id: Q96HY6
gene_symbol: DDRGK1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 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.
existing_annotations:
- term:
    id: GO:0044389
    label: ubiquitin-like protein ligase binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: Direct, experimentally documented binding to the E3 ligase UFL1; this ligase-binding/adaptor activity is a core molecular function.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: Mediates interaction with UFL1
- term:
    id: GO:0051216
    label: cartilage development
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: DDRGK1 is required for cartilage development; loss-of-function variants cause Shohat-type spondyloepimetaphyseal dysplasia, and DDRGK1 stabilizes SOX9.
    action: KEEP_AS_NON_CORE
    reason: A genuine, disease-supported developmental role, but a downstream physiological outcome rather than DDRGK1's core molecular adaptor/reader function.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: Plays a role in cartilage development through SOX9
- term:
    id: GO:1903895
    label: negative regulation of IRE1-mediated unfolded protein response
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: DDRGK1 regulates ERN1/IRE1-alpha stability in a UFM1-dependent manner, modulating the IRE1 arm of the unfolded protein response.
    action: KEEP_AS_NON_CORE
    reason: A valid downstream signaling role mediated by DDRGK1's adaptor function; non-core relative to the molecular function.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: regulating ERN1/IRE1-alpha stability
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: DDRGK1 is a single-pass ER membrane protein; this is its principal site of action where it tethers the UREL complex.
    action: ACCEPT
    reason: ER membrane localization is well established experimentally and is essential to restrict ufmylation to ER-docked ribosomes.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: BioPlex affinity-purification interactions. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records real high-throughput interactions but the term is uninformative; core MF is captured by UFL1 binding and UFM1-reader activity.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:33961781
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35156780
  qualifier: enables
  review:
    summary: High-throughput interactome interaction. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real interaction record but uninformative term.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:35156780
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:36012204
  qualifier: enables
  review:
    summary: High-throughput interactome interaction. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real interaction record but uninformative term.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:36012204
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37595036
  qualifier: enables
  review:
    summary: Interaction reported in the mechanistic UREL-complex study (UFL1/CDK5RAP3 partners). Bare term uninformative but reflects cascade interactions.
    action: KEEP_AS_NON_CORE
    reason: Real cascade interactions; non-core under generic term.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:37595036
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: Multimodal cell-maps interaction. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real interaction record but uninformative term.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:40205054
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: ER localization, consistent with DDRGK1's role as an ER-membrane-anchored adaptor.
    action: ACCEPT
    reason: Correct compartment; agrees with stronger experimental ER-membrane evidence.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0034976
    label: response to endoplasmic reticulum stress
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: DDRGK1 functions in ER-stress-associated ufmylation and reticulophagy.
    action: KEEP_AS_NON_CORE
    reason: Valid pathway context; non-core relative to the molecular function.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: involved in reticulophagy in response to endoplasmic reticulum stress
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Anti-apoptotic role inferred electronically/by similarity; not directly established for human DDRGK1's core function.
    action: KEEP_AS_NON_CORE
    reason: Plausible downstream effect via ER homeostasis; peripheral and electronically inferred.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:0043066 negative regulation of apoptotic process biological_process ECO:0000501 IEA
- term:
    id: GO:0051216
    label: cartilage development
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: Cartilage development, also captured by IBA and IMP evidence.
    action: KEEP_AS_NON_CORE
    reason: Genuine developmental role; non-core relative to molecular function.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: Plays a role in cartilage development through SOX9
- term:
    id: GO:1900100
    label: positive regulation of plasma cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Role in B-cell-to-plasma-cell differentiation via ER expansion and UPR regulation, inferred by similarity.
    action: KEEP_AS_NON_CORE
    reason: Plausible immune-differentiation role by orthology; downstream and non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: promoting differentiation of B-cells into plasma cells
- term:
    id: GO:1903895
    label: negative regulation of IRE1-mediated unfolded protein response
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: Electronic support for the IRE1-UPR regulatory role also documented experimentally.
    action: KEEP_AS_NON_CORE
    reason: Valid downstream signaling role; non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: regulating ERN1/IRE1-alpha stability
- term:
    id: GO:1903898
    label: negative regulation of PERK-mediated unfolded protein response
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Regulation of the PERK arm of the UPR, inferred by similarity.
    action: KEEP_AS_NON_CORE
    reason: Plausible UPR-modulating role by orthology; downstream and non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: regulating the unfolded protein response
- term:
    id: GO:1905552
    label: positive regulation of protein localization to endoplasmic reticulum
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: DDRGK1 promotes protein localization to the ER, inferred electronically; consistent with its ER-tethering role.
