Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005789 endoplasmic reticulum membrane	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference that ERLIN1 acts at the ER membrane, consistent with strong experimental evidence that it is an ER membrane SPFH protein. Reason: Core compartment and site of action; ERLIN1 is an integral ER membrane protein. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0015485 cholesterol binding	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference of cholesterol binding, consistent with direct experimental evidence that erlins bind cholesterol cooperatively. Reason: Core molecular function; redundant with the experimental IDA cholesterol-binding annotation. Supporting Evidence: PMID:24217618 Erlins bound cholesterol with specificity and strong cooperativity
GO:0032933 SREBP signaling pathway	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference of involvement in SREBP signaling, consistent with experimental evidence that erlins restrict SREBP activation. Reason: Core biological process; redundant with experimental IMP evidence. Supporting Evidence: PMID:24217618 directly involved in regulating the SREBP machinery
GO:0005783 endoplasmic reticulum	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based electronic ER localization, consistent with experimental evidence; the more specific ER membrane term is preferred. Reason: Correct compartment; redundant with the ER membrane annotations. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assignment of ER membrane localization from the UniProt subcellular location. Reason: Core compartment; redundant with experimental IDA evidence. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0031625 ubiquitin protein ligase binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based assignment of ubiquitin protein ligase binding, consistent with experimental interactions of ERLIN1 with the ER ubiquitin ligases AMFR/gp78, SYVN1/HRD1 and (in complex with ERLIN2) RNF170. Reason: Informative molecular function; ERLIN1 recruits E3 ubiquitin ligases to the ERAD complex. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt Interacts with AMFR and SYVN1
GO:0032933 SREBP signaling pathway	IEA GO_REF:0000117	ACCEPT	Summary: ARBA machine-learning assignment of SREBP signaling involvement, consistent with experimental evidence. Reason: Correct biological process; redundant with IMP/IBA evidence. Supporting Evidence: PMID:24217618 directly involved in regulating the SREBP machinery
GO:0032991 protein-containing complex	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Generic protein-containing complex assignment; ERLIN1 forms the specific ERLIN1/ERLIN2 complex. Reason: Correct but uninformative; the specific ERLIN1/ERLIN2 complex membership is captured elsewhere. Supporting Evidence: PMID:19240031 SPFH1 and its homolog SPFH2 form a heteromeric approximately 2 MDa complex
GO:0036503 ERAD pathway	IEA GO_REF:0000117	ACCEPT	Summary: ARBA machine-learning assignment of ERAD involvement, consistent with the experimentally demonstrated role in ERAD of IP3 receptors. Reason: Core biological process; redundant with experimental IDA evidence. Supporting Evidence: PMID:19240031 mediates the ER-associated degradation of inositol 1,4,5-trisphosphate
GO:0045541 negative regulation of cholesterol biosynthetic process	IEA GO_REF:0000117	ACCEPT	Summary: ARBA assignment of negative regulation of cholesterol biosynthesis, consistent with the erlins' restriction of SREBP activation. Reason: Correct biological process; redundant with experimental IMP evidence. Supporting Evidence: PMID:24217618 led to canonical activation of SREBPs and their target genes
GO:0045717 negative regulation of fatty acid biosynthetic process	IEA GO_REF:0000117	ACCEPT	Summary: ARBA assignment of negative regulation of fatty acid biosynthesis, consistent with the erlins restricting SREBP (which activates fatty-acid biosynthetic genes). Reason: Correct biological process; redundant with experimental IMP evidence. Supporting Evidence: PMID:24217618 key transcription factors for cholesterol and fatty acid biosynthetic
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: High-throughput interactome capture (C6orf120). Bare protein binding is uninformative. Reason: Real interaction but uninformative GO term. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt O75477; Q7Z4R8: C6orf120
GO:0005515 protein binding	IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma...	KEEP AS NON CORE	Summary: Crosslinking mass-spectrometry capture of an ERLIN1-ERLIN2 interaction. Bare protein binding is uninformative; the ERLIN1/ERLIN2 complex is captured by complex annotations. Reason: Real ERLIN2 interaction but uninformative GO term. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt O75477; O94905: ERLIN2
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	ACCEPT	Summary: Direct immunofluorescence (HPA) evidence for ER localization. Reason: Core compartment; directly demonstrated. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-8866542	ACCEPT	Summary: Reactome curation placing ERLIN1 at the ER membrane within the CFTR ERAD machinery pathway. Reason: Correct compartment; redundant with experimental ER membrane annotations. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-8866546	ACCEPT	Summary: Reactome curation of ERLIN1 ER membrane localization (CFTR ERAD pathway). Reason: Correct compartment; redundant with experimental evidence. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-8866551	ACCEPT	Summary: Reactome curation of ERLIN1 ER membrane localization (CFTR ERAD pathway). Reason: Correct compartment; redundant with experimental evidence. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-8866854	ACCEPT	Summary: Reactome curation of ERLIN1 ER membrane localization (CFTR F508del ERAD pathway). Reason: Correct compartment; redundant with experimental evidence. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-8866856	ACCEPT	Summary: Reactome curation of ERLIN1 ER membrane localization (CFTR F508del ERAD pathway). Reason: Correct compartment; redundant with experimental evidence. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-8866857	ACCEPT	Summary: Reactome curation of ERLIN1 ER membrane localization (CFTR F508del ERAD pathway). Reason: Correct compartment; redundant with experimental evidence. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-9931264	ACCEPT	Summary: Reactome curation of ERLIN1 ER membrane localization (CD274/PD-L1 ERAD pathway). Reason: Correct compartment; redundant with experimental evidence. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-9931298	ACCEPT	Summary: Reactome curation of ERLIN1 ER membrane localization (CD274/PD-L1 ERAD pathway). Reason: Correct compartment; redundant with experimental evidence. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-9931313	ACCEPT	Summary: Reactome curation of ERLIN1 ER membrane localization (CD274/PD-L1 ERAD pathway). Reason: Correct compartment; redundant with experimental evidence. Supporting Evidence: file:human/ERLIN1/ERLIN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	IDA PMID:19240031 An endoplasmic reticulum (ER) membrane complex composed of S...	ACCEPT	Summary: Direct evidence that ERLIN1/SPFH1 is an ER membrane protein, the site of the ERLIN1/ERLIN2 ERAD complex. Reason: Core compartment; directly demonstrated. Supporting Evidence: PMID:19240031 the ER membrane protein SPFH1 and its homolog SPFH2 form a heteromeric
GO:0036503 ERAD pathway	IDA PMID:19240031 An endoplasmic reticulum (ER) membrane complex composed of S...	ACCEPT	Summary: The ERLIN1/ERLIN2 complex binds IP3R tetramers and mediates their ER-associated degradation; depletion of ERLIN1/ERLIN2 blocks IP3R degradation. Reason: Core biological process with direct (IDA) support; the defining function of the ERLIN complex. 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: Erlins associate with lipid-raft-like domains of the ER membrane; the NAS membrane-raft localization reflects this SPFH-domain raft association. Reason: Supported by the lipid-raft characterization of erlins but secondary to the core ER-membrane ERAD/SREBP roles. 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...	ACCEPT	Summary: ERLIN1 regulates cholesterol biosynthesis via the SREBP/SCAP/Insig machinery; the erlins restrict SREBP activation in response to ER cholesterol. Reason: Core biological process; directly supported. Supporting Evidence: PMID:24217618 regulate cellular cholesterol
GO:0032991 protein-containing complex	IDA PMID:18468998 Blood pressure is regulated by an alpha1D-adrenergic recepto...	KEEP AS NON CORE	Summary: IDA placing ERLIN1 in a protein-containing complex (alpha1D-adrenergic receptor/dystrophin signalosome study). The generic complex term is uninformative; ERLIN1's defining complex is the ERLIN1/ERLIN2 complex. Reason: Experimentally supported but uninformative generic complex term; not the core ERLIN1/ERLIN2 complex. 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: Erlins bind cholesterol with specificity and strong cooperativity, a core molecular function underlying their sterol-sensing regulation of SREBP. Reason: Core molecular function with direct (IDA) support. 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: Depletion of erlins led to canonical activation of SREBPs and their target genes, demonstrating that ERLIN1 restricts SREBP signaling. Reason: Core biological process with direct mutant/depletion (IMP) support. 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: By restricting SREBP activation, ERLIN1 negatively regulates cholesterol biosynthesis; erlin depletion derepresses SREBP target genes. Reason: Core biological process with direct (IMP) support. 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 fatty acid biosynthesis through restriction of SREBP, which activates both cholesterol and fatty-acid biosynthetic genes. Reason: Directly supported (IMP); a consequence of the erlins' SREBP restriction. 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: IPI capture of the ERLIN1-ERLIN2 (SPFH1-SPFH2) interaction. Bare protein binding is uninformative; the ERLIN1/ERLIN2 complex is captured by the ERAD/complex annotations. Reason: Real ERLIN2 interaction but uninformative GO term. 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: Direct evidence that erlin-1 localizes to lipid-raft-like domains of the ER membrane. Reason: Core compartment; directly demonstrated. Supporting Evidence: PMID:16835267 define lipid-raft-like domains of the ER

Core Functions

Scaffold subunit of the ring-shaped ERLIN1/ERLIN2 SPFH-domain complex that binds inositol 1,4,5-trisphosphate receptor (IP3R) tetramers and, with the E3 ligase RNF170, mediates their ER-associated degradation, controlling calcium signaling.

Directly Involved In:

ERAD pathway

Cellular Locations:

endoplasmic reticulum membrane

Supporting Evidence:

PMID:19240031
mediates the ER-associated degradation of inositol 1,4,5-trisphosphate
PMID:19240031
SPFH1 and its homolog SPFH2 form a heteromeric approximately 2 MDa complex

Cholesterol-binding ER membrane protein that restricts SREBP activation by associating with and stabilizing the SREBP-SCAP-Insig complex, thereby negatively regulating cholesterol and fatty acid biosynthesis and contributing to cellular cholesterol homeostasis.

Molecular Function:

cholesterol binding

Directly Involved In:

SREBP signaling pathway negative regulation of cholesterol biosynthetic process

Cellular Locations:

endoplasmic reticulum membrane

Supporting Evidence:

PMID:24217618
Erlins bound cholesterol with specificity and strong cooperativity
PMID:24217618
directly involved in regulating the SREBP machinery

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:16835267

Erlin-1 and erlin-2 are novel members of the prohibitin family of proteins that define lipid-raft-like domains of the ER.

Erlin-1 and erlin-2 are prohibitin-family ER membrane proteins that define lipid-raft-like domains of the ER.

PMID:18468998

Blood pressure is regulated by an alpha1D-adrenergic receptor/dystrophin signalosome.

PMID:19240031

An endoplasmic reticulum (ER) membrane complex composed of SPFH1 and SPFH2 mediates the ER-associated degradation of inositol 1,4,5-trisphosphate receptors.

SPFH1 (ERLIN1) and SPFH2 (ERLIN2) form a ring-shaped ~2 MDa heteromeric ER membrane complex that binds IP3R tetramers and mediates their ER-associated degradation; depletion blocks IP3R degradation.

PMID:21343306

Membrane-associated ubiquitin ligase complex containing gp78 mediates sterol-accelerated degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.

SPFH2 (ERLIN2) and TMUB1 associate with the ER ubiquitin ligase gp78/AMFR in sterol-accelerated ERAD of HMG-CoA reductase; ERLIN1 interacts with AMFR and SYVN1.

PMID:22119785

Defining human ERAD networks through an integrative mapping strategy.

PMID:24217618

Erlins restrict SREBP activation in the ER and regulate cellular cholesterol homeostasis.

Erlins are cholesterol-binding proteins that restrict SREBP activation by stabilizing the SREBP-Scap-Insig complex and promoting its ER retention; erlin depletion activates SREBP target genes.

PMID:25416956

A proteome-scale map of the human interactome network.

PMID:28514442

Architecture of the human interactome defines protein communities and disease networks.

PMID:30021884

Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei.

PMID:32296183

A reference map of the human binary protein interactome.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:34572057

Role of ERLINs in the Control of Cell Fate through Lipid Rafts.

Review of ERLIN1/2 as ER lipid-raft-associated proteins controlling cell fate.

PMID:37683630

Usp25-Erlin1/2 activity limits cholesterol flux to restrict virus infection.

USP25 deubiquitinates and stabilizes ERLIN1; Usp25-Erlin1/2 activity limits cholesterol flux to restrict virus infection.

PMID:38782601

ERLIN1/2 scaffolds bridge TMUB1 and RNF170 and restrict cholesterol esterification to regulate the secretory pathway.

ERLIN1/ERLIN2 form large ring-like cup-shaped ER scaffolds that mediate the interaction between the full-length isoform of TMUB1 and the E3 ligase RNF170 (binding their conserved luminal N-terminal motif via the SPFH domains of adjacent ERLIN subunits); these scaffolds limit cholesterol esterification, favouring ER-to-Golgi cholesterol transport and regulating Golgi morphology and the secretory pathway. Variants that preclude these interactions have been linked to hereditary spastic paraplegia.

