ANKRA2 (ankyrin repeat family A protein 2) is a small ankyrin-repeat protein that reads PxLPxI/L motifs. Its ankyrin repeats bind this motif in class IIa histone deacetylases (HDAC4, HDAC5, HDAC9), the endocytic receptor megalin, the transcription factors RFX5 and RFX7, and the 3M-syndrome protein CCDC8. It is a transcriptional co-regulator whose effect depends on its partner. In human cells it binds RFX7 target promoters and is needed for their p53-RFX7-driven activation; in mouse cells the AhR repressor recruits ANKRA2 with HDAC4 and HDAC5 to silence CYP1A1. ANKRA2 is itself a direct p53 target. It is found in the cytosol, on membranes near megalin in kidney epithelia, and in the nucleus. Its close paralog RFXANK uses the same motif recognition in the MHC class II enhanceosome.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Protein binding (IPI) with HDAC4. Modified to histone deacetylase binding. Reason: HDAC4 is a class IIa histone deacetylase whose PxLPxI/L motif ANKRA2 binds [PMID:22649097 "We report that the ankyrin repeat domains of ANKRA2 and its close paralog regulatory factor X-associated ankyrin-containing protein (RFXANK) recognize a PxLPxI/L motif found in diverse binding proteins, including HDAC4, HDAC5, HDAC9, megalin, and regulatory factor X, 5 (RFX5)."]. GO:0042826 names the interaction informatively and matches the existing histone deacetylase binding rows. Proposed replacements: histone deacetylase binding Supporting Evidence: PMID:22649097 We report that the ankyrin repeat domains of ANKRA2 and its close paralog regulatory factor X-associated ankyrin-containing protein (RFXANK) recognize a PxLPxI/L motif found in diverse binding proteins, including HDAC4, HDAC5, HDAC9, megalin, and regulatory factor X, 5 (RFX5). |
| GO:0005515 protein binding | IPI PMID:25752541 Ankyrin repeats of ANKRA2 recognize a PxLPxL motif on the 3M... | MODIFY | Summary: Protein binding (IPI) with RFX7, a DNA-binding transcription factor. Modified to transcription factor binding. Reason: ANKRA2 binds the PxLPxL motif of the transcription factor RFX7, structurally resolved [PMID:31864703 "Our structural analysis reveals that both ANKRA2 and RFXANK recognize the PXLPXL motif of RFX7 and its flanking sequences via extensive hydrophobic interactions."]. Functionally, it binds RFX7's X-box target promoters [PMID:39181888 "We identified that ANKRA2 binds to the same X-box motif in the PDCD4 promoter as RFX7"] and is needed to activate RFX7 targets [PMID:39181888 "RT-qPCR analysis showed that ANKRA2 knockdown significantly impaired the Nutlin-3a-induced activation of PDCD4 and PIK3IP1"]. GO:0061629 names the interaction informatively. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:31864703 Our structural analysis reveals that both ANKRA2 and RFXANK recognize the PXLPXL motif of RFX7 and its flanking sequences via extensive hydrophobic interactions. PMID:39181888 We identified that ANKRA2 binds to the same X-box motif in the PDCD4 promoter as RFX7 PMID:39181888 RT-qPCR analysis showed that ANKRA2 knockdown significantly impaired the Nutlin-3a-induced activation of PDCD4 and PIK3IP1 |
| GO:0005515 protein binding | IPI PMID:25752541 Ankyrin repeats of ANKRA2 recognize a PxLPxL motif on the 3M... | REMOVE | Summary: Protein binding (IPI) with CCDC8. The interaction is real and structurally defined, but generic protein binding is uninformative; removed. Reason: [PMID:25752541 "We show here that that CCDC8 is a major partner of ANKRA2 but not RFXANK in cells."] The functional context (CCDC8 links ANKRA2 to the 3M/CUL7 complex) is captured by the 3M complex and ligase-binding rows in this review; no informative MF term describes the binding itself. Supporting Evidence: PMID:25752541 We show here that that CCDC8 is a major partner of ANKRA2 but not RFXANK in cells. |
