Affinage

ACR

Acrosin · UniProt P10323

Round 2 corrected
Length
421 aa
Mass
45.8 kDa
Annotated
2026-04-28
130 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ACR encodes acrosin, a sperm-specific trypsin-like serine protease stored as the inactive zymogen proacrosin in the acrosomal matrix, where it undergoes autocatalytic activation to 39 kDa and 35 kDa intermediates upon the acrosome reaction (PMID:11839395). Acrosin binds zona pellucida glycoproteins—primarily ZPA—through mannosyl, fucosyl, and sulfated glycan interactions, with the proenzyme region contributing to high-affinity binding, thereby mediating secondary sperm–zona retention and zona penetration (PMID:15950651, PMID:11739644). Combined knockout of ACR and PRSS21 in mice abolishes acrosomal exocytosis on the zona surface and zona/cumulus penetration in vitro (PMID:20484738), and a homozygous ACR nonsense mutation (p.Trp56X) in humans causes total fertilization failure due to zona penetration deficiency, rescued by ICSI (PMID:37004249).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1982 High

    Establishing acrosin's enzymology: purification of bovine (39 kDa) and human (49 kDa) acrosin to homogeneity and demonstration that divalent metal ions reversibly inhibit surface-bound acrosin activity provided the first biochemical framework for acrosin as a regulated trypsin-like protease in sperm.

    Evidence Protein purification to homogeneity with activity assays (BAEE/BANA substrates); metal inhibition and chelation-reversal on washed spermatozoa

    PMID:6802470 PMID:6815104

    Open questions at the time
    • No structural model of acrosin–zinc interaction
    • Physiological zinc concentration at the acrosome not determined
  2. 1983 High

    Immunofluorescence during human spermatogenesis showed that proacrosin first appears in haploid spermatids and is absent in globozoospermic (round-headed) sperm, establishing acrosin as an obligate acrosomal component whose presence is coupled to acrosome biogenesis.

    Evidence Indirect immunofluorescence with anti-acrosin and anti-outer acrosomal membrane antibodies on human testis sections and globozoospermic samples

    PMID:6357995

    Open questions at the time
    • Mechanism of proacrosin trafficking to the developing acrosome unknown
    • Whether proacrosin is required for acrosome formation or merely co-localized was not resolved
  3. 1989 High

    cDNA cloning revealed the complete primary structure of human proacrosin—a 421-amino-acid preproenzyme with a canonical His-Asp-Ser catalytic triad and a unique proline-rich C-terminal domain—and pharmacological inhibition of acrosin activity blocked the human acrosome reaction, linking protease activity to acrosomal function.

    Evidence cDNA cloning/sequencing from human testis; deduced active-site residues; dbcAMP-induced acrosome reaction assay with protease inhibitors

    PMID:2493394 PMID:2550339

    Open questions at the time
    • Function of the proline-rich C-terminal domain remained speculative
    • Substrate(s) of acrosin during the acrosome reaction not identified
  4. 1990 High

    Gene structure determination showed the human ACR gene contains five exons encoding the three catalytic residues on separate exons, and chromosomal mapping placed it at 22q13-qter, enabling comparative genomics with rodent orthologs.

    Evidence Genomic library screening, sequencing, and somatic cell hybrid mapping (human, rat, mouse)

    PMID:1783391 PMID:2114285 PMID:2606479

    Open questions at the time
    • Promoter regulatory elements driving testis-specific expression not functionally characterized
    • Reason for diploid versus haploid expression differences across species unresolved
  5. 1994 High

    Identification of Protein C inhibitor (PCI) as a physiological acrosin inhibitor—forming SDS-stable complexes with a rate constant of 3.7×10⁴ M⁻¹s⁻¹ and localizing near disrupted acrosomal membranes—revealed a scavenging mechanism for prematurely activated acrosin.

    Evidence In vitro kinetic inhibition assay; ELISA complex detection; immunoelectron microscopy on human sperm

    PMID:7521127

    Open questions at the time
    • In vivo relevance of PCI-acrosin inhibition during fertilization not tested genetically
    • Other endogenous acrosin inhibitors not systematically surveyed
  6. 1999 High

    Sulphated zona pellucida glycans were shown to bind a proacrosin domain distinct from the active site and to induce proacrosin activation, while macaque anti-acrosin antibodies failed to block zona penetration, raising the question of whether acrosin is necessary for zona penetration or instead functions in sperm–zona binding/retention.

    Evidence Monoclonal antibody competition and proacrosin activation assays; macaque anti-acrosin blocking IVF and immunoEM

    PMID:10369396 PMID:10418103

    Open questions at the time
    • Species-specific differences in acrosin requirement not explained mechanistically
    • Identity of the proacrosin ZP-binding domain not mapped at residue resolution
  7. 2001 High

    Using proacrosin-null mouse sperm and recombinant ZP proteins, it was established that ZP2 binds proacrosin via polysulfate–basic residue ionic interactions and that this interaction retains acrosome-reacted sperm on the zona; proacrosin also undergoes autocatalytic processing through defined 55→39→35 kDa intermediates.