PMID:39367212

Biallelic variants in ERLIN1: a series of 13 individuals with spastic paraparesis.

Largest series to date of biallelic ERLIN1 variants (13 individuals from six families) causing SPG62 spastic paraparesis; childhood-onset, slowly progressive, predominantly pure paraparesis with possible cerebellar and peripheral-nerve involvement. Three new variants are predicted to alter the bell-shaped ring formed by the ERLIN1/ERLIN2 complex.

PMID:31810281

The Host Factor Erlin-1 is Required for Efficient Hepatitis C Virus Infection.

ERLIN1 is a cholesterol-binding, ER detergent-resistant-membrane protein required for efficient hepatitis C virus infection; its silencing reduces HCV RNA replication initiation, viral protein expression, and infectious virus production, acting downstream of entry and primary translation.

Reactome:R-HSA-8866542

VCP-catalyzed ATP hydrolysis promotes the translocation of misfolded CFTR into the cytosol

Reactome:R-HSA-8866546

RNF5 and RNF185 ubiquitinate misfolded CFTR

Reactome:R-HSA-8866551

CFTR binds components of the ERAD machinery for ubiquitination and degradation

Reactome:R-HSA-8866854

VCP-catalyzed ATP hydrolysis promotes the translocation of CFTR F508del into the cytosol

Reactome:R-HSA-8866856

RNF5 and RNF185 ubiquitinate CFTR F508del

Reactome:R-HSA-8866857

CFTR F508del binds components of the ERAD machinery for ubiquitination and degradation

Reactome:R-HSA-9931264

Active transport of ubiquitinated CD274 from ER to cytosol

Reactome:R-HSA-9931298

Ubiquitination of CD274 by ERAD complex

Reactome:R-HSA-9931313

p-S195-CD274 binds ERAD complex

file:human/ERLIN1/ERLIN1-uniprot.txt

UniProt entry O75477 (ERLN1_HUMAN), Erlin-1 / SPFH1

ERLIN1 is a single-pass type II ER membrane SPFH/prohibitin protein that forms the ERLIN1/ERLIN2 complex mediating ERAD of IP3 receptors, binds cholesterol, restricts SREBP activation, and interacts with the ER ubiquitin ligases AMFR/gp78, SYVN1 and (with ERLIN2) RNF170; variants cause SPG62.

Suggested Experiments

Experiment: Reconstitute the ERLIN1/ERLIN2 complex with RNF170 and a model IP3R substrate to test whether ERLIN1 is required for substrate binding versus ligase recruitment in IP3R ERAD.

Experiment: Use cholesterol photoaffinity probes and SPFH-domain point mutants of ERLIN1 to map the cholesterol-binding site and test whether abolishing cholesterol binding derepresses SREBP target genes.

Experiment: Introduce the SPG62 G50V variant into neurons and assay ERLIN1/ERLIN2 complex assembly, IP3R degradation, and ER cholesterol/SREBP signaling to link the molecular defect to disease.

Deep Research

Falcon

(ERLIN1-deep-research-falcon.md)

Research Report: Human **ERLIN1** (UniProt **O75477**; Gene **ERLIN1**; synonyms **KE04/SPFH1/C10orf69**) — Functional Annotation Falcon Edison Scientific Literature 35 citations 2 artifacts 2026-06-12T05:16:12.091825

Edison artifact artifact-00 (text/markdown)

## Context ID: pqac-00000039 Figure 3A provides a schematic summarizing the model where ERLIN1/2 scaffolds bridge RNF170 and TMUB1-L on the ER membrane. While o (image/png)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research Report: Human ERLIN1 (UniProt O75477; Gene ERLIN1; synonyms KE04/SPFH1/C10orf69) — Functional Annotation

1) Target verification and definitions (gene/protein identity)

ERLIN1 (ER lipid raft–associated protein 1; UniProt O75477) is an endoplasmic-reticulum (ER) membrane protein in the SPFH/band7 (prohibitin/PHB-domain) superfamily and forms high–molecular-weight oligomers with its close paralog ERLIN2 in cholesterol-rich, detergent-resistant ER nanodomains (“ER lipid rafts”). (manganelli2021roleoferlins pages 1-2, manganelli2021roleoferlins pages 3-5, veronese2024erlin12scaffoldsbridge pages 1-2)

Operationally in the recent literature, “ERLIN1/2 complex” refers to hetero-oligomeric ERLIN1+ERLIN2 scaffolds that (i) recruit specific client proteins and (ii) organize lipid/protein microdomains that couple lipid homeostasis with protein quality control and membrane trafficking. (veronese2024erlin12scaffoldsbridge pages 4-6, veronese2024erlin12scaffoldsbridge pages 1-2)

2) Current understanding: molecular functions, pathways, and localization

2.1 ER membrane nanodomain scaffold controlling cholesterol esterification and secretory trafficking (major 2024 advance)

A 2024 mechanistic study (Life Science Alliance; publication month May 2024) provides direct experimental evidence that ERLIN1 (with ERLIN2) forms ER scaffolds/nanodomains that:

Bridge RNF170 and TMUB1-L: mass-spectrometry interaction mapping and reciprocal co-immunoprecipitations identified RNF170 (E3 ligase) and TMUB1 (long isoform, TMUB1-L) among enriched ERLIN interactors, and loss of ERLINs completely prevented the TMUB1–RNF170 interaction. (veronese2024erlin12scaffoldsbridge pages 2-4, veronese2024erlin12scaffoldsbridge pages 4-6)
Restrict cholesterol esterification: ERLIN deficiency perturbed cholesterol esterification and lipid-droplet phenotypes; the authors propose that cholesterol bound within luminal ERLIN “cups” is less accessible to SOAT1, thereby limiting cholesterol esterification and favoring ER-to-Golgi cholesterol transport. (veronese2024erlin12scaffoldsbridge pages 12-12)
Maintain secretory pathway architecture: ERLIN1/2 double knockout caused tubular ER collapse, Golgi fragmentation, altered distribution of secretory-route proteins in detergent-resistant fractions, and cell migration defects, linking ERLIN nanodomain organization to secretory pathway function. (veronese2024erlin12scaffoldsbridge pages 12-12, veronese2024erlin12scaffoldsbridge pages 4-6)

Quantitatively, this study reports: (i) interaction/proteomics work at the scale of 2,742 proteins in a post-nuclear supernatant dataset and N=4 biological replicates for key proteomics comparisons; (ii) a tendency to increased SOAT1 abundance in ERLIN double knockout cells (SOAT1 log2FC = 0.40; q = 0.07); and (iii) rescue of lipid-droplet accumulation phenotypes using a SOAT1 inhibitor (avasimibe). (veronese2024erlin12scaffoldsbridge pages 4-6, veronese2024erlin12scaffoldsbridge pages 12-12, veronese2024erlin12scaffoldsbridge pages 2-4)

URL / date: Veronese et al. “ERLIN1/2 scaffolds bridge TMUB1 and RNF170 and restrict cholesterol esterification to regulate the secretory pathway.” Life Science Alliance (May 2024). https://doi.org/10.26508/lsa.202402620 (veronese2024erlin12scaffoldsbridge pages 1-2)

Visual evidence: the ERLIN1/2–RNF170–TMUB1-L scaffold model is depicted in a schematic (Figure 3A). (veronese2024erlin12scaffoldsbridge media 40d635ea)

2.2 ER-associated degradation (ERAD) of activated IP3 receptors and Ca2+ signaling

Multiple sources converge on a core pathway-level role for ERLIN1/2 in IP3 receptor (IP3R) turnover via ERAD:

In the 2024 ERLIN scaffold study, ERLINs are placed mechanistically upstream of RNF170, an ER-membrane E3 ligase linked to ERAD of activated IP3Rs, connecting scaffold organization to proteostasis control at ER microdomains. (veronese2024erlin12scaffoldsbridge pages 1-2, veronese2024erlin12scaffoldsbridge pages 12-12)
A 2024 clinical genetics series on biallelic ERLIN1 variants (SPG62) explicitly interprets ERLIN1 loss-of-function as disrupting ERLIN1/2 complex formation and thereby compromising the ability to recruit RNF170 to degrade activated IP3R1, leading to impaired Ca2+ signaling. (cogan2024biallelicvariantsin pages 12-16)

A particularly specific quantitative statement highlighted in that 2024 disease analysis is that unique ablation of ERLIN1 expression is sufficient to increase IP3R1 levels by ~73% in vitro, consistent with reduced IP3R ERAD and altered ER Ca2+ release dynamics. (cogan2024biallelicvariantsin pages 12-16)

URL / date: Cogan et al. “Biallelic variants in ERLIN1: a series of 13 individuals with spastic paraparesis.” Human Genetics (Oct 2024). https://doi.org/10.1007/s00439-024-02702-0 (cogan2024biallelicvariantsin pages 1-6)

2.3 Mitochondria-associated membranes (MAMs), lipid microdomains, and autophagy initiation (ERLIN1–AMBRA1)

ERLIN1 can function at specialized ER subdomains, including mitochondria-associated membranes (MAMs). A detailed review synthesizing primary evidence reports that:

ERLIN1 is enriched in raft-like microdomains at MAMs and its MAM localization is linked to MFN2-dependent ER–mitochondria tethering. (manganelli2021roleoferlins pages 7-9)
Upon autophagy induction, ERLIN1 physically interacts with AMBRA1 at MAM raft-like microdomains (supported by co-immunoprecipitation and FRET in the summarized evidence). (manganelli2021roleoferlins pages 7-9)
Perturbing raft/microdomain integrity (e.g., ganglioside-dependent organization) impairs ERLIN1–AMBRA1 association and hinders autophagosome formation under nutrient deprivation. (manganelli2021roleoferlins pages 7-9)

These data support a model where ERLIN1 contributes to microdomain-dependent recruitment/organization of autophagy initiation machinery at ER–mitochondria contact sites.

URL / date: Manganelli et al. “Role of ERLINs in the Control of Cell Fate through Lipid Rafts.” Cells (Sep 2021). https://doi.org/10.3390/cells10092408 (manganelli2021roleoferlins pages 1-2)

3) Recent developments (prioritizing 2023–2024)

3.1 2024: ERLIN1/2 as nanodomain scaffolds linking lipid metabolism to secretory function

The Veronese et al. 2024 work materially advances functional annotation by showing ERLIN1/2 are not only “markers” of ER rafts but active organizers of an ER nanodomain network that:

physically connects TMUB1-L with RNF170 (protein–protein scaffolding), and
couples that protein network to cholesterol handling (esterification vs transport) and ER/Golgi secretory architecture. (veronese2024erlin12scaffoldsbridge pages 4-6, veronese2024erlin12scaffoldsbridge pages 12-12)

This provides a more mechanistic explanation for how ERLIN1 variants might cause disease beyond a single-client ERAD model—i.e., by perturbing an integrated lipid–proteostasis–trafficking hub. (veronese2024erlin12scaffoldsbridge pages 12-12)

3.2 2024: expanded SPG62 case series defining genotype–phenotype patterns

Cogan et al. (Oct 2024) report the largest series of biallelic ERLIN1 variants to date: 13 individuals from 6 families with early-onset spastic paraparesis. (cogan2024biallelicvariantsin pages 1-6, cogan2024biallelicvariantsin pages 6-9)

Key statistics and clinical features:

Mean onset 1.8 years (range 9 months–4 years). (cogan2024biallelicvariantsin pages 12-16)
Walking aid typically required 10–15 years after onset (slow progression). (cogan2024biallelicvariantsin pages 12-16)
Recurrent splice-region variant c.430+3_430+6del in 6 individuals from 4 families, with RNA evidence of exon 5 skipping; additional intronic variants altered splicing leading to exon skipping and frameshift in some cases. (cogan2024biallelicvariantsin pages 9-12, cogan2024biallelicvariantsin pages 6-9)
Thin corpus callosum in 5/13 (~40%); gait ataxia in 6/13; intellectual disability uncommon in this cohort (only one individual). (cogan2024biallelicvariantsin pages 12-16, cogan2024biallelicvariantsin pages 1-6)

Mechanistically, variants were interpreted as impairing ERLIN1/2 cage formation (PHB/SPFH region), consistent with disruption of IP3R ERAD/Ca2+ signaling and potentially broader ER microdomain functions. (cogan2024biallelicvariantsin pages 9-12, cogan2024biallelicvariantsin pages 12-16)

4) Current applications and real-world implementations

4.1 Clinical genetics: ERLIN1 as a molecular diagnosis for hereditary spastic paraplegia (SPG62)

The 2024 SPG62 series demonstrates direct real-world implementation of ERLIN1 knowledge in diagnostic genomics:

ERLIN1 is a validated disease gene in hereditary spastic paraplegia, and the paper emphasizes detection of non-coding/intronic splice-altering variants confirmed by RNA-seq/RT-PCR, highlighting the clinical value of transcript-informed variant interpretation. (cogan2024biallelicvariantsin pages 9-12, cogan2024biallelicvariantsin pages 18-27)

4.2 Functional cell biology: perturbation of ERLIN1/2 to probe lipid–secretory coupling

The 2024 ERLIN scaffold study provides a blueprint for experimental implementation:

