PMID:16835267(https://doi.org/10.1242/jcs.03060): the original publisher PDF's Results on ER colocalization/internal detergent-resistant membranes and Methods for constructs, fractionation and cholesterol depletion were read. Human ERLIN1 was cloned from U937 cells and expressed in HeLa; experiments with human proteins in mouse 3T3 cells are separate. Cholesterol depletion after hypotonic disruption affects internal membrane detergent resistance differently from whole-cell treatment. Engineered N-terminal fragments are targeting probes, not natural products. No figure pixels or separate supplements were inspected.
PMID:19240031(https://doi.org/10.1074/jbc.M809801200): the actual Molecular Properties and IP3-receptor ERAD Results, recovered Plasmids/shRNA/TEM Methods and selected captions were read. Mouse SPFH1 BC011220 and mouse SPFH2 constructs remain mouse proteins in HeLa hosts. Native Rat-1/alphaT3-1 experiments are distinguished from endogenous HeLa glycosylation. The selected Figure 2C caption does not establish its cell context. The original large-complex size is an estimate; it is not a modern structural subunit count. No complete-Methods, figure-pixel or supplemental-data read is claimed.
PMID:21343306(https://doi.org/10.1074/jbc.M110.211326): original XML Results, Figure 2 discussion and construct/immunoprecipitation Methods show human SPFH1 association with human SYVN1/HRD1 and AMFR/gp78 in CHO-7 cells. The SPFH1 result differs from SPFH2 for TRC8 and sterol-triggered HMGCR turnover. Co-immunoprecipitation supports association with an E3 ligase but does not establish purified binary contacts, ubiquitin-transfer catalysis or a universal ERAD substrate relationship. No figure pixels or independent supplementary data were inspected.
PMID:22119785(https://doi.org/10.1038/ncb2383): original Results and experimental-design passages describe tagged-bait affinity purification, mass spectrometry and interaction scoring in human HEK293 cells. Actual IntAct records EBI-25769871/EBI-25770016 identify the ERLIN1–ERLIN2 pair; EBI-25770037 identifies ERLIN1–SYVN1 and EBI-25770556 ERLIN1–AMFR. Detergent dependence and the global validation rate do not establish the precise condition or confidence score for every pair. The separate Online Methods/supplementary files were not independently read. Independent PMID:21343306 supports the two specific E3-association refinements.
PMID:18468998(https://doi.org/10.1074/jbc.M801860200): original Table 3 lists ERLIN1 in the HEK293 ADRA1D tandem-affinity preparation (four peptides, 16% coverage). IntAct EBI-21277437 independently identifies that pair. The association is retained as an ancillary assembly observation. Receptor physiology and dystrophin/syntrophin mechanisms do not establish an ERLIN1-specific signaling role. Operative TAP Methods, raw spectra and figure pixels were not independently read.
PMID:24217618(https://doi.org/10.1083/jcb.201305076): original Results and binding, cell-culture, lipid and biochemical Methods were read. Recombinant human ERLIN1 produced in S2 cells and immobilized through its tag directly binds radiolabeled cholesterol, with competition, saturation and cooperativity. Native mouse-liver complex binding is a separate experiment. Human HeLa ERLIN1 depletion raises SREBP-responsive cholesterol/fatty-acid synthesis transcripts and lipid abundance; processing, localization, SCAP inhibition and Insig turnover connect the phenotype to regulation. FLAG-SREBP processing and Insig turnover use HEK293 cells; HeLa nuclear staining and the fatostatin experiment are distinct assays. A scaffolding mechanism is one proposed model, not an established unique mechanism. These are not direct synthesis-flux measurements. ERLIN2-specific FRAP observations and mixed-species SCAP/Insig preparations are not treated as pure human ERLIN1 experiments. No figure pixels or separate supplementary data were inspected.
PMID:34572057(https://doi.org/10.3390/cells10092408): the cached review's erlin microdomain discussion was read as secondary context. The internal membrane-raft decision also rests on the original PMID:16835267 fractionation/cholesterol-depletion observations; it does not depend on the review alone.
PMID:19751772(https://doi.org/10.1016/j.bbamcr.2009.09.004): genuine fetched full text, actual cell/RNAi/construct Methods and stimulated-IP3-receptor Results were read. Human muscarinic-receptor-expressing HeLa cells with endogenous ERLIN1 depletion show impaired receptor ubiquitination and degradation; the calcium response and the tested IκBα degradation control remain intact. ERLIN2 depletion also partly reduces ERLIN1, and the rescue construct is mouse SPFH2. Selected other model ERAD substrates differ in response, so no universal ERAD requirement is inferred. The human ERLIN1 perturbation is independent of the rodent source experiments in PMID:19240031. No figure pixels or separate supplements were inspected.
