ATF5 (activating transcription factor 5) is a short-lived basic leucine zipper (bZIP) transcription factor of the ATF4/ATF5 subfamily. Like ATF4, its translation is controlled by upstream ORFs and is enhanced when eIF2alpha is phosphorylated, linking it to the integrated stress response. ATF5 binds CRE, ATF5-specific (ARE) and amino acid response (AARE) elements as homo- or heterodimers (notably with C/EBP family members) and activates or represses target genes such as BCL2, CHOP/DDIT3, CCND3 and EGR1. In mammalian cells ATF5 is the functional counterpart of C. elegans ATFS-1 in the mitochondrial unfolded protein response: it is required for stress-induced transcription of mitochondrial chaperones and proteases (HSPD1, HSPE1, HSPA9, LONP1), a fraction of the protein associates with mitochondria in the absence of stress, and human ATF5 restores UPRmt signalling in atfs-1 mutant worms. ATF5 promotes survival of glioma and other cancer cells, acts as a C/EBPB cofactor in adipogenesis, and has a reported non-transcriptional structural role at the pericentriolar material of the mother centriole.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000785 chromatin | ISA GO_REF:0000113 | ACCEPT | Summary: TFClass-based assertion that this bZIP transcription factor is located on chromatin. Reason: ATF5 is a sequence-specific bZIP DNA-binding transcription factor that occupies target promoters (e.g. BCL2, CHOP, mitochondrial chaperone genes); chromatin is a correct location. Supporting Evidence: file:human/ATF5/ATF5-uniprot.txt Transcription factor that either stimulates or represses gene transcription through binding of different DNA regulatory elements such as cAMP response element (CRE) PMID:21212266 ATF5 binds to an ATF5-specific regulatory element that is downstream of and adjacent to the negative regulatory element in the BCL-2 P2 promoter, stimulating BCL-2 expression. |
| GO:0000976 transcription cis-regulatory region binding | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer from mouse Atf5 of cis-regulatory region binding. Reason: ATF5 binds CRE, ARE and AARE elements in promoters; consistent with direct human evidence. Supporting Evidence: file:human/ATF5/ATF5-uniprot.txt Transcription factor that either stimulates or represses gene transcription through binding of different DNA regulatory elements such as cAMP response element (CRE) PMID:21212266 ATF5 binds to an ATF5-specific regulatory element that is downstream of and adjacent to the negative regulatory element in the BCL-2 P2 promoter, stimulating BCL-2 expression. |
| GO:0000976 transcription cis-regulatory region binding | ISS GO_REF:0000024 | ACCEPT | Summary: ISS transfer of cis-regulatory region binding from rat Atf5. Reason: Consistent with direct human evidence of promoter element binding. Supporting Evidence: file:human/ATF5/ATF5-uniprot.txt Transcription factor that either stimulates or represses gene transcription through binding of different DNA regulatory elements such as cAMP response element (CRE) |
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for RNA polymerase II regulatory region sequence-specific DNA binding in the CREB/ATF bZIP family. Reason: ATF5 is within the bZIP clade that inherited sequence-specific DNA binding; human ATF5 itself appears among the experimental sources, as expected. Correct and core. Supporting Evidence: file:human/ATF5/ATF5-uniprot.txt Transcription factor that either stimulates or represses gene transcription through binding of different DNA regulatory elements such as cAMP response element (CRE) PMID:15890932 we show by electrophoretic mobility shift assay that ATFx binds to the TxRE enhancer element via the bZIP domain. |
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | IMP PMID:15890932 The bZIP transcription factor ATFx binds human T-cell leukem... | ACCEPT | Summary: EMSA with bZIP mutants showed ATF5 (ATFx) binds the HTLV-1 Tax-responsive CRE-like element. Reason: Direct DNA-binding evidence mapped to the bZIP domain; the element is a Pol II-transcribed LTR enhancer. Core DNA-binding activity. Supporting Evidence: PMID:15890932 we show by electrophoretic mobility shift assay that ATFx binds to the TxRE enhancer element via the bZIP domain. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISA GO_REF:0000113 | ACCEPT | Summary: TFClass assertion of Pol II-specific DNA-binding transcription factor activity. Reason: ATF5 is a bona fide bZIP transcription factor of the ATF4/ATF5 subfamily. Supporting Evidence: file:human/ATF5/ATF5-uniprot.txt Transcription factor that either stimulates or represses gene transcription through binding of different DNA regulatory elements such as cAMP response element (CRE) |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for Pol II-specific DNA-binding transcription activator activity. Reason: Activator function is supported in human cells for BCL2, CHOP and mitochondrial chaperone genes; the IBA is at an appropriate specificity. Supporting Evidence: PMID:21212266 ATF5 binds to an ATF5-specific regulatory element that is downstream of and adjacent to the negative regulatory element in the BCL-2 P2 promoter, stimulating BCL-2 expression. PMID:20654631 We showed that ATF5 activates the CHOP gene promoter in HepG2 cells. Both deletion analysis and point mutations of the promoter revealed that amino acid response element (AARE) 1 is responsible for ATF5-dependent promoter activation. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:16300731 ATF5 increases cisplatin-induced apoptosis through up-regula... | ACCEPT | Summary: ATF5 overexpression induced cyclin D3 (CCND3) transcription in HeLa cells. Reason: Supports activator activity at a Pol II promoter; abstract-only, defer to curator for the full-text promoter assays. Supporting Evidence: PMID:16300731 induce Cyclin D3 mRNA expression via cooperation with E2F1 transcription factor. |
| GO:0003682 chromatin binding | IDA PMID:21212266 BCL-2 is a downstream target of ATF5 that mediates the prosu... | KEEP AS NON CORE | Summary: Chromatin binding inferred from ATF5 occupancy of the BCL2 P2 promoter. Reason: Correct but less informative than sequence-specific DNA binding, which is already captured. Supporting Evidence: PMID:21212266 ATF5 binds to an ATF5-specific regulatory element that is downstream of and adjacent to the negative regulatory element in the BCL-2 P2 promoter, stimulating BCL-2 expression. |
| GO:0003682 chromatin binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara transfer of chromatin binding from mouse. Reason: Correct but generic relative to sequence-specific DNA-binding terms. Supporting Evidence: file:human/ATF5/ATF5-uniprot.txt Transcription factor that either stimulates or represses gene transcription through binding of different DNA regulatory elements such as cAMP response element (CRE) |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:20654631 Regulation of the human CHOP gene promoter by the stress res... | ACCEPT | Summary: ATF5 activated the CHOP promoter via the AARE1 element in HepG2 cells. Reason: Direct evidence of DNA-binding transcription factor activity. Supporting Evidence: PMID:20654631 We showed that ATF5 activates the CHOP gene promoter in HepG2 cells. Both deletion analysis and point mutations of the promoter revealed that amino acid response element (AARE) 1 is responsible for ATF5-dependent promoter activation. |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO mapping from the bZIP domain. Reason: Correct for a bZIP transcription factor. Supporting Evidence: file:human/ATF5/ATF5-uniprot.txt Transcription factor that either stimulates or represses gene transcription through binding of different DNA regulatory elements such as cAMP response element (CRE) |
| GO:0003700 DNA-binding transcription factor activity | ISS GO_REF:0000024 | ACCEPT | Summary: ISS transfer from rat Atf5. Reason: Consistent with human data. Supporting Evidence: file:human/ATF5/ATF5-uniprot.txt Transcription factor that either stimulates or represses gene transcription through binding of different DNA regulatory elements such as cAMP response element (CRE) |
| GO:0005515 protein binding | IPI PMID:10373550 Human Cdc34 and Rad6B ubiquitin-conjugating enzymes target r... | REMOVE | Summary: Interaction with the ubiquitin-conjugating enzyme CDC34, which targets ATF5 for degradation. Reason: Generic protein binding is uninformative; the reported interaction is not disputed, but it does not describe an ATF5 molecular function. Removal follows the project policy for GO:0005515. Here ATF5 is the degradation substrate. Supporting Evidence: PMID:10373550 Here, we report that an hICER isoform (hICERIIΞ³) and a new ATF homolog (hATF5) are targeted by both hCdc34 and hRad6B UBC enzymes for degradation in vivo. |