    Evidence Solid-phase binding assays with proacrosin-null sperm; IVF displacement assay; zymography and Western blotting of activation intermediates

    PMID:11739644 PMID:11839395

    Open questions at the time
    • Whether ZP2 binding and proteolytic activity are independent or coupled functions was unclear
    • Mouse KO showed only delayed penetration, leaving essentiality for zona penetration unresolved in any species
  8. 2005 High

    Recombinant human proacrosin/acrosin was shown to bind ZPA with highest affinity among ZP glycoproteins (with mannose, fucose, and sulfate as key glycan determinants) and the proenzyme fragment bound ZP 2.6–3× more strongly than mature acrosin, while sp32 (a proacrosin-binding protein) was identified as a capacitation-dependent tyrosine phosphoprotein in the acrosome.

    Evidence Solid-phase binding assay with recombinant ZP glycoproteins and carbohydrate competition; 2D Western blot and mass spectrometry of sp32 phosphorylation

    PMID:15950651 PMID:15955892

    Open questions at the time
    • How sp32 phosphorylation regulates proacrosin activation or release was not determined
    • Full glycan structural determinants on ZPA mediating acrosin binding not resolved
  9. 2010 High

    Double knockout of ACR and PRSS21 in mice produced subfertile males whose sperm completely failed to undergo acrosomal exocytosis on the zona surface and could not penetrate cumulus or zona in vitro, establishing that combined trypsin-like protease activity is essential for gamete interaction even though single knockouts retained partial function.

    Evidence ACR/PRSS21 double-KO mice; IVF, zona penetration assay, uterine injection rescue

    PMID:20484738

    Open questions at the time
    • Molecular substrates cleaved by ACR versus PRSS21 not distinguished
    • Female tract factors that partially compensate in vivo not identified
  10. 2023 High

    A homozygous ACR nonsense mutation (p.Trp56X) in two infertile brothers caused total fertilization failure with zona penetration deficiency but preserved sperm–zona binding, gamete fusion, and oocyte activation; ICSI rescued fertility, providing definitive human genetic evidence that acrosin is specifically required for zona penetration in humans.

    Evidence Whole-exome sequencing; Western blot and immunostaining for acrosin loss; TEM of acrosomal defects; subzonal insemination and ICSI rescue

    PMID:37004249

    Open questions at the time
    • Only one family reported; additional alleles needed to confirm genotype-phenotype spectrum
    • Whether acrosomal ultrastructural defects are secondary to acrosin loss or a direct structural role is unresolved
    • No crystal structure of human acrosin exists

Open questions

Synthesis pass · forward-looking unresolved questions
  • The precise set of acrosomal and zona pellucida substrates cleaved by acrosin during zona penetration, the structural basis for the proenzyme region's enhanced ZP binding, and how acrosin coordinates with other acrosomal proteases remain unresolved.
  • No acrosin substrate profiling by proteomics has been performed
  • No crystal structure of acrosin or proacrosin–ZP complex exists
  • Mechanism of sp32-mediated regulation of proacrosin activation is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0016787 hydrolase activity 6
Localization
GO:0031410 cytoplasmic vesicle 4 GO:0005576 extracellular region 2
Pathway
R-HSA-1474165 Reproduction 6
Partners
ACRV1PRSS21SERPINA5ZP1ZP2ZP3

