ERLIN1 (SPFH1) is a 348-amino-acid, single-pass endoplasmic reticulum membrane protein with a lumenal SPFH domain. It forms an oligomeric complex with ERLIN2 that organizes membrane-associated protein interactions and contributes to selective ER protein turnover. The complex participates in recruitment of the ubiquitin ligase RNF170 to activated inositol 1,4,5-trisphosphate receptors and supports degradation of selected misfolded ER substrates; ERLIN1 itself is not the ubiquitin-transfer enzyme. ERLIN1 also binds cholesterol. Erlin-dependent sterol handling restrains SREBP activation and lipid biosynthetic gene expression, while ERLIN1/ERLIN2 loss increases cholesterol esterification. How cholesterol binding couples to these responses remains unresolved: effects on Insig-dependent regulation and on sterol accessibility to SOAT1 are distinct mechanistic possibilities. Biallelic ERLIN1 variants cause hereditary spastic paraplegia type 62; some variants alter RNA splicing, whereas their effects on protein assembly require separate experimental assessment.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005789 endoplasmic reticulum membrane | IBA GO_REF:0000033 | ACCEPT | Summary: ER-membrane localization has valid ancestral placement and target evidence. Reason: The current PTHR15351 tree places human O75477 leaf PTN002495870 below PTN000794169, where the actual IBD asserts GO:0005789. Its ungapped MSA is exactly the displayed 348-residue sequence, and no target-path NOT is present. Human ERLIN1/ERLIN2 and worm erl-1 are legitimate experimental descendants; target self-WITH is not circular. The actual PMID:19240031 membrane/topology Results and human Reactome entity 8866518 independently agree, with rodent topology experiments, mouse constructs in HeLa and endogenous HeLa glycosylation distinguished in the reference assessment. This preserves localization without transferring the distinct catalytic activities of neighboring ERAD proteins. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000794169 SUPPORTS TRANSFER Verified target-path IBD for ER membrane; full-length target MSA and current human participant location match. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane GO_REF:0000033 Reactome:R-HSA-8866551 |
| GO:0015485 cholesterol binding | IBA GO_REF:0000033 | ACCEPT | Summary: Cholesterol binding is directly measured for human ERLIN1 and correctly propagated. Reason: The actual GO:0015485 IBD is at PTN002692334 within the ERLIN1 clade; human O75477 is its experimental descendant and the target lies below that node with an exact 348-residue MSA. The self-donor is legitimate grounding. Independently inspected PMID:24217618 Results Figure 4B and Methods Erlin purification and lipid binding assay test recombinant human erlin-1 carrying C-terminal V5/His tags, expressed in Schneider S2 cells and purified by metal-affinity and anti-V5 capture. Radiolabeled cholesterol saturation and competition, with matched control beads, support specific sterol binding. The native mouse liver erlin complex in Figure 4C is a separate preparation, not substituted for the human experiment. Exact untagged sequence equivalence was not reconstructed from the article. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002692334 SUPPORTS TRANSFER Verified ERLIN1-clade IBD, exact target MSA and direct human recombinant cholesterol-binding evidence; one self-donor is valid. Supporting Evidence: PMID:24217618 Erlins bound cholesterol with specificity and strong cooperativity GO_REF:0000033 |
| GO:0032933 SREBP signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: The SREBP pathway assertion has valid PAINT placement and direct human support. Reason: The actual GO:0032933 IBD occurs at PTN001282580 on the verified O75477 ancestral path, with ERLIN1 and ERLIN2 experimental descendants. No target-path NOT or target sequence mismatch is present. PMID:24217618 Results Figures 1β3 and operative Methods separately perturb ERLIN1 and ERLIN2 in human cells under cholesterol sufficiency. ERLIN1 depletion increases SREBP target transcripts, SREBP2 cleavage/nuclear accumulation and lipid endpoints; fatostatin suppresses the induced target-gene response. Endogenous erlin-containing complexes associate with the SREBP/SCAP/INSIG machinery, although whether each association is direct remains unresolved. These observations establish participation in controlling the SREBP pathway, not SREBP protease or transcription-factor activity by ERLIN1. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001282580 SUPPORTS TRANSFER Verified target-path SREBP IBD; independently inspected human ERLIN1 perturbation and pathway mechanism agree. Supporting Evidence: PMID:24217618 directly involved in regulating the SREBP machinery GO_REF:0000033 |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000002 | MODIFY | Summary: The Erlin1/2 family location mapping is correct but can be narrowed to ER membrane. Reason: The actual InterPro target record matches IPR033294 across O75477 residues 2β317 and the family entry explicitly maps to GO:0005783. This is a specific erlin family, not a transfer from every SPFH-domain protein. The independently read PMID:19240031 Results, Molecular Properties of SPFH1 and SPFH2 (Figure 2 discussion), reports ER-marker colocalization, detergent-dependent solubilization of microsome-associated SPFH1 and protection of most of its mass from protease until detergent permeabilization. These support membrane attachment rather than merely residence somewhere in the ER. Separately recovered Plasmids Methods and selected captions identify mouse SPFH1 BC011220 and mouse SPFH2 constructs, including experiments in HeLa hosts. Figure 2A colocalization is in Rat-1, Figure 2B microsomal extraction in alphaT3-1, and Figure 2D separately assays endogenous HeLa SPFH1 glycosylation and tagged mouse constructs; the recovered caption does not establish the Figure 2C cell context. Human HPA and participant evidence support the conserved target location without relabeling rodent experiments as human. Current human Reactome entity 8866518 independently identifies O75477 residues 1β348 with its own ER-membrane compartment. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR033294 SUPPORTS TRANSFER Actual target family match and current ER mapping; independent topology and human participant evidence justify the narrower location. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane GO_REF:0000002 Reactome:R-HSA-8866551 |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000120 | ACCEPT | Summary: The combined automated ER-membrane annotation matches the target and independent location evidence. Reason: Current ARBA00028685 condition set 35 requires FunFam 3.30.479.30:FF:000009 and Eukaryota, both present in the official O75477 record. The accompanying SL-0097 mapping is ER membrane. The rule match establishes provenance; the experimentally supported erlin membrane topology in PMID:19240031 (rodent assays and mouse constructs distinguished from endogenous HeLa glycosylation) and explicit human ERLIN1 participant compartment in Reactome supply the independent biological support. No topology is inferred solely from a family label. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00028685 SUPPORTS TRANSFER Actual FunFam/taxon disjunct matches O75477 and agrees with independent ER-membrane evidence. UniProtKB-SubCell:SL-0097 SUPPORTS TRANSFER Official O75477 subcellular-location record specifies ER membrane; independently corroborated by target Results and Reactome entity. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane GO_REF:0000120 Reactome:R-HSA-8866551 |