| GO:0005515 protein binding | IPI PMID:12812986 DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associa... | REMOVE | Summary: Yeast two-hybrid/co-IP interaction with DISC1. Reason: Generic protein binding is uninformative; the reported interaction is not disputed, but it does not describe an ATF5 molecular function. Removal follows the project policy for GO:0005515. Supporting Evidence: PMID:12812986 DISC1 interacts by yeast two-hybrid, mammalian two-hybrid, and co-immunoprecipitation assays with multiple proteins |
| GO:0005515 protein binding | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | MODIFY | Summary: Coiled-coil array interaction of the ATF5 bZIP leucine zipper with CEBPA. Reason: bZIP-bZIP coiled-coil interactions are heterodimerization; protein heterodimerization activity is the informative MF. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:20102225 Basic-region leucine-zipper transcription factors (bZIPs) contain a segment rich in basic amino acids that can bind DNA, followed by a leucine zipper that can interact with other leucine zippers to form coiled-coil homo- or heterodimers. |
| GO:0005515 protein binding | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | MODIFY | Summary: Coiled-coil array interaction of the ATF5 leucine zipper with CEBPG. Reason: bZIP heterodimerization with C/EBP family members; replace with protein heterodimerization activity. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:20102225 Basic-region leucine-zipper transcription factors (bZIPs) contain a segment rich in basic amino acids that can bind DNA, followed by a leucine zipper that can interact with other leucine zippers to form coiled-coil homo- or heterodimers. |
| GO:0005515 protein binding | IPI PMID:20211142 An atlas of combinatorial transcriptional regulation in mous... | MODIFY | Summary: Two-hybrid atlas interaction of ATF5 with CEBPG. Reason: bZIP heterodimerization; replace with protein heterodimerization activity. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:20211142 An atlas of combinatorial transcriptional regulation in mouse and man. |
| GO:0005515 protein binding | IPI PMID:22528486 Nucleophosmin (NPM1/B23) interacts with activating transcrip... | REMOVE | Summary: TAP-MS interaction with NPM1 and HSPA1A/HSPA1B, which control ATF5 stability. Reason: Generic protein binding is uninformative; the reported interaction is not disputed, but it does not describe an ATF5 molecular function. Removal follows the project policy for GO:0005515. NPM1 and HSP70 regulate ATF5 turnover; ATF5 is the client. Supporting Evidence: PMID:22528486 NPM1-promoted ATF5 down-regulation diminished ATF5-mediated repression of cAMP-responsive element-dependent gene transcription and abrogates ATF5-induced G(2)/M cell cycle blockade and inhibition of cell proliferation in HCC cells. |
| GO:0005515 protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MODIFY | Summary: In vitro bZIP dimerization network measurement with CEBPA. Reason: bZIP heterodimerization; replace with protein heterodimerization activity. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:23661758 We studied the basic region-leucine zipper (bZIP) transcription factors and quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs. |
| GO:0005515 protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | MODIFY | Summary: In vitro bZIP dimerization network measurement with CEBPG. Reason: bZIP heterodimerization; replace with protein heterodimerization activity. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:23661758 We studied the basic region-leucine zipper (bZIP) transcription factors and quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs. |