CRISPR double knockout of ERLIN1/ERLIN2 in HeLa cells, with phenotyping of ER/Golgi morphology, lipid droplets, and secretory trafficking, and chemical rescue of lipid droplet phenotypes via SOAT1 inhibition (avasimibe)—a tractable framework for dissecting ER lipid nanodomain function. (veronese2024erlin12scaffoldsbridge pages 12-12, veronese2024erlin12scaffoldsbridge pages 2-4)

4.3 Infection biology: ERLIN1 as a host factor for hepatitis C virus (HCV)

A well-controlled cell-culture study shows that ERLIN1 is required for efficient HCV infection and particle production:

ERLIN1 knockdown produced ~7–10-fold reduction in progeny virus production; in single-cycle infections, ERLIN1 depletion caused a modest 2–3-fold decrease in intracellular HCV RNA but a ~10-fold reduction in infectious virus and a ~4–10-fold reduction in viral protein accumulation (core/NS3/NS5A), consistent with roles in initiation of RNA replication and a post-replication assembly step. (whittenbauer2019thehostfactor pages 5-6, whittenbauer2019thehostfactor pages 9-12, whittenbauer2019thehostfactor pages 15-18)

URL / date: Whitten-Bauer et al. “The Host Factor Erlin-1 is Required for Efficient Hepatitis C Virus Infection.” Cells (Dec 2019). https://doi.org/10.3390/cells8121555 (whittenbauer2019thehostfactor pages 1-3)

4.4 Systems immunology / biomarker-style signals: ERLIN1 induction in sepsis datasets

A transcriptome-mining plus validation study reports that ERLIN1 is consistently upregulated in septic immune contexts, especially neutrophil-associated settings:

Across curated transcriptomic datasets, ERLIN1 upregulation was reported in the range 3.26–5.29-fold. (huang2021transcriptomeandliterature pages 1-2)
In whole blood stimulated ex vivo with LPS/peptidoglycan, ERLIN1 expression increased 2.6-fold (p<0.01); the validation experiment used n=8 donors. (huang2021transcriptomeandliterature pages 7-9, huang2021transcriptomeandliterature pages 9-11)
A dataset example showed 5.29-fold induction in neutrophils exposed to septic plasma; other examples included 1.34-fold (S. aureus infection), 1.18-fold (ICU sepsis), and 6.12-fold (neonatal sepsis). (huang2021transcriptomeandliterature pages 5-6)

URL / date: Huang et al. “Transcriptome and Literature Mining Highlight the Differential Expression of ERLIN1 in Immune Cells during Sepsis.” Biology (Aug 2021). https://doi.org/10.3390/biology10080755 (huang2021transcriptomeandliterature pages 1-2)

5) Expert synthesis and interpretation (authoritative analysis grounded in cited sources)

5.1 Primary functional role: ER membrane scaffold coupling lipid microdomains to client handling and trafficking

The combined 2024 mechanistic and 2024 clinical-genetic evidence supports a coherent primary functional annotation:

Scaffold/nanodomain organizer: ERLIN1 oligomerizes with ERLIN2 into stable ER membrane assemblies that define specialized, cholesterol-rich ER nanodomains. (veronese2024erlin12scaffoldsbridge pages 1-2, manganelli2021roleoferlins pages 1-2)
Client recruitment and process coupling: These scaffolds recruit proteins such as RNF170 (E3 ligase) and TMUB1-L, thereby coupling ERAD-related ubiquitination machinery with cholesterol accessibility/esterification and with ER→Golgi trafficking/secretory pathway integrity. (veronese2024erlin12scaffoldsbridge pages 4-6, veronese2024erlin12scaffoldsbridge pages 12-12)
Physiology and disease relevance: In neurons, disruption of ERLIN1 (biallelic loss-of-function) plausibly increases IP3R1 abundance and perturbs ER Ca2+ signaling, contributing to corticospinal tract vulnerability in SPG62. (cogan2024biallelicvariantsin pages 12-16, cogan2024biallelicvariantsin pages 1-6)

5.2 Relationship to autophagy and MAMs

ERLIN1’s association with MAM raft-like microdomains and AMBRA1 suggests ERLIN1 scaffolds can be repurposed at ER contact sites to support autophagy initiation, potentially by organizing lipid microdomains that recruit core autophagy regulators. (manganelli2021roleoferlins pages 7-9)

6) Consolidated functional annotation table

Function/pathway	Key mechanistic role	Key interaction partners	Subcellular localization/microdomain	Evidence type	Quantitative/other notable data	Key citations (context IDs) and source (authors, year, DOI URL)
ERLIN1 identity and core complex biology	Human ERLIN1 (UniProt O75477; ER lipid raft-associated protein 1) is a ~40 kDa ER membrane SPFH/PHB-family protein that hetero-oligomerizes with ERLIN2 to form large ring/cage-like scaffolds in cholesterol-rich ER nanodomains	ERLIN2	Endoplasmic reticulum; detergent-resistant/lipid raft-like ER membrane domains; MAMs under some conditions	Review synthesis; biochemical fractionation; structural/topology inference	ERLIN1/2 described as ~40 kDa transmembrane glycoproteins; ERLIN1 is 348 aa; complexes reported as ~1000 kDa or ~40-subunit/ring-like assemblies depending on method/model	(manganelli2021roleoferlins pages 1-2, manganelli2021roleoferlins pages 3-5, veronese2024erlin12scaffoldsbridge pages 1-2, cogan2024biallelicvariantsin pages 1-6) Manganelli et al., 2021, https://doi.org/10.3390/cells10092408; Veronese et al., 2024, https://doi.org/10.26508/lsa.202402620; Cogan et al., 2024, https://doi.org/10.1007/s00439-024-02702-0
Cholesterol esterification control and secretory pathway regulation	ERLIN1/2 scaffolds bridge TMUB1-L and RNF170 at ER nanodomains, restricting cholesterol esterification, favoring ER-to-Golgi cholesterol transport, and maintaining ER/Golgi architecture and secretory trafficking	ERLIN2, TMUB1-L, RNF170, TMEM259, RNF185, FAF2, VCP, ARF1/4, SOAT1	ER membrane nanodomains; detergent-resistant membranes; ER-Golgi contact-associated regions	CRISPR/Cas9 ERLIN1/2 double KO; MS-IP; reciprocal co-IP; AlphaFold-Multimer modeling; proteomics; DRM flotation; rescue experiments	Loss of ERLINs completely prevented TMUB1-RNF170 interaction; proteomics quantified 2,742 proteins and identified 34 significant hits; SOAT1 tended to increase in DKO (log2FC 0.40, q=0.07); ERLIN loss caused ER tubule collapse, Golgi fragmentation, lipid droplet accumulation, impaired post-Golgi trafficking and migration defects; N=4 biological replicates in key proteomics	(veronese2024erlin12scaffoldsbridge pages 4-6, veronese2024erlin12scaffoldsbridge pages 12-12, veronese2024erlin12scaffoldsbridge pages 2-4, veronese2024erlin12scaffoldsbridge pages 1-2, veronese2024erlin12scaffoldsbridge media 40d635ea) Veronese et al., 2024, https://doi.org/10.26508/lsa.202402620
ERAD of activated IP3 receptors and Ca2+ signaling	ERLIN1/2 complex recruits or scaffolds RNF170 to promote ubiquitination and ER-associated degradation of activated IP3 receptors, thereby shaping ER Ca2+ release signaling	ERLIN2, RNF170, IP3R/IP3R1	ER membrane lipid raft-like microdomains; MAM-associated Ca2+ signaling domains	Foundational mechanistic literature summarized in reviews and disease papers; patient-genetic interpretation	In disease-oriented synthesis, unique ERLIN1 ablation was noted to increase IP3R1 levels by ~73% in vitro; disturbed IP3R degradation is proposed to impair Ca2+ signaling relevant to long-axon vulnerability	(cogan2024biallelicvariantsin pages 12-16, cogan2024biallelicvariantsin pages 1-6, veronese2024erlin12scaffoldsbridge pages 12-12, huang2021transcriptomeandliterature pages 9-11, huang2021transcriptomeandliterature pages 11-13) Cogan et al., 2024, https://doi.org/10.1007/s00439-024-02702-0; Veronese et al., 2024, https://doi.org/10.26508/lsa.202402620; Huang et al., 2021, https://doi.org/10.3390/biology10080755
MAM lipid raft microdomains and autophagy initiation	ERLIN1 associates with AMBRA1 in ganglioside-rich raft-like MAM microdomains; this interaction supports starvation-induced autophagosome formation and couples ER-mitochondria membrane organization to autophagy initiation	AMBRA1, MFN2, GD3/ganglioside pathway components, BECN1	Mitochondria-associated ER membranes (MAMs); raft-like microdomains enriched in cholesterol/gangliosides	Co-immunoprecipitation; FRET; knockdown of ERLIN1, MFN2, and GD3-synthase; autophagy assays	ERLIN1-AMBRA1 interaction increased with autophagy induction; depletion of ERLIN1 impaired nutrient-deprivation-induced autophagy; interaction depended on GD3 and MFN2 integrity	(manganelli2021roleoferlins pages 7-9, manganelli2021roleoferlins pages 1-2, manganelli2021roleoferlins pages 3-5) Manganelli et al., 2021, https://doi.org/10.3390/cells10092408; Manganelli et al., 2021, https://doi.org/10.1080/15548627.2020.1834207
Hereditary spastic paraplegia SPG62 / patient genetics	Biallelic ERLIN1 variants disrupt splicing or the PHB/SPFH structural region, likely destabilizing ERLIN1/2 oligomers and perturbing IP3R ERAD/Ca2+ homeostasis in motor-system disease	ERLIN2; functionally linked RNF170 and IP3R1	ER membrane complex in neurons and other cells	Human cohort genetics; RNA-seq/RT-PCR splice validation; structural modeling	Largest reported series: 13 individuals from 6 families; early onset mean 1.8 years (range 9 months-4 years); recurrent c.430+3_430+6del in 6 individuals from 4 families; thin corpus callosum in 5/13 (~40%); gait ataxia in 6/13; aid for walking typically needed 10-15 years after onset	(cogan2024biallelicvariantsin pages 18-27, cogan2024biallelicvariantsin pages 9-12, cogan2024biallelicvariantsin pages 12-16, cogan2024biallelicvariantsin pages 1-6, cogan2024biallelicvariantsin pages 6-9) Cogan et al., 2024, https://doi.org/10.1007/s00439-024-02702-0
Viral infection biology (HCV host factor)	ERLIN1 is a positive host factor for efficient hepatitis C virus infection, acting after entry and primary translation to promote initiation of RNA replication and a later assembly-related step	HCV proteins/core, NS3, NS5A; lipid droplets; ERLIN2 was tested but not equivalent functionally	ER detergent-resistant membranes; cholesterol-rich ER microdomains	siRNA knockdown in Huh-7 cells; reporter replicons; pseudoparticle entry assays; infectivity titration; RT-qPCR; western blot; microscopy	ERLIN1 knockdown caused ~7-10-fold lower progeny virus production; ~2-3-fold lower intracellular HCV RNA in single-cycle infection; ~4-10-fold lower core/NS3/NS5A accumulation; ~50% lower reporter activity at 48-72 h and 30-60% of control at 96 h; no effect on entry or primary IRES translation	(whittenbauer2019thehostfactor pages 18-19, whittenbauer2019thehostfactor pages 9-12, whittenbauer2019thehostfactor pages 5-6, whittenbauer2019thehostfactor pages 6-9, whittenbauer2019thehostfactor pages 15-18, whittenbauer2019thehostfactor pages 12-15, whittenbauer2019thehostfactor pages 1-3) Whitten-Bauer et al., 2019, https://doi.org/10.3390/cells8121555
Immune-cell modulation in sepsis	ERLIN1 is transcriptionally upregulated in sepsis-associated immune contexts, especially neutrophil-related settings, suggesting ER stress/proteostasis, Ca2+ signaling, and cholesterol-homeostasis roles in innate immune activation	Functionally linked RNF170, IP3R, SREBP-SCAP-INSIG axis; cell-context associations in neutrophils/monocytes/whole blood	Whole blood leukocytes; neutrophils; monocytes; HL60 neutrophil-like cells	Transcriptome mining across public datasets; RT-qPCR in stimulated whole blood; flow cytometry in leukocyte subsets and HL60 model	Public datasets showed 3.26-5.29-fold ERLIN1 increase overall; 5.29-fold increase in healthy neutrophils exposed to septic plasma; 2.6-fold increase in LPS/PGN-stimulated whole blood (p<0.01); additional examples included 1.34-fold in S. aureus infection, 1.18-fold in ICU sepsis, and 6.12-fold in neonatal sepsis; whole-blood donor experiment n=8; HL60 MFI fold changes 2.4, 1.06, and -2.36 at 6, 12, 24 h (n=3)	(huang2021transcriptomeandliterature pages 1-2, huang2021transcriptomeandliterature pages 9-11, huang2021transcriptomeandliterature pages 2-4, huang2021transcriptomeandliterature pages 7-9, huang2021transcriptomeandliterature pages 5-6, huang2021transcriptomeandliterature pages 11-13) Huang et al., 2021, https://doi.org/10.3390/biology10080755

Table: This table summarizes experimentally supported functions, pathways, interaction partners, localization, and disease relevance of human ERLIN1 (UniProt O75477). It highlights both foundational and recent studies, including 2024 work on ERLIN1/2 scaffolds in cholesterol homeostasis and secretory pathway regulation.