| GO:0031625 ubiquitin protein ligase binding | IEA GO_REF:0000002 | ACCEPT | Summary: ERLIN1 association with ubiquitin ligases supports the specific binding annotation. Reason: IPR033294 is an actual O75477 family match and its current GO mapping includes ubiquitin protein ligase binding. Independent PMID:21343306 Experimental Procedures, Expression Plasmids, and Results Figure 2 explicitly test human SPFH1-T7 in CHO-7 cells: anti-T7 precipitation recovers gp78/AMFR and Hrd1/SYVN1, whereas Trc8 is not recovered in that comparison. This supports association with E3 ligases under the stated cellular-complex conditions without requiring or claiming purified binary binding. It does not give ERLIN1 E3 catalytic activity or transfer the paperβs SPFH2-specific HMG-CoA reductase degradation result to ERLIN1. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR033294 SUPPORTS TRANSFER Verified target family mapping is independently supported by the original human SPFH1 ligase-association experiment. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt Interacts with AMFR and SYVN1 GO_REF:0000002 |
| GO:0032933 SREBP signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: The SREBP electronic rule matches ERLIN1 and the pathway role is independently supported. Reason: Actual ARBA00087340 condition set 0 requires FunFam 3.30.479.30:FF:000009 and Chordata; both match O75477. The rule is provenance, not an independent experiment. PMID:24217618 Results Figures 1β3 and operative Methods separately perturb ERLIN1 and ERLIN2 in human cells under cholesterol sufficiency. ERLIN1 depletion increases SREBP target transcripts, SREBP2 cleavage/nuclear accumulation and lipid endpoints; fatostatin suppresses the induced target-gene response. Endogenous erlin-containing complexes associate with the SREBP/SCAP/INSIG machinery, although whether each association is direct remains unresolved. These observations establish participation in controlling the SREBP pathway, not SREBP protease or transcription-factor activity by ERLIN1. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00087340 SUPPORTS TRANSFER Target matches the erlin FunFam/Chordata rule; human SREBP experiments corroborate its output. Supporting Evidence: PMID:24217618 directly involved in regulating the SREBP machinery GO_REF:0000117 |
| GO:0032991 protein-containing complex | IEA GO_REF:0000117 | MODIFY | Summary: The assembled ERLIN1/ERLIN2 complex permits a more informative ER-complex term. Reason: ARBA00028902 condition set 381 matches the target FunFam, but protein-containing complex is unnecessarily broad. Current human Reactome complex 8866522 explicitly contains O75477 ERLIN1 and ERLIN2 at the ER membrane. Independently read PMID:19240031 Results describe reciprocal complex isolation, native electrophoresis and association of the two proteins, with alphaT3-1 and Rat-1 contexts distinct from tagged coassembly in HeLa. The separately recovered Plasmids Methods explicitly identify mouse SPFH1 BC011220 and mouse SPFH2 constructs; a human host does not make those recombinant proteins human. Current human participant membership corroborates conservation, without an exact modern stoichiometry claim. GO:0140534 describes a protein complex that is part of the ER and is a current descendant of GO:0032991. It captures the established assembly without implying that ERLIN1 itself is a ubiquitin ligase. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00028902 SUPPORTS TRANSFER The matching broad complex rule is biologically sound; actual target assembly/location permits the specific ER protein-containing-complex refinement. Proposed replacements: endoplasmic reticulum protein-containing complex Supporting Evidence: PMID:19240031 SPFH1 and its homolog SPFH2 form a heteromeric approximately 2 MDa complex GO_REF:0000117 Reactome:R-HSA-8866551 |
| GO:0036503 ERAD quality control pathway | IEA GO_REF:0000117 | ACCEPT | Summary: The current electronic ERAD rule agrees with the experimentally supported assembly role. Reason: ARBA00029018 condition set 18 requires FunFam 3.30.479.30:FF:000009 and Catarrhini; both match human O75477. PMID:19240031 Results show SPFH1/2 association with activated IP3 receptors before substantial polyubiquitination, loss of receptor polyubiquitination/degradation after Rat-1 SPFH1 depletion and rescue by reintroduction, with preserved calcium mobilization. This supports a substrate-recognition/processing assembly role in ERAD rather than merely a downstream disease phenotype. The recovered Plasmids and retroviral-expression Methods identify mouse SPFH1 and SPFH2 cDNAs; the Rat-1 depletion/rescue and alphaT3-1 native-complex experiments are rodent evidence for the conserved assembly role, not direct human ERAD perturbations. HeLa tagged-coassembly experiments also use mouse constructs. SPFH2-specific effects are not reassigned to ERLIN1. Complete Methods, figure pixels and supplements were not inspected. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00029018 SUPPORTS TRANSFER Verified target FunFam/Catarrhini match; functional support comes from the original ERAD processing experiments, not rule membership alone. Supporting Evidence: PMID:19240031 mediates the ER-associated degradation of inositol 1,4,5-trisphosphate GO_REF:0000117 |
| GO:0045541 negative regulation of cholesterol biosynthetic process | IEA GO_REF:0000117 | ACCEPT | Summary: ERLIN1 restrains cholesterol production through the SREBP regulatory machinery. Reason: ARBA00085017 condition set 0 matches the target erlin FunFam and Chordata. Independently, PMID:24217618 Results Figures 1B/1D and 2, with Methods q-RT-PCR, Cellular lipid determination and Proteolytic SREBP-2 activation assay, show that individual ERLIN1 depletion under cholesterol sufficiency increases HMGR/HMGS transcripts, cholesterol content and canonical SREBP2 activation. Fatostatin sensitivity and erlin association with the regulatory machinery support a negative regulatory role rather than direct cholesterol synthesis by ERLIN1. Lipid content and transcriptional endpoints are not a direct isotope-flux measurement, and the separate SPFH2-specific HMGCR degradation experiment is not used as ERLIN1 evidence. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00085017 SUPPORTS TRANSFER Target FunFam/Chordata condition matches; human ERLIN1 perturbation and SREBP mechanism substantiate the negative regulatory output with explicit assay limits. Supporting Evidence: PMID:24217618 led to canonical activation of SREBPs and their target genes GO_REF:0000117 |
