positively regulated by ZBTB7A (PubMed:25514493). Interacts with PACS2 (PubMed:29656858). Forms a complex comprising APPL1, RUVBL2, APPL2, CTNNB1 and HDAC2 (PubMed:19433865). Interacts with ZNF638 (PubMed:30487602). Interacts with SPHK2 (PubMed:19729656). Interacts with ERCC6 (PubMed:26030138).TISSUE SPECIFICITY Ubiquitous, with higher levels in heart, pancreas and testis, and lower levels in kidney and brain.PTM Sumoylated on Lys-444 and Lys-476; which promotes enzymatic activity. Desumoylated by SENP1.PTM Phosphorylation on Ser-421 and Ser-423 promotes enzymatic activity and interactions with NuRD and SIN3 complexes. Phosphorylated by CDK5.PTM Ubiquitinated by CHFR, leading to its degradation by the proteasome. Ubiquitinated by KCTD11, leading to proteasomal degradation.SIMILARITY Belongs to the histone deacetylase family. HD type 1 subfamily.

UniProtQ13547

EQUAL

482

EQUAL

Reactome DB_ID: 3299557

TLE1 tetramer [nucleoplasm]

TLE1 tetramer

Reactome DB_ID: 212327

UniProt:Q04724 TLE1

TLE1

TLE1FUNCTION Transcriptional corepressor that binds to a number of transcription factors. Inhibits NF-kappa-B-regulated gene expression. Inhibits the transcriptional activation mediated by FOXA2, and by CTNNB1 and TCF family members in Wnt signaling. The effects of full-length TLE family members may be modulated by association with dominant-negative AES. Unusual function as coactivator for ESRRG.SUBUNIT Homooligomer and heterooligomer with other family members. Binds LEF1, RUNX1, RUNX3, FOXA2, KDM6A, UTY, histone H3, HESX1, ESRRG and the NF-kappa-B subunit RELA. Interacts with HES1 (via WRPW motif). Interacts with SIX3. Interacts with EFNB1.TISSUE SPECIFICITY In all tissues examined, mostly in brain, liver and muscle.DOMAIN WD repeat Groucho/TLE family members are characterized by 5 regions, a glutamine-rich Q domain, a glycine/proline-rich GP domain, a central CcN domain, containing a nuclear localization signal, and a serine/proline-rich SP domain. The most highly conserved are the N-terminal Q domain and the C-terminal WD-repeat domain.PTM Phosphorylated, probably by CDK1. The degree of phosphorylation varies throughout the cell cycle, and is highest at the G2/M transition. Becomes hyperphosphorylated in response to cell differentiation and interaction with HES1 or RUNX1.PTM Ubiquitinated by XIAP/BIRC4.SIMILARITY Belongs to the WD repeat Groucho/TLE family.

UniProtQ04724

EQUAL

770

EQUAL

Reactome Database ID Release 753299557Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3299557ReactomeR-HSA-3299557

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-3299557.1Reactome Database ID Release 753299553Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3299553ReactomeR-HSA-3299553

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-3299553.1

Reactome DB_ID: 3361756

APC:CTBP:CTNNB1:BTRC [nucleoplasm]

APC:CTBP:CTNNB1:BTRC

Reactome DB_ID: 3361755

EQUAL

2843

EQUAL

Reactome DB_ID: 3361753

EQUAL

605

EQUAL

Reactome DB_ID: 3451168

EQUAL

781

EQUAL

Reactome DB_ID: 212372

EQUAL

440

EQUAL

Reactome Database ID Release 753361756Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3361756ReactomeR-HSA-3361756

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-3361756.1

Reactome DB_ID: 3299555

TCF/LEF:TLE:HDAC1 [nucleoplasm]

TCF/LEF:TLE:HDAC1

Converted from EntitySet in Reactome

Reactome DB_ID: 3299546

Reactome DB_ID: 3772506

TLE:HDAC1 [nucleoplasm]

TLE:HDAC1

Converted from EntitySet in Reactome

Reactome DB_ID: 3299565

TLE tetramer [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity

Reactome DB_ID: 205021

EQUAL

482

EQUAL

Reactome Database ID Release 753772506Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3772506ReactomeR-HSA-3772506

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-3772506.1Reactome Database ID Release 753299555Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3299555ReactomeR-HSA-3299555

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-3299555.1Reactome Database ID Release 753361751Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3361751ReactomeR-HSA-3361751

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-3361751.216510874Pubmed2006The APC tumor suppressor counteracts beta-catenin activation and H3K4 methylation at Wnt target genesSierra, JoseYoshida, TomonoriJoazeiro, Claudio AJones, Katherine AGenes Dev. 20:586-600