The 348-residue displayed human ERLIN1 sequence is the identified natural product. None of these engineered fragments, expression hosts or complex-size estimates establishes another natural isoform. No publication quotation is added.
These assertions concern human ERLIN1/O75477, whose displayed sequence has 348 residues. No alternative product is declared in the captured official record. The fresh database assertions are assessed separately from the older review; no legacy quotation or source context is moved, merged or retired here.
| Source | Observed target evidence and limits |
|---|---|
| PANTHER PTHR15351 tree, MSA, IBD | Human leaf PTN002495870 has an ungapped alignment exactly matching the 348-residue O75477 sequence. Its path contains PTN000794169 (ER membrane and ERAD), PTN001282580 (SREBP pathway) and ERLIN1-clade PTN002692334 (cholesterol binding). All four actual IBD records match; no target-path NOT is present. Human self-WITH evidence is valid experimental grounding. The ERLIN2 and worm erl-1 leaves are identified explicitly; a family-wide claim about every substrate or species is not made. |
| InterPro O75477, IPR033294 | The Erlin1/2 family matches residues 2–317. Its current mappings include ER and ubiquitin-ligase binding. The entry also describes the broad taxonomic range and a worm ERAD caveat; that caveat is not evidence that human ERLIN1 lacks the experimentally supported function. No transfer is made simply from the broad SPFH domain. |
| HPA ERLIN1, structured record | Supported ICC/IF ER localization with HPA011252 in A-431, U-251MG, U2OS and KOLF2.1J. The complete antigen maps to O75477 residues 254–344. The complete identical antigen is absent from ERLIN2; this is a sequence fact, not proof of antibody specificity or an experimental cross-reactivity result. Images were not independently inspected. HPA alone does not establish membrane topology; the more specific membrane proposal uses independent target evidence below. |
| ARBA00028685, ARBA00028902, ARBA00029018 | Actual matching condition sets are respectively 35, 381 and 18 (zero-based). All use target FunFam 3.30.479.30:FF:000009, with Eukaryota for membrane, no added taxon for complex, and Catarrhini for ERAD. These rules establish provenance; independent protein/complex evidence substantiates their target claims. |
| ARBA00087340, ARBA00085017, ARBA00084177 | Matching sets 0, 0 and 1 use the same target FunFam plus Chordata for SREBP signaling, negative cholesterol biosynthesis and negative fatty-acid biosynthesis. Other unrelated disjuncts are not used. Rule matching does not replace the original experiments. |
| Human Reactome ERLIN1, ERLIN1:ERLIN2 complex | The actual terminal protein record is O75477, human, residues 1–348, with its own ER-membrane compartment. Every imported reaction reaches that participant through the ERAD complex 8866531 and ERLIN1:ERLIN2 complex 8866522. This provides location evidence without assigning neighboring enzymatic chemistry to ERLIN1. |
All arrows below are actual input/output or hasComponent relationships, ending at human ERLIN1 8866518:
| Imported reaction | Target chain | Interpretation |
|---|---|---|
| 8866542 | output 8866531 → 8866522 → 8866518 | ER membrane; VCP performs the attributed ATP-driven extraction. |
| 8866546 | input 8866538 → 8866531 → 8866522 → 8866518 | ER membrane; RNF5/RNF185 perform the attributed ubiquitination. |
| 8866551 | input 8866531 → 8866522 → 8866518 | ER membrane; no inferred binary ERLIN1–CFTR contact. |
| 8866854 | output 8866531 → 8866522 → 8866518 | ER membrane in the CFTR F508del extraction context. |
| 8866856 | input 8866848 → 8866531 → 8866522 → 8866518 | ER membrane in the CFTR F508del ubiquitination context. |
| 8866857 | input 8866531 → 8866522 → 8866518 | ER membrane in the CFTR F508del assembly context. |
| 9931264 | output 8866531 → 8866522 → 8866518 | ERLIN1's own membrane compartment is distinct from other cytosolic/luminal event species. |
| 9931298 | input 9931263 → 8866531 → 8866522 → 8866518 | ER membrane; common assembly does not confer CD274 ligase activity on ERLIN1. |
| 9931313 | input 8866531 → 8866522 → 8866518 | ER membrane; no inferred binary ERLIN1–CD274 contact. |
Current GO:0005789 refines ER to its membrane, and GO:0140534 refines a generic protein-containing complex to one that is part of the ER. Their typed ancestry and unrestricted current usage were checked. A bounded current GO search returned no erlin-named complex; the broader ER-complex term is used without inventing a complex identifier or enzymatic role.
