ID   ACRO_HUMAN              Reviewed;         421 AA.
AC   P10323; Q6ICK2;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   03-OCT-2006, sequence version 4.
DT   04-NOV-2026, entry version 230.
DE   RecName: Full=Acrosin;
DE            EC=3.4.21.10;
DE   Contains:
DE     RecName: Full=Acrosin light chain;
DE   Contains:
DE     RecName: Full=Acrosin heavy chain;
DE   Flags: Precursor;
GN   Name=ACR; Synonyms=ACRS;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Testis;
RX   PubMed=2493394; DOI=10.1016/0014-5793(89)80549-6;
RA   Baba T., Watanabe K., Kashiwabara S., Arai Y.;
RT   "Primary structure of human proacrosin deduced from its cDNA sequence.";
RL   FEBS Lett. 244:296-300(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Leukocyte;
RX   PubMed=2114285; DOI=10.1111/j.1432-1033.1990.tb15564.x;
RA   Keime S., Adham I.M., Engel W.;
RT   "Nucleotide sequence and exon-intron organization of the human proacrosin
RT   gene.";
RL   Eur. J. Biochem. 190:195-200(1990).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2298447; DOI=10.1007/bf00208925;
RA   Adham I.M., Klemm U., Maier W.-M., Engel W.;
RT   "Molecular cloning of human preproacrosin cDNA.";
RL   Hum. Genet. 84:125-128(1990).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=1628652; DOI=10.1111/j.1432-1033.1992.tb17014.x;
RA   Vazquez-Levin M.H., Reventos J., Gordon J.W.;
RT   "Molecular cloning, sequencing and restriction mapping of the genomic
RT   sequence encoding human proacrosin.";
RL   Eur. J. Biochem. 207:23-26(1992).
RN   [5]
RP   ERRATUM OF PUBMED:1628652, AND DISCUSSION OF PUBMED:1628652.
RA   Adham I.M., Spitzer U., Schloesser M., Kremling H., Keime S., Engel W.;
RL   Eur. J. Biochem. 207:27-28(1992).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA   Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA   Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA   Beare D.M., Dunham I.;
RT   "A genome annotation-driven approach to cloning the human ORFeome.";
RL   Genome Biol. 5:R84.1-R84.11(2004).
RN   [7]
RP   ACTIVITY REGULATION, AND HETERODIMER WITH SERPINA5.
RX   PubMed=7521127; DOI=10.1152/ajpcell.1994.267.2.c466;
RA   Zheng X., Geiger M., Ecke S., Bielek E., Donner P., Eberspacher U.,
RA   Schleuning W.D., Binder B.R.;
RT   "Inhibition of acrosin by protein C inhibitor and localization of protein C
RT   inhibitor to spermatozoa.";
RL   Am. J. Physiol. 267:C466-C472(1994).
RN   [8]
RP   PROPEPTIDE, AND ACTIVATION.
RX   PubMed=11839395; DOI=10.1016/s0165-0378(01)00080-8;
RA   Zahn A., Furlong L.I., Biancotti J.C., Ghiringhelli P.D.,
RA   Marijn-Briggiler C.I., Vazquez-Levin M.H.;
RT   "Evaluation of the proacrosin/acrosin system and its mechanism of
RT   activation in human sperm extracts.";
RL   J. Reprod. Immunol. 54:43-63(2002).
RN   [9]
RP   INVOLVEMENT IN SPGF87, VARIANT SPGF87 56-TRP--SER-421 DEL, CHARACTERIZATION
RP   OF VARIANT SPGF87 56-TRP--SER-421 DEL, AND FUNCTION.
RX   PubMed=37004249; DOI=10.1093/humrep/dead059;
RA   Hua R., Xue R., Liu Y., Li Y., Sha X., Li K., Gao Y., Shen Q., Lv M.,
RA   Xu Y., Zhang Z., He X., Cao Y., Wu H.;
RT   "ACROSIN deficiency causes total fertilization failure in humans by
RT   preventing the sperm from penetrating the zona pellucida.";
RL   Hum. Reprod. 38:1213-1223(2023).
CC   -!- FUNCTION: Acrosin is the major protease of mammalian spermatozoa. It is
CC       a serine protease of trypsin-like cleavage specificity, it is
CC       synthesized in a zymogen form, proacrosin and stored in the acrosome.
CC       {ECO:0000269|PubMed:37004249}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.; EC=3.4.21.10;
CC   -!- ACTIVITY REGULATION: Inhibited by SERPINA5.
CC       {ECO:0000269|PubMed:7521127}.
CC   -!- SUBUNIT: Heavy chain (catalytic) and a light chain linked by two
CC       disulfide bonds. Forms a heterodimer with SERPINA5.
CC   -!- INTERACTION:
CC       P10323; Q05996: ZP2; NbExp=4; IntAct=EBI-21280149, EBI-1755919;
CC       P10323; P21754: ZP3; NbExp=2; IntAct=EBI-21280149, EBI-11783624;
CC       P10323; Q12836: ZP4; NbExp=2; IntAct=EBI-21280149, EBI-11783805;
CC   -!- DISEASE: Spermatogenic failure 87 (SPGF87) [MIM:620500]: An autosomal
CC       recessive male infertility disorder characterized by inability of
CC       mutant sperm to penetrate the zona pellucida, resulting in
CC       fertilization failure. {ECO:0000269|PubMed:37004249}. Note=The disease
CC       may be caused by variants affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC       ProRule:PRU00274}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; Y00970; CAA68784.1; -; mRNA.
DR   EMBL; X54017; CAA37964.1; -; Genomic_DNA.