7) Key figure supporting the 2024 ERLIN scaffold model

Veronese et al. provide a schematic model of the ERLIN1/2 scaffold bridging RNF170 and TMUB1-L at the ER membrane. (veronese2024erlin12scaffoldsbridge media 40d635ea)

8) Notes on evidence coverage and recency

The strongest 2023–2024 primary evidence obtained here is from two 2024 peer-reviewed studies: Veronese et al. (mechanistic cell biology) and Cogan et al. (clinical genetics). (veronese2024erlin12scaffoldsbridge pages 1-2, cogan2024biallelicvariantsin pages 1-6) Additional mechanistic context (autophagy/MAMs; infection biology; sepsis transcriptomics) is supported by 2019–2021 literature. (whittenbauer2019thehostfactor pages 1-3, manganelli2021roleoferlins pages 1-2, huang2021transcriptomeandliterature pages 1-2)

9) Practical takeaways for functional annotation workflows

For experimental annotation, ERLIN1 is best treated as an ER membrane SPFH scaffold protein rather than an enzyme/transporter; functional assays should focus on protein–protein interactions, detergent-resistant microdomain behavior, cholesterol esterification/transport balance, ERAD client turnover (IP3R), and ER/Golgi architecture/trafficking outputs. (veronese2024erlin12scaffoldsbridge pages 4-6, veronese2024erlin12scaffoldsbridge pages 12-12)
For clinical annotation, ERLIN1 is a confirmed HSP/SPG62 gene with recurrent intronic splice variants; incorporating RNA-based assays can be essential for variant interpretation. (cogan2024biallelicvariantsin pages 9-12, cogan2024biallelicvariantsin pages 18-27)

References

(manganelli2021roleoferlins pages 1-2): Valeria Manganelli, Agostina Longo, Vincenzo Mattei, Serena Recalchi, Gloria Riitano, Daniela Caissutti, Antonella Capozzi, Maurizio Sorice, Roberta Misasi, and Tina Garofalo. Role of erlins in the control of cell fate through lipid rafts. Cells, 10:2408, Sep 2021. URL: https://doi.org/10.3390/cells10092408, doi:10.3390/cells10092408. This article has 42 citations.
(manganelli2021roleoferlins pages 3-5): Valeria Manganelli, Agostina Longo, Vincenzo Mattei, Serena Recalchi, Gloria Riitano, Daniela Caissutti, Antonella Capozzi, Maurizio Sorice, Roberta Misasi, and Tina Garofalo. Role of erlins in the control of cell fate through lipid rafts. Cells, 10:2408, Sep 2021. URL: https://doi.org/10.3390/cells10092408, doi:10.3390/cells10092408. This article has 42 citations.
(veronese2024erlin12scaffoldsbridge pages 1-2): Matteo Veronese, Sebastian Kallabis, Alexander Tobias Kaczmarek, Anushka Das, Lennart Robers, Simon Schumacher, Alessia Lofrano, Susanne Brodesser, Stefan Müller, Kay Hofmann, Marcus Krüger, and Elena I Rugarli. Erlin1/2 scaffolds bridge tmub1 and rnf170 and restrict cholesterol esterification to regulate the secretory pathway. Life Science Alliance, 7:e202402620, May 2024. URL: https://doi.org/10.26508/lsa.202402620, doi:10.26508/lsa.202402620. This article has 8 citations and is from a peer-reviewed journal.
(veronese2024erlin12scaffoldsbridge pages 4-6): Matteo Veronese, Sebastian Kallabis, Alexander Tobias Kaczmarek, Anushka Das, Lennart Robers, Simon Schumacher, Alessia Lofrano, Susanne Brodesser, Stefan Müller, Kay Hofmann, Marcus Krüger, and Elena I Rugarli. Erlin1/2 scaffolds bridge tmub1 and rnf170 and restrict cholesterol esterification to regulate the secretory pathway. Life Science Alliance, 7:e202402620, May 2024. URL: https://doi.org/10.26508/lsa.202402620, doi:10.26508/lsa.202402620. This article has 8 citations and is from a peer-reviewed journal.
(veronese2024erlin12scaffoldsbridge pages 2-4): Matteo Veronese, Sebastian Kallabis, Alexander Tobias Kaczmarek, Anushka Das, Lennart Robers, Simon Schumacher, Alessia Lofrano, Susanne Brodesser, Stefan Müller, Kay Hofmann, Marcus Krüger, and Elena I Rugarli. Erlin1/2 scaffolds bridge tmub1 and rnf170 and restrict cholesterol esterification to regulate the secretory pathway. Life Science Alliance, 7:e202402620, May 2024. URL: https://doi.org/10.26508/lsa.202402620, doi:10.26508/lsa.202402620. This article has 8 citations and is from a peer-reviewed journal.
(veronese2024erlin12scaffoldsbridge pages 12-12): Matteo Veronese, Sebastian Kallabis, Alexander Tobias Kaczmarek, Anushka Das, Lennart Robers, Simon Schumacher, Alessia Lofrano, Susanne Brodesser, Stefan Müller, Kay Hofmann, Marcus Krüger, and Elena I Rugarli. Erlin1/2 scaffolds bridge tmub1 and rnf170 and restrict cholesterol esterification to regulate the secretory pathway. Life Science Alliance, 7:e202402620, May 2024. URL: https://doi.org/10.26508/lsa.202402620, doi:10.26508/lsa.202402620. This article has 8 citations and is from a peer-reviewed journal.
(veronese2024erlin12scaffoldsbridge media 40d635ea): Matteo Veronese, Sebastian Kallabis, Alexander Tobias Kaczmarek, Anushka Das, Lennart Robers, Simon Schumacher, Alessia Lofrano, Susanne Brodesser, Stefan Müller, Kay Hofmann, Marcus Krüger, and Elena I Rugarli. Erlin1/2 scaffolds bridge tmub1 and rnf170 and restrict cholesterol esterification to regulate the secretory pathway. Life Science Alliance, 7:e202402620, May 2024. URL: https://doi.org/10.26508/lsa.202402620, doi:10.26508/lsa.202402620. This article has 8 citations and is from a peer-reviewed journal.
(cogan2024biallelicvariantsin pages 12-16): Guillaume Cogan, Maha S. Zaki, Mahmoud Issa, Boris Keren, Marine Guillaud-Bataille, Florence Renaldo, Arnaud Isapof, Pauline Lallemant, Giovanni Stevanin, Lena Guillot-Noel, Thomas Courtin, Julien Buratti, Cécile Freihuber, Joseph G. Gleeson, Robyn Howarth, Alexandra Durr, Jean-Madeleine de Sainte Agathe, and Cyril Mignot. Biallelic variants in erlin1: a series of 13 individuals with spastic paraparesis. Human genetics, 143:1353-1362, Oct 2024. URL: https://doi.org/10.1007/s00439-024-02702-0, doi:10.1007/s00439-024-02702-0. This article has 3 citations and is from a peer-reviewed journal.
(cogan2024biallelicvariantsin pages 1-6): Guillaume Cogan, Maha S. Zaki, Mahmoud Issa, Boris Keren, Marine Guillaud-Bataille, Florence Renaldo, Arnaud Isapof, Pauline Lallemant, Giovanni Stevanin, Lena Guillot-Noel, Thomas Courtin, Julien Buratti, Cécile Freihuber, Joseph G. Gleeson, Robyn Howarth, Alexandra Durr, Jean-Madeleine de Sainte Agathe, and Cyril Mignot. Biallelic variants in erlin1: a series of 13 individuals with spastic paraparesis. Human genetics, 143:1353-1362, Oct 2024. URL: https://doi.org/10.1007/s00439-024-02702-0, doi:10.1007/s00439-024-02702-0. This article has 3 citations and is from a peer-reviewed journal.
(manganelli2021roleoferlins pages 7-9): Valeria Manganelli, Agostina Longo, Vincenzo Mattei, Serena Recalchi, Gloria Riitano, Daniela Caissutti, Antonella Capozzi, Maurizio Sorice, Roberta Misasi, and Tina Garofalo. Role of erlins in the control of cell fate through lipid rafts. Cells, 10:2408, Sep 2021. URL: https://doi.org/10.3390/cells10092408, doi:10.3390/cells10092408. This article has 42 citations.
(cogan2024biallelicvariantsin pages 6-9): Guillaume Cogan, Maha S. Zaki, Mahmoud Issa, Boris Keren, Marine Guillaud-Bataille, Florence Renaldo, Arnaud Isapof, Pauline Lallemant, Giovanni Stevanin, Lena Guillot-Noel, Thomas Courtin, Julien Buratti, Cécile Freihuber, Joseph G. Gleeson, Robyn Howarth, Alexandra Durr, Jean-Madeleine de Sainte Agathe, and Cyril Mignot. Biallelic variants in erlin1: a series of 13 individuals with spastic paraparesis. Human genetics, 143:1353-1362, Oct 2024. URL: https://doi.org/10.1007/s00439-024-02702-0, doi:10.1007/s00439-024-02702-0. This article has 3 citations and is from a peer-reviewed journal.
(cogan2024biallelicvariantsin pages 9-12): Guillaume Cogan, Maha S. Zaki, Mahmoud Issa, Boris Keren, Marine Guillaud-Bataille, Florence Renaldo, Arnaud Isapof, Pauline Lallemant, Giovanni Stevanin, Lena Guillot-Noel, Thomas Courtin, Julien Buratti, Cécile Freihuber, Joseph G. Gleeson, Robyn Howarth, Alexandra Durr, Jean-Madeleine de Sainte Agathe, and Cyril Mignot. Biallelic variants in erlin1: a series of 13 individuals with spastic paraparesis. Human genetics, 143:1353-1362, Oct 2024. URL: https://doi.org/10.1007/s00439-024-02702-0, doi:10.1007/s00439-024-02702-0. This article has 3 citations and is from a peer-reviewed journal.
(cogan2024biallelicvariantsin pages 18-27): Guillaume Cogan, Maha S. Zaki, Mahmoud Issa, Boris Keren, Marine Guillaud-Bataille, Florence Renaldo, Arnaud Isapof, Pauline Lallemant, Giovanni Stevanin, Lena Guillot-Noel, Thomas Courtin, Julien Buratti, Cécile Freihuber, Joseph G. Gleeson, Robyn Howarth, Alexandra Durr, Jean-Madeleine de Sainte Agathe, and Cyril Mignot. Biallelic variants in erlin1: a series of 13 individuals with spastic paraparesis. Human genetics, 143:1353-1362, Oct 2024. URL: https://doi.org/10.1007/s00439-024-02702-0, doi:10.1007/s00439-024-02702-0. This article has 3 citations and is from a peer-reviewed journal.
(whittenbauer2019thehostfactor pages 5-6): Christina Whitten-Bauer, Josan Chung, Andoni Gómez-Moreno, Pilar Gomollón-Zueco, Michael D. Huber, Larry Gerace, and Urtzi Garaigorta. The host factor erlin-1 is required for efficient hepatitis c virus infection. Cells, 8:1555, Dec 2019. URL: https://doi.org/10.3390/cells8121555, doi:10.3390/cells8121555. This article has 9 citations.
(whittenbauer2019thehostfactor pages 9-12): Christina Whitten-Bauer, Josan Chung, Andoni Gómez-Moreno, Pilar Gomollón-Zueco, Michael D. Huber, Larry Gerace, and Urtzi Garaigorta. The host factor erlin-1 is required for efficient hepatitis c virus infection. Cells, 8:1555, Dec 2019. URL: https://doi.org/10.3390/cells8121555, doi:10.3390/cells8121555. This article has 9 citations.
(whittenbauer2019thehostfactor pages 15-18): Christina Whitten-Bauer, Josan Chung, Andoni Gómez-Moreno, Pilar Gomollón-Zueco, Michael D. Huber, Larry Gerace, and Urtzi Garaigorta. The host factor erlin-1 is required for efficient hepatitis c virus infection. Cells, 8:1555, Dec 2019. URL: https://doi.org/10.3390/cells8121555, doi:10.3390/cells8121555. This article has 9 citations.
(whittenbauer2019thehostfactor pages 1-3): Christina Whitten-Bauer, Josan Chung, Andoni Gómez-Moreno, Pilar Gomollón-Zueco, Michael D. Huber, Larry Gerace, and Urtzi Garaigorta. The host factor erlin-1 is required for efficient hepatitis c virus infection. Cells, 8:1555, Dec 2019. URL: https://doi.org/10.3390/cells8121555, doi:10.3390/cells8121555. This article has 9 citations.
(huang2021transcriptomeandliterature pages 1-2): Susie S. Y. Huang, Mohammed Toufiq, Luis R. Saraiva, Nicholas Van Panhuys, Damien Chaussabel, and Mathieu Garand. Transcriptome and literature mining highlight the differential expression of erlin1 in immune cells during sepsis. Biology, 10:755, Aug 2021. URL: https://doi.org/10.3390/biology10080755, doi:10.3390/biology10080755. This article has 8 citations.
(huang2021transcriptomeandliterature pages 7-9): Susie S. Y. Huang, Mohammed Toufiq, Luis R. Saraiva, Nicholas Van Panhuys, Damien Chaussabel, and Mathieu Garand. Transcriptome and literature mining highlight the differential expression of erlin1 in immune cells during sepsis. Biology, 10:755, Aug 2021. URL: https://doi.org/10.3390/biology10080755, doi:10.3390/biology10080755. This article has 8 citations.
(huang2021transcriptomeandliterature pages 9-11): Susie S. Y. Huang, Mohammed Toufiq, Luis R. Saraiva, Nicholas Van Panhuys, Damien Chaussabel, and Mathieu Garand. Transcriptome and literature mining highlight the differential expression of erlin1 in immune cells during sepsis. Biology, 10:755, Aug 2021. URL: https://doi.org/10.3390/biology10080755, doi:10.3390/biology10080755. This article has 8 citations.
(huang2021transcriptomeandliterature pages 5-6): Susie S. Y. Huang, Mohammed Toufiq, Luis R. Saraiva, Nicholas Van Panhuys, Damien Chaussabel, and Mathieu Garand. Transcriptome and literature mining highlight the differential expression of erlin1 in immune cells during sepsis. Biology, 10:755, Aug 2021. URL: https://doi.org/10.3390/biology10080755, doi:10.3390/biology10080755. This article has 8 citations.
(huang2021transcriptomeandliterature pages 11-13): Susie S. Y. Huang, Mohammed Toufiq, Luis R. Saraiva, Nicholas Van Panhuys, Damien Chaussabel, and Mathieu Garand. Transcriptome and literature mining highlight the differential expression of erlin1 in immune cells during sepsis. Biology, 10:755, Aug 2021. URL: https://doi.org/10.3390/biology10080755, doi:10.3390/biology10080755. This article has 8 citations.
(whittenbauer2019thehostfactor pages 18-19): Christina Whitten-Bauer, Josan Chung, Andoni Gómez-Moreno, Pilar Gomollón-Zueco, Michael D. Huber, Larry Gerace, and Urtzi Garaigorta. The host factor erlin-1 is required for efficient hepatitis c virus infection. Cells, 8:1555, Dec 2019. URL: https://doi.org/10.3390/cells8121555, doi:10.3390/cells8121555. This article has 9 citations.
(whittenbauer2019thehostfactor pages 6-9): Christina Whitten-Bauer, Josan Chung, Andoni Gómez-Moreno, Pilar Gomollón-Zueco, Michael D. Huber, Larry Gerace, and Urtzi Garaigorta. The host factor erlin-1 is required for efficient hepatitis c virus infection. Cells, 8:1555, Dec 2019. URL: https://doi.org/10.3390/cells8121555, doi:10.3390/cells8121555. This article has 9 citations.
(whittenbauer2019thehostfactor pages 12-15): Christina Whitten-Bauer, Josan Chung, Andoni Gómez-Moreno, Pilar Gomollón-Zueco, Michael D. Huber, Larry Gerace, and Urtzi Garaigorta. The host factor erlin-1 is required for efficient hepatitis c virus infection. Cells, 8:1555, Dec 2019. URL: https://doi.org/10.3390/cells8121555, doi:10.3390/cells8121555. This article has 9 citations.
(huang2021transcriptomeandliterature pages 2-4): Susie S. Y. Huang, Mohammed Toufiq, Luis R. Saraiva, Nicholas Van Panhuys, Damien Chaussabel, and Mathieu Garand. Transcriptome and literature mining highlight the differential expression of erlin1 in immune cells during sepsis. Biology, 10:755, Aug 2021. URL: https://doi.org/10.3390/biology10080755, doi:10.3390/biology10080755. This article has 8 citations.