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 The primary structure of human proacrosin was deduced from cDNA cloning: the 421-amino-acid preproenzyme contains a 19-residue signal peptide, a light chain segment, and a heavy chain with a catalytic site. The active-site residues histidine (69), aspartic acid (123), and serine (221) were identified, and a proline-rich C-terminal domain unique to acrosin was noted. cDNA cloning and sequencing from human testis library; deduced amino acid sequence analysis FEBS letters High 2493394
1989 The chromosomal gene encoding human preproacrosin (ACR) was mapped to chromosome 22q13-qter using somatic cell hybrid analysis; a restriction fragment length polymorphism with SstI was identified in the gene. Somatic cell hybrid analysis with human-rodent hybrids containing variant chromosome 22 complements; Southern blotting Human genetics High 2606479
1990 The human proacrosin gene contains four introns and five exons; the three active-site residues (His, Asp, Ser) are each encoded by separate exons (E2, E3, E5), and the proline-rich domain is co-encoded with the serine active-site residue in exon E5. The gene lacks canonical TATA and CAAT boxes near the transcription start site. Genomic library screening, restriction mapping, sequencing, primer extension analysis European journal of biochemistry High 2114285
1990 Human preproacrosin cDNA cloning confirmed 70% amino acid sequence identity with boar proacrosin; the leader sequence, catalytic triad (His, Asp, Ser), disulfide-bonding cysteine positions, and C-terminal proline-rich sequence are conserved between species, while the proline-rich region is species-specific. cDNA library screening, nucleotide sequencing, comparative amino acid sequence analysis Human genetics High 2298447
1991 The rat proacrosin gene (ACR) was mapped to chromosome 7 by analysis of mouse × rat somatic cell hybrids, establishing synteny with the human chromosome 22q13-qter locus. Somatic cell hybrid panel analysis with rat chromosome segregation Cytogenetics and cell genetics High 1906796
1991 The mouse proacrosin gene comprises six exons and five introns (one intron in the 5'-UTR); the gene is located on mouse chromosome 15 bands E/F, and unusually is expressed diploid (in pre-meiotic spermatocytes) in the mouse, contrasting with haploid expression in bull, boar, and rat. Active-site residues His, Asp, and Ser are encoded by exons E2, E3, and E5 respectively. Cosmid library screening, gene mapping, primer extension, in situ hybridization, expression analysis during spermatogenesis Genomics High 1783391
1991 Acrosin is a sperm-specific serine protease stored as proacrosin in the acrosome; the acrosin molecule contains a novel proline-rich C-terminal domain (absent from other serine proteases) that may confer DNA-binding properties, in addition to the standard serine protease catalytic triad. Biochemical characterization and primary structure analysis across species Human genetics High 1937464
1982 Divalent metal ions (Zn²⁺, Cu²⁺, Hg²⁺, Co²⁺, Cd²⁺) potently inhibit surface-bound acrosin activity on human and bovine spermatozoa; removal of zinc or copper from the inhibited enzyme completely restores activity, suggesting that zinc in genital tract fluids physiologically regulates acrosin activity. Enzymatic activity assay (BANA substrate) on washed spermatozoa; metal chelation and restoration experiments International journal of andrology Medium 6815104
1982 Bovine acrosin (MW 39 kDa; specific activity 93 U/mg) and human acrosin (MW 49 kDa) were purified to homogeneity using HCl extraction, gel filtration, and affinity chromatography, providing the first detailed purification schemes for both species. Protein purification: saline/Triton X-100 washes, HCl extraction, gel filtration, ion-exchange and affinity chromatography; activity assay with BAEE Canadian journal of biochemistry High 6802470
1983 Immunofluorescence during human spermatogenesis showed that proacrosin and the outer acrosomal membrane first appear in haploid spermatids and increase through spermiogenesis; round-headed (globozoospermic) spermatozoa completely lack proacrosin, acrosin, and the outer acrosomal membrane, demonstrating that acrosin is an obligate acrosomal component. Indirect immunofluorescence with anti-acrosin and anti-outer acrosomal membrane antibodies; gelatin substrate film technique for gelatinolytic activity Human genetics High 6357995
1985 Purified bovine sperm acrosin activates platelet adenylate cyclase 5–8-fold, comparable in potency to trypsin and α-chymotrypsin; this activation is blocked by serine protease inhibitors (leupeptin, SBTI, α2-macroglobulin), identifying acrosin as a trypsin-like protease capable of activating adenylate cyclase via proteolytic activity. Adenylate cyclase activity assay with purified acrosin; protease inhibitor panel; enzyme extraction from bovine sperm The Journal of biological chemistry Medium 3880736
1989 Proteinase inhibitors of proacrosin activation and acrosin activity (AGB and para-aminobenzamidine) significantly inhibit the dbcAMP-induced human sperm acrosome reaction at concentrations of 10⁻⁶–10⁻⁴ M, demonstrating that acrosin (a serine proteinase) plays a functional role in the human sperm acrosome reaction downstream of the adenylate cyclase system. Human synchronous acrosome reaction assay with dbcAMP stimulation; acrosome reaction scoring with proteinase inhibitors added at onset or after capacitation Gamete research Medium 2550339
1994 Protein C inhibitor (PCI) directly inhibits acrosin: purified human PCI inhibited boar acrosin amidolytic activity with an apparent second-order rate constant of 3.7 × 10⁴ M⁻¹·s⁻¹, forming SDS-stable complexes with acrosin. PCI was immunolocalized exclusively near disrupted acrosomal membranes of morphologically abnormal spermatozoa, suggesting PCI scavenges prematurely activated acrosin. In vitro enzymatic inhibition assay; ELISA for complex formation; immunocytochemistry and immunoelectron microscopy The American journal of physiology High 7521127
