DDRGK1 (DDRGK domain-containing protein 1; also called UFBP1, Dashurin) is a single-pass endoplasmic-reticulum membrane protein that is an obligate component of the UFM1 ribosome E3 ligase (UREL) complex, together with the E3 ligase UFL1 and CDK5RAP3. DDRGK1 tethers the complex to the ER membrane through its N-terminal transmembrane helix, thereby restricting ufmylation activity to ER-docked ribosomes, and stabilizes UFL1. Following mono-ufmylation of the 60S ribosomal protein RPL26/uL24, DDRGK1 acts as a UFM1 reader, in that its UFM1-interacting motif (UFIM) binds ufmylated RPL26, producing stable association of the 60S subunit with the UREL complex and promoting release and recycling of the large subunit from SEC61 translocons. DDRGK1 is itself a substrate of ufmylation (at Lys-267). Through ER-resident ufmylation it participates in ribosome recycling, reticulophagy (ER-phagy), the response to ER stress and the unfolded protein response (regulating IRE1-alpha/ERN1 stability). Biallelic loss-of-function variants cause Shohat-type spondyloepimetaphyseal dysplasia, reflecting a role in cartilage development via SOX9 stabilization.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0044389 ubiquitin-like protein ligase binding | IBA GO_REF:0000033 | ACCEPT | Summary: DDRGK1 binds the UFM1 E3 ligase UFL1 directly via its C-terminal region, forming the core of the UREL complex. This binding is central to DDRGK1's adaptor function. Reason: Direct, experimentally documented binding to the E3 ligase UFL1; this ligase-binding/adaptor activity is a core molecular function. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt Mediates interaction with UFL1 |
| GO:0051216 cartilage development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: DDRGK1 is required for cartilage development; loss-of-function variants cause Shohat-type spondyloepimetaphyseal dysplasia, and DDRGK1 stabilizes SOX9. Reason: A genuine, disease-supported developmental role, but a downstream physiological outcome rather than DDRGK1's core molecular adaptor/reader function. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt Plays a role in cartilage development through SOX9 |
| GO:1903895 negative regulation of IRE1-mediated unfolded protein response | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: DDRGK1 regulates ERN1/IRE1-alpha stability in a UFM1-dependent manner, modulating the IRE1 arm of the unfolded protein response. Reason: A valid downstream signaling role mediated by DDRGK1's adaptor function; non-core relative to the molecular function. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt regulating ERN1/IRE1-alpha stability |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: DDRGK1 is a single-pass ER membrane protein; this is its principal site of action where it tethers the UREL complex. Reason: ER membrane localization is well established experimentally and is essential to restrict ufmylation to ER-docked ribosomes. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BioPlex affinity-purification interactions. Bare protein binding is uninformative. Reason: Records real high-throughput interactions but the term is uninformative; core MF is captured by UFL1 binding and UFM1-reader activity. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:33961781 |
| GO:0005515 protein binding | IPI PMID:35156780 CFTR interactome mapping using the mammalian membrane two-hy... | KEEP AS NON CORE | Summary: High-throughput interactome interaction. Bare protein binding is uninformative. Reason: Real interaction record but uninformative term. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:35156780 |
| GO:0005515 protein binding | IPI PMID:36012204 Differential CFTR-Interactome Proximity Labeling Procedures ... | KEEP AS NON CORE | Summary: High-throughput interactome interaction. Bare protein binding is uninformative. Reason: Real interaction record but uninformative term. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:36012204 |