The screen evidence supports the reported interactions while leaving the molecular role of each interaction unresolved. Generic binding is retained as non-core under the campaign curation instructions; a more specific role requires additional evidence. No publication quotations are added.
| Source | Actual evidence and locator | Scope |
|---|---|---|
| PMID:25416956, HI-II-14 | Results A proteome-wide binary interactome map, Figure 1 caption, and Experimental Procedures Generation of the binary protein-protein interaction map. Current IntAct has three method records apiece for O75477 with B2RDE6, Q8N511, Q8TD06 and Q96IW7, attributed to Table S2G. Validated records: EBI-10506376, EBI-10587316, EBI-10594318 and EBI-10506388. | Yeast two-hybrid pooling/array and pairwise retesting. The author S2G workbook was not recovered; global orthogonal benchmarks do not establish pair-specific mammalian validation. Preserve B2RDE6 as its tested 280-residue accession. |
| PMID:28514442, BioPlex 2.0 | Results describing the BioPlex pipeline; Online Experimental Methods Clone Construction and Cell Culture, Affinity-Purification Mass Spectrometry, and Identification of Interacting Proteins. Author directed table, line 23956: ERLIN1 bait → C6orf120 prey. | Human C-terminal HA-FLAG bait, anti-HA enrichment in HEK293T, mass spectrometry and CompPASS-Plus. Affinity association can be indirect. Gene-level collapsing limits product specificity. |
| PMID:30021884, nuclear cross-linking proteomics | Experimental Procedures: U2OS preparation, DSSO reaction, detergent fractionation, data processing and experimental design. Results, Figure 1: nuclear preparation retains connected ER and can co-isolate other organelles. Exact IntAct EBI-20904152 / IM-26653-5549 maps O75477–O94905 to Table S1 and the pink Table S2 fraction. | Positive ERLIN1–ERLIN2 cross-link association in unfractionated nuclei and Triton-soluble preparations; no inference of a nuclear physiological role. The peptide workbooks returned HTML, so exact cross-linked residues were not independently inspected. |
| PMID:32296183, HuRI | Results Generation and characterization of HuRI, Extended Data Figure 1 caption; author PSI dataset contains 18 method records for six exact pairs. ERLIN1 ORF8101 pairs with BNIP2, SEC23A, FA2H, RBFA, AGR3 and SEC22A. | Quadruplicate pairwise retesting and sequence confirmation. Current IntAct maps the ERLIN1 region to 3–348 and FA2H to 93–372. Original PSI identifiers, clones and vector records are preserved. Detailed supplementary Methods and pair-specific orthogonal assays were not read. |
| PMID:33961781, BioPlex 3.0 | STAR Methods Clone Construction, Creation of Stable Cell Lines, Affinity-Purification Mass Spectrometry, Inferring Protein Interactions from LC-MS Data. HEK293T table line 51957: ERLIN1 → C6orf120. HCT116 table lines 13690 and 13696: ERLIN1 → ERLIN2 and C6orf120. | Anti-HA affinity associations analyzed separately by cell line. The 293T version includes reanalysis of earlier BioPlex experiments. These data do not establish purified pairwise contact, stoichiometry or identical functions of every product. |
The current official IntAct target query supplies exact pair, assay, host, construct-feature and publication records. Author tables confirm all six HuRI pairs and all three assigned BioPlex contexts. The HI-II-14 S2G and cross-link peptide workbooks remain unread; their pair attribution is checked against the actual curated interaction records rather than inferred from the paper titles.
Current official B2RDE6 is a 280-residue unreviewed cDNA product. Its sequence aligns across residues 93–372 of FA2H Q7L5A8 with one residue difference; the sequences and product lengths are not identical. No source accession is rewritten. Likewise, the HuRI mapping of an assay construct is not a newly asserted natural splice product of ERLIN1.
Integral complex structure and cargo recruitment. Veronese et al., PMID:38782601, Results/Figures 1–3 and 6–8, Discussion and the cell/knockout/rescue, interaction, lipid and AlphaFold Methods, was read from the actual author-manuscript text. Endogenous human HeLa interactions and double ERLIN1/ERLIN2 knockout with combined rescue support erlin-complex-dependent TMUB1-L/RNF170 association. TMUB1 association with RNF185/TMEM259 persists, so the effect is not simply universal loss of detected interaction. These experiments do not resolve individual ERLIN1 contact surfaces or demonstrate purified ERLIN1 bridging two partners. The Discussion explicitly permits separate complexes containing TMUB1 or RNF170. Rescue cloning provides coding-region primers without independently resolving the original template provenance. AlphaFold uses human sequences; the adjacent-subunit interfaces are predictions. The tested interface mutants are ERLIN2-FLAG, including G48V as an analogy to ERLIN1 G50V. No exact whole-complex subunit count is inferred from this study.