1999 Sulphated polymers (fucoidan, solubilised zona pellucida glycoproteins [ZPGs], and ARIS) bind to a domain on proacrosin distinct from the active site, induce proacrosin activation, and inhibit sperm binding to the zona pellucida; heparin did not share this activity. ARIS induced human proacrosin activation, indicating that ZP glycan chains regulate acrosomal protease activity. Monoclonal antibody competition binding assay; proacrosin activation assay; sperm-ZP binding inhibition assay Zygote (Cambridge, England) Medium 10418103
1999 In macaque sperm, acrosin is not detectable on the inner acrosomal membrane after zona pellucida-induced acrosome reaction (only in the acrosomal shroud), and anti-acrosin antibodies do not inhibit sperm penetration of the zona pellucida; in contrast, anti-PH-20 IgG completely blocks zona penetration, indicating acrosin is not critical for secondary sperm-zona binding or zona penetration in macaques. Immunoelectron microscopy with anti-acrosin IgG/SBTI; in vitro fertilization zona penetration blocking assay Molecular reproduction and development High 10369396
2001 Mouse zona pellucida glycoprotein ZP2 binds to proacrosin/acrosin via a strong ionic interaction between polysulfate groups on mZP2 and basic residues on an internal proacrosin peptide; proacrosin-null sperm bind mZP2 considerably less effectively than wild-type. Suramin and sulphated polymers compete with mZP2 for proacrosin binding and displace sperm from eggs in an IVF system, establishing that mZP2-proacrosin interaction is required for retention of acrosome-reacted sperm on the zona during fertilization. Solid-phase binding assays; proacrosin-null mouse sperm; in vitro fertilization sperm displacement; genetic (null) and biochemical approaches Journal of cell science High 11739644
2002 Acrosin (encoded by ACR) exhibits trypsin-like serine protease activity in the acrosome; knockout of proacrosin/acrosin in mice produces sperm that penetrate the zona pellucida with a delay but can still fertilize, indicating acrosin is not essential for zona penetration in mice but functions in limited proteolysis and/or processing of acrosomal proteins during the acrosome reaction. Review integrating gene-knockout mouse data and enzymatic studies Human reproduction update High 12398221
2002 Human proacrosin (55 kDa) undergoes autocatalytic activation to enzymatically active intermediates of 39 and 35 kDa; activation is completely inhibited by 9 mM CaCl₂ or 100 mM benzamidine. Immunoreactive bands of 52, 43, 34, 21–26, and 16 kDa were identified during activation, mapping the sequential processing steps of proacrosin to acrosin. Zymography; Western blotting with monoclonal antibody AcrC5F10; immunocytochemistry; protease inhibitor assays Journal of reproductive immunology High 11839395
2005 The sp32 proacrosin-binding protein is tyrosine-phosphorylated during capacitation of pig sperm: sp32 appears as a phosphotyrosine-positive Mr 32,000 spot only under capacitating conditions. After the ionophore-induced acrosome reaction, both anti-phosphotyrosine and anti-sp32 labeling on the acrosome disappear, linking proacrosin's binding partner sp32 to the capacitation-dependent phosphorylation cascade. 2D Western blotting; mass spectrometry/MS identification; immunoprecipitation with anti-phosphotyrosine and anti-sp32; indirect immunofluorescence Journal of andrology High 15955892
2005 Recombinant human proacrosin/acrosin binds to ZP glycoproteins in a saturable, high-affinity manner: rec-hZPA is the primary ligand (highest binding activity), followed by ZPB and ZPC. Binding is mediated by mannosyl, fucosyl, and sulfated glycans (inhibited by dextran sulfate, fucose, and mannose). The N-terminal proenzyme fragment (Rec-40) showed 2.6–3× higher binding than mature acrosin fragments, indicating the proregion participates in ZP binding. In vitro solid-phase binding assay with recombinant ZP glycoproteins; competition with carbohydrate inhibitors; Kd determination Fertility and sterility High 15950651
2010 Double-knockout mice lacking both ACR (acrosin) and PRSS21 (testisin) are subfertile; the double-KO sperm are completely unable to undergo acrosomal exocytosis on the zona pellucida surface and cannot traverse the zona or penetrate cumulus matrix in vitro, demonstrating that the combined trypsin-like protease activity of ACR and PRSS21 is essential for sperm penetration through cumulus and zona in vitro, while the female reproductive tract partially compensates in vivo. Double-knockout mouse generation; in vitro fertilization assay; zona penetration assay; uterine injection of mutant sperm; recovery of 2-cell embryos Biology of reproduction High 20484738
2019 Fluoride exposure reduces sperm fertilizing ability by downregulating ACR protein expression specifically in the epididymis (not testis), along with SPAM1 and PRSS21; fluoride also reduces the ability of sperm to break down the egg cumulus cell layer, linking ACR's trypsin-like activity to cumulus matrix penetration. Animal (rat) fluoride exposure model; Western blot; immunofluorescence; RNA extraction; sperm-egg binding assay Journal of agricultural and food chemistry Medium 31008594
2019 Sperm mitochondrial membrane potential (MMP) is positively correlated with acrosin activity; experimental MMP dissipation (by CCCP) causes significant declines in acrosin activity, acrosome reaction capability, and chromatin integrity, while increasing ROS and decreasing ATP, establishing that mitochondrial function is required to maintain ACR enzymatic activity in human sperm. JC-1 staining for MMP; BAPNA substrate assay for acrosin activity; CCCP treatment in vitro; chlortetracycline staining for AR; SCSA for DNA fragmentation; flow cytometry Human reproduction (Oxford, England) Medium 30428044
2023 A homozygous nonsense mutation in ACR (c.167G>A, p.Trp56X) identified by whole-exome sequencing in two infertile brothers causes ACROSIN deficiency, acrosomal ultrastructural defects, and total fertilization failure (TFF) in humans. Mutant sperm cannot penetrate the zona pellucida but retain normal sperm-zona binding, gamete fusion, and oocyte activation capacity (normal ACTL7A and PLCζ expression); fertilization was rescued by subzonal insemination and ICSI, confirming ACR's specific role in zona penetration. Whole-exome sequencing; protein expression analysis (Western blot/immunostaining); transmission electron microscopy of acrosome; subzonal insemination; ICSI rescue; IVF zona penetration assay Human reproduction (Oxford, England) High 37004249

