HSPA13

Summary: The inherited localization remains unresolved alongside well-supported ER enrichment.

Reason: The PAINT location assertion traces to PTN002500132. PMID:36244454 directly confirms microsomal recovery and preferential ER-luminal proximity labeling of HSPA13; this establishes its principal tested compartment but does not establish exclusivity. PMID:33672238 infers an interaction with the cytoplasmic NKCC2 tail at the ER, without directly defining a soluble cytosolic pool. Neither a signal sequence nor ER enrichment alone refutes nuclear, surface or cytosolic localization in another context. A focused compartment-specific assessment is pending.

Summary: The inherited localization remains unresolved alongside well-supported ER enrichment.

Reason: The PAINT location assertion traces to PTN002500132. PMID:36244454 directly confirms microsomal recovery and preferential ER-luminal proximity labeling of HSPA13; this establishes its principal tested compartment but does not establish exclusivity. PMID:33672238 infers an interaction with the cytoplasmic NKCC2 tail at the ER, without directly defining a soluble cytosolic pool. Neither a signal sequence nor ER enrichment alone refutes nuclear, surface or cytosolic localization in another context. A focused compartment-specific assessment is pending.

Summary: STCH retains the HSP70 ATPase domain and has documented ATPase activity (peptide-independent). ATP hydrolysis is a genuine, core molecular function.

Reason: Directly supported by the original characterization showing STCH ATPase activity, consistent with phylogenetic inference from the HSP70 family.

Summary: HSPA13 associates with multiple heat-shock-protein chaperones in its ER interaction network.

Reason: PMID:36244454 identifies BiP, ERdj3 and Grp94 among HSPA13-associated ER chaperones by crosslinking-assisted affinity purification/mass spectrometry. This target-specific evidence supports the inherited binding annotation beyond a family-name inference, although it does not establish purified binary affinities or an autonomous folding reaction.

Summary: Canonical HSP70 folding chemistry is disrupted, but the broad folding-chaperone claim is not decisively resolved.

Reason: The missing canonical substrate-binding domain and peptide-independent ATPase are genuine target-specific divergence evidence, so canonical HSP70 client-clamping cannot simply be assumed. However, GO:0044183 also covers binding a protein-containing complex to assist folding. PMID:36244454 establishes ER-chaperone/translocon associations and effects on proteostasis, without a direct folding assay. Its observation that both HSPA13 and BiP overexpression can impair translocation also undermines the provider claim that antagonistic overexpression phenotypes alone exclude chaperone capacity. Retain uncertainty about an indirect complex-dependent folding contribution rather than treating absence of the canonical domain as impossibility of every qualifying mechanism.

Summary: The inherited localization remains unresolved alongside well-supported ER enrichment.

Reason: The PAINT location assertion traces to PTN002500132. PMID:36244454 directly confirms microsomal recovery and preferential ER-luminal proximity labeling of HSPA13; this establishes its principal tested compartment but does not establish exclusivity. PMID:33672238 infers an interaction with the cytoplasmic NKCC2 tail at the ER, without directly defining a soluble cytosolic pool. Neither a signal sequence nor ER enrichment alone refutes nuclear, surface or cytosolic localization in another context. A focused compartment-specific assessment is pending.

Summary: HSPA13 involvement in refolding requires a process-specific mechanistic test.

Reason: A refolding biological process need not mean that HSPA13 independently executes the canonical HSP70 foldase cycle. SBD loss is relevant divergence, but ER-chaperone and translocon interactions allow possible assistance through other proteins. Existing studies measure import, maturation, aggregation and turnover rather than recovery of a denatured protein's biological activity. The inherited process is therefore unresolved, not disproved solely by domain truncation.

Summary: STCH contains the HSP70 nucleotide-binding domain and binds ATP. ATP binding is a core molecular function underlying its ATPase activity.

Reason: Directly supported by the conserved HSP70 ATPase domain and documented ATPase activity.

Summary: Endoplasmic reticulum / microsomal localization, the documented compartment for STCH, which carries an N-terminal signal sequence and is enriched in microsomes.

Reason: Directly supported by the original characterization showing microsome enrichment and by the UniProt subcellular-location record.

Summary: InterPro-based electronic annotation of ATP hydrolysis activity, redundant with the IBA annotation and supported by direct evidence.

Reason: Consistent with the documented peptide-independent ATPase activity of STCH.

Summary: Proteome-scale interactome screen capturing an STCH-UBQLN1 (Q9UMX0) interaction. The bare protein binding term is uninformative; the partner is a ubiquilin, consistent with the documented UbL-protein interaction.

Reason: The recorded interaction is retained as evidence, but generic protein binding does not identify a molecular activity. No more specific functional replacement is established by this interaction record alone; removal does not deny the interaction.

Summary: Inherited-ataxia interactome network capturing an STCH-UBQLN4 (Q9NRR5) interaction. The bare protein binding term is uninformative; the partner is a ubiquilin.

Reason: The recorded interaction is retained as evidence, but generic protein binding does not identify a molecular activity. No more specific functional replacement is established by this interaction record alone; removal does not deny the interaction.

Summary: Human liver interactome screen capturing an STCH-UBQLN1 (Q9UMX0) interaction. The bare protein binding term is uninformative.

Reason: The recorded interaction is retained as evidence, but generic protein binding does not identify a molecular activity. No more specific functional replacement is established by this interaction record alone; removal does not deny the interaction.

Summary: Yeast two-hybrid interactome map capturing STCH interactions with SGTA (O43765) and UBQLN1 (Q9UMX0). The bare protein binding term is uninformative.

Reason: The recorded interaction is retained as evidence, but generic protein binding does not identify a molecular activity. No more specific functional replacement is established by this interaction record alone; removal does not deny the interaction.

Summary: Human interactome (protein communities) study capturing an STCH-B4GALT5 (O43286) interaction. The bare protein binding term is uninformative.

Reason: The recorded interaction is retained as evidence, but generic protein binding does not identify a molecular activity. No more specific functional replacement is established by this interaction record alone; removal does not deny the interaction.

Summary: Reference binary interactome map capturing multiple STCH interactions, including SGTA, SGTB, CRYGA and the ubiquilins UBQLN1/UBQLN2. The bare protein binding term is uninformative.

Reason: The recorded interaction is retained as evidence, but generic protein binding does not identify a molecular activity. No more specific functional replacement is established by this interaction record alone; removal does not deny the interaction.

Summary: BioPlex affinity-purification interactome capturing an STCH-B4GALT5 (O43286) interaction. The bare protein binding term is uninformative.

Reason: The recorded interaction is retained as evidence, but generic protein binding does not identify a molecular activity. No more specific functional replacement is established by this interaction record alone; removal does not deny the interaction.

Summary: Chromosome-21 protein-protein interaction study capturing STCH interactions with SGTB and the ubiquilins UBQLN1/UBQLN2/UBQLN4. The bare protein binding term is uninformative.

Reason: The recorded interaction is retained as evidence, but generic protein binding does not identify a molecular activity. No more specific functional replacement is established by this interaction record alone; removal does not deny the interaction.

Summary: High-throughput proteomic detection of STCH in extracellular exosomes. A peripheral localization, not the principal site of STCH function.

Reason: Mass-spectrometry detection in exosomes records a real pool but is peripheral to STCH's ER/microsomal quality-control function.

Summary: The microsomal/ER localization supports this broad core organelle annotation.

Reason: The original microsome enrichment and later ER-luminal proximity-labeling evidence place HSPA13 in an intracellular membrane-bounded organelle. A broader location term remains correct and core alongside endoplasmic reticulum.