    action: KEEP_AS_NON_CORE
    reason: Plausible but electronically inferred; non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:1905552 positive regulation of protein localization to endoplasmic reticulum
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Direct (HPA) immunofluorescence ER localization.
    action: ACCEPT
    reason: IDA-supported ER localization consistent with site of action.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:0005783 endoplasmic reticulum cellular_component ECO:0000314 IDA GO_REF:0000052
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: EXP
  original_reference_id: PMID:20018847
  qualifier: located_in
  review:
    summary: Experimental ER membrane localization from the paper identifying the UFM1 E3 ligase.
    action: ACCEPT
    reason: Direct experimental support for the principal compartment.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0043123
    label: positive regulation of canonical NF-kappaB signal transduction
  evidence_type: IMP
  original_reference_id: PMID:23675531
  qualifier: involved_in
  review:
    summary: DDRGK1 modulates NF-kappaB activity through regulation of NFKBIA/IkappaB-alpha stability.
    action: KEEP_AS_NON_CORE
    reason: A documented signaling role but downstream of and separable from DDRGK1's core UREL-adaptor function.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: May play a role in NF-
- term:
    id: GO:0071569
    label: protein ufmylation
  evidence_type: IDA
  original_reference_id: PMID:36121123
  qualifier: involved_in
  review:
    summary: DDRGK1 is required as a UREL-complex component for protein ufmylation.
    action: ACCEPT
    reason: Direct evidence for DDRGK1's role in the ufmylation process.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: Component of the UFM1 ribosome E3 ligase (UREL) complex
- term:
    id: GO:1990234
    label: transferase complex
  evidence_type: IPI
  original_reference_id: PMID:36121123
  qualifier: part_of
  review:
    summary: DDRGK1 is part of the UREL transferase complex (with UFL1 and CDK5RAP3).
    action: ACCEPT
    reason: DDRGK1 is a bona fide subunit of the UFM1 E3 ligase (transferase) complex.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:1990234 transferase complex cellular_component ECO:0000353 IPI PMID:36121123
- term:
    id: GO:0141185
    label: UFM1-modified protein reader activity
  evidence_type: IDA
  original_reference_id: PMID:36121123
  qualifier: enables
  review:
    summary: DDRGK1 reads ufmylated RPL26/uL24 via its UFM1-interacting motif (UFIM), a defining molecular function of the adaptor.
    action: ACCEPT
    reason: Direct evidence for UFM1-modified protein reader activity; this is a core molecular function of DDRGK1.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: DDRGK1 specifically binds to ufmylated RPL26/uL24 via its UFIM motif
- term:
    id: GO:0141185
    label: UFM1-modified protein reader activity
  evidence_type: IDA
  original_reference_id: PMID:36543799
  qualifier: enables
  review:
    summary: Reader activity for ufmylated substrate via the UFIM, demonstrated in the CYB5R3/ER-phagy study.
    action: ACCEPT
    reason: Direct support for the core UFM1-reader molecular function.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: The UFM1-interacting motif (UFIM) specifically recognizes and binds ufmylated RPL26/uL24
- term:
    id: GO:0141185
    label: UFM1-modified protein reader activity
  evidence_type: IDA
  original_reference_id: PMID:37595036
  qualifier: enables
  review:
    summary: UFIM-dependent reading of ufmylated RPL26 demonstrated mechanistically.
    action: ACCEPT
    reason: Direct support for the core reader molecular function.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: The UFM1-interacting motif (UFIM) specifically recognizes and binds ufmylated RPL26/uL24
- term:
    id: GO:0141185
    label: UFM1-modified protein reader activity
  evidence_type: IDA
  original_reference_id: PMID:38383785
  qualifier: enables
  review:
    summary: Cryo-EM of the UREL-60S complex shows DDRGK1 UFIM binding ufmylated RPL26.
    action: ACCEPT
    reason: Direct structural support for the core reader molecular function.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: The UFM1-interacting motif (UFIM) specifically recognizes and binds ufmylated RPL26/uL24
- term:
    id: GO:0141185
    label: UFM1-modified protein reader activity
  evidence_type: IDA
  original_reference_id: PMID:38383789
  qualifier: enables
  review:
    summary: Structural demonstration of DDRGK1 reading ufmylated RPL26 in the UREL-60S complex.
    action: ACCEPT
    reason: Direct structural support for the core reader molecular function.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: The UFM1-interacting motif (UFIM) specifically recognizes and binds ufmylated RPL26/uL24
- term:
    id: GO:1900100
    label: positive regulation of plasma cell differentiation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Plasma-cell differentiation role transferred from ortholog by sequence similarity.
