| Feature | Detail | Key Reference |
|---|---|---|
| Gene identity | **hsp-110** corresponds to **C30C11.4** in **Caenorhabditis elegans** and encodes the organism’s **single cytosolic HSP110-type nucleotide exchange factor (NEF)** for HSP70; this matches the UniProt entry Q05036 and distinguishes it from two ER-localized Grp170 family members. | (pqac-00000013, pqac-00000023) |
| Protein family | HSP-110 belongs to the **HSP70 superfamily / HSP110 subfamily**. Like other HSP110 proteins, it contains an **N-terminal nucleotide-binding domain**, **β-sandwich peptide-binding domain**, and **α-helical bundle**, with characteristic insertions including an acidic loop that distinguishes HSP110 proteins from canonical HSP70s. | (pqac-00000015, pqac-00000016, pqac-00000021, pqac-00000022) |
| Primary molecular function | The best-supported primary function is to act as a **nucleotide exchange factor for HSP70/HSC70**, promoting **ADP release and ATP rebinding** on HSP70 and thereby enabling substrate release and repeated chaperone cycles during protein quality control. In metazoan disaggregation, this NEF activity is the key catalytic contribution of HSP110. | (pqac-00000004, pqac-00000015, pqac-00000018, pqac-00000020) |
| Biochemical role in disaggregation | HSP-110 is essential for the **HSP70-HSP40-HSP110 disaggregase system** that solubilizes and reactivates aggregated proteins after stress. Direct work in C. elegans showed that HSP-110 is required for clearing heat-induced luciferase aggregates in vivo. | (pqac-00000000, pqac-00000002, pqac-00000007, pqac-00000013) |
| ATP dependence / mechanism | Structural and biochemical studies of the HSP110 family show that **ATP binding to HSP110 is required for productive interaction with HSP70**, whereas **ATP hydrolysis by HSP110 is not essential** for its NEF function. HSP110 opens the HSP70 NBD through extensive NBD-NBD contacts and associated conformational changes. | (pqac-00000015, pqac-00000016, pqac-00000017) |
| Additional chaperone properties | Beyond NEF activity, HSP110 family proteins can function as **holdase chaperones** that bind unfolded proteins and help prevent aggregation, though in disaggregation assays the central requirement is still the HSP70-directed NEF activity. | (pqac-00000018, pqac-00000034, pqac-00000036) |
| Subcellular localization | In C. elegans, HSP-110 is identified as the **sole cytosolic HSP110-type NEF**. Available direct evidence supports **cytosolic function**, especially in muscle-cell proteostasis assays; by analogy with other eukaryotic HSP110 systems, related proteins can support disaggregation in both cytosol and nucleus, but C. elegans-specific nuclear localization evidence is limited. | (pqac-00000023, pqac-00000014) |
| Key interacting partners | Core functional partners are **HSP70/HSC70** and **J-domain proteins (HSP40s)**. The disaggregation machinery depends on cooperation between HSP110 and HSP70, while class A and class B J-proteins target aggregates and help recruit/activate HSP70 for extraction and refolding cycles. | (pqac-00000024, pqac-00000025, pqac-00000027, pqac-00000032, pqac-00000033) |
| Pathway involvement | hsp-110 functions in the **cytosolic proteostasis network**, specifically the **metazoan HSP70-based protein disaggregation pathway** that responds to heat stress, age-associated aggregation, and misfolded proteins. It is part of stress-recovery and aggregate-clearance pathways rather than a classic signaling enzyme pathway. | (pqac-00000024, pqac-00000025, pqac-00000027) |
| Relationship to heat stress | In worms subjected to heat shock, HSP-110 is required for efficient **recovery from proteotoxic stress**. Loss of HSP-110 leaves heat-induced aggregates persistent and insoluble, indicating failure of post-stress protein recovery. | (pqac-00000001, pqac-00000007, pqac-00000013) |
| Loss-of-function phenotype: viability | **Complete hsp-110 knockout is lethal**, indicating an essential housekeeping role in proteostasis. More moderate systemic RNAi knockdown also affects growth, development, and fertility. | (pqac-00000009) |
| Loss-of-function phenotype: aggregate clearance | RNAi depletion of hsp-110 causes a strong defect in **resolubilization of heat-induced luciferase aggregates** in vivo; aggregates persist at 12–24 h after heat shock instead of clearing during recovery. | (pqac-00000002, pqac-00000007, pqac-00000013) |
| Loss-of-function phenotype: lifespan after stress | Under normal conditions, hsp-110 knockdown causes only a modest lifespan decrease, but after heat shock it causes a **dramatic shortening of lifespan (~4.5 days)**, indicating that HSP-110 becomes especially critical under high aggregation load. | (pqac-00000002, pqac-00000007) |
| Loss-of-function phenotype: amyloid models | In contrast to its protective role in general proteostasis, HSP-110 depletion can **reduce α-synuclein and polyQ foci formation, spreading, and toxicity** in worm disease models, showing that the disaggregase can be a **double-edged sword** by generating toxic amyloid-competent species while still supporting overall protein homeostasis. | (pqac-00000006, pqac-00000010, pqac-00000011) |
| Expert interpretation | Authoritative reviews and mechanistic papers converge on the view that HSP110 is the **major metazoan HSP70 NEF** and a central amplifier of disaggregation capacity, acting early in aggregate processing and enabling efficient HSP70 cycling on difficult aggregate substrates. | (pqac-00000005, pqac-00000032, pqac-00000033, pqac-00000036) |


*Table: This table summarizes the core functional annotation of C. elegans hsp-110/C30C11.4, including identity, molecular role, localization, partners, phenotypes, and pathway context. It is useful as a concise evidence-backed overview for gene annotation and literature review.*