Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Electronic Gene Ontology annotations created by ARBA machine learning models
The MRH protein Erlectin is a member of the endoplasmic reticulum synexpression group and functions in N-glycan recognition.
OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD.
Human XTP3-B forms an endoplasmic reticulum quality control scaffold with the HRD1-SEL1L ubiquitin ligase complex and BiP.
Mannose trimming is required for delivery of a glycoprotein from EDEM1 to XTP3-B and to late endoplasmic reticulum-associated degradation steps.
Identification of ERAD components essential for dislocation of the null Hong Kong variant of α-1-antitrypsin (NHK).
Human XTP3-B binds to 1-antitrypsin variant nullHong Kong via the C-terminal MRH domain in a glycan-dependent manner
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ERLEC1/XTP3-B C-terminal MRH domain mediates binding to Man9GlcNAc2 and Man5-type high-mannose N-glycans with specificity for a terminal Manα1,6Man motif
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Glycan-dependent binding to misfolded alpha1-antitrypsin NHK was abolished by Endo H treatment (p < 0.001)
Endoplasmic reticulum lectin <scp>XTP</scp>3‐B inhibits endoplasmic reticulum‐associated degradation of a misfolded α1‐antitrypsin variant
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ERLEC1/XTP3-B inhibits ERAD of misfolded alpha1-antitrypsin NHK carrying M9 glycans, acting as a negative regulator that may protect newly synthesized glycoproteins from premature degradation
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Lectin activity is required for substrate engagement but not for SEL1L association
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SEL1L depletion causes accelerated ERLEC1 degradation (~40% protein loss over 10 hours in cycloheximide chase, mRNA unchanged), indicating SEL1L stabilizes ERLEC1 protein
Redundant and antagonistic roles of XTP3B and OS9 in decoding glycan and non-glycan degrons in ER-associated degradation.
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OS9 and XTP3B redundantly promote glycoprotein ERAD and stabilize the SEL1L-HRD1 complex
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XTP3B strongly inhibits degradation of non-glycosylated substrates, with OS9 antagonizing this inhibition
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Relative abundance of OS9 vs XTP3B and distribution of glycan vs non-glycan degrons within substrates shapes ERAD fidelity and processivity
Deep research synthesis for ERLEC1 (falcon provider): ERAD lectin, SEL1L-HRD1 association, and context-dependent triage function
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Synthesis reconciles the apparently conflicting facilitator vs inhibitor observations for ERLEC1, supporting a model in which ERLEC1 is a context-dependent triage factor that both promotes glycoprotein ERAD (redundantly with OS9) and restrains degradation of certain substrates, especially non-glycosylated ones
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SEL1L stabilizes ERLEC1 protein (~40% loss over 10-hour cycloheximide chase upon SEL1L depletion, mRNA unchanged; DOI:10.1111/febs.12157), and SEL1L-lectin interactions with OS9/ERLEC1 are preserved even in a SEL1L hypomorphic variant with ~5-fold reduced SEL1L-HRD1 interaction (DOI:10.1038/s41467-024-45633-0)
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ERLEC1 C-terminal MRH domain binds high-mannose glycans (Man5/Man9) in a glycan-dependent manner (Endo H treatment abolishes binding, p < 0.001; DOI:10.1093/glycob/cwp182)
The role of MRH domain-containing lectins in ERAD.
SEL1L-HRD1 interaction is required to form a functional HRD1 ERAD complex.
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SEL1L hypomorphic variant SEL1L-S658P attenuates SEL1L-HRD1 interaction (~5-fold reduction) while preserving SEL1L-lectin interactions with OS9/ERLEC1
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ERLEC1 interaction with SEL1L is maintained even when the overall ERAD complex is compromised
SYVN1 ubiquitinates Hh C-terminal fragments
C-terminal Hh fragments are bound by lectins
C-terminal Hh fragments are recruited to SEL1:SYVN1 at the ER membrane
Hh processing variants bind lectins
VCP-catalyzed ATP hydrolysis promotes the translocation of Hh-C into the cytosol
Hh processing variants are recruited to SEL1:SYVN at the ER membrane
Hh processing variants are translocated to the cytosol in a VCP-dependent manner
Hh processing variants are ubiquitinated
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