| GO:0005515 protein binding | IPI PMID:26213385 ATF5 Connects the Pericentriolar Materials to the Proximal E... | REMOVE | Summary: Interaction with PCNT, TUBGCP2 and TUBGCP4 at the centrosome. Reason: Generic protein binding is uninformative; the reported interaction is not disputed, but it does not describe an ATF5 molecular function. Removal follows the project policy for GO:0005515. The centrosomal scaffold role is captured by centrosome location and regulation of centrosome cycle. Supporting Evidence: PMID:26213385 Interaction of ATF5 with polyglutamylated tubulin (PGT) on the mother centriole and with PCNT in the PCM renders ATF5 as a required molecule in mother centriole-directed PCM accumulation and in PCM-dependent centriole formation. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI binary interaction with TTR. Reason: Generic protein binding is uninformative; the reported interaction is not disputed, but it does not describe an ATF5 molecular function. Removal follows the project policy for GO:0005515. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: HuRI binary interaction with CEBPG. Reason: bZIP heterodimerization partner; replace with protein heterodimerization activity. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI binary interaction with GPS2. Reason: Generic protein binding is uninformative; the reported interaction is not disputed, but it does not describe an ATF5 molecular function. Removal follows the project policy for GO:0005515. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI binary interaction with EIF2B1. Reason: Generic protein binding is uninformative; the reported interaction is not disputed, but it does not describe an ATF5 molecular function. Removal follows the project policy for GO:0005515. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI binary interaction with CCDC6. Reason: Generic protein binding is uninformative; the reported interaction is not disputed, but it does not describe an ATF5 molecular function. Removal follows the project policy for GO:0005515. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome. |
| GO:0005634 nucleus | EXP PMID:15358120 Cyclin D3 interacts with human activating transcription fact... | ACCEPT | Summary: Nuclear localization of ATF5 with cyclin D3. Reason: ATF5 acts in the nucleus as a transcription factor. Supporting Evidence: PMID:15358120 Confocal microscopy analysis showed that Cyclin D3 could colocalize with hATF5 in the nuclear region. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA: nucleus is the site of activity for the bZIP TF family. Reason: Correct and core location of activity. Supporting Evidence: file:human/ATF5/ATF5-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15358120}. Nucleus |
| GO:0005634 nucleus | IDA PMID:22528486 Nucleophosmin (NPM1/B23) interacts with activating transcrip... | ACCEPT | Summary: Nuclear (partly nucleolar) staining of ATF5 in HCC cells. Reason: Correct location. Supporting Evidence: PMID:22528486 NPM1 association with ATF5, whose staining patterns partially overlap in the nucleoli, promotes ATF5 protein degradation through proteasome-dependent and caspase-dependent pathways. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic nucleus annotation from UniProt subcellular location/Ensembl. Reason: Correct. Supporting Evidence: file:human/ATF5/ATF5-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15358120}. Nucleus |
| GO:0005634 nucleus | NAS PMID:20102225 Identification of bZIP interaction partners of viral protein... | ACCEPT | Summary: Author statement of nuclear localization for bZIP transcription factors. Reason: Correct location; better supported by IDA rows. Supporting Evidence: PMID:20102225 Basic-region leucine-zipper transcription factors (bZIPs) contain a segment rich in basic amino acids that can bind DNA, followed by a leucine zipper that can interact with other leucine zippers to form coiled-coil homo- or heterodimers. |
| GO:0005634 nucleus | NAS PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | ACCEPT | Summary: Author statement of nuclear localization (bZIP network study). Reason: Correct location; better supported by IDA rows. Supporting Evidence: PMID:23661758 We studied the basic region-leucine zipper (bZIP) transcription factors and quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Human Protein Atlas immunofluorescence: nucleoplasm. Reason: Consistent with transcription factor function. Supporting Evidence: file:human/ATF5/ATF5-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15358120}. Nucleus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9857071 | ACCEPT | Summary: Reactome: ATF5 binds the HSPD1/HSPE1 bidirectional promoter in the nucleoplasm during mitochondrial protein-folding stress. Reason: Correct; reflects ATF5 UPRmt function. Supporting Evidence: Reactome:R-HSA-9857071 Both HSF1 and ATF5 bind the bidirectional promoter of the HSPD1 gene (HSP60 gene) and HSPE1 gene (HSP10 gene) after unfolded proteins accumulate in the mitochondrial matrix |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9857083 | ACCEPT | Summary: Reactome: ATF5 binds the HSPA9 promoter in the nucleoplasm. Reason: Correct; reflects ATF5 UPRmt function. Supporting Evidence: Reactome:R-HSA-9857083 Both HSF1 and ATF5 bind the promoter of the HSPA9 gene (mt-HSP70 gene) after unfolded proteins accumulate in the mitochondrial matrix |
