EFR3A

UniProt ID: Q14156
Organism: Homo sapiens
Review Status: IN PROGRESS
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Gene Description

EFR3A is a palmitoylated peripheral membrane scaffold that helps anchor the PI4KA phosphatidylinositol 4-kinase complex to the plasma membrane. Its N-terminal cysteine cluster is required for membrane localization, allowing the complex to maintain plasma-membrane phosphatidylinositol 4-phosphate.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005829 cytosol
IDA
GO_REF:0000052 		KEEP AS NON CORE
Summary: A minor cytosolic pool is compatible with regulated membrane anchoring, but membrane-localized scaffolding is the principal mechanism.
Reason: A minor cytosolic pool is compatible with regulated membrane anchoring, but membrane-localized scaffolding is the principal mechanism.
Supporting Evidence:
file:human/EFR3A/EFR3A-uniprot.txt
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825}; Lipid-anchor CC {ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:25380825}. Cytoplasm, CC cytosol {ECO:0000269|PubMed:25380825}. Note=Palmitoylation anchors the CC protein to the plasma membrane (PubMed:23229899, PubMed:25380825, CC PubMed:26571211). A small amount is observed in the cytosol CC (PubMed:25380825). {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825, ECO:0000269|PubMed:26571211}.
PMID:23229899
Accordingly, a bioorthogonal metabolic labeling approach (Hang et al., 2011) revealed that FLAG-tagged EFR3A and EFR3B were palmitoylated at the N-terminal Cys-rich motif (Fig. 4 B). Importantly, palmitoylation-deficient mutants (C6S/C7S/C8S/C9S for EFR3A and C5S/C7S/C8S for EFR3B) were localized in the cytosol (Fig. 4 C), and the EFR3B palmitoylation-deficient mutant was unable to recruit tagged TTC7B and M1-PI4KIIIฮฑ to the plasma membrane (Fig. S2).
GO:0005829 cytosol
IEA
GO_REF:0000044 		KEEP AS NON CORE
Summary: A minor cytosolic pool is compatible with regulated membrane anchoring, but membrane-localized scaffolding is the principal mechanism.
Reason: A minor cytosolic pool is compatible with regulated membrane anchoring, but membrane-localized scaffolding is the principal mechanism.
Supporting Evidence:
file:human/EFR3A/EFR3A-uniprot.txt
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825}; Lipid-anchor CC {ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:25380825}. Cytoplasm, CC cytosol {ECO:0000269|PubMed:25380825}. Note=Palmitoylation anchors the CC protein to the plasma membrane (PubMed:23229899, PubMed:25380825, CC PubMed:26571211). A small amount is observed in the cytosol CC (PubMed:25380825). {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825, ECO:0000269|PubMed:26571211}.
PMID:23229899
Accordingly, a bioorthogonal metabolic labeling approach (Hang et al., 2011) revealed that FLAG-tagged EFR3A and EFR3B were palmitoylated at the N-terminal Cys-rich motif (Fig. 4 B). Importantly, palmitoylation-deficient mutants (C6S/C7S/C8S/C9S for EFR3A and C5S/C7S/C8S for EFR3B) were localized in the cytosol (Fig. 4 C), and the EFR3B palmitoylation-deficient mutant was unable to recruit tagged TTC7B and M1-PI4KIIIฮฑ to the plasma membrane (Fig. S2).
GO:0005886 plasma membrane
EXP
PMID:25380825
EFR3s are palmitoylated plasma membrane proteins that contro... 		ACCEPT
Summary: Palmitoylation of the N-terminal cysteine cluster anchors EFR3A to the plasma membrane; the quadruple cysteine mutant becomes cytosolic.
Reason: Palmitoylation of the N-terminal cysteine cluster anchors EFR3A to the plasma membrane; the quadruple cysteine mutant becomes cytosolic.
Supporting Evidence:
file:human/EFR3A/EFR3A-uniprot.txt
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825}; Lipid-anchor CC {ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:25380825}. Cytoplasm, CC cytosol {ECO:0000269|PubMed:25380825}. Note=Palmitoylation anchors the CC protein to the plasma membrane (PubMed:23229899, PubMed:25380825, CC PubMed:26571211). A small amount is observed in the cytosol CC (PubMed:25380825). {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825, ECO:0000269|PubMed:26571211}.
PMID:23229899
