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
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Automatic assignment of GO terms using logical inference, based on on inter-ontology links
Electronic Gene Ontology annotations created by ARBA machine learning models
Integral and associated lysosomal membrane proteins.
The Cl-/H+ antiporter ClC-7 is the primary chloride permeation pathway in lysosomes.
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ClC-7 is a Cl-/H+ antiporter that constitutes the major chloride permeability of lysosomes and is important for lysosomal acidification.
"The Cl-/H+ antiporter ClC-7 is the primary chloride permeation pathway in lysosomes."
Defining the membrane proteome of NK cells.
ClC-7 is a slowly voltage-gated 2Cl(-)/1H(+)-exchanger and requires Ostm1 for transport activity.
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ClC-7 exchanges chloride for protons with a 2Cl-/1H+ stoichiometry and is slowly voltage-gated.
"Reversal potentials of tail currents revealed a 2Cl(-)/1H(+)-exchange stoichiometry."
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ClC-7 requires the beta-subunit Ostm1 for transport activity.
"ClC-7 is a slowly voltage-gated 2Cl(-)/1H(+)-exchanger and requires Ostm1 for transport activity."
A reference map of the human binary protein interactome.
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
Molecular insights into the human CLC-7/Ostm1 transporter.
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CLC-7 mainly resides in lysosomes and osteoclast ruffled membranes, consistent with an intracellular endolysosomal transporter rather than a transepithelial one.
"CLC-7 functions as an electrogenic antiporter that mainly resides in lysosomes and osteoclast ruffled membranes."
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Cryo-EM shows the glycosylated Ostm1 forms a lid over CLC-7 and interacts extensively within the membrane, defining the obligate complex.
"the highly glycosylated Ostm1 functions like a lid positioned above CLC-7 and interacts extensively with CLC-7 within the membrane."
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
OpenCell: Endogenous tagging for the cartography of human cellular organization.
Multimodal cell maps as a foundation for structural and functional genomics.
The solute carrier superfamily interactome.
ClC-6 and ClC-7 are two novel broadly expressed members of the CLC chloride channel family.
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ClC-7 was cloned as a CLC-family member but could not be expressed as a chloride channel in Xenopus oocytes, foreshadowing its later identification as an antiporter.
"ClC-6 and ClC-7 are two novel broadly expressed members of the CLC chloride channel family."
CLCN7:OSTM1 exchanges Cl- for H+
Tonic inhibition of the chloride/proton antiporter ClC-7 by PI(3,5)P2 is crucial for lysosomal pH maintenance.
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The lysosomal lipid PI(3,5)P2 tonically inhibits ClC-7 transport; relieving this inhibition activates the antiporter and modulates V-ATPase-driven lysosomal acidification, establishing PI(3,5)P2 binding as a physiological regulatory function.
"PI(3,5)P2 inhibits ClC-7-mediated currents."
Gain-of-function variants in CLCN7 cause hypopigmentation and lysosomal storage disease.
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Disease-causing gain-of-function CLCN7 variants (Y715C, K285T) line the PI(3,5)P2-binding pocket and reduce lipid inhibition, increasing transport activity and causing hypopigmentation with lysosomal storage (HOD), distinct from loss-of-function osteopetrosis.
"K285 is located in a suggested binding site for PI(3,5)P2 in the cytoplasmic portion of ClC-7"
Falcon deep research report for CLCN7
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Falcon deep research corroborates the existing review (2Cl-/1H+ antiporter, obligate OSTM1 complex, lysosome/osteoclast localization, osteopetrosis/HOD spectrum) and surfaces the established PI(3,5)P2 regulatory axis plus pH-independent luminal-chloride roles in cathepsin activation and autophagic/phagolysosomal degradation.
"PI(3,5)P2 directly inhibits ClC-7 by binding at the transmembrane-cytosolic interface and remodeling transporter structure"
OpenScientist hypothesis run: CLCN7 transepithelial chloride transport (GO:0030321) over-annotation
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Localization / sorting-signal analysis concluded that GO:0030321 (transepithelial chloride transport) is over-annotated and should be removed; ClC-7 is an endolysosomal antiporter with N-terminal dileucine and acidic-cluster lysosomal targeting motifs, and the annotation traces to a ComplexPortal family-level intro sentence propagated via PANTHER IBA to ~1,198 ortholog annotations. Recommends adding GO:0007042 (lysosomal lumen acidification).
"a PANTHER IBA (Inferred by Biological Aspect of Ancestor) annotation that propagated this error to CLCN7 orthologs across approximately 1,198 annotations in many species."