| GO:0005515 protein binding | IPI PMID:37595036 Mechanistic insights into the roles of the UFM1 E3 ligase co... | KEEP AS NON CORE | Summary: Interaction reported in the mechanistic UREL-complex study (UFL1/CDK5RAP3 partners). Bare term uninformative but reflects cascade interactions. Reason: Real cascade interactions; non-core under generic term. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:37595036 |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: Multimodal cell-maps interaction. Bare protein binding is uninformative. Reason: Real interaction record but uninformative term. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:40205054 |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000107 | ACCEPT | Summary: ER localization, consistent with DDRGK1's role as an ER-membrane-anchored adaptor. Reason: Correct compartment; agrees with stronger experimental ER-membrane evidence. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0034976 response to endoplasmic reticulum stress | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DDRGK1 functions in ER-stress-associated ufmylation and reticulophagy. Reason: Valid pathway context; non-core relative to the molecular function. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt involved in reticulophagy in response to endoplasmic reticulum stress |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Anti-apoptotic role inferred electronically/by similarity; not directly established for human DDRGK1's core function. Reason: Plausible downstream effect via ER homeostasis; peripheral and electronically inferred. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:0043066 negative regulation of apoptotic process biological_process ECO:0000501 IEA |
| GO:0051216 cartilage development | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Cartilage development, also captured by IBA and IMP evidence. Reason: Genuine developmental role; non-core relative to molecular function. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt Plays a role in cartilage development through SOX9 |
| GO:1900100 positive regulation of plasma cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Role in B-cell-to-plasma-cell differentiation via ER expansion and UPR regulation, inferred by similarity. Reason: Plausible immune-differentiation role by orthology; downstream and non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt promoting differentiation of B-cells into plasma cells |
| GO:1903895 negative regulation of IRE1-mediated unfolded protein response | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Electronic support for the IRE1-UPR regulatory role also documented experimentally. Reason: Valid downstream signaling role; non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt regulating ERN1/IRE1-alpha stability |
| GO:1903898 negative regulation of PERK-mediated unfolded protein response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Regulation of the PERK arm of the UPR, inferred by similarity. Reason: Plausible UPR-modulating role by orthology; downstream and non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt regulating the unfolded protein response |
| GO:1905552 positive regulation of protein localization to endoplasmic reticulum | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DDRGK1 promotes protein localization to the ER, inferred electronically; consistent with its ER-tethering role. Reason: Plausible but electronically inferred; non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:1905552 positive regulation of protein localization to endoplasmic reticulum |
| GO:0005783 endoplasmic reticulum | IDA GO_REF:0000052 | ACCEPT | Summary: Direct (HPA) immunofluorescence ER localization. Reason: IDA-supported ER localization consistent with site of action. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:0005783 endoplasmic reticulum cellular_component ECO:0000314 IDA GO_REF:0000052 |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:20018847 A novel type of E3 ligase for the Ufm1 conjugation system. | ACCEPT | Summary: Experimental ER membrane localization from the paper identifying the UFM1 E3 ligase. Reason: Direct experimental support for the principal compartment. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IMP PMID:23675531 DDRGK1 regulates NF-kappaB activity by modulating IkappaBalp... | KEEP AS NON CORE | Summary: DDRGK1 modulates NF-kappaB activity through regulation of NFKBIA/IkappaB-alpha stability. Reason: A documented signaling role but downstream of and separable from DDRGK1's core UREL-adaptor function. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt May play a role in NF- |
