# HSPA13 / STCH (P48723) research notes

## Identity
- Heat shock 70 kDa protein 13 / STCH ("stress-70 protein chaperone, microsome-associated 60 kDa"; "microsomal stress-70 protein ATPase core"), 471 aa, ~52 kDa precursor with N-terminal signal/leader (1-22). HSP70 family.
- Encodes the "ATPase core" of a microsomal stress-70 protein [PMID:8131751 "Stch encodes the 'ATPase core' of a microsomal stress 70 protein."].

## Atypical / non-canonical HSP70 features (KEY)
- Contains the HSP70 nucleotide-binding/ATPase domain but has a ~50-residue insertion in the ATP-binding domain and TRUNCATES the C-terminal peptide (substrate)-binding region [PMID:8131751 "has a 50 residue insertion within the ATP-binding domains and truncates the carboxyl terminal peptide-binding region."].
- UniProt FUNCTION: "Has peptide-independent ATPase activity." [file:human/HSPA13/HSPA13-uniprot.txt].
- ATPase activity is INDEPENDENT of peptide stimulation, unlike BiP/DnaK [PMID:8131751 "In contrast to purified BiP and dnaK, however, STCH demonstrates ATPase activity that is independent of peptide stimulation."]. Because it lacks the canonical substrate-binding domain, classic HSP70 substrate-refolding (foldase) activity is NOT expected; IBA terms transferred from canonical HSP70s (protein refolding, ATP-dependent protein folding chaperone, protein folding chaperone) are likely over-annotations for STCH.

## Localization
- Microsome / endoplasmic reticulum; migrates as a 60 kDa species enriched in membrane-bound microsome fraction [file:human/HSPA13/HSPA13-uniprot.txt "SUBCELLULAR LOCATION: Microsome. Endoplasmic reticulum."; PMID:8131751 "is enriched in a membrane-bound microsome fraction."]. Has a hydrophobic leader/signal sequence.
- GOA also has IBA nucleus, plasma membrane, cytosol (transferred from the broad HSP70 PANTHER family) - these conflict with the documented ER/microsomal localization and should be treated cautiously (likely over-annotation by family transfer).
- extracellular exosome (HDA, PMID:19199708): proteomic detection in exosomes; non-core.

## Expression / induction
- Constitutively expressed in all tissues; induced by calcium ionophore A23187 but NOT by heat shock [PMID:8131751 "constitutively expressed in all human cell types and is induced by incubation with the calcium ionophore A23187, but not by exposure to heat shock."]. HPA: low tissue specificity.

## Interactions / function
- Binds a family of ubiquitin-like (UbL) proteins (ubiquilins) via a short peptide in its ATPase domain [PMID:10675567 "two human ubiquitin-like (UbL) proteins that bind to a short peptide within the ATPase domain of the Hsp70-like Stch protein."]. These = Chap1/Dsk2 (UBQLN-like) and Chap2/scythe (BAG6-related). UniProt SUBUNIT: "Binds UBQLN2." IntAct partners: UBQLN1 (Q9UMX0), UBQLN2 (Q9UHD9), UBQLN4 (Q9NRR5), SGTA (O43765), SGTB (Q96EQ0), CRYGA, B4GALT5. Suggests roles in protein quality control / ubiquitin-proteasome and ER-associated degradation rather than classic refolding.
- The UbL interaction links HSP70-like ATPase family to cell-cycle and apoptosis regulation [PMID:10675567].

## GO review plan
- ATPase activity (GO:0016887, IBA; ATP binding GO:0005524 IEA): ACCEPT - genuine, peptide-independent ATPase is the documented MF.
- ER (GO:0005783, IEA-SubCell): ACCEPT - documented microsomal/ER localization.
- protein refolding (GO:0042026, IBA); protein folding chaperone (GO:0044183, IBA); ATP-dependent protein folding chaperone (GO:0140662, IEA InterPro - note: this term is in the DR lines but not in goa.tsv stub annotations) : MARK_AS_OVER_ANNOTATED / MODIFY - STCH truncates the peptide-binding domain and has peptide-INDEPENDENT ATPase; classic foldase/refolding is not supported and these are family-transfer over-annotations.
- heat shock protein binding (GO:0031072, IBA): KEEP_AS_NON_CORE / ACCEPT - plausible HSP70-family interaction; weakly supported for this paralog.
- nucleus, plasma membrane, cytosol (IBA, broad HSP70 family): MARK_AS_OVER_ANNOTATED - conflict with documented ER/microsome localization.
- protein binding (IPI) WITH UBQLN1/2/4 etc: MODIFY a representative to "ubiquitin-like protein... binding"? The cleanest informative term: these are ubiquilins (UBL-domain shuttle factors). Use "K63-linked..."? No. Safest specific: many partners are co-chaperones (SGTA/SGTB) and ubiquilins. KEEP_AS_NON_CORE the generic high-throughput ones; the UBQLN ones reflect a genuine, documented interaction -> could MODIFY to "ubiquitin protein ligase binding"? Not accurate. Keep most as KEEP_AS_NON_CORE; note UBQLN interaction in findings.
- extracellular exosome (HDA): KEEP_AS_NON_CORE.
- intracellular membrane-bounded organelle (TAS PMID:8131751): consistent with ER/microsome; KEEP_AS_NON_CORE (generic).

## Core function
- Microsomal/ER-associated atypical HSP70-family ATPase with peptide-independent ATPase activity (GO:0016887 / ATP binding GO:0005524), functioning in protein quality control in association with ubiquilin (UbL) shuttle factors and SGT co-chaperones, rather than as a classical substrate-refolding foldase.
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