Artifacts

Edison artifact artifact-00

Citations

cogan2024biallelicvariantsin pages 12-16
cogan2024biallelicvariantsin pages 1-6
manganelli2021roleoferlins pages 7-9
manganelli2021roleoferlins pages 1-2
whittenbauer2019thehostfactor pages 1-3
huang2021transcriptomeandliterature pages 1-2
huang2021transcriptomeandliterature pages 5-6
manganelli2021roleoferlins pages 3-5
cogan2024biallelicvariantsin pages 6-9
cogan2024biallelicvariantsin pages 9-12
cogan2024biallelicvariantsin pages 18-27
whittenbauer2019thehostfactor pages 5-6
whittenbauer2019thehostfactor pages 9-12
whittenbauer2019thehostfactor pages 15-18
huang2021transcriptomeandliterature pages 7-9
huang2021transcriptomeandliterature pages 9-11
huang2021transcriptomeandliterature pages 11-13
whittenbauer2019thehostfactor pages 18-19
whittenbauer2019thehostfactor pages 6-9
whittenbauer2019thehostfactor pages 12-15
huang2021transcriptomeandliterature pages 2-4
https://doi.org/10.26508/lsa.202402620
https://doi.org/10.1007/s00439-024-02702-0
https://doi.org/10.3390/cells10092408
https://doi.org/10.3390/cells8121555
https://doi.org/10.3390/biology10080755
https://doi.org/10.3390/cells10092408;
https://doi.org/10.26508/lsa.202402620;
https://doi.org/10.1007/s00439-024-02702-0;
https://doi.org/10.1080/15548627.2020.1834207
https://doi.org/10.3390/cells10092408,
https://doi.org/10.26508/lsa.202402620,
https://doi.org/10.1007/s00439-024-02702-0,
https://doi.org/10.3390/cells8121555,
https://doi.org/10.3390/biology10080755,

📚 Additional Documentation

Notes

(ERLIN1-notes.md)

ERLIN1 (SPFH1 / ER lipid raft-associated protein 1) review notes

UniProt: O75477 (ERLN1_HUMAN), 348 aa. Synonyms SPFH1, KE04, C10orf69. HGNC:16947.
Single-pass type II ER membrane protein with an SPFH/prohibitin (band 7) domain in the ER lumen.
Belongs to the band 7/mec-2 (prohibitin/stomatin/flotillin) family. Associates with lipid-raft-like
ER membrane domains. Disease: autosomal recessive spastic paraplegia SPG62 (variant G50V).

Core biology

ERLIN1/ERLIN2 complex mediating ERAD of IP3 receptors. ERLIN1 (SPFH1) and ERLIN2 (SPFH2) form a
heteromeric ~2 MDa ring-shaped complex that binds IP3R tetramers and mediates their ERAD with the E3
ligase RNF170.
PMID:19240031
PMID:19240031
ComplexPortal CPX-7121 "ERLIN1-ERLIN2 complex". In complex with ERLIN2, interacts with RNF170.
Cholesterol binding / SREBP regulation. Erlins bind cholesterol cooperatively and restrict SREBP
activation, promoting ER retention of the SCAP-SREBP-Insig complex; they regulate cellular cholesterol
homeostasis and cholesterol/fatty-acid biosynthesis.
PMID:24217618
PMID:24217618
PMID:24217618
Sterol-accelerated HMGCR ERAD (gp78/AMFR module). ERLIN1 interacts with the gp78/AMFR and
SYVN1/HRD1 ER ubiquitin ligases; SPFH2/TMUB1 link gp78 to sterol-accelerated ERAD of HMG-CoA reductase.
PMID:21343306
Lipid-raft ER domains. Erlin-1/2 are prohibitin-family proteins that define lipid-raft-like domains
of the ER.
PMID:16835267
USP25/cholesterol/virus. USP25 deubiquitinates and stabilizes ERLIN1; Usp25-Erlin1/2 activity
limits cholesterol flux to restrict virus infection (PMID:37683630, not cached — referenced via UniProt).

Annotation assessment summary

ER membrane (GO:0005789) / ER (GO:0005783): core compartment → ACCEPT (many redundant Reactome TAS CFTR/CD274
ERAD-machinery annotations → ACCEPT as correct compartment but non-core specifics).
ERLIN1/2 complex / ERAD of IP3R (GO:0036503 ERAD pathway IDA): core → ACCEPT.
cholesterol binding (GO:0015485 IDA): core MF → ACCEPT.
SREBP signaling (GO:0032933), regulation/negative regulation of cholesterol biosynthesis (GO:0045540/45541),
negative regulation of fatty acid biosynthesis (GO:0045717): SREBP/sterol role → ACCEPT.
membrane raft (GO:0045121 NAS): lipid-raft ER domains → ACCEPT (non-core).
ubiquitin protein ligase binding (GO:0031625 IEA InterPro): consistent with AMFR/SYVN1/RNF170 E3 interactions → ACCEPT (informative).
protein-containing complex (GO:0032991): generic → KEEP_AS_NON_CORE.
protein binding (GO:0005515) IPI: uninformative → KEEP_AS_NON_CORE.
Do NOT over-claim catalytic MF: ERLIN1 is a scaffold/lipid-binding SPFH protein, not an enzyme.

Falcon deep-research findings (incorporated 2026-06)

Falcon corroborates the existing review (ERLIN1/2 ring complex, IP3R ERAD with RNF170, cholesterol
binding, SREBP restriction, lipid-raft ER domains) and adds three verifiable, mostly newer references:

ERLIN1/2 scaffolds bridge the full-length isoform of TMUB1 with the E3 ligase RNF170 (conserved
luminal N-terminal motif binding adjacent ERLIN SPFH domains), and restrict cholesterol
esterification, thereby favouring ER-to-Golgi cholesterol transport and regulating Golgi morphology
and the secretory pathway. PMID:38782601 (PubMed-verified;
doi:10.26508/lsa.202402620; Veronese et al. 2024). NEW mechanism (TMUB1-L/RNF170 bridging +
cholesterol esterification/SOAT1 + secretory pathway) beyond the prior single-client IP3R-ERAD
model. Added as a top-level reference (relevance HIGH). Loss of ERLINs abolished the TMUB1-RNF170
interaction; reported SOAT1 tendency to increase in DKO (log2FC 0.40, q=0.07), ER tubule collapse,
Golgi fragmentation, lipid-droplet accumulation, avasimibe (SOAT1 inhibitor) rescue.
Largest SPG62 case series to date: 13 individuals from six families with biallelic ERLIN1 variants,
childhood-onset slowly progressive predominantly pure spastic paraparesis (possible cerebellar /
peripheral-nerve involvement); three new variants predicted to disrupt the bell-shaped ERLIN1/ERLIN2
ring. PMID:39367212 (PubMed-verified;
doi:10.1007/s00439-024-02702-0; Cogan et al. 2024). Expands disease genetics beyond the G50V variant
noted in the prior review. Added as a top-level reference (relevance HIGH).
ERLIN1 is a host factor required for efficient hepatitis C virus infection; it is a cholesterol-
binding ER detergent-resistant-membrane protein, and its knockdown reduces HCV RNA replication
initiation, viral protein expression, and infectious virus production downstream of entry/primary
translation. PMID:31810281 (PubMed-verified; doi:10.3390/cells8121555; Whitten-Bauer
et al. 2019). Corroborates the cholesterol-homeostasis/ER-raft role already in the review (which
also has the USP25-Erlin1/2 antiviral angle via PMID:37683630). Added as a top-level reference
(relevance MEDIUM).
Manganelli 2021 (PMID:34572057, already a review reference) plus its companion paper
(doi:10.1080/15548627.2020.1834207) describe ERLIN1 at MAM raft-like microdomains interacting with
AMBRA1 to support starvation-induced autophagy initiation. Not added as a new annotation/reference;
noted here as additional context for a potential MAM/autophagy role.
Note: none of the three new references were cached in publications/, so no paraphrased
supporting_text was added to existing annotations (reference validator requires verbatim cached
substrings). They were added as top-level references with reference_review only.

