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

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

PMID:20865800

Folding of Toll-like receptors by the HSP90 paralogue gp96 requires a substrate-specific cochaperone.

Mouse Cnpy3 directly binds gp96 in vitro; nucleotide disrupts the interaction, and Cnpy3 was proposed to stabilize a substrate-loading conformation of gp96.
Cnpy3 and gp96 depend on each other for efficient TLR9 binding, and loss of their interaction blocks TLR9 folding and maturation.
Silencing mouse Cnpy3 reduced surface TLR4 and trapped TLR9 precursors in the ER, establishing a role in TLR exit and membrane localization.
Cnpy3 lacks intrinsic ATPase activity and does not significantly alter gp96 ATPase activity, supporting a substrate-loading co-chaperone rather than autonomous foldase mechanism.

PMID:29394991

Biallelic Variants in CNPY3, Encoding an Endoplasmic Reticulum Chaperone, Cause Early-Onset Epileptic Encephalopathy.

Three affected individuals carried biallelic CNPY3 variants, and patient-derived lymphoblastoid cells from two siblings had severely reduced CNPY3 abundance.

PMID:28514442

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

Large-scale AP-MS interactome (BioPlex 2.0); reports a CNPY3 interaction with SLITRK4 as an uncharacterized high-throughput hit without gene-specific functional follow-up.

PMID:32296183

A reference map of the human binary protein interactome.

HuRI binary (Y2H) interactome map; CNPY3 interactions reported are systematic screen hits without functional characterization.

PMID:32814053

Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.

Neurodegenerative-disease interactome mapping; CNPY3 interactions are high-throughput screen hits not individually characterized in the cached abstract.

PMID:33961781

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

BioPlex 3.0 cell-specific AP-MS interactome; CNPY3 interaction reported is a high-throughput screen hit without functional follow-up.

Reactome:R-HSA-1678923

TLR folding by chaperones GP96 and CNPY3

CNPY3 acts in the ER lumen with GP96 (HSP90B1) to fold Toll-like receptors.

Reactome:R-HSA-1678944

Folded full-length TLR7/8/9 dissociates from the GP96:CNPY3 complex

Folded full-length TLR7/8/9 dissociates from the GP96:CNPY3 co-chaperone complex in the ER.

file:human/CNPY3/CNPY3-uniprot.txt

UniProtKB entry Q9BT09 (CNPY3_HUMAN)

Toll-like receptor (TLR)-specific co-chaperone for HSP90B1; required for proper TLR folding (except TLR3) and controls TLR exit from the ER; required for innate and adaptive immune responses. ER-localized; interacts with HSP90B1 (ATP-disrupted) and with TLR1/2/4/9 (strongest with TLR4).