Annotation inferences using phylogenetic trees
Combined Automated Annotation using Multiple IEA Methods.
The human cysteine-rich secretory protein (CRISP) family. Primary structure and tissue distribution of CRISP-1, CRISP-2 and CRISP-3.
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First comprehensive characterization of human CRISP2 (TPX1) showing testis and epididymis-specific expression
"CRISP-2/TPX1 transcripts are detected mainly in the testis and also in the epididymis"
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Established CRISP2 as member of cysteine-rich secretory protein family
"We report the isolation and characterisation of cDNAs encoding three different, human members of the cysteine-rich secretory protein (CRISP) family... CRISP-2 cDNA corresponds to the previously described TPX1 form"
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Described tissue distribution patterns consistent with role in male reproduction
"Northern blot analysis of various human organs indicates that CRISP-1 transcripts are epididymis-specific whereas CRISP-2/TPX1 transcripts are detected mainly in the testis and also in the epididymis"
Deep research summary on CRISP2 gene function and biology
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CRISP2 localizes to acrosome and flagellum of sperm cells
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Functions as ion channel regulator, particularly for calcium channels
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Critical for sperm capacitation, motility, and acrosome reaction
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Contains CAP domain involved in protein-protein interactions and ion channel modulation
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Associated with male infertility when dysregulated
Falcon (Edison) deep research report on CRISP2 functional annotation
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Human-specific 2025 study confirms CRISP2 localization to nuclei across spermatogenic stages and in flagellum/equatorial segment of late elongated spermatids
"Late elongated spermatids:** CRISP2 also seen in the **flagellum** and the **equatorial segment (EqS)** of the acrosome"
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In ejaculated sperm CRISP2 is found in cytoplasmic droplet, flagellum, and equatorial segment
"In ejaculated sperm, CRISP2 is reported in the **cytoplasmic droplet**, **flagellum**, and **EqS**, consistent with roles in motility and gamete fusion"
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CRISP2 regulates sperm Ca2+ signaling through ryanodine receptor-mediated Ca2+ release and broader ion-channel modulation
"Review-level synthesis places CRISP2 in sperm Ca2+ signaling through **ryanodine receptor (RyR)-mediated Ca2+ release** and broader ion-channel modulation"
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Novel 2024 mechanistic advance — CRISP2 binds sterols (cholesterol sulfate) and mediates sterol export via the CAP domain; this is inhibited by A1BG binding (Kd ~13.7 nM, Mg2+-dependent)
"biochemical evidence that CRISP2 participates in **sterol binding and sterol export** in a yeast-based functional model and that this activity can be strongly regulated by A1BG"
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CRISP2 protein levels are negatively associated with miR-27b expression, linking it to sperm motility/morphology phenotypes
"high **miR-27b** expression is associated with reduced progressive motility and shows a **negative association with CRISP2 protein levels**"
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CRISP2 is integrated into sperm protein complexes with MAP3K11/MLK3 and GGN1, and co-precipitates with ACR/ACRBP
"review-level evidence reports CRISP2 binding partners including **MAP3K11/MLK3** (co-localizing in the acrosome) and **GGN1** (in the tail)"
Novel insights into human CRISP2: localization in reproductive tissues and sperm, and molecular characterization†.
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Direct human tissue immunolocalization showing CRISP2 in primary spermatocytes (faint nuclear puncta) through to late elongated spermatids (flagellum and equatorial segment)
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In epididymis, CRISP2 is detected in sperm within the lumen while the epididymal epithelium is negative
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IP-MS recovered CRISP2 with co-detected proteins including ACR and ACRBP, supporting participation in stable sperm complexes
The CAP superfamily: cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins--roles in reproduction, cancer, and immune defense.
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Authoritative review defining CRISPs as two-domain CAP/CRD proteins with N-terminal CAP domain implicated in protein–protein/cell–cell interactions and C-terminal CRISP domain linked to ion-channel regulatory activity
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CRISP2 produced during spermatogenesis and localized to acrosome, accessory tail structures, and developing germ-cell membrane; binding partners include MAP3K11/MLK3 and GGN1
Crisp proteins and sperm chemotaxis: discovery in amphibians and explorations in mammals.
Alpha-1-B glycoprotein (A1BG) inhibits sterol-binding and export by CRISP2.
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Demonstrates that CRISP2 binds cholesterol sulfate and mediates sterol export in a yeast assay, and that A1BG binds CRISP2 with high affinity (Kd ~13.7 nM, Mg2+-dependent) and inhibits sterol export by >50%
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Provides direct biochemical evidence that the CAP domain in CRISP2 has sterol-binding activity inhibited by A1BG
The Application of Ejaculate-Based Shotgun Proteomics for Male Infertility Screening.
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Quantitative LC-MS/MS detection of CRISP2 (P16562) in ejaculate, seminal plasma, and spermatozoa, with functional annotation as ion-channel regulator affecting calcium fluxes during sperm capacitation
MicroRNAs in spermatogenesis dysfunction and male infertility: clinical phenotypes, mechanisms and potential diagnostic biomarkers.
Proteomic biomarkers in seminal plasma as predictors of reproductive potential in azoospermic men.
UniProt entry for CRISP2 (P16562)
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Contains signal peptide (residues 1-21) indicating secretory pathway
"SIGNAL 1..21"
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Annotated as "Secreted" protein
"SUBCELLULAR LOCATION: Secreted"
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Contains SCP domain (41-169) and ShKT domain (205-238)
"DOMAIN 41..169 /note="SCP" ... DOMAIN 205..238 /note="ShKT""
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Testis and epididymis-specific tissue expression
"TISSUE SPECIFICITY: Testis and epididymis."
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May regulate ion channel activity and calcium fluxes during sperm capacitation
"May regulate some ion channels' activity and thereby regulate calcium fluxes during sperm capacitation."