    action: KEEP_AS_NON_CORE
    reason: Plausible by orthology; downstream and non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: promoting differentiation of B-cells into plasma cells
- term:
    id: GO:1903898
    label: negative regulation of PERK-mediated unfolded protein response
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: PERK-UPR regulation transferred from ortholog by sequence similarity.
    action: KEEP_AS_NON_CORE
    reason: Plausible by orthology; downstream and non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: regulating the unfolded protein response
- term:
    id: GO:0071569
    label: protein ufmylation
  evidence_type: IDA
  original_reference_id: PMID:35753586
  qualifier: involved_in
  review:
    summary: DDRGK1 (UREL component) required for ufmylation of P4HB.
    action: ACCEPT
    reason: Direct evidence for the ufmylation process role.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: Component of the UFM1 ribosome E3 ligase (UREL) complex
- term:
    id: GO:0071569
    label: protein ufmylation
  evidence_type: IDA
  original_reference_id: PMID:37795761
  qualifier: involved_in
  review:
    summary: DDRGK1 (UREL component) required for ufmylation of HRD1/SYVN1.
    action: ACCEPT
    reason: Direct evidence for the ufmylation process role.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: Component of the UFM1 ribosome E3 ligase (UREL) complex
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IDA
  original_reference_id: PMID:36543799
  qualifier: is_active_in
  review:
    summary: DDRGK1 acts at the ER membrane within the UREL complex.
    action: ACCEPT
    reason: Direct evidence for the site of action.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: DDRGK1 tethers the complex to the endoplasmic reticulum membrane
- term:
    id: GO:0045732
    label: positive regulation of protein catabolic process
  evidence_type: IDA
  original_reference_id: PMID:36543799
  qualifier: involved_in
  review:
    summary: DDRGK1-mediated ufmylation promotes lysosomal degradation of ufmylated proteins (reticulophagy).
    action: KEEP_AS_NON_CORE
    reason: A downstream consequence of ER ufmylation/reticulophagy; non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: thereby promoting lysosomal degradation of ufmylated proteins
- term:
    id: GO:0071569
    label: protein ufmylation
  evidence_type: IDA
  original_reference_id: PMID:36543799
  qualifier: involved_in
  review:
    summary: DDRGK1 (UREL component) required for ufmylation of CYB5R3.
    action: ACCEPT
    reason: Direct evidence for the ufmylation process role.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: Component of the UFM1 ribosome E3 ligase (UREL) complex
- term:
    id: GO:0071569
    label: protein ufmylation
  evidence_type: IDA
  original_reference_id: PMID:37595036
  qualifier: involved_in
  review:
    summary: DDRGK1 required for RPL26 ufmylation/ribosome-associated quality control.
    action: ACCEPT
    reason: Direct evidence for the ufmylation process role.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: Component of the UFM1 ribosome E3 ligase (UREL) complex
- term:
    id: GO:0072344
    label: rescue of stalled cytosolic ribosome
  evidence_type: IDA
  original_reference_id: PMID:37595036
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: A genuine role in ribosome recycling/RQC; captured as a downstream process while the core MF is the UFM1-reader/adaptor activity.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: plays a key role in ribosome recycling by mediating mono-ufmylation of the RPL26/uL24 subunit
- term:
    id: GO:0140501
    label: positive regulation of reticulophagy
  evidence_type: IDA
  original_reference_id: PMID:36543799
  qualifier: involved_in
  review:
    summary: DDRGK1-dependent ufmylation promotes reticulophagy (ER-phagy).
    action: KEEP_AS_NON_CORE
    reason: Valid downstream process; non-core relative to molecular function.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: involved in reticulophagy in response to endoplasmic reticulum stress
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IDA
  original_reference_id: PMID:38383785
  qualifier: is_active_in
  review:
    summary: DDRGK1 acts at the ER membrane within the UREL-60S complex.
    action: ACCEPT
    reason: Direct structural evidence for the site of action.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: DDRGK1 tethers the complex to the endoplasmic reticulum membrane
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IDA
  original_reference_id: PMID:38383789
  qualifier: is_active_in
  review:
    summary: DDRGK1 acts at the ER membrane within the UREL-60S complex.
    action: ACCEPT
    reason: Direct structural evidence for the site of action.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: DDRGK1 tethers the complex to the endoplasmic reticulum membrane
- term:
    id: GO:0032790
    label: ribosome disassembly
  evidence_type: IDA
  original_reference_id: PMID:38383785
  qualifier: involved_in
  review:
    summary: UREL-mediated ufmylation promotes dissociation/release of the 60S subunit from the ER translocon.