| GO:0005667 transcription regulator complex | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl transfer of transcription regulator complex membership. Reason: ATF5 acts as bZIP homo/heterodimers and with C/EBPB-p300 on promoters; plausible but generic. Supporting Evidence: PMID:24216764 overexpression of ATF5 and an acetylated ATF5 mimic both promoted 3T3-L1 adipocyte differentiation, whereas short interfering RNA-mediated ATF5 downregulation inhibited this process. |
| GO:0005737 cytoplasm | EXP PMID:15358120 Cyclin D3 interacts with human activating transcription fact... | KEEP AS NON CORE | Summary: Cytoplasmic localization reported (UniProt cites this paper for Cytoplasm). Reason: ATF5 has a cytoplasmic pool (including centrosome and mitochondria-associated ATF5); correct but not the site of its transcriptional activity. Supporting Evidence: file:human/ATF5/ATF5-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15358120}. Nucleus |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular location mapping to cytoplasm. Reason: Correct but non-core location. Supporting Evidence: file:human/ATF5/ATF5-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15358120}. Nucleus |
| GO:0005813 centrosome | IDA PMID:26213385 ATF5 Connects the Pericentriolar Materials to the Proximal E... | ACCEPT | Summary: ATF5 forms a 9-fold ring in the PCM at the proximal end of the mother centriole. Reason: Well-supported direct localization; reflects a non-transcriptional centrosomal role. Supporting Evidence: PMID:26213385 ATF5 forms a characteristic 9-fold symmetrical ring structure in the inner layer of the PCM outfitting the proximal end of the mother centriole. |
| GO:0005813 centrosome | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping to centrosome. Reason: Correct, based on PMID:26213385. Supporting Evidence: file:human/ATF5/ATF5-uniprot.txt Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:26213385}. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Human Protein Atlas immunofluorescence: cytosol. Reason: Plausible cytoplasmic pool; non-core. Supporting Evidence: file:human/ATF5/ATF5-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15358120}. Nucleus |
| GO:0006355 regulation of DNA-templated transcription | IDA PMID:20654631 Regulation of the human CHOP gene promoter by the stress res... | ACCEPT | Summary: Regulation of CHOP promoter transcription by ATF5. Reason: Correct, though parent of the more specific Pol II terms. Supporting Evidence: PMID:20654631 We showed that ATF5 activates the CHOP gene promoter in HepG2 cells. Both deletion analysis and point mutations of the promoter revealed that amino acid response element (AARE) 1 is responsible for ATF5-dependent promoter activation. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO from bZIP domain. Reason: Correct general term for a bZIP TF. Supporting Evidence: file:human/ATF5/ATF5-uniprot.txt Transcription factor that either stimulates or represses gene transcription through binding of different DNA regulatory elements such as cAMP response element (CRE) |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA: regulation of transcription by RNA polymerase II. Reason: Correct at the family level. Supporting Evidence: file:human/ATF5/ATF5-uniprot.txt Transcription factor that either stimulates or represses gene transcription through binding of different DNA regulatory elements such as cAMP response element (CRE) |
| GO:0006357 regulation of transcription by RNA polymerase II | NAS PMID:20102225 Identification of bZIP interaction partners of viral protein... | ACCEPT | Summary: Author statement that bZIPs regulate Pol II transcription. Reason: Correct; supported by IDA rows. Supporting Evidence: PMID:20102225 Basic-region leucine-zipper transcription factors (bZIPs) contain a segment rich in basic amino acids that can bind DNA, followed by a leucine zipper that can interact with other leucine zippers to form coiled-coil homo- or heterodimers. |
