Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on curation of immunofluorescence data
Gene Ontology annotation based on curation of intracellular localizations of expressed fusion proteins in living cells
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Erlin-1 and erlin-2 are novel members of the prohibitin family of proteins that define lipid-raft-like domains of the ER.
Blood pressure is regulated by an alpha1D-adrenergic receptor/dystrophin signalosome.
An endoplasmic reticulum (ER) membrane complex composed of SPFH1 and SPFH2 mediates the ER-associated degradation of inositol 1,4,5-trisphosphate receptors.
Membrane-associated ubiquitin ligase complex containing gp78 mediates sterol-accelerated degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.
Defining human ERAD networks through an integrative mapping strategy.
RNF185 is a novel E3 ligase of endoplasmic reticulum-associated degradation (ERAD) that targets cystic fibrosis transmembrane conductance regulator (CFTR).
Erlins restrict SREBP activation in the ER and regulate cellular cholesterol homeostasis.
Flotillin-1 facilitates toll-like receptor 3 signaling in human endothelial cells.
Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei.
Stasimon/Tmem41b localizes to mitochondria-associated ER membranes and is essential for mouse embryonic development.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
Role of ERLINs in the Control of Cell Fate through Lipid Rafts.
ERLIN1/2 scaffolds bridge TMUB1 and RNF170 and restrict cholesterol esterification to regulate the secretory pathway.
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ERLIN1/ERLIN2 form large ring-like cup-shaped ER-membrane scaffolds that bind cholesterol and E3 ubiquitin ligases and mediate the interaction between full-length TMUB1 and RNF170 via a conserved luminal N-terminal motif binding the SPFH/prohibitin domains of two adjacent ERLIN subunits; loss of both ERLINs limits cholesterol esterification, favouring ER-to-Golgi cholesterol transport and regulating Golgi morphology and the secretory pathway. HSP-linked variants map to these interaction interfaces.
Disruption of Intracellular Calcium Homeostasis Leads to ERLIN2-Linked Hereditary Spastic Paraplegia in Patient-Derived Stem Cell Models.
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A heterozygous ERLIN2 missense variant (p.Val71Ala) in an HSP family; patient-derived iPSC models show the mutant ERLIN2 recruits the E3 ligase RNF213 to degrade IP3R1, lowering intracellular free calcium, triggering ER-stress-mediated apoptosis, and suppressing MAPK signaling and proliferation, proposing an autosomal-dominant disease mechanism.
Hereditary spastic paraparesis type 18 (SPG18): new ERLIN2 variants in a series of Italian patients, shedding light upon genetic and phenotypic variability.
Expanding SPG18 clinical spectrum: autosomal dominant mutation causes complicated hereditary spastic paraplegia in a large family.
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An autosomal-dominant ERLIN2 p.V168M mutation segregates in a four-generation family with variable expressivity (phenoconversion to ALS, pure HSP, and a complicated form with psychomotor delay and epilepsy); erlin2 oligomerization was normal, arguing against a dominant-negative oligomerization defect for this variant.
Activated FGFR1 mutants and fusions bind PLCG1
Activated FGFR1 mutants and fusions phosphorylate PLCG1
p-4Y- PLCG1 dissociates from activated FGFR1 mutants and fusions
Activated FGFR1 mutants:p-FRS2 binds GRB2:GAB1:PIK3R1
Activated FGFR1 mutants:p-FRS2:GRB2:GAB1:PIK3R1 binds PIK3CA
Activated FGFR1 mutants:p-FRS2 binds GRB2-SOS1
Activated FGFR1 mutants bind FRS2
Activated FGFR1 mutants phosphorylate FRS2
Activated FGFR1 mutant-associated PI3K phosphorylates PIP2 to PIP3
Activated FGFR1 mutants:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange
Plasma membrane FGFR1 fusions dimerize
Plasma membrane FGFR1 fusions autophosphorylate
VCP-catalyzed ATP hydrolysis promotes the translocation of misfolded CFTR into the cytosol
RNF5 and RNF185 ubiquitinate misfolded CFTR
CFTR binds components of the ERAD machinery for ubiquitination and degradation
VCP-catalyzed ATP hydrolysis promotes the translocation of CFTR F508del into the cytosol
RNF5 and RNF185 ubiquitinate CFTR F508del
CFTR F508del binds components of the ERAD machinery for ubiquitination and degradation
Active transport of ubiquitinated CD274 from ER to cytosol
Ubiquitination of CD274 by ERAD complex
p-S195-CD274 binds ERAD complex
UniProt entry O94905 (ERLN2_HUMAN), Erlin-2 / SPFH2
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ERLIN2 is a single-pass type II ER membrane SPFH/prohibitin protein forming the ERLIN1/ERLIN2 complex that mediates ERAD of IP3 receptors and HMGCR, binds cholesterol, restricts SREBP, and interacts with ER ubiquitin ligases (RNF170, AMFR, SYVN1, RNF139, RNF185/RNF5); variants cause SPG18.