| GO:0005515 protein binding | IPI PMID:25752541 Ankyrin repeats of ANKRA2 recognize a PxLPxL motif on the 3M... | MODIFY | Summary: Protein binding (IPI) with HDAC5. Modified to histone deacetylase binding. Reason: HDAC5 is a class IIa histone deacetylase whose PxLPxI/L motif ANKRA2 binds [PMID:22649097 "We report that the ankyrin repeat domains of ANKRA2 and its close paralog regulatory factor X-associated ankyrin-containing protein (RFXANK) recognize a PxLPxI/L motif found in diverse binding proteins, including HDAC4, HDAC5, HDAC9, megalin, and regulatory factor X, 5 (RFX5)."]. GO:0042826 names the interaction informatively and matches the existing histone deacetylase binding rows. Proposed replacements: histone deacetylase binding Supporting Evidence: PMID:22649097 We report that the ankyrin repeat domains of ANKRA2 and its close paralog regulatory factor X-associated ankyrin-containing protein (RFXANK) recognize a PxLPxI/L motif found in diverse binding proteins, including HDAC4, HDAC5, HDAC9, megalin, and regulatory factor X, 5 (RFX5). |
| GO:0005515 protein binding | IPI PMID:31864703 Structural basis for the recognition of RFX7 by ANKRA2 and R... | MODIFY | Summary: Protein binding (IPI) with RFX7, a DNA-binding transcription factor. Modified to transcription factor binding. Reason: ANKRA2 binds the PxLPxL motif of the transcription factor RFX7, structurally resolved [PMID:31864703 "Our structural analysis reveals that both ANKRA2 and RFXANK recognize the PXLPXL motif of RFX7 and its flanking sequences via extensive hydrophobic interactions."]. Functionally, it binds RFX7's X-box target promoters [PMID:39181888 "We identified that ANKRA2 binds to the same X-box motif in the PDCD4 promoter as RFX7"] and is needed to activate RFX7 targets [PMID:39181888 "RT-qPCR analysis showed that ANKRA2 knockdown significantly impaired the Nutlin-3a-induced activation of PDCD4 and PIK3IP1"]. GO:0061629 names the interaction informatively. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:31864703 Our structural analysis reveals that both ANKRA2 and RFXANK recognize the PXLPXL motif of RFX7 and its flanking sequences via extensive hydrophobic interactions. PMID:39181888 We identified that ANKRA2 binds to the same X-box motif in the PDCD4 promoter as RFX7 PMID:39181888 RT-qPCR analysis showed that ANKRA2 knockdown significantly impaired the Nutlin-3a-induced activation of PDCD4 and PIK3IP1 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with TSHZ3, from a proteome-scale screen. Uninformative; removed. Reason: A high-throughput binary interaction with TSHZ3, with no follow-up. Generic protein binding is not informative. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with SAMD4A, from a proteome-scale screen. Uninformative; removed. Reason: A high-throughput binary interaction with SAMD4A, with no follow-up. Generic protein binding is not informative. |
| GO:0005515 protein binding | IPI PMID:35044719 Proteome-scale mapping of binding sites in the unstructured ... | MODIFY | Summary: Protein binding (IPI) with HDAC5. Modified to histone deacetylase binding. Reason: HDAC5 is a class IIa histone deacetylase whose PxLPxI/L motif ANKRA2 binds [PMID:22649097 "We report that the ankyrin repeat domains of ANKRA2 and its close paralog regulatory factor X-associated ankyrin-containing protein (RFXANK) recognize a PxLPxI/L motif found in diverse binding proteins, including HDAC4, HDAC5, HDAC9, megalin, and regulatory factor X, 5 (RFX5)."]