| GO:0045717 negative regulation of fatty acid biosynthetic process | IEA GO_REF:0000117 | ACCEPT | Summary: ERLIN1-dependent restraint of the SREBP lipogenic program supports negative regulation of fatty-acid biosynthesis. Reason: ARBA00084177 condition set 1 matches the erlin FunFam and Chordata. PMID:24217618 Results Figure 1B/1D explicitly measure increased FASN and ACC1 transcripts after individual ERLIN1 depletion and increased free-fatty-acid content, with unchanged triglyceride content. Figures 2β3 support canonical SREBP regulation and association with the SREBP/SCAP/INSIG machinery; Methods identify human-cell siRNAs, q-RT-PCR and enzymatic lipid-content assays. This is positive evidence for regulation of the lipogenic program, not fatty-acid synthase activity by ERLIN1. It does not establish a direct synthesis-flux rate or every fatty-acid class. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00084177 SUPPORTS TRANSFER The relevant human erlin disjunct matches; unrelated rule alternatives are not used. Target-specific transcriptional/lipid and pathway evidence supports negative regulation. Supporting Evidence: PMID:24217618 key transcription factors for cholesterol and fatty acid biosynthetic GO_REF:0000117 |
| GO:0005515 protein binding | IPI PMID:21343306 Membrane-associated ubiquitin ligase complex containing gp78... | KEEP AS NON CORE | Summary: IPI interactions with the ER ubiquitin ligases AMFR/gp78 and SYVN1 (and ERLIN2). Bare protein binding is uninformative; the E3-ligase binding is captured by the ubiquitin-protein-ligase-binding annotation. Reason: Real E3-ligase interactions but uninformative GO term. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt Interacts with AMFR and SYVN1 |
| GO:0005515 protein binding | IPI PMID:22119785 Defining human ERAD networks through an integrative mapping ... | KEEP AS NON CORE | Summary: ERAD-network interactome capture (including ERLIN2, SYVN1, AMFR). Bare protein binding is uninformative. Reason: Real ERAD-network interactions but uninformative GO term. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt O75477; O94905: ERLIN2 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Proteome-scale interactome capture. Bare protein binding is uninformative. Reason: Real interactions from a large-scale interactome but uninformative GO term. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt O75477; Q96IW7: SEC22A |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: ERLIN1 associates with C6orf120 in the BioPlex 2.0 HEK293T affinity-purification screen. Reason: The author BioPlex 2.0 directed-edge table contains ERLIN1 bait (GeneID 10613) and C6orf120 prey (387263) at line 23956; current IntAct record EBI-21872519 independently records the same pair. The original Online Experimental Methods describe sequence-validated human ORFeome baits with a C-terminal HA-FLAG tag, anti-HA purification from HEK293T lysates and CompPASS-Plus filtering. This is an affinity association that can include an indirect co-complex interaction. Protein identifiers were collapsed to Entrez gene IDs during analysis, limiting product-specific inference. The source establishes no more specific ERLIN1 binding role, so retain supported non-core protein binding. |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | KEEP AS NON CORE | Summary: Cross-linking mass spectrometry supports close association of ERLIN1 and ERLIN2 in the analyzed U2OS preparations. Reason: The exact human ERLIN1βERLIN2 record EBI-20904152 (IM-26653-5549) attributes the cross-link to Table S1 and the pink Table S2 fraction, identifying both unfractionated nuclei and the Triton X-100-soluble fraction. The actual original Experimental Procedures describe digitonin/dounce-prepared U2OS nuclei, DSSO cross-linking before detergent fractionation, and cross-link identification controlled at 1% FDR. Results for Figure 1 explicitly note that the isolated nuclei retain connected endoplasmic reticulum and other co-isolated material. The supplementary peptide workbooks were not recovered, so exact cross-linked residues and peptide assignment have not been independently inspected. The positive curated pair record supports non-core protein binding; this preparation does not establish a physiological nuclear function or oligomer stoichiometry. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Binary-interactome (HuRI) captures of ERLIN1 interactions. Bare protein binding is uninformative. Reason: Real binary interactions but uninformative GO term. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt O75477; Q15436: SEC23A |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Dual proteome-scale network capture (ERLIN2, C6orf120). Bare protein binding is uninformative. Reason: Real interactions but uninformative GO term. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt O75477; O94905: ERLIN2 |
| GO:0005783 endoplasmic reticulum | IDA GO_REF:0000052 | MODIFY | Summary: ER localization is supported; the combined evidence specifies the ER membrane. Reason: Current HPA ERLIN1 ICC/IF reports ER signal with HPA011252 in A-431, U-251MG, U2OS and KOLF2.1J. The complete antigen exactly matches O75477 residues 254β344; no complete identical antigen occurs in ERLIN2, although this sequence check is not an experimental cross-reactivity test. HPA alone does not resolve membrane topology. The independently read PMID:19240031 Results, Molecular Properties of SPFH1 and SPFH2 (Figure 2 discussion), reports ER-marker colocalization, detergent-dependent solubilization of microsome-associated SPFH1 and protection of most of its mass from protease until detergent permeabilization. These support membrane attachment rather than merely residence somewhere in the ER. Separately recovered Plasmids Methods and selected captions identify mouse SPFH1 BC011220 and mouse SPFH2 constructs, including experiments in HeLa hosts. Figure 2A colocalization is in Rat-1, Figure 2B microsomal extraction in alphaT3-1, and Figure 2D separately assays endogenous HeLa SPFH1 glycosylation and tagged mouse constructs; the recovered caption does not establish the Figure 2C cell context. Human HPA and participant evidence support the conserved target location without relabeling rodent experiments as human. Current human Reactome entity 8866518 independently identifies O75477 residues 1β348 with its own ER-membrane compartment. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane GO_REF:0000052 Reactome:R-HSA-8866551 |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-8866542 | ACCEPT | Summary: The cited human reaction explicitly contains ERLIN1 at the ER membrane. Reason: The current Reactome participant chain 8866542 β 8866531 β 8866522 β 8866518 reaches ERLIN1 entity 8866518 through the ERAD complex 8866531 and ERLIN1:ERLIN2 complex 8866522. The terminal entity identifies human O75477, residues 1β348, and its own GO:0005789 compartment. This is target-level location evidence, not merely an event label. The event attributes ATP-driven extraction to VCP, not ERLIN1. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane Reactome:R-HSA-8866542 |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-8866546 | ACCEPT | Summary: The cited human reaction explicitly contains ERLIN1 at the ER membrane. Reason: The current Reactome participant chain 8866546 β 8866538 β 8866531 β 8866522 β 8866518 reaches ERLIN1 entity 8866518 through the ERAD complex 8866531 and ERLIN1:ERLIN2 complex 8866522. The terminal entity identifies human O75477, residues 1β348, and its own GO:0005789 compartment. This is target-level location evidence, not merely an event label. The event attributes ubiquitination to RNF5/RNF185; complex membership does not give ERLIN1 their ligase chemistry. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane Reactome:R-HSA-8866546 |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-8866551 | ACCEPT | Summary: The cited human reaction explicitly contains ERLIN1 at the ER membrane. Reason: The current Reactome participant chain 8866551 β 8866531 β 8866522 β 8866518 reaches ERLIN1 entity 8866518 through the ERAD complex 8866531 and ERLIN1:ERLIN2 complex 8866522. The terminal entity identifies human O75477, residues 1β348, and its own GO:0005789 compartment. This is target-level location evidence, not merely an event label. The chain establishes the ERLIN1-containing assembly and location, without proving a binary ERLIN1βCFTR contact. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane Reactome:R-HSA-8866551 |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-8866854 | ACCEPT | Summary: The cited human reaction explicitly contains ERLIN1 at the ER membrane. Reason: The current Reactome participant chain 8866854 β 8866531 β 8866522 β 8866518 reaches ERLIN1 entity 8866518 through the ERAD complex 8866531 and ERLIN1:ERLIN2 complex 8866522. The terminal entity identifies human O75477, residues 1β348, and its own GO:0005789 compartment. This is target-level location evidence, not merely an event label. The event attributes ATP-driven extraction to VCP, not ERLIN1. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane Reactome:R-HSA-8866854 |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-8866856 | ACCEPT | Summary: The cited human reaction explicitly contains ERLIN1 at the ER membrane. Reason: The current Reactome participant chain 8866856 β 8866848 β 8866531 β 8866522 β 8866518 reaches ERLIN1 entity 8866518 through the ERAD complex 8866531 and ERLIN1:ERLIN2 complex 8866522. The terminal entity identifies human O75477, residues 1β348, and its own GO:0005789 compartment. This is target-level location evidence, not merely an event label. The event attributes ubiquitination to RNF5/RNF185; complex membership does not give ERLIN1 their ligase chemistry. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane Reactome:R-HSA-8866856 |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-8866857 | ACCEPT | Summary: The cited human reaction explicitly contains ERLIN1 at the ER membrane. Reason: The current Reactome participant chain 8866857 β 8866531 β 8866522 β 8866518 reaches ERLIN1 entity 8866518 through the ERAD complex 8866531 and ERLIN1:ERLIN2 complex 8866522. The terminal entity identifies human O75477, residues 1β348, and its own GO:0005789 compartment. This is target-level location evidence, not merely an event label. The chain establishes the ERLIN1-containing assembly and location, without proving a binary ERLIN1βCFTR contact. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane Reactome:R-HSA-8866857 |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9931264 | ACCEPT | Summary: The cited human reaction explicitly contains ERLIN1 at the ER membrane. Reason: The current Reactome participant chain 9931264 β 8866531 β 8866522 β 8866518 reaches ERLIN1 entity 8866518 through the ERAD complex 8866531 and ERLIN1:ERLIN2 complex 8866522. The terminal entity identifies human O75477, residues 1β348, and its own GO:0005789 compartment. This is target-level location evidence, not merely an event label. The event also includes cytosolic/luminal species, but ERLIN1 itself is explicitly an ER-membrane participant; ATP-dependent transport is not assigned to ERLIN1. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane Reactome:R-HSA-9931264 |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9931298 | ACCEPT | Summary: The cited human reaction explicitly contains ERLIN1 at the ER membrane. Reason: The current Reactome participant chain 9931298 β 9931263 β 8866531 β 8866522 β 8866518 reaches ERLIN1 entity 8866518 through the ERAD complex 8866531 and ERLIN1:ERLIN2 complex 8866522. The terminal entity identifies human O75477, residues 1β348, and its own GO:0005789 compartment. This is target-level location evidence, not merely an event label. The event assigns CD274 ubiquitination to an ERAD ligase, most likely HRD1, not ERLIN1; its common assembly does not prove substrate-specific catalytic responsibility. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane Reactome:R-HSA-9931298 |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9931313 | ACCEPT | Summary: The cited human reaction explicitly contains ERLIN1 at the ER membrane. Reason: The current Reactome participant chain 9931313 β 8866531 β 8866522 β 8866518 reaches ERLIN1 entity 8866518 through the ERAD complex 8866531 and ERLIN1:ERLIN2 complex 8866522. The terminal entity identifies human O75477, residues 1β348, and its own GO:0005789 compartment. This is target-level location evidence, not merely an event label. The common ERAD assembly establishes ERLIN1 location, not an independently verified binary ERLIN1βCD274 interaction. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane Reactome:R-HSA-9931313 |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:19240031 An endoplasmic reticulum (ER) membrane complex composed of S... | ACCEPT | Summary: The source supports the conserved ER membrane location of erlin-1. Reason: PMID:19240031 Results distinguish ER colocalization, microsomal membrane extraction and protease protection from soluble luminal protein behavior. Recovered Plasmids Methods identify mouse SPFH1 BC011220 and mouse SPFH2 constructs, including those used in HeLa host cells; endogenous HeLa glycosylation is a separate observation. The selected Figure 2C caption does not independently establish its cell context. These experiments support the conserved membrane topology, and independent PMID:16835267 directly localizes human ERLIN1 to the ER. Accept the location without relabeling the rodent constructs as human or assigning an untested alternative product. Supporting Evidence: PMID:19240031 the ER membrane protein SPFH1 and its homolog SPFH2 form a heteromeric |