    action: KEEP_AS_NON_CORE
    reason: Genuine role in 60S release/recycling; downstream process, non-core relative to the reader/adaptor MF.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: dissociation of the 60S ribosome subunit from the endoplasmic reticulum membrane
- term:
    id: GO:0032790
    label: ribosome disassembly
  evidence_type: IDA
  original_reference_id: PMID:38383789
  qualifier: involved_in
  review:
    summary: UREL-mediated ufmylation promotes 60S release from the ER translocon.
    action: KEEP_AS_NON_CORE
    reason: Genuine role in 60S release/recycling; downstream process, non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: dissociation of the 60S ribosome subunit from the endoplasmic reticulum membrane
- term:
    id: GO:0071569
    label: protein ufmylation
  evidence_type: IMP
  original_reference_id: PMID:30626644
  qualifier: involved_in
  review:
    summary: DDRGK1 is required for ufmylation; RPL26 is the principal target.
    action: ACCEPT
    reason: Functional support for DDRGK1's role in ufmylation.
    supported_by:
    - reference_id: PMID:30626644
      supporting_text: Ribosomal protein RPL26 is the principal target of UFMylation
- term:
    id: GO:0071569
    label: protein ufmylation
  evidence_type: IDA
  original_reference_id: PMID:38383785
  qualifier: involved_in
  review:
    summary: DDRGK1 (UREL component) required for RPL26 ufmylation.
    action: ACCEPT
    reason: Direct evidence for the ufmylation process role.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: Component of the UFM1 ribosome E3 ligase (UREL) complex
- term:
    id: GO:0071569
    label: protein ufmylation
  evidence_type: IDA
  original_reference_id: PMID:38383789
  qualifier: involved_in
  review:
    summary: DDRGK1 (UREL component) required for RPL26 ufmylation.
    action: ACCEPT
    reason: Direct evidence for the ufmylation process role.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: Component of the UFM1 ribosome E3 ligase (UREL) complex
- term:
    id: GO:0072344
    label: rescue of stalled cytosolic ribosome
  evidence_type: IDA
  original_reference_id: PMID:38383785
  qualifier: involved_in
  review:
    summary: DDRGK1, within UREL, contributes to recycling of post-termination/stalled 60S ribosomes at the ER.
    action: KEEP_AS_NON_CORE
    reason: Genuine ribosome-recycling/RQC role; downstream process, non-core relative to the reader/adaptor MF.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: plays a key role in ribosome recycling by mediating mono-ufmylation of the RPL26/uL24 subunit
- term:
    id: GO:0072344
    label: rescue of stalled cytosolic ribosome
  evidence_type: IDA
  original_reference_id: PMID:38383789
  qualifier: involved_in
  review:
    summary: DDRGK1, within UREL, contributes to release/recycling of stalled 60S ribosomes from the ER translocon.
    action: KEEP_AS_NON_CORE
    reason: Genuine ribosome-recycling/RQC role; downstream process, non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: promoting release and recycling of the large ribosomal subunit
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28128204
  qualifier: enables
  review:
    summary: Interaction with ERN1/IRE1-alpha (UFM1-dependent). Bare term uninformative but reflects a functionally important interaction.
    action: KEEP_AS_NON_CORE
    reason: Real, mechanistically relevant interaction; non-core under generic term.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:28128204
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32160526
  qualifier: enables
  review:
    summary: Interaction with UFL1 from the ER-phagy screen. Bare term uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real cascade interaction; non-core under generic term.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32160526
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IDA
  original_reference_id: PMID:32160526
  qualifier: located_in
  review:
    summary: ER membrane localization from the ER-phagy screen.
    action: ACCEPT
    reason: Direct evidence for principal compartment.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0031647
    label: regulation of protein stability
  evidence_type: IDA
  original_reference_id: PMID:28128204
  qualifier: involved_in
  review:
    summary: DDRGK1 regulates ERN1/IRE1-alpha stability in a UFM1-dependent manner.
    action: KEEP_AS_NON_CORE
    reason: Documented regulatory role; downstream of the adaptor function, non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: regulating ERN1/IRE1-alpha stability
- term:
    id: GO:0034976
    label: response to endoplasmic reticulum stress
  evidence_type: IDA
  original_reference_id: PMID:28128204
  qualifier: involved_in
  review:
    summary: DDRGK1 functions in ER homeostasis/UPR via IRE1-alpha.
