Affinage

ACR

Acrosin · UniProt P10323

Length
421 aa
Mass
45.8 kDa
Annotated
2026-06-09
100 papers in source corpus 4 papers cited in narrative 4 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ACR encodes proacrosin/acrosin, a sperm protease that, together with PRSS21, provides the trypsin-like serine protease activity required for sperm penetration through the cumulus matrix and zona pellucida during fertilization (PMID:20484738). Genetic ablation in mice demonstrates that this proteolytic activity is essential for acrosomal exocytosis on the zona pellucida surface and for traversal of the zona pellucida in vitro, while loss is partially compensated by the female reproductive tract in vivo (PMID:20484738). The protein contributes to fertilizing capacity at the cumulus-penetration step, with epididymal ACR expression correlating with this function (PMID:31008594). The human gene is a single-copy locus on chromosome 22q13-qter (PMID:2606479). Beyond these functional and mapping data, no further mechanistic detail on substrate specificity or structural regulation has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 4 steps
  1. 1989 Medium

    Establishing the human ACR locus answered where the preproacrosin gene resides in the genome and confirmed it as a single-copy gene, a prerequisite for genetic and clinical follow-up.

    Evidence Somatic cell hybrid segregation analysis with Southern blotting and SstI RFLP in human cell panels

    PMID:2606479

    Open questions at the time
    • No functional characterization of the gene product
    • Mapping resolution limited to 22q13-qter band region
  2. 1991 Low

    Mapping the rodent ortholog confirmed conserved chromosomal localization of proacrosin across mammals, supporting cross-species relevance of the locus.

    Evidence Mouse × rat somatic cell hybrid segregation analysis

    PMID:1906796

    Open questions at the time
    • Chromosomal assignment only, no functional follow-up
    • Single method, single lab
  3. 2010 High

    Whether acrosin's protease activity is genuinely required for fertilization was resolved by double-knockout genetics, distinguishing an essential in vitro role from in vivo compensation.

    Evidence ACR/PRSS21 double-knockout mice with in vitro fertilization, acrosomal exocytosis on ZP, cumulus penetration, and intrauterine sperm injection assays

    PMID:20484738

    Open questions at the time
    • Redundancy between ACR and PRSS21 not fully partitioned to individual contributions
    • Molecular substrates cleaved during ZP traversal not identified
    • Mechanism of female-tract compensation in vivo unknown
  4. 2019 Low

    Linking epididymal ACR protein levels to cumulus-penetration capacity addressed whether post-testicular ACR expression contributes functionally to sperm fertilizing ability.

    Evidence In vivo fluoride exposure with western blot, immunofluorescence, RT-PCR, and sperm-egg binding assays in rat

    PMID:31008594

    Open questions at the time
    • Correlative toxicology design without genetic rescue
    • Cannot exclude off-target effects of fluoride on other sperm proteins
    • Single lab observational study

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular substrates of acrosin during zona pellucida penetration and the structural basis of proacrosin activation remain undefined in the available corpus.
  • No identified physiological substrates
  • No structural model of proacrosin activation
  • Mechanism of in vivo compensation uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 1 GO:0140096 catalytic activity, acting on a protein 1
Pathway
R-HSA-1474165 Reproduction 1
Partners
PRSS21

Evidence

Reading pass · 4 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 The human preproacrosin gene (ACR) was mapped to chromosomal region 22q13-qter using somatic cell hybrid panels, establishing it as a single-copy gene on chromosome 22. Somatic cell hybrid segregation analysis with Southern blotting; restriction fragment length polymorphism (RFLP) with SstI Human genetics Medium 2606479
1991 The rat proacrosin gene (ACR) was assigned to rat chromosome 7 by analysis of mouse × rat somatic cell hybrids, confirming orthologous chromosomal localization in rodents. Somatic cell hybrid segregation analysis Cytogenetics and cell genetics Low 1906796
2010 ACR (acrosin) and PRSS21 together provide trypsin-like serine protease activity required for sperm penetration through cumulus matrix and zona pellucida (ZP); double-knockout male mice were subfertile, and double-knockout epididymal sperm failed to undergo acrosomal exocytosis on the ZP surface and could not traverse the ZP in vitro, demonstrating that ACR's protease activity is essential for in vitro fertilization but partially compensated by the female reproductive tract in vivo. Double-knockout mouse generation (ACR and PRSS21 null); in vitro fertilization assays; intrauterine sperm injection; acrosomal exocytosis assay on ZP Biology of reproduction High 20484738
2019 Fluoride exposure selectively downregulated ACR protein expression in the rat epididymis (but not testis), correlating with reduced sperm ability to penetrate the egg cumulus cell layer, indicating that epididymal ACR protein contributes to sperm fertilizing capacity at the cumulus penetration step. In vivo fluoride exposure (NaF via drinking water); western blot; immunofluorescence; RT-PCR; sperm-egg binding assay Journal of agricultural and food chemistry Low 31008594