| GO:0071569 protein ufmylation | IDA PMID:36121123 A non-canonical scaffold-type E3 ligase complex mediates pro... | ACCEPT | Summary: DDRGK1 is required as a UREL-complex component for protein ufmylation. Reason: Direct evidence for DDRGK1's role in the ufmylation process. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt Component of the UFM1 ribosome E3 ligase (UREL) complex |
| GO:1990234 transferase complex | IPI PMID:36121123 A non-canonical scaffold-type E3 ligase complex mediates pro... | ACCEPT | Summary: DDRGK1 is part of the UREL transferase complex (with UFL1 and CDK5RAP3). Reason: DDRGK1 is a bona fide subunit of the UFM1 E3 ligase (transferase) complex. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:1990234 transferase complex cellular_component ECO:0000353 IPI PMID:36121123 |
| GO:0141185 UFM1-modified protein reader activity | IDA PMID:36121123 A non-canonical scaffold-type E3 ligase complex mediates pro... | ACCEPT | Summary: DDRGK1 reads ufmylated RPL26/uL24 via its UFM1-interacting motif (UFIM), a defining molecular function of the adaptor. Reason: Direct evidence for UFM1-modified protein reader activity; this is a core molecular function of DDRGK1. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt DDRGK1 specifically binds to ufmylated RPL26/uL24 via its UFIM motif |
| GO:0141185 UFM1-modified protein reader activity | IDA PMID:36543799 The UFM1 system regulates ER-phagy through the ufmylation of... | ACCEPT | Summary: Reader activity for ufmylated substrate via the UFIM, demonstrated in the CYB5R3/ER-phagy study. Reason: Direct support for the core UFM1-reader molecular function. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt The UFM1-interacting motif (UFIM) specifically recognizes and binds ufmylated RPL26/uL24 |
| GO:0141185 UFM1-modified protein reader activity | IDA PMID:37595036 Mechanistic insights into the roles of the UFM1 E3 ligase co... | ACCEPT | Summary: UFIM-dependent reading of ufmylated RPL26 demonstrated mechanistically. Reason: Direct support for the core reader molecular function. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt The UFM1-interacting motif (UFIM) specifically recognizes and binds ufmylated RPL26/uL24 |
| GO:0141185 UFM1-modified protein reader activity | IDA PMID:38383785 UFM1 E3 ligase promotes recycling of 60S ribosomal subunits ... | ACCEPT | Summary: Cryo-EM of the UREL-60S complex shows DDRGK1 UFIM binding ufmylated RPL26. Reason: Direct structural support for the core reader molecular function. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt The UFM1-interacting motif (UFIM) specifically recognizes and binds ufmylated RPL26/uL24 |
| GO:0141185 UFM1-modified protein reader activity | IDA PMID:38383789 The UFM1 E3 ligase recognizes and releases 60S ribosomes fro... | ACCEPT | Summary: Structural demonstration of DDRGK1 reading ufmylated RPL26 in the UREL-60S complex. Reason: Direct structural support for the core reader molecular function. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt The UFM1-interacting motif (UFIM) specifically recognizes and binds ufmylated RPL26/uL24 |
| GO:1900100 positive regulation of plasma cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Plasma-cell differentiation role transferred from ortholog by sequence similarity. Reason: Plausible by orthology; downstream and non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt promoting differentiation of B-cells into plasma cells |
| GO:1903898 negative regulation of PERK-mediated unfolded protein response | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: PERK-UPR regulation transferred from ortholog by sequence similarity. Reason: Plausible by orthology; downstream and non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt regulating the unfolded protein response |
| GO:0071569 protein ufmylation | IDA PMID:35753586 P4HB UFMylation regulates mitochondrial function and oxidati... | ACCEPT | Summary: DDRGK1 (UREL component) required for ufmylation of P4HB. Reason: Direct evidence for the ufmylation process role. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt Component of the UFM1 ribosome E3 ligase (UREL) complex |