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2000 DNA cloning using in vitro site-specific recombination. Genome research 815 11076863
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2023 The 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria. Arthritis & rheumatology (Hoboken, N.J.) 332 37635643
2023 2023 ACR/EULAR antiphospholipid syndrome classification criteria. Annals of the rheumatic diseases 287 37640450
1998 The 16-kDa alpha-crystallin (Acr) protein of Mycobacterium tuberculosis is required for growth in macrophages. Proceedings of the National Academy of Sciences of the United States of America 276 9689123
2018 The circular RNA ACR attenuates myocardial ischemia/reperfusion injury by suppressing autophagy via modulation of the Pink1/ FAM65B pathway. Cell death and differentiation 219 30349076
2023 Breast Cancer Screening for Women at Higher-Than-Average Risk: Updated Recommendations From the ACR. Journal of the American College of Radiology : JACR 199 37150275
2011 Pain persists in DAS28 rheumatoid arthritis remission but not in ACR/EULAR remission: a longitudinal observational study. Arthritis research & therapy 199 21651807
2011 Remission and radiographic outcome in rheumatoid arthritis: application of the 2011 ACR/EULAR remission criteria in an observational cohort. Annals of the rheumatic diseases 141 21994234
2005 acr-16 encodes an essential subunit of the levamisole-resistant nicotinic receptor at the Caenorhabditis elegans neuromuscular junction. The Journal of biological chemistry 120 15917232
2011 Proteomic characterization of the human sperm nucleus. Proteomics 116 21630459
2005 The Ror receptor tyrosine kinase CAM-1 is required for ACR-16-mediated synaptic transmission at the C. elegans neuromuscular junction. Neuron 109 15944127
2012 Near misses of ACR/EULAR criteria for remission: effects of patient global assessment in Boolean and index-based definitions. Annals of the rheumatic diseases 104 22736085
2004 Mapping DNA-protein interactions in large genomes by sequence tag analysis of genomic enrichment. Nature methods 93 15782160
2012 Charting the landscape of tandem BRCT domain-mediated protein interactions. Science signaling 92 22990118
2011 ACR appropriateness criteria retreatment of recurrent head and neck cancer after prior definitive radiation expert panel on radiation oncology-head and neck cancer. International journal of radiation oncology, biology, physics 85 21530100
1991 Acrosin, the peculiar sperm-specific serine protease. Human genetics 83 1937464
2003 A family of acr-coregulated Mycobacterium tuberculosis genes shares a common DNA motif and requires Rv3133c (dosR or devR) for expression. Infection and immunity 81 12933881
1976 Segmentation of human chromosomes induced by 5-ACR (5-azacytidine). Human genetics 78 63442
2002 Role of acrosomal matrix proteases in sperm-zona pellucida interactions. Human reproduction update 72 12398221
1989 Primary structure of human proacrosin deduced from its cDNA sequence. FEBS letters 69 2493394
2019 Mitochondrial functionality modifies human sperm acrosin activity, acrosome reaction capability and chromatin integrity. Human reproduction (Oxford, England) 65 30428044
2002 Identification of a Mycobacterium tuberculosis putative classical nitroreductase gene whose expression is coregulated with that of the acr aene within macrophages, in standing versus shaking cultures, and under low oxygen conditions. Infection and immunity 65 11854240
2010 Mice lacking two sperm serine proteases, ACR and PRSS21, are subfertile, but the mutant sperm are infertile in vitro. Biology of reproduction 64 20484738
2001 Interactions between mouse ZP2 glycoprotein and proacrosin; a mechanism for secondary binding of sperm to the zona pellucida during fertilization. Journal of cell science 64 11739644
2004 Dermatology position paper on the revision of the 1982 ACR criteria for systemic lupus erythematosus. Lupus 63 15580979
2005 The proacrosin binding protein, sp32, is tyrosine phosphorylated during capacitation of pig sperm. Journal of andrology 60 15955892
2005 An Isolate of Alternaria alternata That Is Pathogenic to Both Tangerines and Rough Lemon and Produces Two Host-Selective Toxins, ACT- and ACR-Toxins. Phytopathology 60 18943116
1991 Mouse proacrosin gene: nucleotide sequence, diploid expression, and chromosomal localization. Genomics 58 1783391
2015 ACR Appropriateness Criteria indeterminate renal mass. Journal of the American College of Radiology : JACR 57 25842014
2021 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) SLE classification criteria item performance. Annals of the rheumatic diseases 56 33568386
2018 Performance characteristics of rheumatoid factor and anti-cyclic citrullinated peptide antibody assays may impact ACR/EULAR classification of rheumatoid arthritis. Annals of the rheumatic diseases 55 29363510
2004 Review of ACR renal criteria in systemic lupus erythematosus. Lupus 54 15580982
2010 ACR appropriateness criteria on metastatic bone disease. Journal of the American College of Radiology : JACR 53 20522392