| GO:0036503 ERAD quality control pathway | IDA PMID:19240031 An endoplasmic reticulum (ER) membrane complex composed of S... | ACCEPT | Summary: ERLIN1 contributes to substrate-selective ER-associated degradation. Reason: PMID:19240031 tests SPFH1 depletion during stimulated IP3-receptor ubiquitination and turnover in rodent cells, with calcium-response controls and mouse-construct rescue; the two erlins are not functionally interchangeable. Independent PMID:19751772 directly tests endogenous ERLIN1 depletion in muscarinic-receptor-expressing human HeLa cells: IP3-receptor ubiquitination and degradation are inhibited while the measured calcium response and IΞΊBΞ± degradation remain intact. Its tagged rescue is mouse SPFH2, not a human ERLIN1 rescue. These experiments support ERLIN1 participation in substrate handling before degradation, without claiming a universal requirement for all ERAD substrates or assigning E3 ligase chemistry. Supporting Evidence: PMID:19240031 mediates the ER-associated degradation of inositol 1,4,5-trisphosphate |
| GO:0045121 membrane raft | NAS PMID:34572057 Role of ERLINs in the Control of Cell Fate through Lipid Raf... | KEEP AS NON CORE | Summary: ERLIN1 occupies cholesterol-dependent internal membrane microdomains. Reason: The PMID:34572057 review describes erlin-associated ER microdomains. Independent original PMID:16835267 separates buoyant detergent-resistant internal membranes and shows cholesterol sensitivity after hypotonic membrane disruption; whole-cell cyclodextrin treatment has a different effect. Together with direct ER localization this supports an operational internal membrane-raft assignment. The preparation does not imply plasma-membrane localization, a fixed nanoscale domain geometry or an exact stoichiometric complex. This operational fractionation-defined membrane domain is retained as a supported non-core location; the primary functional location is the ER membrane. Supporting Evidence: PMID:16835267 define lipid-raft-like domains of the ER |
| GO:0045540 regulation of cholesterol biosynthetic process | IDA PMID:24217618 Erlins restrict SREBP activation in the ER and regulate cell... | MODIFY | Summary: ERLIN1 restrains cholesterol biosynthesis through SREBP regulation. Reason: PMID:24217618 connects ERLIN1 depletion in human HeLa cells to increased cholesterol abundance and increased expression of cholesterol-biosynthesis genes, with SREBP processing and SCAP inhibition supporting the regulatory route. The direction is inhibitory in the tested sterol-replete setting, so refine the broad regulation term to negative regulation of cholesterol biosynthetic process. The study measures transcript and lipid endpoints rather than a direct synthesis-flux assay; ERLIN1 is not assigned catalytic cholesterol-biosynthesis chemistry. Proposed replacements: negative regulation of cholesterol biosynthetic process |
| GO:0032991 protein-containing complex | IDA PMID:18468998 Blood pressure is regulated by an alpha1D-adrenergic recepto... | KEEP AS NON CORE | Summary: ERLIN1 is recovered in an ADRA1D-associated protein preparation. Reason: Actual PMID:18468998 Table 3 lists ERLIN1 in tandem-affinity-purified ADRA1D material from HEK293 cells, with four peptides and 16% coverage; IntAct EBI-21277437 independently records this target association. This is positive evidence for an associated protein assembly despite the paper focusing on the receptor and dystrophin-associated proteins. Retain the observation as non-core because no ERLIN1-specific receptor mechanism or stable stoichiometric subunit role was tested in the inspected material. The receptor physiology is not transferred to ERLIN1. Its independently established ERLIN1/ERLIN2 complex is a distinct assembly context. Supporting Evidence: PMID:19240031 SPFH1 and its homolog SPFH2 form a heteromeric approximately 2 MDa complex |
| GO:0015485 cholesterol binding | IDA PMID:24217618 Erlins restrict SREBP activation in the ER and regulate cell... | ACCEPT | Summary: ERLIN1 binds cholesterol directly in the tested recombinant preparation. Reason: PMID:24217618 cholesterol-binding Results and corresponding Methods use human ERLIN1 expressed in Drosophila S2 cells, purified to greater than 90% and immobilized through its tag. Radiolabeled cholesterol binding is saturable, competed by unlabeled cholesterol and cooperative; the reported apparent dissociation constant is approximately 13.2 micromolar. Native mouse-liver erlin complex binding is a separate preparation. Accept direct cholesterol binding without treating the solid-phase assay as a measurement of affinity in an intact human ER membrane or inferring that every erlin-associated lipid binds the same way. Supporting Evidence: PMID:24217618 Erlins bound cholesterol with specificity and strong cooperativity |
| GO:0032933 SREBP signaling pathway | IMP PMID:24217618 Erlins restrict SREBP activation in the ER and regulate cell... | ACCEPT | Summary: ERLIN1 contributes to sterol-sensitive control of SREBP signaling. Reason: PMID:24217618 Results show that individual ERLIN1 depletion in human HeLa cells increases SREBP-regulated lipid-synthesis transcripts and lipid abundance; SREBP processing, nuclear redistribution and SCAP inhibition connect these effects to the pathway. Erlin association with the Insig/SCAP/SREBP machinery and altered Insig stability provide a mechanistic account of ER retention. Human ERLIN1 binding experiments are distinguished from native mouse complex and ERLIN2-specific mobility measurements. ERLIN1 participates as an ER-associated, sterol-responsive regulator, not as the SREBP protease or a lipid-synthesis enzyme. Supporting Evidence: PMID:24217618 led to canonical activation of SREBPs and their target genes |
| GO:0045541 negative regulation of cholesterol biosynthetic process | IMP PMID:24217618 Erlins restrict SREBP activation in the ER and regulate cell... | ACCEPT | Summary: ERLIN1 negatively regulates the cholesterol-biosynthetic program. Reason: PMID:24217618 individual ERLIN1 knockdown in human HeLa cells increases cholesterol-biosynthesis gene expression and cholesterol abundance. SREBP cleavage/nuclear localization and the SCAP inhibitor experiment connect the phenotype to sterol-responsive transcriptional control. Accept the inhibitory regulatory role under the tested conditions, while distinguishing measured transcript/lipid endpoints from direct synthesis flux and from ERLIN2-specific HMGCR turnover. Supporting Evidence: PMID:24217618 led to canonical activation of SREBPs and their target genes |