Accordingly, a bioorthogonal metabolic labeling approach (Hang et al., 2011) revealed that FLAG-tagged EFR3A and EFR3B were palmitoylated at the N-terminal Cys-rich motif (Fig. 4 B). Importantly, palmitoylation-deficient mutants (C6S/C7S/C8S/C9S for EFR3A and C5S/C7S/C8S for EFR3B) were localized in the cytosol (Fig. 4 C), and the EFR3B palmitoylation-deficient mutant was unable to recruit tagged TTC7B and M1-PI4KIIIฮฑ to the plasma membrane (Fig. S2).
GO:0005886 plasma membrane
IBA
GO_REF:0000033 		ACCEPT
Summary: Palmitoylation of the N-terminal cysteine cluster anchors EFR3A to the plasma membrane; the quadruple cysteine mutant becomes cytosolic.
Reason: Palmitoylation of the N-terminal cysteine cluster anchors EFR3A to the plasma membrane; the quadruple cysteine mutant becomes cytosolic.
Supporting Evidence:
file:human/EFR3A/EFR3A-uniprot.txt
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825}; Lipid-anchor CC {ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:25380825}. Cytoplasm, CC cytosol {ECO:0000269|PubMed:25380825}. Note=Palmitoylation anchors the CC protein to the plasma membrane (PubMed:23229899, PubMed:25380825, CC PubMed:26571211). A small amount is observed in the cytosol CC (PubMed:25380825). {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825, ECO:0000269|PubMed:26571211}.
PMID:23229899
Accordingly, a bioorthogonal metabolic labeling approach (Hang et al., 2011) revealed that FLAG-tagged EFR3A and EFR3B were palmitoylated at the N-terminal Cys-rich motif (Fig. 4 B). Importantly, palmitoylation-deficient mutants (C6S/C7S/C8S/C9S for EFR3A and C5S/C7S/C8S for EFR3B) were localized in the cytosol (Fig. 4 C), and the EFR3B palmitoylation-deficient mutant was unable to recruit tagged TTC7B and M1-PI4KIIIฮฑ to the plasma membrane (Fig. S2).
GO:0005886 plasma membrane
IDA
GO_REF:0000052 		ACCEPT
Summary: Palmitoylation of the N-terminal cysteine cluster anchors EFR3A to the plasma membrane; the quadruple cysteine mutant becomes cytosolic.
Reason: Palmitoylation of the N-terminal cysteine cluster anchors EFR3A to the plasma membrane; the quadruple cysteine mutant becomes cytosolic.
Supporting Evidence:
file:human/EFR3A/EFR3A-uniprot.txt
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825}; Lipid-anchor CC {ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:25380825}. Cytoplasm, CC cytosol {ECO:0000269|PubMed:25380825}. Note=Palmitoylation anchors the CC protein to the plasma membrane (PubMed:23229899, PubMed:25380825, CC PubMed:26571211). A small amount is observed in the cytosol CC (PubMed:25380825). {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825, ECO:0000269|PubMed:26571211}.
PMID:23229899
Accordingly, a bioorthogonal metabolic labeling approach (Hang et al., 2011) revealed that FLAG-tagged EFR3A and EFR3B were palmitoylated at the N-terminal Cys-rich motif (Fig. 4 B). Importantly, palmitoylation-deficient mutants (C6S/C7S/C8S/C9S for EFR3A and C5S/C7S/C8S for EFR3B) were localized in the cytosol (Fig. 4 C), and the EFR3B palmitoylation-deficient mutant was unable to recruit tagged TTC7B and M1-PI4KIIIฮฑ to the plasma membrane (Fig. S2).
GO:0005886 plasma membrane
IDA
PMID:23229899
PtdIns4P synthesis by PI4KIIIฮฑ at the plasma membrane and it... 		ACCEPT
Summary: Palmitoylation of the N-terminal cysteine cluster anchors EFR3A to the plasma membrane; the quadruple cysteine mutant becomes cytosolic.
Reason: Palmitoylation of the N-terminal cysteine cluster anchors EFR3A to the plasma membrane; the quadruple cysteine mutant becomes cytosolic.
Supporting Evidence:
file:human/EFR3A/EFR3A-uniprot.txt
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825}; Lipid-anchor CC {ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:25380825}. Cytoplasm, CC cytosol {ECO:0000269|PubMed:25380825}. Note=Palmitoylation anchors the CC protein to the plasma membrane (PubMed:23229899, PubMed:25380825, CC PubMed:26571211). A small amount is observed in the cytosol CC (PubMed:25380825). {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825, ECO:0000269|PubMed:26571211}.
PMID:23229899