    action: KEEP_AS_NON_CORE
    reason: Valid pathway context; non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: A critical role of DDRGK1 in endoplasmic reticulum homoeostasis
- term:
    id: GO:0034976
    label: response to endoplasmic reticulum stress
  evidence_type: IDA
  original_reference_id: PMID:32160526
  qualifier: involved_in
  review:
    summary: DDRGK1 functions in ER-stress-associated ufmylation/reticulophagy.
    action: KEEP_AS_NON_CORE
    reason: Valid pathway context; non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: involved in reticulophagy in response to endoplasmic reticulum stress
- term:
    id: GO:0061709
    label: reticulophagy
  evidence_type: IDA
  original_reference_id: PMID:32160526
  qualifier: involved_in
  review:
    summary: DDRGK1 contributes to reticulophagy driven by ER ufmylation.
    action: KEEP_AS_NON_CORE
    reason: Valid downstream process; non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: involved in reticulophagy in response to endoplasmic reticulum stress
- term:
    id: GO:0070972
    label: protein localization to endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: PMID:32160526
  qualifier: involved_in
  review:
    summary: DDRGK1 promotes protein localization to the ER.
    action: KEEP_AS_NON_CORE
    reason: Plausible role consistent with ER-tethering; non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:0070972 protein localization to endoplasmic reticulum biological_process ECO:0000314 IDA PMID:32160526
- term:
    id: GO:0071569
    label: protein ufmylation
  evidence_type: IDA
  original_reference_id: PMID:32160526
  qualifier: involved_in
  review:
    summary: DDRGK1 required for ufmylation in the ER-phagy context.
    action: ACCEPT
    reason: Direct evidence for the ufmylation process role.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: Component of the UFM1 ribosome E3 ligase (UREL) complex
- term:
    id: GO:1903895
    label: negative regulation of IRE1-mediated unfolded protein response
  evidence_type: IDA
  original_reference_id: PMID:28128204
  qualifier: involved_in
  review:
    summary: DDRGK1 negatively regulates the IRE1 arm of the UPR via control of IRE1-alpha stability.
    action: KEEP_AS_NON_CORE
    reason: Documented signaling role; downstream, non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: inhibits the unfolded protein response (UPR) by regulating ERN1/IRE1-alpha stability
- term:
    id: GO:1903895
    label: negative regulation of IRE1-mediated unfolded protein response
  evidence_type: IDA
  original_reference_id: PMID:32160526
  qualifier: involved_in
  review:
    summary: ER-phagy screen supports negative regulation of the IRE1 UPR arm.
    action: KEEP_AS_NON_CORE
    reason: Documented signaling role; downstream, non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: inhibits the unfolded protein response (UPR) by regulating ERN1/IRE1-alpha stability
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28263186
  qualifier: enables
  review:
    summary: Interaction with SOX9 (from the SEMDSH/cartilage study). Bare term uninformative but reflects a functionally relevant interaction.
    action: KEEP_AS_NON_CORE
    reason: Real interaction relevant to the cartilage role; non-core under generic term.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:28263186
- term:
    id: GO:0032435
    label: negative regulation of proteasomal ubiquitin-dependent protein catabolic process
  evidence_type: IMP
  original_reference_id: PMID:28263186
  qualifier: involved_in
  review:
    summary: DDRGK1 inhibits ubiquitin-mediated proteasomal degradation of SOX9, stabilizing it.
    action: KEEP_AS_NON_CORE
    reason: Documented effect underlying the cartilage role; downstream, non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: inhibiting the ubiquitin-mediated proteasomal degradation of this transcriptional regulator
- term:
    id: GO:0051216
    label: cartilage development
  evidence_type: IMP
  original_reference_id: PMID:28263186
  qualifier: involved_in
  review:
    summary: Loss of DDRGK1 causes SEMDSH; DDRGK1 acts in cartilage development through SOX9.
    action: KEEP_AS_NON_CORE
    reason: Genuine disease-supported developmental role; non-core relative to molecular function.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: Plays a role in cartilage development through SOX9
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:23675531
  qualifier: involved_in
  review:
    summary: Inferred from DDRGK1's modulation of NF-kappaB-dependent transcription.
    action: KEEP_AS_NON_CORE
    reason: Indirect, downstream transcriptional effect via NF-kappaB signaling; non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: May play a role in NF-
- term:
    id: GO:1902808
    label: positive regulation of cell cycle G1/S phase transition
  evidence_type: IC
  original_reference_id: PMID:23675531
  qualifier: involved_in
  review:
    summary: Inferred (IC) cell-cycle effect downstream of DDRGK1's NF-kappaB/proliferation role.