| GO:0045717 negative regulation of fatty acid biosynthetic process | IMP PMID:24217618 Erlins restrict SREBP activation in the ER and regulate cell... | ACCEPT | Summary: ERLIN1 negatively regulates the fatty-acid-biosynthetic program through SREBP signaling. Reason: PMID:24217618 shows that ERLIN1 depletion in human HeLa cells raises FASN and ACC1 expression and lipid abundance in the same SREBP-responsive setting. The pathway and SCAP-inhibition evidence support a negative regulatory role rather than direct fatty-acid synthase activity. The lipid/transcript endpoints do not independently measure synthesis flux, and the tested sterol-replete human-cell conditions are retained. Supporting Evidence: PMID:24217618 key transcription factors for cholesterol and fatty acid biosynthetic |
| GO:0005515 protein binding | IPI PMID:19240031 An endoplasmic reticulum (ER) membrane complex composed of S... | KEEP AS NON CORE | Summary: ERLIN1 associates with ERLIN2 in the erlin assembly. Reason: PMID:19240031 supports the SPFH1/SPFH2 association through endogenous rodent complexes and tagged mouse constructs, including mouse SPFH1 BC011220 expressed in HeLa hosts. Host species does not change construct identity. Independent human-cell interaction evidence in PMID:22119785 supports ERLIN1βERLIN2 association. Retain the supported generic binding as non-core under the project instruction; the cellular assembly and specific sterol-binding function carry the more informative functional account. No homogeneous two-protein binding preparation or exact complex stoichiometry is inferred from these observations. Supporting Evidence: PMID:19240031 SPFH1 and its homolog SPFH2 form a heteromeric approximately 2 MDa complex |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:16835267 Erlin-1 and erlin-2 are novel members of the prohibitin fami... | ACCEPT | Summary: ERLIN1 is an endoplasmic-reticulum membrane protein. Reason: PMID:16835267 Results and Methods identify full-length human ERLIN1 cloned from U937 cells and expressed as a GFP fusion in HeLa cells, with ER-marker colocalization. Endogenous staining and cholesterol-sensitive detergent-resistant internal membrane fractions independently support the ER membrane location. Human proteins expressed in mouse 3T3 cells are separate experiments. The engineered N-terminal targeting fragments are not natural isoforms, and detergent resistance is not interpreted as universal plasma-membrane residence. |
| GO:0005515 protein binding | IPI PMID:21343306 Membrane-associated ubiquitin ligase complex containing gp78... | KEEP AS NON CORE | Summary: The ERLIN1βERLIN2 interaction is supported within the erlin assembly. Reason: Preserve the experimentally curated association. PMID:21343306 uses tagged human SPFH proteins in CHO-7 cells and places their interactions in the ER ligase network. Independent PMID:19240031 supports the erlin assembly with rodent proteins, while the target-specific PMID:22119785 IntAct records EBI-25769871 and EBI-25770016 support human ERLIN1βERLIN2 association by pull-down. Generic binding is retained as non-core; the SPFH2-selective HMGCR degradation phenotype in the 2011 study is not attributed to ERLIN1. |
| GO:0005515 protein binding | IPI PMID:21343306 Membrane-associated ubiquitin ligase complex containing gp78... | MODIFY | Summary: ERLIN1 associates with the ubiquitin E3 ligase SYVN1/HRD1. Reason: PMID:21343306 Figure 2A/B Results and plasmid/immunoprecipitation Methods test tagged human SPFH1 with human ER E3 ligases in CHO-7 cells. SPFH1 co-immunoprecipitates with SYVN1/HRD1 (Q86TM6); unlike SPFH2 it does not show the same TRC8 association. This identifies the functional class of the binding partner and supports refinement to ubiquitin protein ligase binding. Co-immunoprecipitation does not establish a purified binary interface or make ERLIN1 a ubiquitin-transfer enzyme. The SPFH2-dependent HMGCR degradation findings and TMUB1 bridge are not transferred to ERLIN1. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21343306 Membrane-associated ubiquitin ligase complex containing gp78... | MODIFY | Summary: ERLIN1 associates with the ubiquitin E3 ligase AMFR/gp78. Reason: PMID:21343306 Figure 2A/B Results and plasmid/immunoprecipitation Methods test tagged human SPFH1 with human ER E3 ligases in CHO-7 cells. SPFH1 co-immunoprecipitates with AMFR/gp78 (Q9UKV5); unlike SPFH2 it does not show the same TRC8 association. This identifies the functional class of the binding partner and supports refinement to ubiquitin protein ligase binding. Co-immunoprecipitation does not establish a purified binary interface or make ERLIN1 a ubiquitin-transfer enzyme. The SPFH2-dependent HMGCR degradation findings and TMUB1 bridge are not transferred to ERLIN1. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22119785 Defining human ERAD networks through an integrative mapping ... | KEEP AS NON CORE | Summary: Human ERLIN1 and ERLIN2 are recovered together in the ER protein-interaction network. Reason: PMID:22119785 uses affinity purification and mass spectrometry in human HEK293 cells, with detergent-dependent interaction recovery explicitly considered. Actual target-pair IntAct records EBI-25769871 and EBI-25770016 report ERLIN1βERLIN2 pull-down evidence. Preserve the supported generic association as non-core. Network membership alone does not specify a distinct catalytic activity, binary interface or exact native assembly stoichiometry; no pair-specific score or detergent condition is invented from the global validation rate. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22119785 Defining human ERAD networks through an integrative mapping ... | MODIFY | Summary: The ERLIN1 association with SYVN1/HRD1 supports ubiquitin protein ligase binding. Reason: The actual PMID:22119785 target-pair record EBI-25770037 identifies ERLIN1 and the E3 ligase SYVN1/HRD1 (Q86TM6) in a human-cell affinity-purification experiment. This identifies a specific functional partner class rather than merely an unspecified protein. Independent PMID:21343306 Figure 2 directly tests human SPFH1 association with this ligase by co-immunoprecipitation in CHO-7 cells. Refine to ubiquitin protein ligase binding while keeping complex-mediated association distinct from a purified binary contact. Neither ligase catalysis nor a particular substrate-ubiquitination step is assigned to ERLIN1 from the network experiment. Proposed replacements: ubiquitin protein ligase binding |