Accordingly, a bioorthogonal metabolic labeling approach (Hang et al., 2011) revealed that FLAG-tagged EFR3A and EFR3B were palmitoylated at the N-terminal Cys-rich motif (Fig. 4 B). Importantly, palmitoylation-deficient mutants (C6S/C7S/C8S/C9S for EFR3A and C5S/C7S/C8S for EFR3B) were localized in the cytosol (Fig. 4 C), and the EFR3B palmitoylation-deficient mutant was unable to recruit tagged TTC7B and M1-PI4KIIIฮฑ to the plasma membrane (Fig. S2).
GO:0005886 plasma membrane
IEA
GO_REF:0000120 		ACCEPT
Summary: Palmitoylation of the N-terminal cysteine cluster anchors EFR3A to the plasma membrane; the quadruple cysteine mutant becomes cytosolic.
Reason: Palmitoylation of the N-terminal cysteine cluster anchors EFR3A to the plasma membrane; the quadruple cysteine mutant becomes cytosolic.
Supporting Evidence:
file:human/EFR3A/EFR3A-uniprot.txt
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825}; Lipid-anchor CC {ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:25380825}. Cytoplasm, CC cytosol {ECO:0000269|PubMed:25380825}. Note=Palmitoylation anchors the CC protein to the plasma membrane (PubMed:23229899, PubMed:25380825, CC PubMed:26571211). A small amount is observed in the cytosol CC (PubMed:25380825). {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825, ECO:0000269|PubMed:26571211}.
PMID:23229899
Accordingly, a bioorthogonal metabolic labeling approach (Hang et al., 2011) revealed that FLAG-tagged EFR3A and EFR3B were palmitoylated at the N-terminal Cys-rich motif (Fig. 4 B). Importantly, palmitoylation-deficient mutants (C6S/C7S/C8S/C9S for EFR3A and C5S/C7S/C8S for EFR3B) were localized in the cytosol (Fig. 4 C), and the EFR3B palmitoylation-deficient mutant was unable to recruit tagged TTC7B and M1-PI4KIIIฮฑ to the plasma membrane (Fig. S2).
GO:0016082 synaptic vesicle priming
IEA
GO_REF:0000107 		UNDECIDED
Summary: The accessible PI4KA-recruitment experiments do not resolve the specific synaptic-vesicle priming claim; evidence from the orthologous neuronal experiment is needed.
Reason: The accessible PI4KA-recruitment experiments do not resolve the specific synaptic-vesicle priming claim; evidence from the orthologous neuronal experiment is needed.
Supporting Evidence:
file:human/EFR3A/EFR3A-uniprot.txt
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825}; Lipid-anchor CC {ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:25380825}. Cytoplasm, CC cytosol {ECO:0000269|PubMed:25380825}. Note=Palmitoylation anchors the CC protein to the plasma membrane (PubMed:23229899, PubMed:25380825, CC PubMed:26571211). A small amount is observed in the cytosol CC (PubMed:25380825). {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825, ECO:0000269|PubMed:26571211}.
GO:0046854 phosphatidylinositol phosphate biosynthetic process
TAS
PMID:23229899
PtdIns4P synthesis by PI4KIIIฮฑ at the plasma membrane and it... 		ACCEPT
Summary: EFR3A participates in phosphoinositide biosynthesis by membrane recruitment of the PI4KA complex, without itself catalyzing lipid phosphorylation.
Reason: EFR3A participates in phosphoinositide biosynthesis by membrane recruitment of the PI4KA complex, without itself catalyzing lipid phosphorylation.
Supporting Evidence:
file:human/EFR3A/EFR3A-uniprot.txt
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825}; Lipid-anchor CC {ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:25380825}. Cytoplasm, CC cytosol {ECO:0000269|PubMed:25380825}. Note=Palmitoylation anchors the CC protein to the plasma membrane (PubMed:23229899, PubMed:25380825, CC PubMed:26571211). A small amount is observed in the cytosol CC (PubMed:25380825). {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825, ECO:0000269|PubMed:26571211}.
PMID:23229899
Accordingly, a bioorthogonal metabolic labeling approach (Hang et al., 2011) revealed that FLAG-tagged EFR3A and EFR3B were palmitoylated at the N-terminal Cys-rich motif (Fig. 4 B). Importantly, palmitoylation-deficient mutants (C6S/C7S/C8S/C9S for EFR3A and C5S/C7S/C8S for EFR3B) were localized in the cytosol (Fig. 4 C), and the EFR3B palmitoylation-deficient mutant was unable to recruit tagged TTC7B and M1-PI4KIIIฮฑ to the plasma membrane (Fig. S2).
GO:0072659 protein localization to plasma membrane
IBA
GO_REF:0000033 		ACCEPT
Summary: EFR3A is a palmitoylated membrane anchor in the conserved complex that recruits PI4KA to the plasma membrane.