    action: KEEP_AS_NON_CORE
    reason: Indirect downstream effect; non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:1902808 positive regulation of cell cycle G1/S phase transition biological_process ECO:0000305 IC PMID:23675531
- term:
    id: GO:0030335
    label: positive regulation of cell migration
  evidence_type: IMP
  original_reference_id: PMID:23675531
  qualifier: involved_in
  review:
    summary: DDRGK1 promotes cell migration in the NF-kappaB study.
    action: KEEP_AS_NON_CORE
    reason: Downstream cellular phenotype; non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:0030335 positive regulation of cell migration biological_process ECO:0000315 IMP PMID:23675531
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23675531
  qualifier: enables
  review:
    summary: Interaction with NFKBIA/IkappaB-alpha. Bare term uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real interaction relevant to the NF-kappaB role; non-core under generic term.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:23675531
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: TAS
  original_reference_id: PMID:23675531
  qualifier: located_in
  review:
    summary: Cytoplasmic localization asserted in the NF-kappaB study; DDRGK1 is an ER-membrane protein with a large cytoplasmic domain.
    action: KEEP_AS_NON_CORE
    reason: Consistent with the cytoplasmic-facing topology, but the principal compartment is the ER membrane.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: Cytoplasmic
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IMP
  original_reference_id: PMID:23675531
  qualifier: involved_in
  review:
    summary: DDRGK1 promotes proliferation in the NF-kappaB study.
    action: KEEP_AS_NON_CORE
    reason: Downstream cellular phenotype; non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:0008284 positive regulation of cell population proliferation biological_process ECO:0000315 IMP PMID:23675531
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:23675531
  qualifier: involved_in
  review:
    summary: Gene-expression effects downstream of NF-kappaB modulation.
    action: KEEP_AS_NON_CORE
    reason: Indirect downstream effect; non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:0010628 positive regulation of gene expression biological_process ECO:0000315 IMP PMID:23675531
- term:
    id: GO:0010629
    label: negative regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:23675531
  qualifier: involved_in
  review:
    summary: Gene-expression effects downstream of NF-kappaB modulation.
    action: KEEP_AS_NON_CORE
    reason: Indirect downstream effect; non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:0010629 negative regulation of gene expression biological_process ECO:0000315 IMP PMID:23675531
- term:
    id: GO:0032436
    label: positive regulation of proteasomal ubiquitin-dependent protein catabolic process
  evidence_type: IMP
  original_reference_id: PMID:23675531
  qualifier: involved_in
  review:
    summary: DDRGK1 promotes NFKBIA proteasomal degradation in the NF-kappaB study.
    action: KEEP_AS_NON_CORE
    reason: Downstream effect within NF-kappaB signaling; non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process biological_process ECO:0000315 IMP PMID:23675531
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Anti-apoptotic role transferred from ortholog by sequence similarity.
    action: KEEP_AS_NON_CORE
    reason: Plausible by orthology; downstream and non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:0043066 negative regulation of apoptotic process biological_process ECO:0000250 ISS GO_REF:0000024
- term:
    id: GO:1905552
    label: positive regulation of protein localization to endoplasmic reticulum
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Transferred from ortholog by sequence similarity; consistent with ER-tethering role.
    action: KEEP_AS_NON_CORE
    reason: Plausible by orthology; non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:1905552 positive regulation of protein localization to endoplasmic reticulum biological_process ECO:0000250 ISS GO_REF:0000024
- term:
    id: GO:1990592
    label: protein K69-linked ufmylation
  evidence_type: IDA
  original_reference_id: PMID:25219498
  qualifier: involved_in
  review:
    summary: DDRGK1 participates in UFM1 conjugation, including K69-linked UFM1 chains.
    action: KEEP_AS_NON_CORE
    reason: Specific chain-linkage sub-aspect of ufmylation; narrow process annotation.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:1990592 protein K69-linked ufmylation biological_process ECO:0000314 IDA PMID:25219498
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20228063
  qualifier: enables
  review:
    summary: Interaction with CDK5RAP3 (a UREL component). Bare term uninformative but reflects a cascade interaction.
    action: KEEP_AS_NON_CORE
    reason: Real cascade interaction; non-core under generic term.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:20228063
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IDA
  original_reference_id: PMID:20228063
  qualifier: located_in
  review:
    summary: Experimental ER membrane localization.
    action: ACCEPT
    reason: Direct evidence for principal compartment.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0033146
    label: regulation of intracellular estrogen receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:25219498
  qualifier: involved_in
  review:
    summary: DDRGK1 contributes to ufmylation of ASC1/TRIP4, affecting ERalpha transactivation.