| GO:0005515 protein binding | IPI PMID:22119785 Defining human ERAD networks through an integrative mapping ... | MODIFY | Summary: The ERLIN1 association with AMFR/gp78 supports ubiquitin protein ligase binding. Reason: The actual PMID:22119785 target-pair record EBI-25770556 identifies ERLIN1 and the E3 ligase AMFR/gp78 (Q9UKV5) in a human-cell affinity-purification experiment. This identifies a specific functional partner class rather than merely an unspecified protein. Independent PMID:21343306 Figure 2 directly tests human SPFH1 association with this ligase by co-immunoprecipitation in CHO-7 cells. Refine to ubiquitin protein ligase binding while keeping complex-mediated association distinct from a purified binary contact. Neither ligase catalysis nor a particular substrate-ubiquitination step is assigned to ERLIN1 from the network experiment. Proposed replacements: ubiquitin protein ligase binding |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Human ERLIN1 interacts with the 280-residue B2RDE6 cDNA product in the HI-II-14 yeast two-hybrid screen. Reason: PMID:25416956 Results, A proteome-wide binary interactome map, and Experimental Procedures describe pairwise quadruplicate retesting with identity confirmation. The actual IntAct records for ERLIN1 and B2RDE6 contain pooling, array and validated two-hybrid entries attributed to Table S2G (records intact:EBI-10175843, intact:EBI-10334347, intact:EBI-10506376). These support the reported binary screen interaction. The author Table S2G workbook could not be opened; no pair-specific mammalian orthogonal validation is claimed. B2RDE6 is preserved as the tested 280-residue accession: its current sequence is not identical to the full 372-residue FA2H product or to that productβs entire 93β372 segment. The study does not establish a specific regulatory, adaptor or substrate-recruitment role for this pair. Retain the supported interaction as non-core protein binding. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Human ERLIN1 interacts with VMA12 (formerly TMEM199) in the HI-II-14 yeast two-hybrid screen. Reason: PMID:25416956 Results, A proteome-wide binary interactome map, and Experimental Procedures describe pairwise quadruplicate retesting with identity confirmation. The actual IntAct records for ERLIN1 and Q8N511 contain pooling, array and validated two-hybrid entries attributed to Table S2G (records intact:EBI-10420167, intact:EBI-10587316, intact:EBI-10265829). These support the reported binary screen interaction. The author Table S2G workbook could not be opened; no pair-specific mammalian orthogonal validation is claimed. The study does not establish a specific regulatory, adaptor or substrate-recruitment role for this pair. Retain the supported interaction as non-core protein binding. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Human ERLIN1 interacts with AGR3 in the HI-II-14 yeast two-hybrid screen. Reason: PMID:25416956 Results, A proteome-wide binary interactome map, and Experimental Procedures describe pairwise quadruplicate retesting with identity confirmation. The actual IntAct records for ERLIN1 and Q8TD06 contain pooling, array and validated two-hybrid entries attributed to Table S2G (records intact:EBI-10428441, intact:EBI-10594318, intact:EBI-10274356). These support the reported binary screen interaction. The author Table S2G workbook could not be opened; no pair-specific mammalian orthogonal validation is claimed. The study does not establish a specific regulatory, adaptor or substrate-recruitment role for this pair. Retain the supported interaction as non-core protein binding. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Human ERLIN1 interacts with SEC22A in the HI-II-14 yeast two-hybrid screen. Reason: PMID:25416956 Results, A proteome-wide binary interactome map, and Experimental Procedures describe pairwise quadruplicate retesting with identity confirmation. The actual IntAct records for ERLIN1 and Q96IW7 contain pooling, array and validated two-hybrid entries attributed to Table S2G (records intact:EBI-10442912, intact:EBI-10289315, intact:EBI-10506388). These support the reported binary screen interaction. The author Table S2G workbook could not be opened; no pair-specific mammalian orthogonal validation is claimed. The study does not establish a specific regulatory, adaptor or substrate-recruitment role for this pair. Retain the supported interaction as non-core protein binding. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: ERLIN1 binds BNIP2 in the HuRI binary interaction assay. Reason: The original HuRI PSI dataset contains three method records for this exact pair (lines 40697, 61696, 155126), including a validated two-hybrid record; the ERLIN1 clone is hORFeome 8101, mapped to O75477 and ENSG00000107566. The current IntAct feature annotation maps the tested ERLIN1 region to residues 3β348. PMID:32296183 Results, Generation and characterization of HuRI, describes quadruplicate pairwise retesting and sequence confirmation. Orthogonal benchmarking of sampled pairs does not establish separate orthogonal validation of this particular pair. The screen supports binding without establishing an ERLIN1 enzymatic, transport or adaptor role, so retain the interaction as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: ERLIN1 binds SEC23A in the HuRI binary interaction assay. Reason: The original HuRI PSI dataset contains three method records for this exact pair (lines 35332, 140857, 148998), including a validated two-hybrid record; the ERLIN1 clone is hORFeome 8101, mapped to O75477 and ENSG00000107566. The current IntAct feature annotation maps the tested ERLIN1 region to residues 3β348. PMID:32296183 Results, Generation and characterization of HuRI, describes quadruplicate pairwise retesting and sequence confirmation. Orthogonal benchmarking of sampled pairs does not establish separate orthogonal validation of this particular pair. The screen supports binding without establishing an ERLIN1 enzymatic, transport or adaptor role, so retain the interaction as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: ERLIN1 binds FA2H in the HuRI binary interaction assay. Reason: The original HuRI PSI dataset contains three method records for this exact pair (lines 29187, 38216, 103737), including a validated two-hybrid record; the ERLIN1 clone is hORFeome 8101, mapped to O75477 and ENSG00000107566. The current IntAct feature annotation maps the tested ERLIN1 region to residues 3β348. The corresponding FA2H region is 93β372; the experiment is not an assay of the complete FA2H protein. PMID:32296183 Results, Generation and characterization of HuRI, describes quadruplicate pairwise retesting and sequence confirmation. Orthogonal benchmarking of sampled pairs does not establish separate orthogonal validation of this particular pair. The screen supports binding without establishing an ERLIN1 enzymatic, transport or adaptor role, so retain the interaction as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: ERLIN1 binds RBFA in the HuRI binary interaction assay. Reason: The original HuRI PSI dataset contains three method records for this exact pair (lines 56028, 76523, 126605), including a validated two-hybrid record; the ERLIN1 clone is hORFeome 8101, mapped to O75477 and ENSG00000107566. The current IntAct feature annotation maps the tested ERLIN1 region to residues 3β348. PMID:32296183 Results, Generation and characterization of HuRI, describes quadruplicate pairwise retesting and sequence confirmation. Orthogonal benchmarking of sampled pairs does not