Reason: EFR3A is a palmitoylated membrane anchor in the conserved complex that recruits PI4KA to the plasma membrane.
Supporting Evidence:
file:human/EFR3A/EFR3A-uniprot.txt
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825}; Lipid-anchor CC {ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:25380825}. Cytoplasm, CC cytosol {ECO:0000269|PubMed:25380825}. Note=Palmitoylation anchors the CC protein to the plasma membrane (PubMed:23229899, PubMed:25380825, CC PubMed:26571211). A small amount is observed in the cytosol CC (PubMed:25380825). {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825, ECO:0000269|PubMed:26571211}.
PMID:23229899
Accordingly, a bioorthogonal metabolic labeling approach (Hang et al., 2011) revealed that FLAG-tagged EFR3A and EFR3B were palmitoylated at the N-terminal Cys-rich motif (Fig. 4 B). Importantly, palmitoylation-deficient mutants (C6S/C7S/C8S/C9S for EFR3A and C5S/C7S/C8S for EFR3B) were localized in the cytosol (Fig. 4 C), and the EFR3B palmitoylation-deficient mutant was unable to recruit tagged TTC7B and M1-PI4KIIIฮฑ to the plasma membrane (Fig. S2).
GO:0072659 protein localization to plasma membrane
IMP
PMID:23229899
PtdIns4P synthesis by PI4KIIIฮฑ at the plasma membrane and it... 		ACCEPT
Summary: EFR3A is a palmitoylated membrane anchor in the conserved complex that recruits PI4KA to the plasma membrane.
Reason: EFR3A is a palmitoylated membrane anchor in the conserved complex that recruits PI4KA to the plasma membrane.
Supporting Evidence:
file:human/EFR3A/EFR3A-uniprot.txt
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825}; Lipid-anchor CC {ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:25380825}. Cytoplasm, CC cytosol {ECO:0000269|PubMed:25380825}. Note=Palmitoylation anchors the CC protein to the plasma membrane (PubMed:23229899, PubMed:25380825, CC PubMed:26571211). A small amount is observed in the cytosol CC (PubMed:25380825). {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825, ECO:0000269|PubMed:26571211}.
PMID:23229899
Accordingly, a bioorthogonal metabolic labeling approach (Hang et al., 2011) revealed that FLAG-tagged EFR3A and EFR3B were palmitoylated at the N-terminal Cys-rich motif (Fig. 4 B). Importantly, palmitoylation-deficient mutants (C6S/C7S/C8S/C9S for EFR3A and C5S/C7S/C8S for EFR3B) were localized in the cytosol (Fig. 4 C), and the EFR3B palmitoylation-deficient mutant was unable to recruit tagged TTC7B and M1-PI4KIIIฮฑ to the plasma membrane (Fig. S2).
GO:0098793 presynapse
IEA
GO_REF:0000108 		UNDECIDED
Summary: Presynaptic localization is not established by the accessible plasma-membrane recruitment experiments.
Reason: Presynaptic localization is not established by the accessible plasma-membrane recruitment experiments.
Supporting Evidence:
file:human/EFR3A/EFR3A-uniprot.txt
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825}; Lipid-anchor CC {ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:25380825}. Cytoplasm, CC cytosol {ECO:0000269|PubMed:25380825}. Note=Palmitoylation anchors the CC protein to the plasma membrane (PubMed:23229899, PubMed:25380825, CC PubMed:26571211). A small amount is observed in the cytosol CC (PubMed:25380825). {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825, ECO:0000269|PubMed:26571211}.
GO:0098978 glutamatergic synapse
IEA
GO_REF:0000107 		UNDECIDED
Summary: The specific glutamatergic-synapse assignment requires neuronal localization evidence beyond the broadly expressed membrane scaffold mechanism.
Reason: The specific glutamatergic-synapse assignment requires neuronal localization evidence beyond the broadly expressed membrane scaffold mechanism.
Supporting Evidence:
file:human/EFR3A/EFR3A-uniprot.txt
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825}; Lipid-anchor CC {ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:25380825}. Cytoplasm, CC cytosol {ECO:0000269|PubMed:25380825}. Note=Palmitoylation anchors the CC protein to the plasma membrane (PubMed:23229899, PubMed:25380825, CC PubMed:26571211). A small amount is observed in the cytosol CC (PubMed:25380825). {ECO:0000269|PubMed:23229899, CC ECO:0000269|PubMed:25380825, ECO:0000269|PubMed:26571211}.