. GO:0042826 names the interaction informatively and matches the existing histone deacetylase binding rows. Proposed replacements: histone deacetylase binding Supporting Evidence: PMID:22649097 We report that the ankyrin repeat domains of ANKRA2 and its close paralog regulatory factor X-associated ankyrin-containing protein (RFXANK) recognize a PxLPxI/L motif found in diverse binding proteins, including HDAC4, HDAC5, HDAC9, megalin, and regulatory factor X, 5 (RFX5). |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Nucleus (IBA). ANKRA2 acts at promoters as a corepressor; accepted. Reason: [PMID:17949687 "We have found that under normal conditions, CYP1A1 gene is kept silent in MEF cells by AhRR/Arnt heterodimer, which binds to the XRE sequence in its promoter and recruits ANKRA2, HDAC4, and HDAC5 as co-repressors."] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001538048 SUPPORTS TRANSFER Same node as the regulation-of-gene-expression IBA; ANKRA2 acts at promoters (PMID:17949687). Supporting Evidence: PMID:17949687 We have found that under normal conditions, CYP1A1 gene is kept silent in MEF cells by AhRR/Arnt heterodimer, which binds to the XRE sequence in its promoter and recruits ANKRA2, HDAC4, and HDAC5 as co-repressors. |
| GO:0005634 nucleus | IEA GO_REF:0000107 | ACCEPT | Summary: Nucleus (IEA). ANKRA2 acts at promoters as a corepressor; accepted. Reason: [PMID:17949687 "We have found that under normal conditions, CYP1A1 gene is kept silent in MEF cells by AhRR/Arnt heterodimer, which binds to the XRE sequence in its promoter and recruits ANKRA2, HDAC4, and HDAC5 as co-repressors."] Supporting Evidence: PMID:17949687 We have found that under normal conditions, CYP1A1 gene is kept silent in MEF cells by AhRR/Arnt heterodimer, which binds to the XRE sequence in its promoter and recruits ANKRA2, HDAC4, and HDAC5 as co-repressors. |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | ACCEPT | Summary: Cytoplasm (IEA). ANKRA2 is found in the cytosol; accepted. Reason: [PMID:11095640 "By cell fractionation, ANKRA is found both in the cytosol and associated with membranes enriched in megalin in L2 cells and proximal tubule cells."] Supporting Evidence: PMID:11095640 By cell fractionation, ANKRA is found both in the cytosol and associated with membranes enriched in megalin in L2 cells and proximal tubule cells. |
| GO:0005829 cytosol | IDA PMID:11095640 Characterization of ANKRA, a novel ankyrin repeat protein th... | ACCEPT | Summary: Cytosol (IDA). ANKRA2 is found in the cytosol; accepted. Reason: [PMID:11095640 "By cell fractionation, ANKRA is found both in the cytosol and associated with membranes enriched in megalin in L2 cells and proximal tubule cells."] Supporting Evidence: PMID:11095640 By cell fractionation, ANKRA is found both in the cytosol and associated with membranes enriched in megalin in L2 cells and proximal tubule cells. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Cytoskeleton (UniProt SubCell IEA). No direct evidence places ANKRA2 on the cytoskeleton; kept as non-core. Reason: The SubCell mapping is not supported by a cited experiment; ANKRA2's documented locations are cytosol, membranes near megalin, and the nucleus. |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Plasma membrane (IDA, Human Protein Atlas). Consistent with ANKRA2 binding the megalin tail; kept as non-core. Reason: [PMID:11095640 "By immunofluorescence, ANKRA is concentrated near megalin along the plasma membrane of L2 cells"] The plasma membrane pool reflects binding to membrane receptors such as megalin; ANKRA2 is a peripheral, not integral, membrane protein. Supporting Evidence: PMID:11095640 By immunofluorescence, ANKRA is concentrated near megalin along the plasma membrane of L2 cells |