| GO:0071569 protein ufmylation | IDA PMID:37795761 UFMylation of HRD1 regulates endoplasmic reticulum homeostas... | ACCEPT | Summary: DDRGK1 (UREL component) required for ufmylation of HRD1/SYVN1. Reason: Direct evidence for the ufmylation process role. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt Component of the UFM1 ribosome E3 ligase (UREL) complex |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:36543799 The UFM1 system regulates ER-phagy through the ufmylation of... | ACCEPT | Summary: DDRGK1 acts at the ER membrane within the UREL complex. Reason: Direct evidence for the site of action. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt DDRGK1 tethers the complex to the endoplasmic reticulum membrane |
| GO:0045732 positive regulation of protein catabolic process | IDA PMID:36543799 The UFM1 system regulates ER-phagy through the ufmylation of... | KEEP AS NON CORE | Summary: DDRGK1-mediated ufmylation promotes lysosomal degradation of ufmylated proteins (reticulophagy). Reason: A downstream consequence of ER ufmylation/reticulophagy; non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt thereby promoting lysosomal degradation of ufmylated proteins |
| GO:0071569 protein ufmylation | IDA PMID:36543799 The UFM1 system regulates ER-phagy through the ufmylation of... | ACCEPT | Summary: DDRGK1 (UREL component) required for ufmylation of CYB5R3. Reason: Direct evidence for the ufmylation process role. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt Component of the UFM1 ribosome E3 ligase (UREL) complex |
| GO:0071569 protein ufmylation | IDA PMID:37595036 Mechanistic insights into the roles of the UFM1 E3 ligase co... | ACCEPT | Summary: DDRGK1 required for RPL26 ufmylation/ribosome-associated quality control. Reason: Direct evidence for the ufmylation process role. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt Component of the UFM1 ribosome E3 ligase (UREL) complex |
| GO:0072344 rescue of stalled cytosolic ribosome | IDA PMID:37595036 Mechanistic insights into the roles of the UFM1 E3 ligase co... | KEEP AS NON CORE | Summary: DDRGK1, within UREL, contributes to recycling of stalled/post-termination 60S ribosomes at the ER. GOA cross-references this as rescue of stalled ribosome. Reason: A genuine role in ribosome recycling/RQC; captured as a downstream process while the core MF is the UFM1-reader/adaptor activity. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt plays a key role in ribosome recycling by mediating mono-ufmylation of the RPL26/uL24 subunit |
| GO:0140501 positive regulation of reticulophagy | IDA PMID:36543799 The UFM1 system regulates ER-phagy through the ufmylation of... | KEEP AS NON CORE | Summary: DDRGK1-dependent ufmylation promotes reticulophagy (ER-phagy). Reason: Valid downstream process; non-core relative to molecular function. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt involved in reticulophagy in response to endoplasmic reticulum stress |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:38383785 UFM1 E3 ligase promotes recycling of 60S ribosomal subunits ... | ACCEPT | Summary: DDRGK1 acts at the ER membrane within the UREL-60S complex. Reason: Direct structural evidence for the site of action. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt DDRGK1 tethers the complex to the endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:38383789 The UFM1 E3 ligase recognizes and releases 60S ribosomes fro... | ACCEPT | Summary: DDRGK1 acts at the ER membrane within the UREL-60S complex. Reason: Direct structural evidence for the site of action. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt DDRGK1 tethers the complex to the endoplasmic reticulum membrane |
| GO:0032790 ribosome disassembly | IDA PMID:38383785 UFM1 E3 ligase promotes recycling of 60S ribosomal subunits ... | KEEP AS NON CORE | Summary: UREL-mediated ufmylation promotes dissociation/release of the 60S subunit from the ER translocon. Reason: Genuine role in 60S release/recycling; downstream process, non-core relative to the reader/adaptor MF. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt dissociation of the 60S ribosome subunit from the endoplasmic reticulum membrane |
| GO:0032790 ribosome disassembly | IDA PMID:38383789 The UFM1 E3 ligase recognizes and releases 60S ribosomes fro... | KEEP AS NON CORE | Summary: UREL-mediated ufmylation promotes 60S release from the ER translocon. Reason: Genuine role in 60S release/recycling; downstream process, non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt dissociation of the 60S ribosome subunit from the endoplasmic reticulum membrane |