The structural activity is represented by GO:0140378, whose integral-complex-component definition is more direct than a second, redundant adaptor activity. Its coupling to selective protein turnover uses separate primary evidence. Lu et al., PMID:21610068, Experimental Procedures, Results including Priority of Binding to Activated IP3 Receptors, Figures 4–5 captions and Discussion, was read from recovered indexed original text. In human mHeLa cells, ERLIN2 depletion inhibits RNF170 recruitment whereas RNF170 depletion does not prevent erlin-complex recruitment. This orders the complex upstream of the ligase; it is not an isolated ERLIN1 recruitment perturbation. Native alphaT3-1/Rat-1 experiments are rodent, while SH-SY5Y association and mHeLa depletion provide distinct human evidence. The 257-aa RNF170 constructs are mouse even when expressed in HeLa. The ligase assay establishes RNF170 chemistry, not ERLIN1 enzymatic activity. The normal PMID:21610068 cache remains unchanged and abstract-only; manual reviewer access is broader because the operative original was recovered separately.
Wang et al., PMID:19751772, Figure 6/Results, supplies positive quality-control evidence: combined SPFH1/SPFH2 depletion modestly stabilizes misfolded A1AT-NHK and TTR-D18G in human HEK/HeLa assays, while other tested reporters differ. This supports the current GO:0036503 ERAD quality control pathway, without reclassifying activated IP3 receptors as misfolded substrates or claiming a universal ERAD requirement. Figure 7 reports no effect on the tested sterol-induced HMGCR degradation; interaction with gp78/HRD1 does not automatically transfer ERLIN2-specific HMGCR claims to ERLIN1.
Sterol binding and regulatory coupling. The previously assessed PMID:24217618(https://doi.org/10.1083/jcb.201305076) separates recombinant human ERLIN1 sterol binding from native mouse complex assays and cellular SREBP endpoints. In PMID:38782601, actual lipid, morphology and inhibitor-rescue Results support restraint of cholesterol esterification. Sterol sequestration/accessibility to SOAT1 and effects on Insig regulation remain mechanistic alternatives. They do not constitute a direct ERLIN1 cholesterol-transport assay.
PMID:37683630(https://doi.org/10.1016/j.devcel.2023.08.013), actual PMC10914638, Results/Figures 6–7 captions, Discussion/Limitations and operative cell, virus, perturbation, interaction, pulse-chase and lipid Methods, was read independently of its unchanged abstract-only normal cache. Human A549 experiments support USP25-dependent erlin stabilization and contextual effects on SREBP processing, HMGCR abundance, total cholesterol and influenza output. Figure 7J's labeled-cholesterol efflux assay uses shERLIN2, and Figure 7D's T65I mutant is ERLIN2. HMGCR abundance and total cholesterol do not directly measure de-novo sterol synthetic flux. ERLIN1 is not assigned USP25 deubiquitinase activity.
Disease and virus-specific boundaries. Cogan et al., PMID:39367212, participant/DNA/RNA and protein-modeling Methods, variant Results, Discussion and Figures 1–2 captions, was read from the actual manuscript. The 13-person, six-family series supplies positive clinical and patient RNA-splicing evidence for the investigated variants. Effects on complex assembly are predictions from human-sequence AlphaFold models and a bacterial SPFH/FtsH analogy, not experimentally measured assembly defects or stoichiometry. The 2026 PMID:41887216 abstract reports a later structural study, but its operative body was not recovered or read here; no quantitative structural result from that abstract is adopted in the cores.
Whitten-Bauer et al., PMID:31810281, Methods and full Results/Discussion, was read from the genuine full original cache. Human Huh-7 depletion separates an effect on establishing HCV RNA replication and efficient particle production from tested entry, initial translation and established-replicon maintenance. Different depletion efficiencies limit an absolute ERLIN1/ERLIN2 specificity claim. These HCV findings and the influenza context above are not generalized into a universal proviral or antiviral core function.
For this synthesis, no figure pixels, separate supplementary data, deposited atomic model or raw omics data were inspected. Main-text captions and operative prose were read as specified above. The official product record supplies one displayed 348-aa O75477 chain and no alternative-product comment; model organisms, transfection hosts, recombinant constructs and the natural human product remain distinct.
The core scaffold relation was narrowed after exact-head review. PMID:19240031 supports physical oligomeric composition and assembly; PMID:38782601 supports human complex-dependent association. Together these support the subunit's structural contribution and contribution to complex scaffold activity, without an independently resolved ERLIN1 bridging mechanism. No new original access, figure inspection or source assertion is implied by this slot correction. The membrane-raft source remains positive but is now explicitly non-core.