| GO:0010468 regulation of gene expression | IBA GO_REF:0000033 | ACCEPT | Summary: Regulation of gene expression (IBA). ANKRA2 represses target genes by recruiting class IIa HDACs; accepted. Reason: [PMID:17949687 "RNA interference experiments using ANKRA2 and AhRR siRNAs indicate that ANKRA2 is important for transcriptional repression by AhRR."] [PMID:17949687 "We have found that under normal conditions, CYP1A1 gene is kept silent in MEF cells by AhRR/Arnt heterodimer, which binds to the XRE sequence in its promoter and recruits ANKRA2, HDAC4, and HDAC5 as co-repressors."] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001538048 SUPPORTS TRANSFER Node spanning ANKRA2 and its paralog RFXANK (interpro/panther/PTHR24124/PTHR24124-paint.tsv). UniProtKB:O14593 SUPPORTS TRANSFER RFXANK, a transcriptional regulator in the MHC II enhanceosome; ANKRA2's own corepressor evidence (PMID:17949687) agrees. Supporting Evidence: PMID:17949687 RNA interference experiments using ANKRA2 and AhRR siRNAs indicate that ANKRA2 is important for transcriptional repression by AhRR. PMID:17949687 We have found that under normal conditions, CYP1A1 gene is kept silent in MEF cells by AhRR/Arnt heterodimer, which binds to the XRE sequence in its promoter and recruits ANKRA2, HDAC4, and HDAC5 as co-repressors. |
| GO:0016020 membrane | IDA PMID:11095640 Characterization of ANKRA, a novel ankyrin repeat protein th... | ACCEPT | Summary: Membrane (IDA). ANKRA2 associates with megalin-enriched membranes; accepted. Reason: [PMID:11095640 "By cell fractionation, ANKRA is found both in the cytosol and associated with membranes enriched in megalin in L2 cells and proximal tubule cells."] Supporting Evidence: PMID:11095640 By cell fractionation, ANKRA is found both in the cytosol and associated with membranes enriched in megalin in L2 cells and proximal tubule cells. |
| GO:0016020 membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Membrane (IEA). ANKRA2 associates with megalin-enriched membranes; accepted. Reason: [PMID:11095640 "By cell fractionation, ANKRA is found both in the cytosol and associated with membranes enriched in megalin in L2 cells and proximal tubule cells."] Supporting Evidence: PMID:11095640 By cell fractionation, ANKRA is found both in the cytosol and associated with membranes enriched in megalin in L2 cells and proximal tubule cells. |
| GO:0016020 membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Membrane (ISS). ANKRA2 associates with megalin-enriched membranes; accepted. Reason: [PMID:11095640 "By cell fractionation, ANKRA is found both in the cytosol and associated with membranes enriched in megalin in L2 cells and proximal tubule cells."] Supporting Evidence: PMID:11095640 By cell fractionation, ANKRA is found both in the cytosol and associated with membranes enriched in megalin in L2 cells and proximal tubule cells. |
| GO:0019901 protein kinase binding | IPI PMID:20873783 Characterization of hNek6 interactome reveals an important r... | KEEP AS NON CORE | Summary: Protein kinase binding (IPI) with NEK6, from an interactome screen of NEK6. Kept as non-core. Reason: A single interaction from a NEK6-centred interactome screen (abstract-only), with no follow-up on ANKRA2's role. The term is informative about the partner class but the interaction is not part of ANKRA2's characterized function. |
| GO:0031625 ubiquitin protein ligase binding | IDA PMID:25752541 Ankyrin repeats of ANKRA2 recognize a PxLPxL motif on the 3M... | KEEP AS NON CORE | Summary: Ubiquitin protein ligase binding (IDA). ANKRA2 associates with the CUL7 ligase complex through CCDC8; kept as non-core. Reason: ANKRA2 binds CCDC8 [PMID:25752541 "We show here that that CCDC8 is a major partner of ANKRA2 but not RFXANK in cells."], which joins OBSL1 to the CUL7 ligase complex [PMID:25752541 "The N-terminal part interacts with OBSL1 to form a CUL7 ligase complex."]. The curator read the full text (abstract only cached); the association is via CCDC8, and its consequence for ANKRA2 or the ligase is not established. Supporting Evidence: PMID:25752541 We show here that that CCDC8 is a major partner of ANKRA2 but not RFXANK in cells. PMID:25752541 The N-terminal part interacts with OBSL1 to form a CUL7 ligase complex. |