2012 The Canadian Early Arthritis Cohort (CATCH): patients with new-onset synovitis meeting the 2010 ACR/EULAR classification criteria but not the 1987 ACR classification criteria present with less severe disease activity. The Journal of rheumatology 50 22896026
2000 Anthelmintic actions on homomer-forming nicotinic acetylcholine receptor subunits: chicken alpha7 and ACR-16 from the nematode Caenorhabditis elegans. Neuroscience 49 11113327
2005 The American College of Rheumatology (ACR) Core Data Set and derivative "patient only" indices to assess rheumatoid arthritis. Clinical and experimental rheumatology 48 16273794
1994 Inhibition of acrosin by protein C inhibitor and localization of protein C inhibitor to spermatozoa. The American journal of physiology 48 7521127
1989 Inhibition of the human sperm acrosome reaction by proteinase inhibitors. Gamete research 48 2550339
2017 The 2010 ACR/EULAR criteria are not sufficiently accurate in the early identification of autoantibody-negative rheumatoid arthritis: Results from the Leiden-EAC and ESPOIR cohorts. Seminars in arthritis and rheumatism 46 28601249
2013 ACR-12 ionotropic acetylcholine receptor complexes regulate inhibitory motor neuron activity in Caenorhabditis elegans. The Journal of neuroscience : the official journal of the Society for Neuroscience 46 23536067
2020 ACR Appropriateness Criteria® Indeterminate Renal Mass. Journal of the American College of Radiology : JACR 45 33153554
1995 Tissue plasminogen activator coexpressed in Chinese hamster ovary cells with alpha(2,6)-sialyltransferase contains NeuAc alpha(2,6)Gal beta(1,4)Glc-N-AcR linkages. Biotechnology progress 45 7619404
2018 Comparing the disease course of patients with seronegative and seropositive rheumatoid arthritis fulfilling the 2010 ACR/EULAR classification criteria in a treat-to-target setting: 2-year data from the ARCTIC trial. RMD open 42 30564452
2019 ACR Appropriateness Criteria® Noninvasive Clinical Staging of Primary Lung Cancer. Journal of the American College of Radiology : JACR 40 31054745
2011 Level of agreement of the 1987 ACR and 2010 ACR/EULAR rheumatoid arthritis classification criteria: an analysis based on ESPOIR cohort data. Annals of the rheumatic diseases 40 22039167
1999 PH-20 but not acrosin is involved in sperm penetration of the macaque zona pellucida. Molecular reproduction and development 40 10369396
2020 The Oncogenic PRL Protein Causes Acid Addiction of Cells by Stimulating Lysosomal Exocytosis. Developmental cell 39 32918875
2011 ACR appropriateness criteria® adjuvant therapy for resected squamous cell carcinoma of the head and neck. Oral oncology 39 21664857
2013 American College of Radiology (ACR) and American Society for Radiation Oncology (ASTRO) practice guideline for the performance of total body irradiation (TBI). American journal of clinical oncology 38 23334484
2018 ACR Appropriateness Criteria® Breast Implant Evaluation. Journal of the American College of Radiology : JACR 37 29724416
1985 Extraction of the adenylate cyclase-activating factor of bovine sperm and its identification as a trypsin-like protease. The Journal of biological chemistry 37 3880736
2015 Oral administration of a select mixture of Bacillus probiotics generates Tr1 cells in weaned F4ab/acR- pigs challenged with an F4+ ETEC/VTEC/EPEC strain. Veterinary research 36 26384321
2012 ACR Appropriateness Criteria® ipsilateral radiation for squamous cell carcinoma of the tonsil. Head & neck 36 22250010
1995 Molecular cloning and functional co-expression of a Caenorhabditis elegans nicotinic acetylcholine receptor subunit (acr-2). Receptors & channels 36 8581398
2013 acr-23 Encodes a monepantel-sensitive channel in Caenorhabditis elegans. PLoS pathogens 34 23950710
2004 A genome annotation-driven approach to cloning the human ORFeome. Genome biology 32 15461802
1990 Nucleotide sequence and exon-intron organization of the human proacrosin gene. European journal of biochemistry 32 2114285
2016 Using the American College of Rheumatology (ACR) and Systemic Lupus International Collaborating Clinics (SLICC) criteria to determine the diagnosis of systemic lupus erythematosus (SLE) in patients with subacute cutaneous lupus erythematosus (SCLE). Journal of the American Academy of Dermatology 31 26897388
2016 ACR Appropriateness Criteria Renal Cell Carcinoma Staging. Journal of the American College of Radiology : JACR 31 27016804
1990 Molecular cloning of human preproacrosin cDNA. Human genetics 31 2298447
1983 Acrosin and the acrosome in human spermatogenesis. Human genetics 31 6357995
2008 Expression of the Mycobacterium tuberculosis acr-coregulated genes from the DevR (DosR) regulon is controlled by multiple levels of regulation. Infection and immunity 30 18391009
2006 Expression of mycobacterial cell division protein, FtsZ, and dormancy proteins, DevR and Acr, within lung granulomas throughout guinea pig infection. FEMS immunology and medical microbiology 30 17059468
2002 Evaluation of the proacrosin/acrosin system and its mechanism of activation in human sperm extracts. Journal of reproductive immunology 30 11839395
2019 Fluoride Interferes with the Sperm Fertilizing Ability via Downregulated SPAM1, ACR, and PRSS21 Expression in Rat Epididymis. Journal of agricultural and food chemistry 29 31008594