Pn Notes

(ERLIN1-pn-notes.md)

ERLIN1 PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: O75477
AIGR review status: COMPLETE
Review batch: proteostasis-batch-2026-06-11
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/ERLIN1/ERLIN1-ai-review.yaml
AIGR review HTML: missing - genes/human/ERLIN1/ERLIN1-ai-review.html
Gene notes: present - genes/human/ERLIN1/ERLIN1-notes.md
GOA TSV: present - genes/human/ERLIN1/ERLIN1-goa.tsv
UniProt record: present - genes/human/ERLIN1/ERLIN1-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/ERLIN1.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/ERLIN1.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

genes/human/ERLIN1/ERLIN1-deep-research-falcon.md

AIGR Review Snapshot

Description: ERLIN1 (SPFH1, ER lipid raft-associated protein 1) is a single-pass type II endoplasmic reticulum (ER) membrane protein with a lumenal SPFH/prohibitin (band 7) domain, belonging to the band 7/mec-2 (stomatin-prohibitin-flotillin) family. It associates with lipid-raft-like domains of the ER membrane and functions as a scaffold rather than an enzyme. ERLIN1 forms a large ring-shaped heteromeric complex with its homolog ERLIN2 (SPFH2); the ERLIN1/ERLIN2 complex binds inositol 1,4,5-trisphosphate receptor (IP3R) tetramers and, together with the ER ubiquitin ligase RNF170, mediates the ER-associated degradation (ERAD) of activated IP3Rs, thereby controlling calcium signaling. The erlins are cholesterol-binding proteins that restrict SREBP activation: they associate with the SCAP-SREBP-Insig machinery to promote its ER retention and thus negatively regulate cholesterol and fatty acid biosynthesis, contributing to cellular cholesterol homeostasis. ERLIN1 also interacts with the ER ubiquitin ligases AMFR/gp78 and SYVN1/HRD1, linking it to sterol-accelerated ERAD. Loss-of-function variants in ERLIN1 cause autosomal recessive hereditary spastic paraplegia (SPG62).
Existing/core annotation action counts: ACCEPT: 28; KEEP_AS_NON_CORE: 11

PN Consistency Summary

Consistency: Strong. Deep research (Veronese 2024 scaffold/TMUB1-RNF170; Cogan 2024 SPG62; Manganelli 2021 rafts/MAM) ↔ review YAML (ERAD of IP3R, cholesterol binding, SREBP restriction, ER-membrane raft, E3-ligase binding) ↔ PN annotation (BAND 7 noncatalytic ERLIN/RNF170 complex; ERAD) all agree. No contradictions. ERLIN dossier identical to ERLIN2 (shared complex).
PN story / NEW pressure: PN asserts ERAD + non-catalytic E3-complex membership. Both already captured: GO:0036503 (IDA PMID:19240031, multiple ECs) and GO:0031625 ubiquitin protein ligase binding (IEA) are present. The 2024 scaffold/cholesterol-esterification/secretory-pathway role (Veronese, PMID:38782601) is NOT in GOA but is cited in references. No new term is forced; the most defensible additions would be MF GO:0160072 "ubiquitin ligase complex scaffold activity" (verified real) capturing the non-catalytic adaptor role. Verdict: largely already captured; scaffold-activity term is an optional ADD.
Evidence alignment: PN cites only opaque workbook IDs (1610068, 41481136 — not PMIDs of the key ERLIN papers). Review/notes anchor to PMID:19240031, 24217618, 21343306, 38782601 + ComplexPortal CPX-7121. Divergence is presentational, not substantive.
Verdict: Consistent and high-quality; PN story already captured by GOA/review. GO:0000151 projection mildly over-reaches (non-catalytic scaffold); prefer GO:0000835 / GO:0160072.

Full Consistency Review

UniProt: O75477 (ERLN1_HUMAN, SPFH1) · batch: proteostasis-batch-2026-06-11 · review status: COMPLETE (all annotations actioned; no PENDING).
PN placement: ER proteostasis|Organelle-specific protein degradation|ER associated degradation|ER handling of ERAD substrates and Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|idiosyncratic RING complex|RNF170 / ERLIN complex|noncatalytic / BAND 7 ; PN-node mapping: [group ERAD] mapped/exact GO:0036503; [type ER-handling] mapped/ok_for_propagation GO:0036503; [group idiosyncratic RING complex] mapped/ok_for_propagation GO:0000151 ubiquitin ligase complex; subtype/type/branch no_mapping; UPS class context_only/too_broad GO:0061630.
Consistency: Strong. Deep research (Veronese 2024 scaffold/TMUB1-RNF170; Cogan 2024 SPG62; Manganelli 2021 rafts/MAM) ↔ review YAML (ERAD of IP3R, cholesterol binding, SREBP restriction, ER-membrane raft, E3-ligase binding) ↔ PN annotation (BAND 7 noncatalytic ERLIN/RNF170 complex; ERAD) all agree. No contradictions. ERLIN dossier identical to ERLIN2 (shared complex).
PN story / NEW pressure: PN asserts ERAD + non-catalytic E3-complex membership. Both already captured: GO:0036503 (IDA PMID:19240031, multiple ECs) and GO:0031625 ubiquitin protein ligase binding (IEA) are present. The 2024 scaffold/cholesterol-esterification/secretory-pathway role (Veronese, PMID:38782601) is NOT in GOA but is cited in references. No new term is forced; the most defensible additions would be MF GO:0160072 "ubiquitin ligase complex scaffold activity" (verified real) capturing the non-catalytic adaptor role. Verdict: largely already captured; scaffold-activity term is an optional ADD.
Mapping strategy: ERAD mapping (GO:0036503) is correct and already-in-GOA-exact. The GO:0000151 projection over-reaches slightly: the ERLIN1/2 complex (CPX-7121) is a non-catalytic BAND 7 scaffold, whereas GO:0000151 is a catalytic ubiquitin-ligase complex. GO:0000835 "ER ubiquitin ligase complex" (verified real) is the more accurate, still-broader-than-GOA target if a complex CC is projected.
Evidence alignment: PN cites only opaque workbook IDs (1610068, 41481136 — not PMIDs of the key ERLIN papers). Review/notes anchor to PMID:19240031, 24217618, 21343306, 38782601 + ComplexPortal CPX-7121. Divergence is presentational, not substantive.
Verdict: Consistent and high-quality; PN story already captured by GOA/review. GO:0000151 projection mildly over-reaches (non-catalytic scaffold); prefer GO:0000835 / GO:0160072.

Recommended edits: [MAP] Replace/qualify the GO:0000151 group projection with GO:0000835 "ER ubiquitin ligase complex" (CC) for the ERLIN/RNF170 assembly, noting ERLINs are non-catalytic BAND 7 subunits. [YAML, optional] Consider adding MF GO:0160072 "ubiquitin ligase complex scaffold activity" to core_functions for the adaptor role.

PN Dossier Context

review_batch: proteostasis-batch-2026-06-11
review_yaml: genes/human/ERLIN1/ERLIN1-ai-review.yaml
PN workbook rows: 2

PN row 1: ER proteostasis | Organelle-specific protein degradation | ER associated degradation | ER handling of ERAD substrates

UniProt: O75477
In branches: ER, UPS
PN-node mapping records (path + ancestors):
- [type] ER proteostasis|Organelle-specific protein degradation|ER associated degradation|ER handling of ERAD substrates
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0036503 ERAD pathway]
  rationale: This PN type captures ER-lumenal and membrane-local ERAD handling steps prior to retrotranslocation. These steps are mechanistic parts of the broader ERAD pathway, so propagation to ERAD pathway is appropriate.
- [group] ER proteostasis|Organelle-specific protein degradation|ER associated degradation
  status=mapped scope=exact GO=[GO:0036503 ERAD pathway]
  rationale: The PN group "ER associated degradation" is a direct lexical and biological match to the GO ERAD pathway term. The additional branch and class context disambiguates the source string from any broader degradation language.
- [class] ER proteostasis|Organelle-specific protein degradation
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN category rather than a single GO class. The member genes span multiple activities, complexes, or contexts, so direct propagation from this node would overstate the shared biology.
- [branch] ER proteostasis
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a top-level PN branch. This is a systems/taxonomy umbrella, not a direct GO assertion; narrower child curations carry any propagating GO mappings.

PN row 2: Ubiquitin Proteasome System | E3 ubiquitin and UBL ligases | idiosyncratic RING complex | RNF170 / ERLIN complex | noncatalytic / BAND 7

UniProt: O75477
In branches: ER, UPS
Signature domains: (none)
Auxiliary domains: IPR001107
PN references (titles):
- 1610068
- 41481136
PN-node mapping records (path + ancestors):
- [subtype] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|idiosyncratic RING complex|RNF170 / ERLIN complex|noncatalytic / BAND 7
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a narrower E3-ligase architecture, component, or domain subdivision already covered by the curated parent E3 mapping. No additional direct GO mapping is needed at this node.
- [type] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|idiosyncratic RING complex|RNF170 / ERLIN complex
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a narrower E3-ligase architecture, component, or domain subdivision already covered by the curated parent E3 mapping. No additional direct GO mapping is needed at this node.
- [group] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|idiosyncratic RING complex
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0000151 ubiquitin ligase complex]
  rationale: This PN group is an E3 ligase complex bucket. The safest shared GO target is ubiquitin ligase complex membership rather than assigning catalytic activity to every subunit.
- [class] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases
  status=context_only scope=too_broad_to_propagate GO=[GO:0061630 ubiquitin protein ligase activity]
  rationale: This class is a genuine E3-ligase context, but its descendants include catalytic ligases, cullin scaffolds, substrate receptors, adaptors, cofactors, regulators, and UBL modifier systems. A class-level propagation would over-annotate.
- [branch] Ubiquitin Proteasome System
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level UPS branch. It is a project taxonomy umbrella rather than a direct GO assertion; UPS propagation must come from manually curated child nodes.

Projected GO annotations (3)

GO:0036503 ERAD pathway | scope=exact | goa_status=already_in_goa_exact | from=ER proteostasis|Organelle-specific protein degradation|ER associated degradation
GO:0036503 ERAD pathway | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=ER proteostasis|Organelle-specific protein degradation|ER associated degradation|ER handling of ERAD substrates
GO:0000151 ubiquitin ligase complex | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|idiosyncratic RING complex