| GO:0032991 protein-containing complex | IDA PMID:20873783 Characterization of hNek6 interactome reveals an important r... | KEEP AS NON CORE | Summary: Protein-containing complex (IDA). Correct but uninformative; kept as non-core. Reason: A generic complex annotation from the NEK6 interactome study (abstract only cached). ANKRA2 does form complexes with its motif-bearing partners, but this term does not say which. |
| GO:0042826 histone deacetylase binding | IDA PMID:22649097 Sequence-specific recognition of a PxLPxI/L motif by an anky... | ACCEPT | Summary: Histone deacetylase binding (IDA). ANKRA2's ankyrin repeats bind the PxLPxI/L motif of class IIa HDACs; accepted. Reason: [PMID:22649097 "Ankyrin repeat family A protein 2 (ANKRA2) interacts with the plasma membrane receptor megalin and the class IIa histone deacetylases HDAC4 and HDAC5."] [PMID:22649097 "We report that the ankyrin repeat domains of ANKRA2 and its close paralog regulatory factor X-associated ankyrin-containing protein (RFXANK) recognize a PxLPxI/L motif found in diverse binding proteins, including HDAC4, HDAC5, HDAC9, megalin, and regulatory factor X, 5 (RFX5)."] Supporting Evidence: PMID:22649097 Ankyrin repeat family A protein 2 (ANKRA2) interacts with the plasma membrane receptor megalin and the class IIa histone deacetylases HDAC4 and HDAC5. PMID:22649097 We report that the ankyrin repeat domains of ANKRA2 and its close paralog regulatory factor X-associated ankyrin-containing protein (RFXANK) recognize a PxLPxI/L motif found in diverse binding proteins, including HDAC4, HDAC5, HDAC9, megalin, and regulatory factor X, 5 (RFX5). |
| GO:0042826 histone deacetylase binding | IEA GO_REF:0000107 | ACCEPT | Summary: Histone deacetylase binding (IEA). ANKRA2's ankyrin repeats bind the PxLPxI/L motif of class IIa HDACs; accepted. Reason: [PMID:22649097 "Ankyrin repeat family A protein 2 (ANKRA2) interacts with the plasma membrane receptor megalin and the class IIa histone deacetylases HDAC4 and HDAC5."] [PMID:22649097 "We report that the ankyrin repeat domains of ANKRA2 and its close paralog regulatory factor X-associated ankyrin-containing protein (RFXANK) recognize a PxLPxI/L motif found in diverse binding proteins, including HDAC4, HDAC5, HDAC9, megalin, and regulatory factor X, 5 (RFX5)."] Supporting Evidence: PMID:22649097 Ankyrin repeat family A protein 2 (ANKRA2) interacts with the plasma membrane receptor megalin and the class IIa histone deacetylases HDAC4 and HDAC5. PMID:22649097 We report that the ankyrin repeat domains of ANKRA2 and its close paralog regulatory factor X-associated ankyrin-containing protein (RFXANK) recognize a PxLPxI/L motif found in diverse binding proteins, including HDAC4, HDAC5, HDAC9, megalin, and regulatory factor X, 5 (RFX5). |
