HSPA2 is annotated to chaperone/ATPase-related GO terms via InterPro-to-GO mapping reflecting HSP70 family membership.

Manual transfer of experimentally-verified annotation by curator judgment of sequence similarity supports HSPA2 spermatogenesis-related and chaperone roles inferred from mouse Hspa2 orthology.

PANTHER phylogenetic-tree annotation propagates conserved Hsp70 chaperone functions (ATP binding, ATP hydrolysis, protein folding chaperone, refolding, protein binding) to human HSPA2.

UniProtKB keyword 'Nucleotide-binding' maps to GO:0000166 nucleotide binding for HSPA2 based on its conserved HSP70 ATPase domain.

HSPA2 UniProt subcellular location annotations (cytoplasm, nucleus) are mapped to corresponding GO cellular component terms.

Ensembl Compara orthology-based transfer propagates experimentally validated HSPA2 functions (spermatogenesis, meiotic regulation, chaperone activity) from mouse Hspa2 (Hsp70-2) orthologs.

ARBA machine-learning model assigns HSPA2 to chaperone/cellular-stress GO terms based on HSP70 family signatures.

Combined automated IEA pipelines annotate HSPA2 with ATP binding, ATP hydrolysis activity, and protein folding terms from UniProt features.

HSPA2 is a human HSP70-family ATP-dependent molecular chaperone whose major supported roles are proteostasis, male germ-cell/sperm maturation, and extracellular vesicle-associated redistribution under proteotoxic stress.

HSPA2 was identified in a proteome-scale map of the human protein-protein interaction network.

HSPA2 was captured in a protein-protein interaction network curated for human inherited ataxias and disorders.

HSPA2 is detected in urinary exosomes by large-scale proteomics, supporting an extracellular vesicle-associated pool.

HSPA2 was detected in the membrane proteome of NK cells, consistent with cell-surface or membrane-associated chaperone pools.

HSPA2 is part of the mammalian HSP70 machine and exhibits distinct chaperone-like activities including foldase and refolding capacities differentiated from other HSP70 paralogs.

HSPA2 is detected in proteomic characterization of the human sperm nucleus, consistent with its prominent expression and role in spermatogenesis.

HSPA2 was identified in plasma microvesicles from healthy donors, consistent with extracellular vesicle association.

A novel methyltransferase modulates HSP70 protein function through lysine methylation, with effects on the HSP70 family including HSPA2.

HSPA2 is part of a quantitative chaperone interaction network defining the architecture of cellular protein homeostasis pathways.

HSPA2 is included in a proteome-scale map of the human binary interactome.

HSPA2 appears in a human interactome map defining protein communities and disease networks.

Structure and expression of an HSP70 'cognate' family member, contextualizing HSPA2 within the HSPA family architecture.

Genetic variants extensively disrupt HSPA2 protein interactions, supporting its broad chaperone-network role.

HSPA2 is included in a reference map of the human binary protein interactome.

Interactome mapping highlights HSPA2 in a network of neurodegenerative disease proteins, consistent with chaperone roles in protein-aggregation pathology.

HSPA2 is part of dual proteome-scale networks revealing cell-specific remodeling of the human interactome.

OpenCell endogenous-tagging map places HSPA2 in cytoplasmic locations, supporting its primary cytosolic chaperone role.

Multimodal cell maps integrating localization and interaction data place HSPA2 within structural/functional genomics modules consistent with chaperone network membership.

Cloning and chromosomal mapping of the human HSP70-2 (HSPA2) gene establishes the genomic identity of HSPA2 on chromosome 14.

Targeted disruption of mouse Hsp70-2 (HSPA2 ortholog) causes failed meiosis and germ-cell loss, providing in vivo IMP evidence for HSPA2 in spermatogenesis and meiotic progression.

Demonstrates HSPA2 is an EV-associated protein. Proteotoxic stress (proteasome inhibition with bortezomib) shifts HSPA2 from intracellular pools to extracellular release in EVs. Validated using CRISPR/Cas9 HSPA2 knockout pools and GFP-HSPA2 overexpression. EV mean size approximately 105.6 nm.

HSPA2 supports spermatogenesis and post-meiotic sperm remodeling, including cytoplasmic extrusion and plasma membrane remodeling required for zona pellucida binding competence. Roles in enabling surface relocation of proteins needed for oocyte zona interaction during capacitation.

Quantified HSPA2 in human sperm (16 donors, approximately 19,200 sperm assessed). HA-bound sperm showed 68.9% HSPA2 positivity vs 28.6% uncapacitated and 22.9% capacitated (p<0.001). HA-bound sperm fraction was 21.4 plus/minus 7.4%.

Among 917 quantified proteins in seminal plasma proteomics, HSPA2 was more abundant in healthy controls than Sertoli cell-only phenotype (fold-change HC/SCO = 7.31, adjusted p=0.0217). Identifies HSPA2 as a promising non-invasive biomarker for spermatogenic function.

GTEx analysis (425 RA and 428 LV samples) showed diabetes associated with higher Hspa2 expression in LV myocardium. Higher circulating HSPA2 (highest quartile) was associated with impaired LV contractility, higher LV mass, and increased incident heart failure and cardiovascular death.

Lists HSPA2-associated interactors including DNAJB12, STIP1, HSPBP1, HSPA1A, HSPA8, HSP90AA1. Notes HSPA2 role in spermatogenesis and proposed interaction with SHCBP1L to support spindle integrity during male meiosis.