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

id: O75477
gene_symbol: ERLIN1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  ERLIN1 (SPFH1, ER lipid raft-associated protein 1) is a single-pass type II
  endoplasmic reticulum (ER) membrane protein with a lumenal SPFH/prohibitin
  (band 7) domain, belonging to the band 7/mec-2 (stomatin-prohibitin-flotillin)
  family. It associates with lipid-raft-like domains of the ER membrane and
  functions as a scaffold rather than an enzyme. ERLIN1 forms a large
  ring-shaped heteromeric complex with its homolog ERLIN2 (SPFH2); the
  ERLIN1/ERLIN2 complex binds inositol 1,4,5-trisphosphate receptor (IP3R)
  tetramers and, together with the ER ubiquitin ligase RNF170, mediates the
  ER-associated degradation (ERAD) of activated IP3Rs, thereby controlling
  calcium signaling. The erlins are cholesterol-binding proteins that restrict
  SREBP activation: they associate with the SCAP-SREBP-Insig machinery to
  promote its ER retention and thus negatively regulate cholesterol and fatty
  acid biosynthesis, contributing to cellular cholesterol homeostasis. ERLIN1
  also interacts with the ER ubiquitin ligases AMFR/gp78 and SYVN1/HRD1, linking
  it to sterol-accelerated ERAD. Loss-of-function variants in ERLIN1 cause
  autosomal recessive hereditary spastic paraplegia (SPG62).
existing_annotations:
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic inference that ERLIN1 acts at the ER membrane, consistent with strong experimental evidence that it is an ER membrane SPFH protein.
    action: ACCEPT
    reason: Core compartment and site of action; ERLIN1 is an integral ER membrane protein.
    supported_by:
    - reference_id: file:human/ERLIN1/ERLIN1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0015485
    label: cholesterol binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic inference of cholesterol binding, consistent with direct experimental evidence that erlins bind cholesterol cooperatively.
    action: ACCEPT
    reason: Core molecular function; redundant with the experimental IDA cholesterol-binding annotation.
    supported_by:
    - reference_id: PMID:24217618
      supporting_text: Erlins bound cholesterol with specificity and strong cooperativity
- term:
    id: GO:0032933
    label: SREBP signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic inference of involvement in SREBP signaling, consistent with experimental evidence that erlins restrict SREBP activation.
    action: ACCEPT
    reason: Core biological process; redundant with experimental IMP evidence.
    supported_by:
    - reference_id: PMID:24217618
      supporting_text: directly involved in regulating the SREBP machinery
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: located_in
  review:
    summary: InterPro-based electronic ER localization, consistent with experimental evidence; the more specific ER membrane term is preferred.
    action: ACCEPT
    reason: Correct compartment; redundant with the ER membrane annotations.
    supported_by:
    - reference_id: file:human/ERLIN1/ERLIN1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Electronic assignment of ER membrane localization from the UniProt subcellular location.
    action: ACCEPT
    reason: Core compartment; redundant with experimental IDA evidence.
    supported_by:
    - reference_id: file:human/ERLIN1/ERLIN1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0031625
    label: ubiquitin protein ligase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro-based assignment of ubiquitin protein ligase binding, consistent with experimental interactions of ERLIN1 with the ER ubiquitin ligases AMFR/gp78, SYVN1/HRD1 and (in complex with ERLIN2) RNF170.
    action: ACCEPT
    reason: Informative molecular function; ERLIN1 recruits E3 ubiquitin ligases to the ERAD complex.
    supported_by:
    - reference_id: file:human/ERLIN1/ERLIN1-uniprot.txt
      supporting_text: Interacts with AMFR and SYVN1
- term:
    id: GO:0032933
    label: SREBP signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: ARBA machine-learning assignment of SREBP signaling involvement, consistent with experimental evidence.
    action: ACCEPT
    reason: Correct biological process; redundant with IMP/IBA evidence.
    supported_by:
    - reference_id: PMID:24217618
      supporting_text: directly involved in regulating the SREBP machinery
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: part_of
  review:
    summary: Generic protein-containing complex assignment; ERLIN1 forms the specific ERLIN1/ERLIN2 complex.
    action: KEEP_AS_NON_CORE
    reason: Correct but uninformative; the specific ERLIN1/ERLIN2 complex membership is captured elsewhere.
    supported_by:
    - reference_id: PMID:19240031
      supporting_text: SPFH1 and its homolog SPFH2 form a heteromeric approximately 2 MDa complex
- term:
    id: GO:0036503
    label: ERAD pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: ARBA machine-learning assignment of ERAD involvement, consistent with the experimentally demonstrated role in ERAD of IP3 receptors.
    action: ACCEPT
    reason: Core biological process; redundant with experimental IDA evidence.
    supported_by:
    - reference_id: PMID:19240031
      supporting_text: mediates the ER-associated degradation of inositol 1,4,5-trisphosphate
- term:
    id: GO:0045541
    label: negative regulation of cholesterol biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: ARBA assignment of negative regulation of cholesterol biosynthesis, consistent with the erlins' restriction of SREBP activation.
    action: ACCEPT
    reason: Correct biological process; redundant with experimental IMP evidence.
    supported_by:
    - reference_id: PMID:24217618
      supporting_text: led to canonical activation of SREBPs and their target genes
- term:
    id: GO:0045717
    label: negative regulation of fatty acid biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: ARBA assignment of negative regulation of fatty acid biosynthesis, consistent with the erlins restricting SREBP (which activates fatty-acid biosynthetic genes).
    action: ACCEPT
    reason: Correct biological process; redundant with experimental IMP evidence.
    supported_by:
    - reference_id: PMID:24217618
      supporting_text: key transcription factors for cholesterol and fatty acid biosynthetic
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21343306
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Real E3-ligase interactions but uninformative GO term.
    supported_by:
    - reference_id: file:human/ERLIN1/ERLIN1-uniprot.txt
      supporting_text: Interacts with AMFR and SYVN1
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22119785
  qualifier: enables
  review:
    summary: ERAD-network interactome capture (including ERLIN2, SYVN1, AMFR). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real ERAD-network interactions but uninformative GO term.
    supported_by:
    - reference_id: file:human/ERLIN1/ERLIN1-uniprot.txt
      supporting_text: 'O75477; O94905: ERLIN2'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: Proteome-scale interactome capture. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real interactions from a large-scale interactome but uninformative GO term.
    supported_by:
    - reference_id: file:human/ERLIN1/ERLIN1-uniprot.txt
      supporting_text: 'O75477; Q96IW7: SEC22A'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: High-throughput interactome capture (C6orf120). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real interaction but uninformative GO term.
    supported_by:
    - reference_id: file:human/ERLIN1/ERLIN1-uniprot.txt
      supporting_text: 'O75477; Q7Z4R8: C6orf120'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30021884
  qualifier: enables
  review:
    summary: Crosslinking mass-spectrometry capture of an ERLIN1-ERLIN2 interaction. Bare protein binding is uninformative; the ERLIN1/ERLIN2 complex is captured by complex annotations.
    action: KEEP_AS_NON_CORE
    reason: Real ERLIN2 interaction but uninformative GO term.
    supported_by:
    - reference_id: file:human/ERLIN1/ERLIN1-uniprot.txt
      supporting_text: 'O75477; O94905: ERLIN2'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Binary-interactome (HuRI) captures of ERLIN1 interactions. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real binary interactions but uninformative GO term.
    supported_by:
    - reference_id: file:human/ERLIN1/ERLIN1-uniprot.txt
      supporting_text: 'O75477; Q15436: SEC23A'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Dual proteome-scale network capture (ERLIN2, C6orf120). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real interactions but uninformative GO term.
    supported_by:
    - reference_id: file:human/ERLIN1/ERLIN1-uniprot.txt
      supporting_text: 'O75477; O94905: ERLIN2'
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Direct immunofluorescence (HPA) evidence for ER localization.
    action: ACCEPT
    reason: Core compartment; directly demonstrated.
    supported_by:
    - reference_id: file:human/ERLIN1/ERLIN1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8866542
  qualifier: located_in
  review:
    summary: Reactome curation placing ERLIN1 at the ER membrane within the CFTR ERAD machinery pathway.
    action: ACCEPT
    reason: Correct compartment; redundant with experimental ER membrane annotations.
    supported_by:
    - reference_id: file:human/ERLIN1/ERLIN1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8866546
  qualifier: located_in
  review:
    summary: Reactome curation of ERLIN1 ER membrane localization (CFTR ERAD pathway).
    action: ACCEPT
    reason: Correct compartment; redundant with experimental evidence.
    supported_by:
    - reference_id: file:human/ERLIN1/ERLIN1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8866551
  qualifier: located_in
  review:
    summary: Reactome curation of ERLIN1 ER membrane localization (CFTR ERAD pathway).
    action: ACCEPT
    reason: Correct compartment; redundant with experimental evidence.
    supported_by:
    - reference_id: file:human/ERLIN1/ERLIN1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8866854
  qualifier: located_in
  review:
    summary: Reactome curation of ERLIN1 ER membrane localization (CFTR F508del ERAD pathway).
    action: ACCEPT
    reason: Correct compartment; redundant with experimental evidence.
    supported_by:
    - reference_id: file:human/ERLIN1/ERLIN1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8866856
  qualifier: located_in
  review:
    summary: Reactome curation of ERLIN1 ER membrane localization (CFTR F508del ERAD pathway).
    action: ACCEPT
    reason: Correct compartment; redundant with experimental evidence.
    supported_by:
    - reference_id: file:human/ERLIN1/ERLIN1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8866857
  qualifier: located_in
  review:
    summary: Reactome curation of ERLIN1 ER membrane localization (CFTR F508del ERAD pathway).
    action: ACCEPT
    reason: Correct compartment; redundant with experimental evidence.
    supported_by:
    - reference_id: file:human/ERLIN1/ERLIN1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9931264
  qualifier: located_in
  review:
    summary: Reactome curation of ERLIN1 ER membrane localization (CD274/PD-L1 ERAD pathway).
    action: ACCEPT
    reason: Correct compartment; redundant with experimental evidence.
    supported_by:
    - reference_id: file:human/ERLIN1/ERLIN1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9931298
  qualifier: located_in
  review:
    summary: Reactome curation of ERLIN1 ER membrane localization (CD274/PD-L1 ERAD pathway).
    action: ACCEPT
    reason: Correct compartment; redundant with experimental evidence.
    supported_by:
    - reference_id: file:human/ERLIN1/ERLIN1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9931313
  qualifier: located_in
  review:
    summary: Reactome curation of ERLIN1 ER membrane localization (CD274/PD-L1 ERAD pathway).
    action: ACCEPT
    reason: Correct compartment; redundant with experimental evidence.
    supported_by:
    - reference_id: file:human/ERLIN1/ERLIN1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IDA
  original_reference_id: PMID:19240031
  qualifier: located_in
  review:
    summary: Direct evidence that ERLIN1/SPFH1 is an ER membrane protein, the site of the ERLIN1/ERLIN2 ERAD complex.
    action: ACCEPT
    reason: Core compartment; directly demonstrated.
    supported_by:
    - reference_id: PMID:19240031
      supporting_text: the ER membrane protein SPFH1 and its homolog SPFH2 form a heteromeric
- term:
    id: GO:0036503
    label: ERAD pathway
  evidence_type: IDA
  original_reference_id: PMID:19240031
  qualifier: involved_in
  review:
    summary: The ERLIN1/ERLIN2 complex binds IP3R tetramers and mediates their ER-associated degradation; depletion of ERLIN1/ERLIN2 blocks IP3R degradation.
    action: ACCEPT
    reason: Core biological process with direct (IDA) support; the defining function of the ERLIN complex.
    supported_by:
    - reference_id: PMID:19240031
      supporting_text: mediates the ER-associated degradation of inositol 1,4,5-trisphosphate
- term:
    id: GO:0045121
    label: membrane raft
  evidence_type: NAS
  original_reference_id: PMID:34572057
  qualifier: located_in
  review:
    summary: Erlins associate with lipid-raft-like domains of the ER membrane; the NAS membrane-raft localization reflects this SPFH-domain raft association.
    action: KEEP_AS_NON_CORE
    reason: Supported by the lipid-raft characterization of erlins but secondary to the core ER-membrane ERAD/SREBP roles.
    supported_by:
    - reference_id: PMID:16835267
      supporting_text: define lipid-raft-like domains of the ER
- term:
    id: GO:0045540
    label: regulation of cholesterol biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:24217618
  qualifier: involved_in
  review:
    summary: ERLIN1 regulates cholesterol biosynthesis via the SREBP/SCAP/Insig machinery; the erlins restrict SREBP activation in response to ER cholesterol.
    action: ACCEPT
    reason: Core biological process; directly supported.
    supported_by:
    - reference_id: PMID:24217618
      supporting_text: regulate cellular cholesterol
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IDA
  original_reference_id: PMID:18468998
  qualifier: part_of
  review:
    summary: IDA placing ERLIN1 in a protein-containing complex (alpha1D-adrenergic receptor/dystrophin signalosome study). The generic complex term is uninformative; ERLIN1's defining complex is the ERLIN1/ERLIN2 complex.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported but uninformative generic complex term; not the core ERLIN1/ERLIN2 complex.
    supported_by:
    - reference_id: PMID:19240031
      supporting_text: SPFH1 and its homolog SPFH2 form a heteromeric approximately 2 MDa complex
- term:
    id: GO:0015485
    label: cholesterol binding
  evidence_type: IDA
  original_reference_id: PMID:24217618
  qualifier: enables
  review:
    summary: Erlins bind cholesterol with specificity and strong cooperativity, a core molecular function underlying their sterol-sensing regulation of SREBP.
    action: ACCEPT
    reason: Core molecular function with direct (IDA) support.
    supported_by:
    - reference_id: PMID:24217618
      supporting_text: Erlins bound cholesterol with specificity and strong cooperativity
- term:
    id: GO:0032933
    label: SREBP signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:24217618
  qualifier: involved_in
  review:
    summary: Depletion of erlins led to canonical activation of SREBPs and their target genes, demonstrating that ERLIN1 restricts SREBP signaling.
    action: ACCEPT
    reason: Core biological process with direct mutant/depletion (IMP) support.
    supported_by:
    - reference_id: PMID:24217618
      supporting_text: led to canonical activation of SREBPs and their target genes
- term:
    id: GO:0045541
    label: negative regulation of cholesterol biosynthetic process
  evidence_type: IMP
  original_reference_id: PMID:24217618
  qualifier: involved_in
  review:
    summary: By restricting SREBP activation, ERLIN1 negatively regulates cholesterol biosynthesis; erlin depletion derepresses SREBP target genes.
    action: ACCEPT
    reason: Core biological process with direct (IMP) support.
    supported_by:
    - reference_id: PMID:24217618
      supporting_text: led to canonical activation of SREBPs and their target genes
- term:
    id: GO:0045717
    label: negative regulation of fatty acid biosynthetic process
  evidence_type: IMP
  original_reference_id: PMID:24217618
  qualifier: involved_in
  review:
    summary: ERLIN1 negatively regulates fatty acid biosynthesis through restriction of SREBP, which activates both cholesterol and fatty-acid biosynthetic genes.
    action: ACCEPT
    reason: Directly supported (IMP); a consequence of the erlins' SREBP restriction.
    supported_by:
    - reference_id: PMID:24217618
      supporting_text: key transcription factors for cholesterol and fatty acid biosynthetic
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19240031
  qualifier: enables
  review:
    summary: IPI capture of the ERLIN1-ERLIN2 (SPFH1-SPFH2) interaction. Bare protein binding is uninformative; the ERLIN1/ERLIN2 complex is captured by the ERAD/complex annotations.
    action: KEEP_AS_NON_CORE
    reason: Real ERLIN2 interaction but uninformative GO term.
    supported_by:
    - reference_id: PMID:19240031
      supporting_text: SPFH1 and its homolog SPFH2 form a heteromeric approximately 2 MDa complex
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IDA
  original_reference_id: PMID:16835267
  qualifier: located_in
  review:
    summary: Direct evidence that erlin-1 localizes to lipid-raft-like domains of the ER membrane.
    action: ACCEPT
    reason: Core compartment; directly demonstrated.
    supported_by:
    - reference_id: PMID:16835267
      supporting_text: define lipid-raft-like domains of the ER
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:16835267
  title: Erlin-1 and erlin-2 are novel members of the prohibitin family of proteins
    that define lipid-raft-like domains of the ER.
  findings:
  - statement: Erlin-1 and erlin-2 are prohibitin-family ER membrane proteins that define lipid-raft-like domains of the ER.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes ERLIN1/2 as prohibitin-family ER lipid-raft proteins; source of ER membrane and membrane-raft localization.
- id: PMID:18468998
  title: Blood pressure is regulated by an alpha1D-adrenergic receptor/dystrophin
    signalosome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: alpha1D-AR/dystrophin signalosome study; source of a generic protein-containing-complex IDA annotation, peripheral to ERLIN1's core function.
- id: PMID:19240031
  title: An endoplasmic reticulum (ER) membrane complex composed of SPFH1 and SPFH2
    mediates the ER-associated degradation of inositol 1,4,5-trisphosphate receptors.
  findings:
  - statement: SPFH1 (ERLIN1) and SPFH2 (ERLIN2) form a ring-shaped ~2 MDa heteromeric ER membrane complex that binds IP3R tetramers and mediates their ER-associated degradation; depletion blocks IP3R degradation.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Definitive study establishing the ERLIN1/ERLIN2 complex and its role in ERAD of IP3 receptors.
- id: PMID:21343306
  title: Membrane-associated ubiquitin ligase complex containing gp78 mediates sterol-accelerated
    degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.
  findings:
  - statement: SPFH2 (ERLIN2) and TMUB1 associate with the ER ubiquitin ligase gp78/AMFR in sterol-accelerated ERAD of HMG-CoA reductase; ERLIN1 interacts with AMFR and SYVN1.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Source of the ERLIN1-AMFR/SYVN1 IPI interactions; the abstract names SPFH2/TMUB1 but UniProt records ERLIN1 interaction with AMFR and SYVN1.
- id: PMID:22119785
  title: Defining human ERAD networks through an integrative mapping strategy.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: ERAD interactome mapping; source of ERLIN1 IPI interactions (ERLIN2, SYVN1, AMFR).
- id: PMID:24217618
  title: Erlins restrict SREBP activation in the ER and regulate cellular cholesterol
    homeostasis.
  findings:
  - statement: Erlins are cholesterol-binding proteins that restrict SREBP activation by stabilizing the SREBP-Scap-Insig complex and promoting its ER retention; erlin depletion activates SREBP target genes.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes the cholesterol-binding and SREBP-restricting functions of erlins.
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Large-scale interactome; source of ERLIN1 IPI annotations.
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease
    networks.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interactome; source of an ERLIN1 IPI annotation.
- id: PMID:30021884
  title: Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry
    in Intact Cell Nuclei.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Crosslinking MS study; source of an ERLIN1-ERLIN2 IPI annotation.
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Binary interactome (HuRI); source of ERLIN1 IPI annotations.
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Proteome-scale interactome; source of ERLIN1 IPI annotations.
- id: PMID:34572057
  title: Role of ERLINs in the Control of Cell Fate through Lipid Rafts.
  findings:
  - statement: Review of ERLIN1/2 as ER lipid-raft-associated proteins controlling cell fate.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Review used by ComplexPortal for the membrane-raft NAS annotation.
- id: PMID:37683630
  title: Usp25-Erlin1/2 activity limits cholesterol flux to restrict virus infection.
  findings:
  - statement: USP25 deubiquitinates and stabilizes ERLIN1; Usp25-Erlin1/2 activity limits cholesterol flux to restrict virus infection.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: UNVERIFIED
    review_notes: Not in publication cache; cited in UniProt for ERLIN1 stabilization by USP25 and cholesterol/SREBP regulation.
- id: PMID:38782601
  title: ERLIN1/2 scaffolds bridge TMUB1 and RNF170 and restrict cholesterol esterification
    to regulate the secretory pathway.
  findings:
  - statement: ERLIN1/ERLIN2 form large ring-like cup-shaped ER scaffolds that mediate the interaction between the full-length isoform of TMUB1 and the E3 ligase RNF170 (binding their conserved luminal N-terminal motif via the SPFH domains of adjacent ERLIN subunits); these scaffolds limit cholesterol esterification, favouring ER-to-Golgi cholesterol transport and regulating Golgi morphology and the secretory pathway. Variants that preclude these interactions have been linked to hereditary spastic paraplegia.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified (PMID:38782601, doi:10.26508/lsa.202402620; Veronese
      et al. 2024, Life Sci Alliance). Mechanistic study extending ERLIN1/2 scaffold
      function to TMUB1-L/RNF170 bridging, restriction of cholesterol esterification
      (SOAT1), ER-to-Golgi cholesterol transport, and secretory-pathway/Golgi morphology
      regulation. Connects SPG62 disease variants to disruption of these interfaces.
      Not in publication cache; supporting_text not added to annotations to satisfy
      verbatim-substring validation.
- id: PMID:39367212
  title: 'Biallelic variants in ERLIN1: a series of 13 individuals with spastic paraparesis.'
  findings:
  - statement: Largest series to date of biallelic ERLIN1 variants (13 individuals from six families) causing SPG62 spastic paraparesis; childhood-onset, slowly progressive, predominantly pure paraparesis with possible cerebellar and peripheral-nerve involvement. Three new variants are predicted to alter the bell-shaped ring formed by the ERLIN1/ERLIN2 complex.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified (PMID:39367212, doi:10.1007/s00439-024-02702-0;
      Cogan et al. 2024, Hum Genet). Expands the SPG62 disease genetics beyond the
      single G50V variant previously noted; variants interpreted as disrupting ERLIN1/ERLIN2
      ring assembly. Not in publication cache.
- id: PMID:31810281
  title: The Host Factor Erlin-1 is Required for Efficient Hepatitis C Virus Infection.
  findings:
  - statement: ERLIN1 is a cholesterol-binding, ER detergent-resistant-membrane protein required for efficient hepatitis C virus infection; its silencing reduces HCV RNA replication initiation, viral protein expression, and infectious virus production, acting downstream of entry and primary translation.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-verified (PMID:31810281, doi:10.3390/cells8121555; Whitten-Bauer
      et al. 2019, Cells). ERLIN1 as an HCV host factor; corroborates its cholesterol-homeostasis/ER
      detergent-resistant-membrane role. Peripheral to core ERAD/SREBP functions.
      Not in publication cache.
- id: Reactome:R-HSA-8866542
  title: VCP-catalyzed ATP hydrolysis promotes the translocation of misfolded CFTR
    into the cytosol
  findings: []
- id: Reactome:R-HSA-8866546
  title: RNF5 and RNF185 ubiquitinate misfolded CFTR
  findings: []
- id: Reactome:R-HSA-8866551
  title: CFTR binds components of the ERAD machinery for ubiquitination and degradation
  findings: []
- id: Reactome:R-HSA-8866854
  title: VCP-catalyzed ATP hydrolysis promotes the translocation of CFTR F508del into
    the cytosol
  findings: []
- id: Reactome:R-HSA-8866856
  title: RNF5 and RNF185 ubiquitinate CFTR F508del
  findings: []
- id: Reactome:R-HSA-8866857
  title: CFTR F508del binds components of the ERAD machinery for ubiquitination and
    degradation
  findings: []
- id: Reactome:R-HSA-9931264
  title: Active transport of ubiquitinated CD274 from ER to cytosol
  findings: []
- id: Reactome:R-HSA-9931298
  title: Ubiquitination of CD274 by ERAD complex
  findings: []
- id: Reactome:R-HSA-9931313
  title: p-S195-CD274 binds ERAD complex
  findings: []
- id: file:human/ERLIN1/ERLIN1-uniprot.txt
  title: UniProt entry O75477 (ERLN1_HUMAN), Erlin-1 / SPFH1
  findings:
  - statement: ERLIN1 is a single-pass type II ER membrane SPFH/prohibitin protein that forms the ERLIN1/ERLIN2 complex mediating ERAD of IP3 receptors, binds cholesterol, restricts SREBP activation, and interacts with the ER ubiquitin ligases AMFR/gp78, SYVN1 and (with ERLIN2) RNF170; variants cause SPG62.
    reference_section_type: OTHER
core_functions:
- description: Scaffold subunit of the ring-shaped ERLIN1/ERLIN2 SPFH-domain complex that binds inositol 1,4,5-trisphosphate receptor (IP3R) tetramers and, with the E3 ligase RNF170, mediates their ER-associated degradation, controlling calcium signaling.
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  directly_involved_in:
  - id: GO:0036503
    label: ERAD pathway
  supported_by:
  - reference_id: PMID:19240031
    supporting_text: mediates the ER-associated degradation of inositol 1,4,5-trisphosphate
  - reference_id: PMID:19240031
    supporting_text: SPFH1 and its homolog SPFH2 form a heteromeric approximately 2 MDa complex
- description: Cholesterol-binding ER membrane protein that restricts SREBP activation by associating with and stabilizing the SREBP-SCAP-Insig complex, thereby negatively regulating cholesterol and fatty acid biosynthesis and contributing to cellular cholesterol homeostasis.
  molecular_function:
    id: GO:0015485
    label: cholesterol binding
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  directly_involved_in:
  - id: GO:0032933
    label: SREBP signaling pathway
  - id: GO:0045541
    label: negative regulation of cholesterol biosynthetic process
  supported_by:
  - reference_id: PMID:24217618
    supporting_text: Erlins bound cholesterol with specificity and strong cooperativity
  - reference_id: PMID:24217618
    supporting_text: directly involved in regulating the SREBP machinery
proposed_new_terms: []
suggested_questions:
- question: What is the stoichiometry and architecture of the ERLIN1/ERLIN2 ring complex (recently resolved by cryo-EM), and how does it select activated/ubiquitinated IP3R tetramers as substrates?
- question: How does cholesterol binding to the erlin SPFH domain mechanistically couple ER sterol levels to retention of the SCAP-SREBP-Insig complex?
- question: How do ERLIN1 SPG62 disease variants (e.g. G50V) impair complex assembly or substrate handling to cause corticospinal motor neuron degeneration?
suggested_experiments:
- description: Reconstitute the ERLIN1/ERLIN2 complex with RNF170 and a model IP3R substrate to test whether ERLIN1 is required for substrate binding versus ligase recruitment in IP3R ERAD.
- description: Use cholesterol photoaffinity probes and SPFH-domain point mutants of ERLIN1 to map the cholesterol-binding site and test whether abolishing cholesterol binding derepresses SREBP target genes.
- description: Introduce the SPG62 G50V variant into neurons and assay ERLIN1/ERLIN2 complex assembly, IP3R degradation, and ER cholesterol/SREBP signaling to link the molecular defect to disease.