| GO:0071569 protein ufmylation | IMP PMID:30626644 Ribosomal protein RPL26 is the principal target of UFMylatio... | ACCEPT | Summary: DDRGK1 is required for ufmylation; RPL26 is the principal target. Reason: Functional support for DDRGK1's role in ufmylation. Supporting Evidence: PMID:30626644 Ribosomal protein RPL26 is the principal target of UFMylation |
| GO:0071569 protein ufmylation | IDA PMID:38383785 UFM1 E3 ligase promotes recycling of 60S ribosomal subunits ... | ACCEPT | Summary: DDRGK1 (UREL component) required for RPL26 ufmylation. Reason: Direct evidence for the ufmylation process role. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt Component of the UFM1 ribosome E3 ligase (UREL) complex |
| GO:0071569 protein ufmylation | IDA PMID:38383789 The UFM1 E3 ligase recognizes and releases 60S ribosomes fro... | ACCEPT | Summary: DDRGK1 (UREL component) required for RPL26 ufmylation. Reason: Direct evidence for the ufmylation process role. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt Component of the UFM1 ribosome E3 ligase (UREL) complex |
| GO:0072344 rescue of stalled cytosolic ribosome | IDA PMID:38383785 UFM1 E3 ligase promotes recycling of 60S ribosomal subunits ... | KEEP AS NON CORE | Summary: DDRGK1, within UREL, contributes to recycling of post-termination/stalled 60S ribosomes at the ER. Reason: Genuine ribosome-recycling/RQC role; downstream process, non-core relative to the reader/adaptor MF. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt plays a key role in ribosome recycling by mediating mono-ufmylation of the RPL26/uL24 subunit |
| GO:0072344 rescue of stalled cytosolic ribosome | IDA PMID:38383789 The UFM1 E3 ligase recognizes and releases 60S ribosomes fro... | KEEP AS NON CORE | Summary: DDRGK1, within UREL, contributes to release/recycling of stalled 60S ribosomes from the ER translocon. Reason: Genuine ribosome-recycling/RQC role; downstream process, non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt promoting release and recycling of the large ribosomal subunit |
| GO:0005515 protein binding | IPI PMID:28128204 A critical role of DDRGK1 in endoplasmic reticulum homoeosta... | KEEP AS NON CORE | Summary: Interaction with ERN1/IRE1-alpha (UFM1-dependent). Bare term uninformative but reflects a functionally important interaction. Reason: Real, mechanistically relevant interaction; non-core under generic term. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:28128204 |
| GO:0005515 protein binding | IPI PMID:32160526 A genome-wide ER-phagy screen highlights key roles of mitoch... | KEEP AS NON CORE | Summary: Interaction with UFL1 from the ER-phagy screen. Bare term uninformative. Reason: Real cascade interaction; non-core under generic term. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32160526 |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:32160526 A genome-wide ER-phagy screen highlights key roles of mitoch... | ACCEPT | Summary: ER membrane localization from the ER-phagy screen. Reason: Direct evidence for principal compartment. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0031647 regulation of protein stability | IDA PMID:28128204 A critical role of DDRGK1 in endoplasmic reticulum homoeosta... | KEEP AS NON CORE | Summary: DDRGK1 regulates ERN1/IRE1-alpha stability in a UFM1-dependent manner. Reason: Documented regulatory role; downstream of the adaptor function, non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt regulating ERN1/IRE1-alpha stability |
| GO:0034976 response to endoplasmic reticulum stress | IDA PMID:28128204 A critical role of DDRGK1 in endoplasmic reticulum homoeosta... | KEEP AS NON CORE | Summary: DDRGK1 functions in ER homeostasis/UPR via IRE1-alpha. Reason: Valid pathway context; non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt A critical role of DDRGK1 in endoplasmic reticulum homoeostasis |
| GO:0034976 response to endoplasmic reticulum stress | IDA PMID:32160526 A genome-wide ER-phagy screen highlights key roles of mitoch... | KEEP AS NON CORE | Summary: DDRGK1 functions in ER-stress-associated ufmylation/reticulophagy. Reason: Valid pathway context; non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt involved in reticulophagy in response to endoplasmic reticulum stress |
