Combined Automated Annotation using Multiple IEA Methods

Huntingtin interacting proteins are genetic modifiers of neurodegeneration.

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

PMID:9473517

Characterisation of a new human and murine member of the DnaJ family of proteins.

DNAJC4/HSPF2 was identified as a new member of the DnaJ/HSP40 family; assignment to this family is the basis for its inferred protein-folding/unfolded-protein-response and membrane annotations.

file:human/DNAJC4/DNAJC4-notes.md

Reviewer notes for DNAJC4

Local review notes emphasize that DNAJC4 is a Tdark J-domain protein with family-level HSP70 co-chaperone inference, predicted membrane localization, and no direct experimental characterization of chaperone activity, HSP70 partner, topology, or client repertoire.

file:human/DNAJC4/DNAJC4-pn-notes.md

Proteostasis-network notes for DNAJC4

PN review notes flag that the HSP70 co-chaperone assignment is family-level and unverified experimentally, and that mitochondrial-branch placement is unsupported by the dossier.

file:human/DNAJC4/DNAJC4-hypotheses/kgap-dnajc4-hsp70-cochaperone-activity/openscientist.md

OpenScientist report on DNAJC4 HSP70 co-chaperone activity

A focused report found that DNAJC4's HSP70 co-chaperone activity, direct HSP70 binding, and client-recruitment activity remain untested despite the intact HPD motif in its J-domain.

"no published study has ever tested DNAJC4 in an ATPase stimulation assay, a direct HSP70 binding assay, or a client recruitment experiment."
Current HTT/WFS1 high-throughput interaction data do not establish a specific HSP70 partner or an HSP70-dependent DNAJC4 mechanism.

"No specific HSP70 paralog partner (HSPA8/Hsc70, HSPA1A/Hsp70, or otherwise) has been established for DNAJC4."
The HTT and WFS1 interactions remain high-throughput only, so they do not define a validated client-recruitment mechanism for DNAJC4.

"Critically, none of these interactions has been validated by low-throughput, targeted methods"