| Category | Key points | Evidence type (review/primary/proteomics) | Top citations (pqac-IDs) |
|---|---|---|---|
| Identity/domains | Human CRISP2 is UniProt P16562; recent human sperm work explicitly maps peptides to isoforms P16562-1 and P16562-2. It is a CAP superfamily/CRISP-family protein with an N-terminal CAP domain and a C-terminal cysteine-rich CRISP domain (including hinge/ICR features); the family is linked to ion-channel regulation and reproduction. | Primary + review | (pqac-00000001, pqac-00000003, pqac-00000008, pqac-00000010, pqac-00000014) |
| Expression | CRISP2 is the mammalian CRISP most tightly associated with testicular germ cells and spermatogenesis. In human tissue, expression is seen through spermatogenic stages and not in epididymal epithelium; in sperm proteomics it is repeatedly detected in ejaculated sperm. | Primary + review + proteomics | (pqac-00000002, pqac-00000018, pqac-00000020, pqac-00000021, pqac-00000028) |
| Subcellular localization | In human testis, hCRISP2 localizes to nuclei of primary spermatocytes, round spermatids, and early elongated spermatids; later also to cytoplasm, flagellum, and equatorial segment. In ejaculated sperm, signal is reported in cytoplasmic droplet, flagellum, equatorial segment, and basal head/connecting-piece regions. Evidence comes from immunofluorescence/confocal z-stacks, antibody controls, western blotting, immunoprecipitation, and MS. | Primary | (pqac-00000018, pqac-00000019, pqac-00000020, pqac-00000021, pqac-00000023, pqac-00000024) |
| Molecular mechanisms | Current understanding supports CRISP2 as a structural/functional sperm protein rather than an enzyme. Review-level evidence places CRISP2 in Ca2+ signaling via regulation of ryanodine receptor-mediated Ca2+ flux and more broadly in ion-channel modulation relevant to motility, capacitation, and acrosome reaction. A 2024 JBC study also shows CRISP2 can bind sterol and mediate sterol export, adding a biochemical activity within the CAP domain framework. | Review + primary | (pqac-00000012, pqac-00000015, pqac-00000017, pqac-00000035, pqac-00000040) |
| Binding partners/regulators | CRISP2 is reported in sperm protein complexes and has literature-supported interactions with MAP3K11/MLK3 and GGN1; human sperm IP-MS recovered CRISP2 with co-detected proteins including ACR and ACRBP. In 2024, A1BG was shown to bind CRISP2 with high affinity and inhibit its sterol-binding/export activity; interaction requires Mg2+ and maps mainly to A1BG Ig3. | Primary + review + proteomics | (pqac-00000003, pqac-00000012, pqac-00000017, pqac-00000034, pqac-00000038) |
| Disease/phenotype links | The strongest human disease link is male infertility, especially sperm motility-related phenotypes. Recent review summaries cite miR-27b/miR-27b-3p and miR-509-5p as CRISP2-related regulators in azoospermia/NOA or asthenozoospermia contexts; higher miR-27b is associated with impaired sperm morphology/progressive motility and inverse association with CRISP2 protein. Open Targets currently lists only weak target–disease association evidence for CRISP2 in male infertility. | Review + database | (pqac-00000029, pqac-00000030, pqac-00000031, pqac-00000032, pqac-00000000) |
| Applications/biomarkers | CRISP2 is already used in sperm/ejaculate proteomics panels as a testis-specific or fertility-relevant protein and is discussed as a candidate biomarker for male infertility screening, though direct clinical implementation remains limited. Its localization and sperm-specificity also keep it of interest as a prospective fertility or contraceptive target. | Proteomics + review | (pqac-00000028, pqac-00000017) |
| Key quantitative data | Human ejaculate proteomics (2023) reported CRISP2 validated unique peptides: ejaculate 11, seminal plasma 30, spermatozoa 8; NSAF values 0.49, 0.383, and 0.474, respectively. In 2024 biochemical studies, A1BG bound CRISP2 with Kd about 13.72 ± 2.5 nM (also ~10.3 ± 2.4 nM under Mg2+ conditions), Ig3 bound with Kd about 13.8 ± 1.14 nM, and A1BG coexpression inhibited CRISP2/Pry-family sterol secretion by >50%; CRISP2 bound cholesterol sulfate with reported Kd values in low micromolar to nanomolar/Mg2+-dependent assay ranges depending on assay conditions. | Proteomics + primary | (pqac-00000028, pqac-00000034, pqac-00000035, pqac-00000038, pqac-00000039) |


*Table: This table summarizes the current evidence-based functional annotation of human CRISP2 (UniProt P16562), including identity, localization, mechanisms, fertility links, and quantitative findings. It emphasizes recent 2023-2024 data where available while anchoring claims to authoritative reviews and primary studies.*