| GO:0042826 histone deacetylase binding | IPI PMID:22649097 Sequence-specific recognition of a PxLPxI/L motif by an anky... | ACCEPT | Summary: Histone deacetylase binding (IPI). ANKRA2's ankyrin repeats bind the PxLPxI/L motif of class IIa HDACs; accepted. Reason: [PMID:22649097 "Ankyrin repeat family A protein 2 (ANKRA2) interacts with the plasma membrane receptor megalin and the class IIa histone deacetylases HDAC4 and HDAC5."] [PMID:22649097 "We report that the ankyrin repeat domains of ANKRA2 and its close paralog regulatory factor X-associated ankyrin-containing protein (RFXANK) recognize a PxLPxI/L motif found in diverse binding proteins, including HDAC4, HDAC5, HDAC9, megalin, and regulatory factor X, 5 (RFX5)."] Supporting Evidence: PMID:22649097 Ankyrin repeat family A protein 2 (ANKRA2) interacts with the plasma membrane receptor megalin and the class IIa histone deacetylases HDAC4 and HDAC5. PMID:22649097 We report that the ankyrin repeat domains of ANKRA2 and its close paralog regulatory factor X-associated ankyrin-containing protein (RFXANK) recognize a PxLPxI/L motif found in diverse binding proteins, including HDAC4, HDAC5, HDAC9, megalin, and regulatory factor X, 5 (RFX5). |
| GO:0043254 regulation of protein-containing complex assembly | IDA PMID:25752541 Ankyrin repeats of ANKRA2 recognize a PxLPxL motif on the 3M... | KEEP AS NON CORE | Summary: Regulation of protein-containing complex assembly (IDA). From the CCDC8/3M study; kept as non-core. Reason: The curator annotated an effect on complex assembly from the CCDC8 study (abstract only cached). ANKRA2's direct role is binding the CCDC8 motif [PMID:25752541 "We show here that that CCDC8 is a major partner of ANKRA2 but not RFXANK in cells."]; any effect on 3M complex assembly is secondary. Supporting Evidence: PMID:25752541 We show here that that CCDC8 is a major partner of ANKRA2 but not RFXANK in cells. |
| GO:0050750 low-density lipoprotein particle receptor binding | IPI PMID:22649097 Sequence-specific recognition of a PxLPxI/L motif by an anky... | ACCEPT | Summary: Low-density lipoprotein particle receptor binding (IPI). ANKRA2 binds the cytoplasmic tail of megalin, an LDL receptor family member; accepted. Reason: [PMID:11095640 "Ankyrin-repeat family A protein (ANKRA) is a novel protein that interacts directly and specifically with the cytoplasmic tail of megalin in the yeast two-hybrid system and glutathione-S-transferase pull-down assays."] [PMID:22649097 "We report that the ankyrin repeat domains of ANKRA2 and its close paralog regulatory factor X-associated ankyrin-containing protein (RFXANK) recognize a PxLPxI/L motif found in diverse binding proteins, including HDAC4, HDAC5, HDAC9, megalin, and regulatory factor X, 5 (RFX5)."] Supporting Evidence: PMID:11095640 Ankyrin-repeat family A protein (ANKRA) is a novel protein that interacts directly and specifically with the cytoplasmic tail of megalin in the yeast two-hybrid system and glutathione-S-transferase pull-down assays. PMID:22649097 We report that the ankyrin repeat domains of ANKRA2 and its close paralog regulatory factor X-associated ankyrin-containing protein (RFXANK) recognize a PxLPxI/L motif found in diverse binding proteins, including HDAC4, HDAC5, HDAC9, megalin, and regulatory factor X, 5 (RFX5). |
| GO:1990393 3M complex | IDA PMID:25752541 Ankyrin repeats of ANKRA2 recognize a PxLPxL motif on the 3M... | KEEP AS NON CORE | Summary: 3M complex (IDA, colocalizes_with). ANKRA2 binds the 3M complex protein CCDC8; kept as non-core. Reason: [PMID:25752541 "We show here that that CCDC8 is a major partner of ANKRA2 but not RFXANK in cells."] [PMID:25752541 "The N-terminal part interacts with OBSL1 to form a CUL7 ligase complex."] colocalizes_with is the appropriate qualifier for an associated, not core, protein. Supporting Evidence: PMID:25752541 We show here that that CCDC8 is a major partner of ANKRA2 but not RFXANK in cells. PMID:25752541 The N-terminal part interacts with OBSL1 to form a CUL7 ligase complex. |