| GO:0061709 reticulophagy | IDA PMID:32160526 A genome-wide ER-phagy screen highlights key roles of mitoch... | KEEP AS NON CORE | Summary: DDRGK1 contributes to reticulophagy driven by ER ufmylation. Reason: Valid downstream process; non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt involved in reticulophagy in response to endoplasmic reticulum stress |
| GO:0070972 protein localization to endoplasmic reticulum | IDA PMID:32160526 A genome-wide ER-phagy screen highlights key roles of mitoch... | KEEP AS NON CORE | Summary: DDRGK1 promotes protein localization to the ER. Reason: Plausible role consistent with ER-tethering; non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:0070972 protein localization to endoplasmic reticulum biological_process ECO:0000314 IDA PMID:32160526 |
| GO:0071569 protein ufmylation | IDA PMID:32160526 A genome-wide ER-phagy screen highlights key roles of mitoch... | ACCEPT | Summary: DDRGK1 required for ufmylation in the ER-phagy context. Reason: Direct evidence for the ufmylation process role. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt Component of the UFM1 ribosome E3 ligase (UREL) complex |
| GO:1903895 negative regulation of IRE1-mediated unfolded protein response | IDA PMID:28128204 A critical role of DDRGK1 in endoplasmic reticulum homoeosta... | KEEP AS NON CORE | Summary: DDRGK1 negatively regulates the IRE1 arm of the UPR via control of IRE1-alpha stability. Reason: Documented signaling role; downstream, non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt inhibits the unfolded protein response (UPR) by regulating ERN1/IRE1-alpha stability |
| GO:1903895 negative regulation of IRE1-mediated unfolded protein response | IDA PMID:32160526 A genome-wide ER-phagy screen highlights key roles of mitoch... | KEEP AS NON CORE | Summary: ER-phagy screen supports negative regulation of the IRE1 UPR arm. Reason: Documented signaling role; downstream, non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt inhibits the unfolded protein response (UPR) by regulating ERN1/IRE1-alpha stability |
| GO:0005515 protein binding | IPI PMID:28263186 Loss of DDRGK1 modulates SOX9 ubiquitination in spondyloepim... | KEEP AS NON CORE | Summary: Interaction with SOX9 (from the SEMDSH/cartilage study). Bare term uninformative but reflects a functionally relevant interaction. Reason: Real interaction relevant to the cartilage role; non-core under generic term. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:28263186 |
| GO:0032435 negative regulation of proteasomal ubiquitin-dependent protein catabolic process | IMP PMID:28263186 Loss of DDRGK1 modulates SOX9 ubiquitination in spondyloepim... | KEEP AS NON CORE | Summary: DDRGK1 inhibits ubiquitin-mediated proteasomal degradation of SOX9, stabilizing it. Reason: Documented effect underlying the cartilage role; downstream, non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt inhibiting the ubiquitin-mediated proteasomal degradation of this transcriptional regulator |
| GO:0051216 cartilage development | IMP PMID:28263186 Loss of DDRGK1 modulates SOX9 ubiquitination in spondyloepim... | KEEP AS NON CORE | Summary: Loss of DDRGK1 causes SEMDSH; DDRGK1 acts in cartilage development through SOX9. Reason: Genuine disease-supported developmental role; non-core relative to molecular function. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt Plays a role in cartilage development through SOX9 |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:23675531 DDRGK1 regulates NF-kappaB activity by modulating IkappaBalp... | KEEP AS NON CORE | Summary: Inferred from DDRGK1's modulation of NF-kappaB-dependent transcription. Reason: Indirect, downstream transcriptional effect via NF-kappaB signaling; non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt May play a role in NF- |
| GO:1902808 positive regulation of cell cycle G1/S phase transition | IC PMID:23675531 DDRGK1 regulates NF-kappaB activity by modulating IkappaBalp... | KEEP AS NON CORE | Summary: Inferred (IC) cell-cycle effect downstream of DDRGK1's NF-kappaB/proliferation role. Reason: Indirect downstream effect; non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:1902808 positive regulation of cell cycle G1/S phase transition biological_process ECO:0000305 IC PMID:23675531 |
| GO:0030335 positive regulation of cell migration | IMP PMID:23675531 DDRGK1 regulates NF-kappaB activity by modulating IkappaBalp... | KEEP AS NON CORE | Summary: DDRGK1 promotes cell migration in the NF-kappaB study. Reason: Downstream cellular phenotype; non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:0030335 positive regulation of cell migration biological_process ECO:0000315 IMP PMID:23675531 |