establish separate orthogonal validation of this particular pair. The screen supports binding without establishing an ERLIN1 enzymatic, transport or adaptor role, so retain the interaction as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: ERLIN1 binds AGR3 in the HuRI binary interaction assay. Reason: The original HuRI PSI dataset contains three method records for this exact pair (lines 83331, 85410, 134200), including a validated two-hybrid record; the ERLIN1 clone is hORFeome 8101, mapped to O75477 and ENSG00000107566. The current IntAct feature annotation maps the tested ERLIN1 region to residues 3β348. PMID:32296183 Results, Generation and characterization of HuRI, describes quadruplicate pairwise retesting and sequence confirmation. Orthogonal benchmarking of sampled pairs does not establish separate orthogonal validation of this particular pair. The screen supports binding without establishing an ERLIN1 enzymatic, transport or adaptor role, so retain the interaction as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: ERLIN1 binds SEC22A in the HuRI binary interaction assay. Reason: The original HuRI PSI dataset contains three method records for this exact pair (lines 56001, 131603, 165785), including a validated two-hybrid record; the ERLIN1 clone is hORFeome 8101, mapped to O75477 and ENSG00000107566. The current IntAct feature annotation maps the tested ERLIN1 region to residues 3β348. PMID:32296183 Results, Generation and characterization of HuRI, describes quadruplicate pairwise retesting and sequence confirmation. Orthogonal benchmarking of sampled pairs does not establish separate orthogonal validation of this particular pair. The screen supports binding without establishing an ERLIN1 enzymatic, transport or adaptor role, so retain the interaction as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BioPlex 3.0 supports an affinity association between ERLIN1 and ERLIN2. Reason: The author BioPlex 3.0 HCT116 directed-edge table contains ERLIN1 bait (10613) and ERLIN2 prey (11160) at line 13690, matching IntAct EBI-54942295. This assigned pair was detected in HCT116 cells; the inspected HEK293T directed table does not supply this pair. PMID:33961781 STAR Methods describe human C-terminal FLAG-HA bait expression, anti-HA purification and separate CompPASS-Plus analyses of the two cell lines. The data are gene-level affinity associations, not a purified two-protein assay or a stoichiometric demonstration. BioPlex 3.0 reanalyzes earlier 293T data, so overlap with BioPlex 2.0 is not counted as wholly independent replication. Retain the supported generic interaction as non-core; this screen alone does not establish a specific molecular binding role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BioPlex 3.0 supports an affinity association between ERLIN1 and C6orf120. Reason: The author directed-edge tables contain ERLIN1 bait (10613) and C6orf120 prey (387263) in HEK293T at line 51957 and HCT116 at line 13696, with matching current IntAct records EBI-54793945 and EBI-54942295. PMID:33961781 STAR Methods describe human C-terminal FLAG-HA bait expression, anti-HA purification and separate CompPASS-Plus analyses of the two cell lines. The data are gene-level affinity associations, not a purified two-protein assay or a stoichiometric demonstration. BioPlex 3.0 reanalyzes earlier 293T data, so overlap with BioPlex 2.0 is not counted as wholly independent replication. Retain the supported generic interaction as non-core; this screen alone does not establish a specific molecular binding role. Supporting Evidence: |
| GO:0036503 ERAD quality control pathway | IBA GO_REF:0000033 | ACCEPT | Summary: The fresh ERAD IBA is a genuine inherited functional context. Reason: The actual IBD at PTN000794169 asserts GO:0036503 from experimentally annotated human ERLIN1 and ERLIN2 descendants. O75477 lies inside that clade, its target MSA is exact, and no target-path NOT is present. The annotation is not invalidated by self-WITH or by its absence from the older local review. PMID:19240031 Results show SPFH1/2 association with activated IP3 receptors before substantial polyubiquitination, loss of receptor polyubiquitination/degradation after Rat-1 SPFH1 depletion and rescue by reintroduction, with preserved calcium mobilization. This supports a substrate-recognition/processing assembly role in ERAD rather than merely a downstream disease phenotype. The recovered Plasmids and retroviral-expression Methods identify mouse SPFH1 and SPFH2 cDNAs; the Rat-1 depletion/rescue and alphaT3-1 native-complex experiments are rodent evidence for the conserved assembly role, not direct human ERAD perturbations. HeLa tagged-coassembly experiments also use mouse constructs. SPFH2-specific effects are not reassigned to ERLIN1. Complete Methods, figure pixels and supplements were not inspected. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000794169 SUPPORTS TRANSFER Verified ERAD IBD and target inheritance, with independently read substrate-processing evidence. This target conclusion does not validate every possible family-wide ERAD substrate. |
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Download this section (compressed HTML)Q: How does ERLIN1 cholesterol binding couple to SREBP regulation: through Insig stability, sterol accessibility to SOAT1, or separable contributions of both mechanisms?
Q: Which ERLIN1 structural contributions determine cargo selection versus RNF170 recruitment, and can TMUB1-L and RNF170 occupy one functional erlin assembly simultaneously?
Q: For SPG62 variants, how much of the neuronal phenotype reflects abnormal RNA splicing or protein abundance versus a specific defect in erlin assembly, sterol handling or cargo turnover?
Experiment: Compare expression-matched ERLIN1 sterol-binding variants with wild-type rescue while measuring protein stability, ERLIN2 association, accessible ER cholesterol, cholesteryl-esters, Insig abundance and SREBP processing. Include SOAT1 inhibition and a direct isotopic sterol-synthesis readout to distinguish accessibility and regulatory effects from altered biosynthetic flux.
Experiment: Reconstitute composition-defined ERLIN1/ERLIN2 assemblies with TMUB1-L, RNF170 and a controlled activated-IP3-receptor substrate. Measure partner occupancy, cargo association, RNF170 recruitment and substrate ubiquitination separately, with matched assembly/stability controls, to distinguish a structural ERLIN1 contribution from ligase chemistry and to test simultaneous versus separate complexes.
Experiment: Introduce selected splice and missense SPG62 variants into isogenic human neuronal cells. Quantify transcript isoforms, endogenous ERLIN1 abundance and assembly before measuring IP3-receptor turnover and sterol responses; compare genomic variants with expression-matched cDNA rescue to separate RNA defects from protein-level mechanisms.
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