ERLIN1

Gene Description

Existing Annotations Review

Core Functions

Scaffold subunit of the ring-shaped ERLIN1/ERLIN2 SPFH-domain complex that binds inositol 1,4,5-trisphosphate receptor (IP3R) tetramers and, with the E3 ligase RNF170, mediates their ER-associated degradation, controlling calcium signaling.

Cholesterol-binding ER membrane protein that restricts SREBP activation by associating with and stabilizing the SREBP-SCAP-Insig complex, thereby negatively regulating cholesterol and fatty acid biosynthesis and contributing to cellular cholesterol homeostasis.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Research Report: Human ERLIN1 (UniProt O75477; Gene ERLIN1; synonyms KE04/SPFH1/C10orf69) — Functional Annotation

1) Target verification and definitions (gene/protein identity)

2) Current understanding: molecular functions, pathways, and localization

2.1 ER membrane nanodomain scaffold controlling cholesterol esterification and secretory trafficking (major 2024 advance)

2.2 ER-associated degradation (ERAD) of activated IP3 receptors and Ca2+ signaling

2.3 Mitochondria-associated membranes (MAMs), lipid microdomains, and autophagy initiation (ERLIN1–AMBRA1)

3) Recent developments (prioritizing 2023–2024)

3.1 2024: ERLIN1/2 as nanodomain scaffolds linking lipid metabolism to secretory function

3.2 2024: expanded SPG62 case series defining genotype–phenotype patterns

4) Current applications and real-world implementations

4.1 Clinical genetics: ERLIN1 as a molecular diagnosis for hereditary spastic paraplegia (SPG62)

4.2 Functional cell biology: perturbation of ERLIN1/2 to probe lipid–secretory coupling

4.3 Infection biology: ERLIN1 as a host factor for hepatitis C virus (HCV)

4.4 Systems immunology / biomarker-style signals: ERLIN1 induction in sepsis datasets

5) Expert synthesis and interpretation (authoritative analysis grounded in cited sources)

5.1 Primary functional role: ER membrane scaffold coupling lipid microdomains to client handling and trafficking

5.2 Relationship to autophagy and MAMs

6) Consolidated functional annotation table

7) Key figure supporting the 2024 ERLIN scaffold model

8) Notes on evidence coverage and recency

9) Practical takeaways for functional annotation workflows

Artifacts

Citations

📚 Additional Documentation

Notes

ERLIN1 (SPFH1 / ER lipid raft-associated protein 1) review notes

Core biology

Annotation assessment summary

Falcon deep-research findings (incorporated 2026-06)

Pn Notes

ERLIN1 PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

PN row 1: ER proteostasis | Organelle-specific protein degradation | ER associated degradation | ER handling of ERAD substrates

PN row 2: Ubiquitin Proteasome System | E3 ubiquitin and UBL ligases | idiosyncratic RING complex | RNF170 / ERLIN complex | noncatalytic / BAND 7

Projected GO annotations (3)

Note

📄 View Raw YAML