2017 In-hospital mortality in febrile lupus patients based on 2016 EULAR/ACR/PRINTO classification criteria for macrophage activation syndrome. Seminars in arthritis and rheumatism 29 28268026
2012 A polyketide synthase gene, ACRTS2, is responsible for biosynthesis of host-selective ACR-toxin in the rough lemon pathotype of Alternaria alternata. Molecular plant-microbe interactions : MPMI 28 22835272
2005 Resistance to fluoroquinolones linked to gyrA and par C mutations and overexpression of acr AB efflux pump in Salmonella enterica serotype Choleraesuis. Microbial drug resistance (Larchmont, N.Y.) 28 16201927
2021 ACR Appropriateness Criteria® Radiologic Management of Lower Gastrointestinal Tract Bleeding: 2021 Update. Journal of the American College of Radiology : JACR 27 33958109
2016 Pharmacological profile of Ascaris suum ACR-16, a new homomeric nicotinic acetylcholine receptor widely distributed in Ascaris tissues. British journal of pharmacology 27 27238203
1982 Inhibition of human and bovine sperm acrosin by divalent metal ions. Possible role of zinc as a regulator of acrosin activity. International journal of andrology 27 6815104
2019 ACR Appropriateness Criteria® Left Lower Quadrant Pain-Suspected Diverticulitis. Journal of the American College of Radiology : JACR 26 31054740
2014 Monepantel irreversibly binds to and opens Haemonchus contortus MPTL-1 and Caenorhabditis elegans ACR-20 receptors. Molecular pharmacology 26 25352042
2019 Retracted: Circular RNA ACR relieves high glucose-aroused RSC96 cell apoptosis and autophagy via declining microRNA-145-3p. Journal of cellular biochemistry 25 31886589
2023 Performance of the 2022 ACR/EULAR giant cell arteritis classification criteria for diagnosis in patients with suspected giant cell arteritis in routine clinical care. RMD open 24 37094980
2017 Use of SLICC criteria in a large, diverse lupus registry enables SLE classification of a subset of ACR-designated subjects with incomplete lupus. Lupus science & medicine 24 28409015
2014 ACR Appropriateness Criteria® nonsurgical treatment for locally advanced non-small-cell lung cancer: good performance status/definitive intent. Oncology (Williston Park, N.Y.) 24 25140629
2013 A genome-wide RNAi screen in Caenorhabditis elegans identifies the nicotinic acetylcholine receptor subunit ACR-7 as an antipsychotic drug target. PLoS genetics 24 23468647
1989 The gene encoding the human preproacrosin (ACR) maps to the q13-qter region on chromosome 22. Human genetics 24 2606479
2019 Isoform-specific GSK3A activity is negatively correlated with human sperm motility. Molecular human reproduction 23 30824926
2014 ACR appropriateness criteria post-treatment follow-up of renal cell carcinoma. Journal of the American College of Radiology : JACR 23 24793039
1997 ACR-3, a Caenorhabditis elegans nicotinic acetylcholine receptor subunit. Molecular cloning and functional expression. Receptors & channels 23 9606719
2023 ACROSIN deficiency causes total fertilization failure in humans by preventing the sperm from penetrating the zona pellucida. Human reproduction (Oxford, England) 22 37004249
1995 Cloning and partial characterization of the cDNA encoding the fox sperm protein FSA-Acr.1 with similarities to the SP-10 antigen. Molecular reproduction and development 22 7766418
1991 Chromosomal assignment of four rat genes coding for the spermatid-specific proteins proacrosin (ACR), transition proteins 1 (TNP1) and 2 (TNP2), and protamine 1 (PRM1). Cytogenetics and cell genetics 22 1906796
1982 Purification of bovine and human acrosin. Canadian journal of biochemistry 22 6802470
2019 ACR Appropriateness Criteria® Neck Mass-Adenopathy. Journal of the American College of Radiology : JACR 20 31054741
2016 The additional benefit of ultrasonography to 2010 ACR/EULAR classification criteria when diagnosing rheumatoid arthritis in the absence of anti-cyclic citrullinated peptide antibodies. Clinical rheumatology 20 27848057
2012 The features of the synovium in early rheumatoid arthritis according to the 2010 ACR/EULAR classification criteria. PloS one 20 22574210
2006 Usefulness of acr expression for monitoring latent Mycobacterium tuberculosis bacilli in 'in vitro' and 'in vivo' experimental models. Scandinavian journal of immunology 20 16784488
2018 ACR Appropriateness Criteria® Orbits Vision and Visual Loss. Journal of the American College of Radiology : JACR 19 29724415
2015 The advantages of PD1 activating chimeric receptor (PD1-ACR) engineered lymphocytes for PDL1(+) cancer therapy. American journal of translational research 19 26045887
2013 Nicotine-motivated behavior in Caenorhabditis elegans requires the nicotinic acetylcholine receptor subunits acr-5 and acr-15. The European journal of neuroscience 19 23351035
2013 Expression analysis of MND1/GAJ, SPATA22, GAPDHS and ACR genes in testicular biopsies from non-obstructive azoospermia (NOA) patients. Reproductive biology and endocrinology : RB&E 18 23675907
2005 Binding of recombinant human proacrosin/acrosin to zona pellucida (ZP) glycoproteins. I. Studies with recombinant human ZPA, ZPB, and ZPC. Fertility and sterility 18 15950651