| GO:0005515 protein binding | IPI PMID:23675531 DDRGK1 regulates NF-kappaB activity by modulating IkappaBalp... | KEEP AS NON CORE | Summary: Interaction with NFKBIA/IkappaB-alpha. Bare term uninformative. Reason: Real interaction relevant to the NF-kappaB role; non-core under generic term. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:23675531 |
| GO:0005737 cytoplasm | TAS PMID:23675531 DDRGK1 regulates NF-kappaB activity by modulating IkappaBalp... | KEEP AS NON CORE | Summary: Cytoplasmic localization asserted in the NF-kappaB study; DDRGK1 is an ER-membrane protein with a large cytoplasmic domain. Reason: Consistent with the cytoplasmic-facing topology, but the principal compartment is the ER membrane. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt Cytoplasmic |
| GO:0008284 positive regulation of cell population proliferation | IMP PMID:23675531 DDRGK1 regulates NF-kappaB activity by modulating IkappaBalp... | KEEP AS NON CORE | Summary: DDRGK1 promotes proliferation in the NF-kappaB study. Reason: Downstream cellular phenotype; non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:0008284 positive regulation of cell population proliferation biological_process ECO:0000315 IMP PMID:23675531 |
| GO:0010628 positive regulation of gene expression | IMP PMID:23675531 DDRGK1 regulates NF-kappaB activity by modulating IkappaBalp... | KEEP AS NON CORE | Summary: Gene-expression effects downstream of NF-kappaB modulation. Reason: Indirect downstream effect; non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:0010628 positive regulation of gene expression biological_process ECO:0000315 IMP PMID:23675531 |
| GO:0010629 negative regulation of gene expression | IMP PMID:23675531 DDRGK1 regulates NF-kappaB activity by modulating IkappaBalp... | KEEP AS NON CORE | Summary: Gene-expression effects downstream of NF-kappaB modulation. Reason: Indirect downstream effect; non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:0010629 negative regulation of gene expression biological_process ECO:0000315 IMP PMID:23675531 |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | IMP PMID:23675531 DDRGK1 regulates NF-kappaB activity by modulating IkappaBalp... | KEEP AS NON CORE | Summary: DDRGK1 promotes NFKBIA proteasomal degradation in the NF-kappaB study. Reason: Downstream effect within NF-kappaB signaling; non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process biological_process ECO:0000315 IMP PMID:23675531 |
| GO:0043066 negative regulation of apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Anti-apoptotic role transferred from ortholog by sequence similarity. Reason: Plausible by orthology; downstream and non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:0043066 negative regulation of apoptotic process biological_process ECO:0000250 ISS GO_REF:0000024 |
| GO:1905552 positive regulation of protein localization to endoplasmic reticulum | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Transferred from ortholog by sequence similarity; consistent with ER-tethering role. Reason: Plausible by orthology; non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:1905552 positive regulation of protein localization to endoplasmic reticulum biological_process ECO:0000250 ISS GO_REF:0000024 |
| GO:1990592 protein K69-linked ufmylation | IDA PMID:25219498 Modification of ASC1 by UFM1 is crucial for ERΞ± transactivat... | KEEP AS NON CORE | Summary: DDRGK1 participates in UFM1 conjugation, including K69-linked UFM1 chains. Reason: Specific chain-linkage sub-aspect of ufmylation; narrow process annotation. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:1990592 protein K69-linked ufmylation biological_process ECO:0000314 IDA PMID:25219498 |