| GO:0006357 regulation of transcription by RNA polymerase II | NAS PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | ACCEPT | Summary: Author statement that bZIPs regulate Pol II transcription. Reason: Correct; supported by IDA rows. Supporting Evidence: PMID:23661758 We studied the basic region-leucine zipper (bZIP) transcription factors and quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs. |
| GO:0007623 circadian rhythm | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl transfer from mouse of circadian rhythm. Reason: No human evidence that ATF5 performs part of the circadian clock mechanism; the mouse source probably reflects rhythmic expression or an output phenotype rather than clock participation. UniProt function text does not mention a circadian role. Supporting Evidence: file:human/ATF5/ATF5-uniprot.txt Transcription factor that either stimulates or represses gene transcription through binding of different DNA regulatory elements such as cAMP response element (CRE) |
| GO:0008285 negative regulation of cell population proliferation | IDA PMID:22528486 Nucleophosmin (NPM1/B23) interacts with activating transcrip... | KEEP AS NON CORE | Summary: Re-expression of ATF5 in HCC cells induced G2/M blockade and inhibited proliferation. Reason: Cell-type-dependent downstream phenotype of ATF5 transcriptional activity; non-core. Supporting Evidence: PMID:22528486 NPM1-promoted ATF5 down-regulation diminished ATF5-mediated repression of cAMP-responsive element-dependent gene transcription and abrogates ATF5-induced G(2)/M cell cycle blockade and inhibition of cell proliferation in HCC cells. |
| GO:0015631 tubulin binding | IDA PMID:26213385 ATF5 Connects the Pericentriolar Materials to the Proximal E... | KEEP AS NON CORE | Summary: ATF5 binds polyglutamylated tubulin on the mother centriole. Reason: Supported by the centrosome study; relevant only to the non-transcriptional centrosomal role. Supporting Evidence: PMID:26213385 Interaction of ATF5 with polyglutamylated tubulin (PGT) on the mother centriole and with PCNT in the PCM renders ATF5 as a required molecule in mother centriole-directed PCM accumulation and in PCM-dependent centriole formation. |
| GO:0019900 kinase binding | IPI PMID:25512613 Stabilization of ATF5 by TAK1-Nemo-like kinase critically re... | KEEP AS NON CORE | Summary: ATF5 interacts with NLK, which stabilizes ATF5 in a kinase-independent manner. Reason: ATF5 is the stabilized client; kinase binding is accurate but uninformative about ATF5 activity. Supporting Evidence: PMID:25512613 NLK cooperated with ATF5 to activate C/EBP, whereas NLK could not activate C/EBP upon knockdown of ATF5. |
| GO:0021930 cerebellar granule cell precursor proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl transfer from mouse: cerebellar granule cell precursor proliferation. Reason: Mouse genetic evidence (UniProt By similarity) places ATF5 downstream of SHH in granule neuron progenitors; developmental, non-core. Supporting Evidence: file:human/ATF5/ATF5-uniprot.txt Participates in the pathways by which SHH promotes cerebellar granule neuron progenitor cells proliferation (By similarity). |
| GO:0021930 cerebellar granule cell precursor proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse Atf5: cerebellar granule cell precursor proliferation. Reason: Developmental, non-core. Supporting Evidence: file:human/ATF5/ATF5-uniprot.txt Participates in the pathways by which SHH promotes cerebellar granule neuron progenitor cells proliferation (By similarity). |
| GO:0042981 regulation of apoptotic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA prediction of regulation of apoptotic process. Reason: ATF5 regulates apoptosis through transcriptional targets (BCL2), cell-type dependently; non-core. Supporting Evidence: PMID:21212266 ATF5 binds to an ATF5-specific regulatory element that is downstream of and adjacent to the negative regulatory element in the BCL-2 P2 promoter, stimulating BCL-2 expression. |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:21212266 BCL-2 is a downstream target of ATF5 that mediates the prosu... | KEEP AS NON CORE | Summary: Dominant-negative ATF5 caused death of glioma and breast cancer cells, rescued by BCL-2. Reason: Indirect, cell-type-dependent outcome of ATF5 transcriptional activity at BCL2; non-core. Supporting Evidence: PMID:21212266 ATF5 binds to an ATF5-specific regulatory element that is downstream of and adjacent to the negative regulatory element in the BCL-2 P2 promoter, stimulating BCL-2 expression. |