1999 Functional interactions between sulphated polysaccharides and proacrosin: implications in sperm binding and digestion of zona pellucida. Zygote (Cambridge, England) 18 10418103
2023 Hesperidin ameliorates Amyloid-β toxicity and enhances oxidative stress resistance and lifespan of Caenorhabditis elegans through acr-16 mediated activation of the autophagy pathway. Free radical biology & medicine 17 37913913
2014 A novel antigen-carrier system: the Mycobacterium tuberculosis Acr protein carried by raw starch microparticles. International journal of pharmaceutics 17 25093695
2012 Xenopus laevis RIC-3 enhances the functional expression of the C. elegans homomeric nicotinic receptor, ACR-16, in Xenopus oocytes. Journal of neurochemistry 17 22970690
2020 Correlation between urine ACR and 24-h proteinuria in a real-world cohort of systemic AL amyloidosis patients. Blood cancer journal 16 33311451
1995 Construct validation of the ACR 1991 revised criteria for global functional status in rheumatoid arthritis. Clinical and experimental rheumatology 16 7554563
2025 EULAR/ACR risk stratification criteria for development of rheumatoid arthritis in the risk stage of arthralgia. Annals of the rheumatic diseases 15 40447498
2023 ACR Appropriateness Criteria® Staging and Post-Therapy Assessment of Head and Neck Cancer. Journal of the American College of Radiology : JACR 15 38040469
2011 Topography-induced cell adhesion to Acr-sP(EO-stat-PO) hydrogels: the role of protein adsorption. Macromolecular bioscience 15 21786421
2005 Interleukin-10 gene polymorphisms are associated with the SLICC/ACR Damage Index in systemic lupus erythematosus. Rheumatology (Oxford, England) 15 16287924
2016 The Ascaris suum nicotinic receptor, ACR-16, as a drug target: Four novel negative allosteric modulators from virtual screening. International journal for parasitology. Drugs and drug resistance 14 27054065
2016 ACR Appropriateness criteria® for nasopharyngeal carcinoma. Head & neck 14 27131050
2016 ACR Appropriateness Criteria(®) Locoregional therapy for resectable oropharyngeal squamous cell carcinomas. Head & neck 14 27330003
2013 ACR appropriateness criteria nonsurgical treatment for non-small-cell lung cancer: poor performance status or palliative intent. Journal of the American College of Radiology : JACR 14 23890874
2022 Thyroid Cancer Detection in a Routine Clinical Setting: Performance of ACR TI-RADS, FNAC, and Molecular Testing in Prospective Cohort Study. Biomedicines 13 35625691
2014 ACR appropriateness Criteria® early-stage non-small-cell lung cancer. American journal of clinical oncology 13 25180631
2023 Performance of the new 2022 ACR/EULAR classification criteria for giant cell arteritis in clinical practice in relation to its clinical phenotypes. Autoimmunity reviews 12 37598876
2023 Should ACR/EULAR criteria be revised changing the RF and ACPA scores? Autoimmunity reviews 12 37633353
2018 Phrasing of the patient global assessment in the rheumatoid arthritis ACR/EULAR remission criteria: an analysis of 967 patients from two databases of early and established rheumatoid arthritis patients. Clinical rheumatology 12 29468340
2013 ACR Appropriateness Criteria® radiation therapy for small-cell lung cancer. American journal of clinical oncology 12 23511336
2013 ACR Appropriateness Criteria® management of locoregionally advanced squamous cell carcinoma of the vulva. American journal of clinical oncology 12 23872794
2004 ACR classification criteria for systemic lupus erythematosus: complement components. Lupus 12 15580986
2025 EULAR/ACR classification criteria for paediatric chronic nonbacterial osteomyelitis (CNO). Annals of the rheumatic diseases 11 39966038
2023 External validation of the 2022 ACR/EULAR classification criteria in patients with suspected giant cell arteritis in a Dutch fast-track clinic. RMD open 11 37507207
2023 ACR Appropriateness Criteria® Imaging After Total Hip Arthroplasty. Journal of the American College of Radiology : JACR 11 38040462
2021 ACR Appropriateness Criteria® Noncerebral Vasculitis. Journal of the American College of Radiology : JACR 11 34794595
2019 ACR Appropriateness Criteria® Acute Respiratory Illness in Immunocompromised Patients. Journal of the American College of Radiology : JACR 11 31685101
2019 ACR Appropriateness Criteria® Post-Treatment Follow-up and Active Surveillance of Clinically Localized Renal Cell Cancer. Journal of the American College of Radiology : JACR 11 31685108
2016 ACR Appropriateness Criteria Fever Without Source or Unknown Origin-Child. Journal of the American College of Radiology : JACR 11 27374781
2010 ACR Appropriateness Criteria: nonsurgical treatment for non-small-cell lung cancer: good performance status/definitive intent. Current problems in cancer 11 20541060
2010 Combined influence of substrate stiffness and surface topography on the antiadhesive properties of Acr-sP(EO-stat-PO) hydrogels. Biomacromolecules 11 21033738
2005 Computational identification and systematic analysis of the ACR gene family in Oryza sativa. Journal of plant physiology 11 16455358