| GO:0005515 protein binding | IPI PMID:20228063 A novel C53/LZAP-interacting protein regulates stability of ... | KEEP AS NON CORE | Summary: Interaction with CDK5RAP3 (a UREL component). Bare term uninformative but reflects a cascade interaction. Reason: Real cascade interaction; non-core under generic term. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:20228063 |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:20228063 A novel C53/LZAP-interacting protein regulates stability of ... | ACCEPT | Summary: Experimental ER membrane localization. Reason: Direct evidence for principal compartment. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0033146 regulation of intracellular estrogen receptor signaling pathway | IDA PMID:25219498 Modification of ASC1 by UFM1 is crucial for ERΞ± transactivat... | KEEP AS NON CORE | Summary: DDRGK1 contributes to ufmylation of ASC1/TRIP4, affecting ERalpha transactivation. Reason: A documented but specialized signaling role downstream of ufmylation; non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt May also be required for TRIP4 ufmylation |
| GO:0034976 response to endoplasmic reticulum stress | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ER stress response transferred from ortholog by sequence similarity. Reason: Valid pathway context by orthology; non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt involved in reticulophagy in response to endoplasmic reticulum stress |
| GO:1901800 positive regulation of proteasomal protein catabolic process | IMP PMID:23675531 DDRGK1 regulates NF-kappaB activity by modulating IkappaBalp... | KEEP AS NON CORE | Summary: DDRGK1 promotes proteasomal catabolism of NFKBIA in the NF-kappaB study. Reason: Downstream effect within NF-kappaB signaling; non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:1901800 positive regulation of proteasomal protein catabolic process biological_process ECO:0000315 IMP PMID:23675531 |
| GO:1903721 positive regulation of I-kappaB phosphorylation | IMP PMID:23675531 DDRGK1 regulates NF-kappaB activity by modulating IkappaBalp... | KEEP AS NON CORE | Summary: DDRGK1 promotes IkappaB-alpha phosphorylation, activating NF-kappaB. Reason: Downstream signaling effect; non-core. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:1903721 positive regulation of I-kappaB phosphorylation biological_process ECO:0000315 IMP PMID:23675531 |
| GO:0005515 protein binding | IPI PMID:25219498 Modification of ASC1 by UFM1 is crucial for ERΞ± transactivat... | KEEP AS NON CORE | Summary: Interaction with UFL1/TRIP4 in the ASC1/ufmylation study. Bare term uninformative. Reason: Real cascade-relevant interaction; non-core under generic term. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:25219498 |
| GO:0044389 ubiquitin-like protein ligase binding | IPI PMID:25219498 Modification of ASC1 by UFM1 is crucial for ERΞ± transactivat... | ACCEPT | Summary: Direct interaction with the UFM1 E3 ligase UFL1, the core adaptor binding activity of DDRGK1. Reason: Direct experimental support for the core UFL1-binding/adaptor molecular function. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt Mediates interaction with UFL1 |
| GO:0005515 protein binding | IPI PMID:20018847 A novel type of E3 ligase for the Ufm1 conjugation system. | KEEP AS NON CORE | Summary: Interaction with UFL1 from the paper identifying the UFM1 E3 ligase. Bare term uninformative. Reason: Real cascade interaction; non-core under generic term. Supporting Evidence: file:human/DDRGK1/DDRGK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:20018847 |
| GO:0005783 endoplasmic reticulum | IDA PMID:20018847 A novel type of E3 ligase for the Ufm1 conjugation system. | ACCEPT | Summary: Experimental ER localization from the UFM1 E3 ligase paper. Reason: Direct evidence for principal compartment. Supporting Evidence: file:human/DDRGK1/DDRGK1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
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Download this section (compressed HTML)Q: Is ufmylation of DDRGK1 at Lys-267 functionally required for UREL activity or is it a collateral consequence of the reaction it scaffolds?
Q: How are the ER-stress/UPR (IRE1-alpha), NF-kappaB and SOX9/cartilage roles of DDRGK1 related to its UREL ribosome-recycling function - are they separable activities or downstream consequences of ER ufmylation?
Experiment: Separation-of-function mutants (UFIM-dead vs UFL1-binding-dead vs Lys-267 ufmylation-dead) tested in 60S-recycling, IRE1-alpha-stability and SOX9-stability assays to dissect which DDRGK1 activities drive each phenotype.
Experiment: Reconstitute the UREL-60S complex with purified components to quantify the contribution of DDRGK1 membrane-tethering and UFIM reading to RPL26 ufmylation kinetics and 60S release from SEC61.
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