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2023 The 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria. Arthritis & rheumatology (Hoboken, N.J.) 357 37635643
2023 2023 ACR/EULAR antiphospholipid syndrome classification criteria. Annals of the rheumatic diseases 309 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 221 30349076
2011 Pain persists in DAS28 rheumatoid arthritis remission but not in ACR/EULAR remission: a longitudinal observational study. Arthritis research & therapy 207 21651807
2023 Breast Cancer Screening for Women at Higher-Than-Average Risk: Updated Recommendations From the ACR. Journal of the American College of Radiology : JACR 206 37150275
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 124 15917232
2005 The Ror receptor tyrosine kinase CAM-1 is required for ACR-16-mediated synaptic transmission at the C. elegans neuromuscular junction. Neuron 111 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
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
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
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
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
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
2010 ACR appropriateness criteria on metastatic bone disease. Journal of the American College of Radiology : JACR 55 20522392
2004 Review of ACR renal criteria in systemic lupus erythematosus. Lupus 55 15580982
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
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 49 23536067
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
2020 ACR Appropriateness Criteria® Indeterminate Renal Mass. Journal of the American College of Radiology : JACR 47 33153554
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
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 44 30564452
2019 ACR Appropriateness Criteria® Noninvasive Clinical Staging of Primary Lung Cancer. Journal of the American College of Radiology : JACR 42 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
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
2008 ACR Appropriateness Criteria on suspected osteomyelitis in patients with diabetes mellitus. Journal of the American College of Radiology : JACR 37 18657783
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
2013 acr-23 Encodes a monepantel-sensitive channel in Caenorhabditis elegans. PLoS pathogens 36 23950710
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
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
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 30 22835272
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
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
2018 ACR Practice Parameter for the Performance of Gallium-68 DOTATATE PET/CT for Neuroendocrine Tumors. Clinical nuclear medicine 28 30394933
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
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
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
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
2018 ACR Appropriateness Criteria® Orbits Vision and Visual Loss. Journal of the American College of Radiology : JACR 21 29724415
2019 ACR Appropriateness Criteria® Neck Mass-Adenopathy. Journal of the American College of Radiology : JACR 20 31054741
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
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
2025 EULAR/ACR risk stratification criteria for development of rheumatoid arthritis in the risk stage of arthralgia. Annals of the rheumatic diseases 18 40447498
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 18 37913913
2014 A novel antigen-carrier system: the Mycobacterium tuberculosis Acr protein carried by raw starch microparticles. International journal of pharmaceutics 18 25093695
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
2020 Correlation between urine ACR and 24-h proteinuria in a real-world cohort of systemic AL amyloidosis patients. Blood cancer journal 17 33311451
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
2023 ACR Appropriateness Criteria® Staging and Post-Therapy Assessment of Head and Neck Cancer. Journal of the American College of Radiology : JACR 16 38040469
2017 Revelation and cloning of valinomycin synthetase genes in Streptomyces lavendulae ACR-DA1 and their expression analysis under different fermentation and elicitation conditions. Journal of biotechnology 16 28528783
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
2021 ACR Appropriateness Criteria® Noncerebral Vasculitis. Journal of the American College of Radiology : JACR 14 34794595
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
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 13 37598876
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
2019 ACR Appropriateness Criteria® Acute Respiratory Illness in Immunocompromised Patients. Journal of the American College of Radiology : JACR 13 31685101
2014 ACR appropriateness Criteria® early-stage non-small-cell lung cancer. American journal of clinical oncology 13 25180631
2025 EULAR/ACR classification criteria for paediatric chronic nonbacterial osteomyelitis (CNO). Annals of the rheumatic diseases 12 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 12 37507207
2023 Should ACR/EULAR criteria be revised changing the RF and ACPA scores? Autoimmunity reviews 12 37633353
2022 Comparison of diagnostic value of SWE, FNA and BRAF gene detection in ACR TI-RADS 4 and 5 thyroid nodules. Clinical hemorheology and microcirculation 12 35068450
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
2023 ACR Appropriateness Criteria® Breast Implant Evaluation: 2023 Update. Journal of the American College of Radiology : JACR 11 38040459
2023 ACR Appropriateness Criteria® Imaging After Total Hip Arthroplasty. Journal of the American College of Radiology : JACR 11 38040462
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
2019 ACR Appropriateness Criteria® Post-Treatment Surveillance of Bladder Cancer. Journal of the American College of Radiology : JACR 10 31685109

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