| GO:0043565 sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl transfer of sequence-specific DNA binding. Reason: Correct. Supporting Evidence: file:human/ATF5/ATF5-uniprot.txt Transcription factor that either stimulates or represses gene transcription through binding of different DNA regulatory elements such as cAMP response element (CRE) |
| GO:0043565 sequence-specific DNA binding | ISS GO_REF:0000024 | ACCEPT | Summary: ISS transfer of sequence-specific DNA binding from rat. Reason: Correct. Supporting Evidence: file:human/ATF5/ATF5-uniprot.txt Transcription factor that either stimulates or represses gene transcription through binding of different DNA regulatory elements such as cAMP response element (CRE) |
| GO:0045444 fat cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl transfer of fat cell differentiation. Reason: ATF5 acts as a C/EBPB cofactor in adipogenesis; non-core. Supporting Evidence: PMID:24216764 overexpression of ATF5 and an acetylated ATF5 mimic both promoted 3T3-L1 adipocyte differentiation, whereas short interfering RNA-mediated ATF5 downregulation inhibited this process. |
| GO:0045444 fat cell differentiation | IMP PMID:24216764 p300-dependent acetylation of activating transcription facto... | KEEP AS NON CORE | Summary: ATF5 knockdown inhibited 3T3-L1 adipocyte differentiation (mouse cell line; annotated to human). Reason: Supported but non-core; ATF5 acts as a transcriptional cofactor of C/EBPB on the C/EBPalpha promoter. Supporting Evidence: PMID:24216764 overexpression of ATF5 and an acetylated ATF5 mimic both promoted 3T3-L1 adipocyte differentiation, whereas short interfering RNA-mediated ATF5 downregulation inhibited this process. |
| GO:0045892 negative regulation of DNA-templated transcription | IDA PMID:22528486 Nucleophosmin (NPM1/B23) interacts with activating transcrip... | ACCEPT | Summary: ATF5 represses CRE-dependent transcription in HCC cells. Reason: ATF5 has repressor as well as activator activity depending on element and context. Supporting Evidence: PMID:22528486 NPM1-promoted ATF5 down-regulation diminished ATF5-mediated repression of cAMP-responsive element-dependent gene transcription and abrogates ATF5-induced G(2)/M cell cycle blockade and inhibition of cell proliferation in HCC cells. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:21212266 BCL-2 is a downstream target of ATF5 that mediates the prosu... | ACCEPT | Summary: ATF5 stimulates BCL-2 expression via an ATF5-specific element. Reason: Correct. Supporting Evidence: PMID:21212266 ATF5 binds to an ATF5-specific regulatory element that is downstream of and adjacent to the negative regulatory element in the BCL-2 P2 promoter, stimulating BCL-2 expression. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:25512613 Stabilization of ATF5 by TAK1-Nemo-like kinase critically re... | ACCEPT | Summary: ATF5 with NLK activates C/EBP-dependent transcription after IL-1beta. Reason: Correct. Supporting Evidence: PMID:25512613 NLK cooperated with ATF5 to activate C/EBP, whereas NLK could not activate C/EBP upon knockdown of ATF5. |
| GO:0045893 positive regulation of DNA-templated transcription | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from rat: positive regulation of transcription. Reason: Correct. Supporting Evidence: file:human/ATF5/ATF5-uniprot.txt Transcription factor that either stimulates or represses gene transcription through binding of different DNA regulatory elements such as cAMP response element (CRE) |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:16300731 ATF5 increases cisplatin-induced apoptosis through up-regula... | ACCEPT | Summary: ATF5 induces cyclin D3 transcription. Reason: Correct; Pol II activator role. Supporting Evidence: PMID:16300731 induce Cyclin D3 mRNA expression via cooperation with E2F1 transcription factor. |