    action: KEEP_AS_NON_CORE
    reason: A documented but specialized signaling role downstream of ufmylation; non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: May also be required for TRIP4 ufmylation
- term:
    id: GO:0034976
    label: response to endoplasmic reticulum stress
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: ER stress response transferred from ortholog by sequence similarity.
    action: KEEP_AS_NON_CORE
    reason: Valid pathway context by orthology; non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: involved in reticulophagy in response to endoplasmic reticulum stress
- term:
    id: GO:1901800
    label: positive regulation of proteasomal protein catabolic process
  evidence_type: IMP
  original_reference_id: PMID:23675531
  qualifier: involved_in
  review:
    summary: DDRGK1 promotes proteasomal catabolism of NFKBIA in the NF-kappaB study.
    action: KEEP_AS_NON_CORE
    reason: Downstream effect within NF-kappaB signaling; non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:1901800 positive regulation of proteasomal protein catabolic process biological_process ECO:0000315 IMP PMID:23675531
- term:
    id: GO:1903721
    label: positive regulation of I-kappaB phosphorylation
  evidence_type: IMP
  original_reference_id: PMID:23675531
  qualifier: involved_in
  review:
    summary: DDRGK1 promotes IkappaB-alpha phosphorylation, activating NF-kappaB.
    action: KEEP_AS_NON_CORE
    reason: Downstream signaling effect; non-core.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:1903721 positive regulation of I-kappaB phosphorylation biological_process ECO:0000315 IMP PMID:23675531
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25219498
  qualifier: enables
  review:
    summary: Interaction with UFL1/TRIP4 in the ASC1/ufmylation study. Bare term uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real cascade-relevant interaction; non-core under generic term.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:25219498
- term:
    id: GO:0044389
    label: ubiquitin-like protein ligase binding
  evidence_type: IPI
  original_reference_id: PMID:25219498
  qualifier: enables
  review:
    summary: Direct interaction with the UFM1 E3 ligase UFL1, the core adaptor binding activity of DDRGK1.
    action: ACCEPT
    reason: Direct experimental support for the core UFL1-binding/adaptor molecular function.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: Mediates interaction with UFL1
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20018847
  qualifier: enables
  review:
    summary: Interaction with UFL1 from the paper identifying the UFM1 E3 ligase. Bare term uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real cascade interaction; non-core under generic term.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:20018847
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: PMID:20018847
  qualifier: located_in
  review:
    summary: Experimental ER localization from the UFM1 E3 ligase paper.
    action: ACCEPT
    reason: Direct evidence for principal compartment.
    supported_by:
    - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
references:
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:20018847
  title: A novel type of E3 ligase for the Ufm1 conjugation system.
  findings:
  - statement: DDRGK1 interacts with the UFM1 E3 ligase UFL1 and is ufmylated at Lys-267; it localizes to the ER.
    reference_section_type: ABSTRACT
- id: PMID:20228063
  title: A novel C53/LZAP-interacting protein regulates stability of C53/LZAP and DDRGK domain-containing Protein 1 (DDRGK1) and modulates NF-kappaB signaling.
  findings:
  - statement: DDRGK1 interacts with CDK5RAP3/C53 and its stability is co-regulated; it modulates NF-kappaB signaling.
    reference_section_type: ABSTRACT
- id: PMID:23675531
  title: DDRGK1 regulates NF-kappaB activity by modulating IkappaBalpha stability.
  findings:
  - statement: DDRGK1 modulates NF-kappaB activity by regulating NFKBIA/IkappaB-alpha stability.
    reference_section_type: ABSTRACT
- id: PMID:25219498
  title: Modification of ASC1 by UFM1 is crucial for ERα transactivation and breast cancer development.
  findings:
  - statement: DDRGK1 interacts with UFL1 and is required for TRIP4/ASC1 ufmylation, affecting ERalpha transactivation.
    reference_section_type: ABSTRACT
- id: PMID:28128204
  title: A critical role of DDRGK1 in endoplasmic reticulum homoeostasis via regulation of IRE1alpha stability.
  findings:
  - statement: DDRGK1 interacts with ERN1/IRE1-alpha in a UFM1-dependent manner and regulates its stability, inhibiting the IRE1 arm of the UPR.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: UNVERIFIED
    review_notes: Title plausibly establishes the DDRGK1-IRE1alpha/UPR regulatory role, but the publication is not cached and no PMID-anchored GOA evidence ties this claim to a checkable source, so correctness is not yet VERIFIED.