Core Functions

Palmitoylation-dependent membrane scaffolding recruits the PI4KA complex to support plasma-membrane phosphoinositide synthesis.

Directly Involved In:
protein localization to plasma membrane phosphatidylinositol phosphate biosynthetic process
Cellular Locations:
plasma membrane
Supporting Evidence:
  • PMID:23229899
    Accordingly, a bioorthogonal metabolic labeling approach (Hang et al., 2011) revealed that FLAG-tagged EFR3A and EFR3B were palmitoylated at the N-terminal Cys-rich motif (Fig. 4 B). Importantly, palmitoylation-deficient mutants (C6S/C7S/C8S/C9S for EFR3A and C5S/C7S/C8S for EFR3B) were localized in the cytosol (Fig. 4 C), and the EFR3B palmitoylation-deficient mutant was unable to recruit tagged TTC7B and M1-PI4KIIIฮฑ to the plasma membrane (Fig. S2).

References

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Deep Research

Falcon

(EFR3A-deep-research-falcon.md)

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๐Ÿ“š Additional Documentation

Notes

(EFR3A-notes.md)

EFR3A: evidence notes

Paired horse benchmark evidence review

The human reference supplies mechanistic evidence for the corresponding selected horse protein; the human conclusion alone is not validation of the horse sequence. The exact horse comparison is in genes/HORSE/EFR3A/EFR3A-bioinformatics/RESULTS.md. Research reports are source leads; annotation decisions cite the underlying publication or experimentally supported UniProt passages. Unresolved source-specific results retain UNDECIDED.

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