| GO:0046605 regulation of centrosome cycle | IDA PMID:26213385 ATF5 Connects the Pericentriolar Materials to the Proximal E... | KEEP AS NON CORE | Summary: ATF5 depletion blocks PCM accumulation and causes centriole fragmentation. Reason: Supported by a single high-profile study; a non-transcriptional role distinct from the stress-response core. Supporting Evidence: PMID:26213385 Interaction of ATF5 with polyglutamylated tubulin (PGT) on the mother centriole and with PCNT in the PCM renders ATF5 as a required molecule in mother centriole-directed PCM accumulation and in PCM-dependent centriole formation. |
| GO:0090575 RNA polymerase II transcription regulator complex | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | KEEP AS NON CORE | Summary: Coiled-coil arrays detect ATF5 bZIP heterodimers. Reason: In vitro dimerization supports heterodimeric bZIP complexes; complex membership in cells is plausible but not directly shown here. Supporting Evidence: PMID:20102225 Basic-region leucine-zipper transcription factors (bZIPs) contain a segment rich in basic amino acids that can bind DNA, followed by a leucine zipper that can interact with other leucine zippers to form coiled-coil homo- or heterodimers. |
| GO:0090575 RNA polymerase II transcription regulator complex | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | KEEP AS NON CORE | Summary: Quantitative in vitro bZIP dimerization network. Reason: As above; plausible, non-core. Supporting Evidence: PMID:23661758 We studied the basic region-leucine zipper (bZIP) transcription factors and quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs. |
| GO:1902750 negative regulation of cell cycle G2/M phase transition | IDA PMID:22528486 Nucleophosmin (NPM1/B23) interacts with activating transcrip... | KEEP AS NON CORE | Summary: ATF5 re-expression induced G2/M blockade in HCC cells. Reason: Cell-type-dependent downstream phenotype; non-core. Supporting Evidence: PMID:22528486 NPM1-promoted ATF5 down-regulation diminished ATF5-mediated repression of cAMP-responsive element-dependent gene transcription and abrogates ATF5-induced G(2)/M cell cycle blockade and inhibition of cell proliferation in HCC cells. |
| GO:0034514 mitochondrial unfolded protein response | IMP PMID:27426517 The Transcription Factor ATF5 Mediates a Mammalian Mitochond... | NEW | Summary: ATF5 is the transcription factor of the mammalian UPRmt: shRNA knockdown abolished stress-induced transcription of HSPD1, HSPA9, LONP1 and HSPE1, and human ATF5 rescued UPRmt reporter induction in atfs-1-deficient C. elegans via the UPRmt promoter element. Reason: ATF5 performs the transcriptional step of this response (it binds and activates mitochondrial chaperone/protease promoters; Reactome curates ATF5 binding to HSPD1/HSPE1 and HSPA9 promoters), so it passes the participation test. Comparator: the worm functional counterpart ATFS-1 carries GO:0034514, as do other response-effector transcription factors for their stress responses (e.g. XBP1/ATF6 for the ER UPR). Not present in human GOA for ATF5. Supporting Evidence: PMID:27426517 Here, we describe a mammalian transcription factor, ATF5, which is regulated similarly to ATFS-1 and induces a similar transcriptional response. ATF5 expression can rescue UPR(mt) signaling in atfs-1-deficient worms requiring the same UPR(mt) promoter element identified in C. elegans. PMID:27426517 Impressively, transcription of all four genes was significantly reduced when ATF5 was impaired by two different shRNAs Reactome:R-HSA-9857071 Both HSF1 and ATF5 bind the bidirectional promoter of the HSPD1 gene (HSP60 gene) and HSPE1 gene (HSP10 gene) after unfolded proteins accumulate in the mitochondrial matrix |
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Download this section (compressed HTML)Q: Is endogenous ATF5 imported into mitochondria and degraded there under basal conditions (ATFS-1-like partitioning), or is its UPRmt regulation mainly translational via eIF2alpha phosphorylation downstream of HRI/DELE1?
Q: How do ATF4, ATF5 and CHOP divide the transcriptional output of the mammalian mitochondrial stress response, given that HRI-DELE1 signalling induces all three?
Experiment: Tag endogenous ATF5 (knock-in) in liver-derived cells, impair import (e.g. CCCP, TIM23 knockdown) and quantify mitochondrial versus nuclear ATF5 by fractionation and imaging, with ATF5 MTS mutants as controls.
Hypothesis: Endogenous ATF5 partitions between mitochondria and nucleus according to import efficiency.
Type: localization / genetic perturbation
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