- id: PMID:28263186
  title: Loss of DDRGK1 modulates SOX9 ubiquitination in spondyloepimetaphyseal dysplasia.
  findings:
  - statement: Loss-of-function DDRGK1 variants cause Shohat-type spondyloepimetaphyseal dysplasia; DDRGK1 stabilizes SOX9 by inhibiting its ubiquitin-mediated degradation.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Disease gene paper establishing the cartilage/SOX9 role.
- id: PMID:30626644
  title: Ribosomal protein RPL26 is the principal target of UFMylation.
  findings:
  - statement: RPL26 is the principal cellular target of UFMylation.
    reference_section_type: TITLE
- id: PMID:32160526
  title: A genome-wide ER-phagy screen highlights key roles of mitochondrial metabolism and ER-Resident UFMylation.
  findings:
  - statement: DDRGK1 and ER-resident UFMylation are required for ER-phagy and IRE1 UPR regulation.
    reference_section_type: ABSTRACT
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
- id: PMID:35156780
  title: CFTR interactome mapping using the mammalian membrane two-hybrid high-throughput screening system.
  findings: []
- id: PMID:35753586
  title: P4HB UFMylation regulates mitochondrial function and oxidative stress.
  findings: []
- id: PMID:36012204
  title: Differential CFTR-Interactome Proximity Labeling Procedures Identify Enrichment in Multiple SLC Transporters.
  findings: []
- id: PMID:36121123
  title: A non-canonical scaffold-type E3 ligase complex mediates protein UFMylation.
  findings:
  - statement: DDRGK1 is a component of the UREL complex and reads ufmylated RPL26 via its UFIM motif.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Defines DDRGK1 as the UFM1 reader within the scaffold E3 complex.
- id: PMID:36543799
  title: The UFM1 system regulates ER-phagy through the ufmylation of CYB5R3.
  findings:
  - statement: DDRGK1 UFIM reads ufmylated substrate; UREL-dependent ufmylation of CYB5R3 drives ER-phagy.
    reference_section_type: ABSTRACT
- id: PMID:37595036
  title: Mechanistic insights into the roles of the UFM1 E3 ligase complex in ufmylation and ribosome-associated protein quality control.
  findings:
  - statement: DDRGK1 UFIM-dependent reading of ufmylated RPL26 stabilizes 60S-UREL association and supports ribosome-associated quality control.
    reference_section_type: ABSTRACT
- id: PMID:37795761
  title: UFMylation of HRD1 regulates endoplasmic reticulum homeostasis.
  findings: []
- id: PMID:38383785
  title: UFM1 E3 ligase promotes recycling of 60S ribosomal subunits from the ER.
  findings:
  - statement: Cryo-EM of the UREL-60S complex shows DDRGK1 tethering and UFIM reading of ufmylated RPL26 to promote 60S recycling.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Structural basis of DDRGK1 ER-tethering and reader roles.
- id: PMID:38383789
  title: The UFM1 E3 ligase recognizes and releases 60S ribosomes from ER translocons.
  findings:
  - statement: UREL (UFL1/DDRGK1/CDK5RAP3) ufmylates RPL26 to release/recycle 60S ribosomes from ER translocons; DDRGK1 single-pass membrane anchor and UFIM are key.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Structure of DDRGK1 in the UREL-60S complex.
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
core_functions:
- description: Obligate ER-membrane-anchored cofactor/substrate-adaptor of the UFM1 E3 ligase that binds the E3 ligase UFL1 (and CDK5RAP3) to form the UREL complex, tethering ufmylation activity to ER-docked ribosomes and stabilizing UFL1.
  molecular_function:
    id: GO:0044389
    label: ubiquitin-like protein ligase binding
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  supported_by:
  - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
    supporting_text: Mediates interaction with UFL1
  - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
    supporting_text: DDRGK1 tethers the complex to the endoplasmic reticulum membrane
- description: UFM1-modified protein reader that, via its UFM1-interacting motif (UFIM), specifically binds ufmylated RPL26/uL24 on the 60S ribosome, producing stable association of the 60S subunit with the UREL complex and promoting release/recycling of the large subunit from the ER translocon.
  molecular_function:
    id: GO:0141185
    label: UFM1-modified protein reader activity
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  supported_by:
  - reference_id: file:human/DDRGK1/DDRGK1-uniprot.txt
    supporting_text: The UFM1-interacting motif (UFIM) specifically recognizes and binds ufmylated RPL26/uL24
proposed_new_terms: []
suggested_questions:
- question: Is ufmylation of DDRGK1 at Lys-267 functionally required for UREL activity or is it a collateral consequence of the reaction it scaffolds?
- question: 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?
suggested_experiments:
- description: 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.
- description: 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.