| GO:0003713 transcription coactivator activity | IMP PMID:39181888 p53 target ANKRA2 cooperates with RFX7 to regulate tumor sup... | NEW | Summary: Proposed. In human cells ANKRA2 binds RFX7 target promoters and is needed to activate RFX7 target genes. Reason: [PMID:39181888 "We identified that ANKRA2 binds to the same X-box motif in the PDCD4 promoter as RFX7"] [PMID:39181888 "RT-qPCR analysis showed that ANKRA2 knockdown significantly impaired the Nutlin-3a-induced activation of PDCD4 and PIK3IP1"] [PMID:39181888 "Based on these results, we propose a model in which RFX7 cooperates with ANKRA2 to upregulate its target genes."] ANKRA2 does part of the work: it is on the promoter with RFX7 and binds RFX7's PxLPxL motif directly [PMID:31864703 "Our structural analysis reveals that both ANKRA2 and RFXANK recognize the PXLPXL motif of RFX7 and its flanking sequences via extensive hydrophobic interactions."]. This is human-cell evidence (U2OS and HCT116). It sits beside the corepressor row: ANKRA2 represses with the AhR repressor and activates with RFX7, depending on its partner. The two terms are siblings, not ancestor and descendant. Supporting Evidence: PMID:39181888 We identified that ANKRA2 binds to the same X-box motif in the PDCD4 promoter as RFX7 PMID:39181888 RT-qPCR analysis showed that ANKRA2 knockdown significantly impaired the Nutlin-3a-induced activation of PDCD4 and PIK3IP1 PMID:39181888 Based on these results, we propose a model in which RFX7 cooperates with ANKRA2 to upregulate its target genes. PMID:31864703 Our structural analysis reveals that both ANKRA2 and RFXANK recognize the PXLPXL motif of RFX7 and its flanking sequences via extensive hydrophobic interactions. |
| GO:0003714 transcription corepressor activity | ISO PMID:17949687 Molecular mechanism of transcriptional repression of AhR rep... | NEW | Summary: Proposed. ANKRA2 bridges promoter-bound repressors to class IIa HDACs and is needed for their repression. Reason: [PMID:17949687 "RNA interference experiments using ANKRA2 and AhRR siRNAs indicate that ANKRA2 is important for transcriptional repression by AhRR."] [PMID:17949687 "We have found that under normal conditions, CYP1A1 gene is kept silent in MEF cells by AhRR/Arnt heterodimer, which binds to the XRE sequence in its promoter and recruits ANKRA2, HDAC4, and HDAC5 as co-repressors."] ANKRA2 does part of the work: its ankyrin repeats bind the PxLPxI/L motifs of class IIa HDACs [PMID:22649097 "We report that the ankyrin repeat domains of ANKRA2 and its close paralog regulatory factor X-associated ankyrin-containing protein (RFXANK) recognize a PxLPxI/L motif found in diverse binding proteins, including HDAC4, HDAC5, HDAC9, megalin, and regulatory factor X, 5 (RFX5)."], so it recruits the deacetylases to the repressor. The experiments are in mouse embryonic fibroblasts, so this is transferred to human by orthology (ISO) from mouse Ankra2 (Q99PE2). No current ANKRA2 annotation is an ancestor or descendant of this term. Supporting Evidence: PMID:17949687 RNA interference experiments using ANKRA2 and AhRR siRNAs indicate that ANKRA2 is important for transcriptional repression by AhRR. PMID:17949687 We have found that under normal conditions, CYP1A1 gene is kept silent in MEF cells by AhRR/Arnt heterodimer, which binds to the XRE sequence in its promoter and recruits ANKRA2, HDAC4, and HDAC5 as co-repressors. PMID:22649097 We report that the ankyrin repeat domains of ANKRA2 and its close paralog regulatory factor X-associated ankyrin-containing protein (RFXANK) recognize a PxLPxI/L motif found in diverse binding proteins, including HDAC4, HDAC5, HDAC9, megalin, and regulatory factor X, 5 (RFX5). |
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Experiment: Map ANKRA2-dependent genes by RNA-seq in ANKRA2 knockout human cells, and test whether CaMK-driven HDAC4 Ser350 phosphorylation releases ANKRA2 from target promoters.
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