BioPAX pathway converted from "Expression of ANKRD1" in the Reactome database. Expression of ANKRD1 Expression of ANKRD1 The ANKRD1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein. Authored: May, B, 2011-11-08 Reviewed: Kersten, S, 2009-06-08 Edited: May, B, 2011-11-08 Reactome DB_ID: 5649939 1 nucleoplasm GO 0005654 ENSEMBL:ENSG00000148677 ANKRD1 CARP C193 ANKRD1 HA1A2 Reactome http://www.reactome.org Homo sapiens NCBI Taxonomy 9606 ENSEMBL ENSG00000148677 Reactome DB_ID: 561143 1 UniProt:Q15327 ANKRD1 ANKRD1 CARP C193 ANKRD1 HA1A2 FUNCTION May play an important role in endothelial cell activation. May act as a nuclear transcription factor that negatively regulates the expression of cardiac genes. Induction seems to be correlated with apoptotic cell death in hepatoma cells.SUBUNIT Interacts with YBX1 (By similarity). Interacts with TTN/titin.TISSUE SPECIFICITY Mainly expressed in activated vascular endothelial cells. To a lower extent, also expressed in hepatoma cells.INDUCTION By TNF, IL1A/interleukin-1 alpha and parthenolide. UniProt Q15327 Chain Coordinates 1 EQUAL 319 EQUAL Reactome Database ID Release 82 1989779 Database 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=1989779 Reactome R-HSA-1989779 3 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-1989779.3 20110263 Pubmed 2010 Profiling of promoter occupancy by PPAR{alpha} in human hepatoma cells via ChIP-chip analysis van der Meer, DL Degenhardt, T Vaisanen, S de Groot, PJ Heinaniemi, M de Vries, SC Muller, M Carlberg, C Kersten, Sander Nucleic Acids Res ACTIVATION Reactome Database ID Release 82 1989812 Database 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=1989812 Reactome R-HSA-1989812 1 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-1989812.1 Reactome DB_ID: 400154 PPARA:RXRA Coactivator complex [nucleoplasm] PPARA:RXRA Coactivator complex Reactome DB_ID: 351643 1 UniProt:Q9BZK7 TBL1XR1 TBL1XR1 TBLR1 TBL1XR1 IRA1 FUNCTION F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units. Plays an essential role in transcription activation mediated by nuclear receptors. Probably acts as integral component of the N-Cor corepressor complex that mediates the recruitment of the 19S proteasome complex, leading to the subsequent proteasomal degradation of N-Cor complex, thereby allowing cofactor exchange, and transcription activation.SUBUNIT Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1XR1, CORO2A and GPS2 (PubMed:11931768). Probable component of some E3 ubiquitin ligase complex. Interacts with histones H2B and H4 (PubMed:12628926). Interacts with MECP2; bridges interaction between MECP2 and NCOR1 (By similarity).TISSUE SPECIFICITY Widely expressed including the pituitary, hypothalamus, white and brown adipose tissue, muscle and liver.DOMAIN The F-box-like domain is related to the F-box domain, and apparently displays the same function as component of ubiquitin E3 ligase complexes.SIMILARITY Belongs to the WD repeat EBI family. UniProt Q9BZK7 1 EQUAL 514 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 400216 1 Coactivators of PPARalpha [nucleoplasm] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity HELZ2 [nucleoplasm] CREBBP [nucleoplasm] NCOA1 [nucleoplasm] NCOA6 [nucleoplasm] NCOA2 [nucleoplasm] SMARCD3 [nucleoplasm] BIL [nucleoplasm] MED1 [nucleoplasm] TGS1 [nucleoplasm] CARM1 [nucleoplasm] CHD9 [nucleoplasm] UniProt Q9BYK8 UniProt Q92793 UniProt Q15788 UniProt Q14686 UniProt Q15596 UniProt Q6STE5 ChEBI 57977 UniProt Q15648 UniProt Q96RS0 UniProt Q86X55 UniProt Q3L8U1 Reactome DB_ID: 351644 1 UniProt:O60907 TBL1X TBL1X TBL1 TBL1X FUNCTION F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units (PubMed:14980219). Plays an essential role in transcription activation mediated by nuclear receptors. Probably acts as integral component of corepressor complexes that mediates the recruitment of the 19S proteasome complex, leading to the subsequent proteasomal degradation of transcription repressor complexes, thereby allowing cofactor exchange (PubMed:21240272).SUBUNIT Homotetramer; dimer of dimers (PubMed:21240272). Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2 (PubMed:10809664, PubMed:21240272). Interacts with GPS2 (when sumoylated); leading to protect GPS2 against degradation by the proteasome (PubMed:24943844). Component of a E3 ubiquitin ligase complex containing UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X (PubMed:11389839). Probably part of other corepressor complexes, that do not contain NCOR1 and NCOR2. Interacts with histones H2B, H3a and H4. Interacts with MECP2; recruits TBL1X to the heterochromatin foci (By similarity).TISSUE SPECIFICITY Ubiquitous.DOMAIN The F-box-like domain is related to the F-box domain, and apparently displays the same function as component of ubiquitin E3 ligase complexes.SIMILARITY Belongs to the WD repeat EBI family. UniProt O60907 1 EQUAL 577 EQUAL Reactome DB_ID: 422412 1 Activated PPARA:RXRA [nucleoplasm] Activated PPARA:RXRA Reactome DB_ID: 422139 1 Peroxisome Proliferator Receptor Element (PPRE) [nucleoplasm] Peroxisome Proliferator Receptor Element (PPRE) Reactome DB_ID: 381319 1 UniProt:P19793 RXRA RXRA RXRA NR2B1 FUNCTION Receptor for retinoic acid that acts as a transcription factor (PubMed:11162439, PubMed:11915042). Forms homo- or heterodimers with retinoic acid receptors (RARs) and binds to target response elements in response to their ligands, all-trans or 9-cis retinoic acid, to regulate gene expression in various biological processes (PubMed:10195690, PubMed:11162439, PubMed:11915042, PubMed:28167758, PubMed:17761950, PubMed:16107141, PubMed:18800767, PubMed:19167885). The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 to regulate transcription (PubMed:10195690, PubMed:11162439, PubMed:11915042, PubMed:17761950, PubMed:28167758). The high affinity ligand for retinoid X receptors (RXRs) is 9-cis retinoic acid (PubMed:1310260). In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression (PubMed:20215566). On ligand binding, the corepressors dissociate from the receptors and coactivators are recruited leading to transcriptional activation (PubMed:20215566, PubMed:9267036). Serves as a common heterodimeric partner for a number of nuclear receptors, such as RARA, RARB and PPARA (PubMed:10195690, PubMed:11915042, PubMed:28167758, PubMed:29021580). The RXRA/RARB heterodimer can act as a transcriptional repressor or transcriptional activator, depending on the RARE DNA element context (PubMed:29021580). The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes (PubMed:10195690). Together with RARA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (PubMed:28167758). Acts as an enhancer of RARA binding to RARE DNA element (PubMed:28167758). May facilitate the nuclear import of heterodimerization partners such as VDR and NR4A1 (PubMed:12145331, PubMed:15509776). Promotes myelin debris phagocytosis and remyelination by macrophages (PubMed:26463675). Plays a role in the attenuation of the innate immune system in response to viral infections, possibly by negatively regulating the transcription of antiviral genes such as type I IFN genes (PubMed:25417649). Involved in the regulation of calcium signaling by repressing ITPR2 gene expression, thereby controlling cellular senescence (PubMed:30216632).SUBUNIT Homodimer (PubMed:10669605, PubMed:17761950). Heterodimer (via C-terminus) with RARA; required for ligand-dependent retinoic acid receptor transcriptional activity; association with RARA is enhanced by pulsatile shear stress (PubMed:28167758, PubMed:10698945, PubMed:15509776). Heterodimer with PPARA (via the leucine-like zipper in the LBD); the interaction is required for PPARA transcriptional activity (PubMed:10195690, PubMed:11915042, PubMed:11698662). Heterodimerizes with PPARG (PubMed:10882139, PubMed:11698662). Heterodimerizes (via NR LBD) with RARB (PubMed:29021580). Heterodimerizes with NR1H4; the heterodimerization enhances the binding affinity for LXXLL motifs from coactivators (PubMed:30275017). Interacts with NCOA3 and NCOA6 coactivators (PubMed:9267036, PubMed:10567404). Interacts with coactivator FAM120B (By similarity). Interacts with coactivator PELP1, SENP6, SFPQ, DNTTIP2 and RNF8 (PubMed:16574651, PubMed:16912044, PubMed:11259580, PubMed:15047147, PubMed:14981089). Interacts with PRMT2 (PubMed:12039952). Interacts with ASXL1 (By similarity). Interacts with BHLHE40/DEC1, BHLHE41/DEC2, NCOR1 and NCOR2 (PubMed:19786558). Interacts in a ligand-dependent fashion with MED1 and NCOA1 (PubMed:19786558, PubMed:10882139, PubMed:11698662). Interacts with VDR (PubMed:28698609). Interacts with EP300; the interaction is decreased by 9-cis retinoic acid (PubMed:17761950). Heterodimer (via C-terminus) with NR4A1 (via DNA-binding domain); DNA-binding of the heterodimer is enhanced by 9-cis retinoic acid (PubMed:17761950, PubMed:15509776). NR4A1 competes with EP300 for interaction with RXRA and thereby attenuates EP300 mediated acetylation of RXRA (PubMed:17761950). In the absence of hormonal ligand, interacts with TACC1 (PubMed:20078863).SUBUNIT (Microbial infection) Interacts (via the DNA binding domain) with HCV core protein; the interaction enhances the transcriptional activities of the RXRA/RARA and the RXRA/PPARA heterodimers.TISSUE SPECIFICITY Expressed in lung fibroblasts (at protein level) (PubMed:30216632). Expressed in monocytes (PubMed:26463675). Highly expressed in liver, also found in kidney and brain (PubMed:24275569, PubMed:2159111, PubMed:14702039).INDUCTION Down-regulated by aging (PubMed:26463675). Induced by pulsatile shear stress (PubMed:28167758).DOMAIN Composed of three domains: a modulating N-terminal domain (AF1 domain), a DNA-binding domain and a C-terminal ligand-binding domain (AF2 domain).PTM Acetylated by EP300; acetylation enhances DNA binding and transcriptional activity.PTM Phosphorylated on serine and threonine residues mainly in the N-terminal modulating domain (By similarity). Constitutively phosphorylated on Ser-21 in the presence or absence of ligand (By similarity). Under stress conditions, hyperphosphorylated by activated JNK on Ser-56, Ser-70, Thr-82 and Ser-260 (By similarity). Phosphorylated on Ser-27, in vitro, by PKA (PubMed:11162439). This phosphorylation is required for repression of cAMP-mediated transcriptional activity of RARA (PubMed:11162439).PTM Sumoylation negatively regulates transcriptional activity. Desumoylated specifically by SENP6.SIMILARITY Belongs to the nuclear hormone receptor family. NR2 subfamily. UniProt P19793 1 EQUAL 462 EQUAL Reactome DB_ID: 422413 1 PPARA:fatty acid (Activated PPARA) [nucleoplasm] PPARA:fatty acid (Activated PPARA) Converted from EntitySet in Reactome Reactome DB_ID: 400149 1 Ligands of PPARA [nucleoplasm] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity EPA [nucleoplasm] AA [nucleoplasm] ALA [nucleoplasm] Palm [nucleoplasm] LINA [nucleoplasm] ChEBI 28364 ChEBI 32395 ChEBI 27432 ChEBI 15756 ChEBI 17351 Reactome DB_ID: 400186 1 UniProt:Q07869 PPARA PPARA PPAR NR1C1 PPARA FUNCTION Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2. May be required for the propagation of clock information to metabolic pathways regulated by PER2.SUBUNIT Heterodimer; with RXRA. This heterodimerization is required for DNA binding and transactivation activity. Interacts with NCOA3 coactivator. Interacts with CITED2; the interaction stimulates its transcriptional activity. Also interacts with PPARBP in vitro. Interacts with AKAP13, LPIN1, PRDM16 and coactivator NCOA6. Interacts with ASXL1 and ASXL2. Interacts with PER2. Interacts with SIRT1; the interaction seems to be modulated by NAD(+) levels (PubMed:24043310). Interacts with CRY1 and CRY2 (By similarity).TISSUE SPECIFICITY Skeletal muscle, liver, heart and kidney. Expressed in monocytes (PubMed:28167758).INDUCTION Down-regulated by aging.SIMILARITY Belongs to the nuclear hormone receptor family. NR1 subfamily. UniProt Q07869 1 EQUAL 468 EQUAL Reactome Database ID Release 82 422413 Database 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=422413 Reactome R-HSA-422413 1 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-422413.1 Reactome Database ID Release 82 422412 Database 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=422412 Reactome R-HSA-422412 1 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-422412.1 Reactome Database ID Release 82 400154 Database 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=400154 Reactome R-HSA-400154 1 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-400154.1