DR   EMBL; X54018; CAA37964.1; JOINED; Genomic_DNA.
DR   EMBL; X54019; CAA37964.1; JOINED; Genomic_DNA.
DR   EMBL; X54020; CAA37964.1; JOINED; Genomic_DNA.
DR   EMBL; M77378; AAA51572.1; -; Genomic_DNA.
DR   EMBL; M77379; AAA51573.1; -; Genomic_DNA.
DR   EMBL; M77380; AAA51574.1; -; Genomic_DNA.
DR   EMBL; M77381; AAA51575.1; -; Genomic_DNA.
DR   EMBL; X66188; CAA46956.1; -; Genomic_DNA.
DR   EMBL; X54018; CAA46956.1; JOINED; Genomic_DNA.
DR   EMBL; X54019; CAA46956.1; JOINED; Genomic_DNA.
DR   EMBL; X54020; CAA46956.1; JOINED; Genomic_DNA.
DR   EMBL; CR456366; CAG30252.1; -; mRNA.
DR   CCDS; CCDS14101.1; -.
DR   PIR; S11674; S11674.
DR   RefSeq; NP_001088.2; NM_001097.3.
DR   AlphaFoldDB; P10323; -.
DR   SMR; P10323; -.
DR   BioGRID; 106565; 6.
DR   FunCoup; P10323; 103.
DR   IntAct; P10323; 5.
DR   STRING; 9606.ENSP00000216139; -.
DR   BindingDB; P10323; -.
DR   ChEMBL; CHEMBL2738; -.
DR   GuidetoPHARMACOLOGY; 2327; -.
DR   MEROPS; S01.223; -.
DR   GlyCosmos; P10323; 3 sites, No reported glycans.
DR   GlyGen; P10323; 4 sites, 1 O-linked glycan (1 site).
DR   BioMuta; ACR; -.
DR   DMDM; 115502349; -.
DR   MassIVE; P10323; -.
DR   PaxDb; 9606-ENSP00000216139; -.
DR   PeptideAtlas; P10323; -.
DR   ProteomicsDB; 52600; -.
DR   Antibodypedia; 53952; 218 antibodies from 29 providers.
DR   DNASU; 49; -.
DR   Ensembl; ENST00000216139.10; ENSP00000216139.5; ENSG00000100312.11.
DR   Ensembl; ENST00000707314.1; ENSP00000516837.1; ENSG00000291368.1.
DR   GeneID; 49; -.
DR   KEGG; hsa:49; -.
DR   MANE-Select; ENST00000216139.10; ENSP00000216139.5; NM_001097.3; NP_001088.2.
DR   UCSC; uc003bnh.5; human.
DR   AGR; HGNC:126; -.
DR   ClinPGx; PA24451; -.
DR   CTD; 49; -.
DR   DisGeNET; 49; -.
DR   GeneCards; ACR; -.
DR   HGNC; HGNC:126; ACR.
DR   HPA; ENSG00000100312; Tissue enriched (testis).
DR   MalaCards; ACR; -.
DR   MIM; 102480; gene.
DR   MIM; 620500; phenotype.
DR   OpenTargets; ENSG00000100312; -.
DR   VEuPathDB; HostDB:ENSG00000100312; -.
DR   eggNOG; KOG3627; Eukaryota.
DR   GeneTree; ENSGT00940000162430; -.
DR   InParanoid; P10323; -.
DR   OMA; ACTRLCH; -.
DR   OrthoDB; 6339452at2759; -.
DR   PAN-GO; P10323; 2 GO annotations based on evolutionary models.
DR   PhylomeDB; P10323; -.
DR   BRENDA; 3.4.21.10; 2681.
DR   PathwayCommons; P10323; -.
DR   Reactome; R-HSA-1300645; Acrosome Reaction and Sperm:Oocyte Membrane Binding.
DR   SignaLink; P10323; -.
DR   Agora; ENSG00000100312; -.
DR   BioGRID-ORCS; 49; 31 hits in 1152 CRISPR screens.
DR   GeneWiki; Acrosin; -.
DR   GenomeRNAi; 49; -.
DR   Pharos; P10323; Tchem.
DR   PRO; PR:P10323; -.
DR   Proteomes; UP000005640; Chromosome 22.
DR   RNAct; P10323; protein.
DR   Bgee; ENSG00000100312; Expressed in left testis and 85 other cell types or tissues.
DR   ExpressionAtlas; P10323; baseline and differential.
DR   GO; GO:0043159; C:acrosomal matrix; TAS:HGNC-UCL.
DR   GO; GO:0001669; C:acrosomal vesicle; IBA:GO_Central.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005798; C:Golgi-associated vesicle; IEA:Ensembl.
DR   GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR   GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR   GO; GO:0004040; F:amidase activity; ISS:UniProtKB.
DR   GO; GO:0005507; F:copper ion binding; NAS:UniProtKB.
DR   GO; GO:0005537; F:D-mannose binding; IDA:UniProtKB.
DR   GO; GO:0003677; F:DNA binding; NAS:UniProtKB.
DR   GO; GO:0042806; F:fucose binding; ISS:UniProtKB.
DR   GO; GO:0002020; F:protease binding; TAS:Reactome.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB.
DR   GO; GO:0008236; F:serine-type peptidase activity; ISS:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; NAS:UniProtKB.
DR   GO; GO:0002077; P:acrosome matrix dispersal; NAS:UniProtKB.
DR   GO; GO:0007340; P:acrosome reaction; IMP:UniProtKB.
DR   GO; GO:0007190; P:activation of adenylate cyclase activity; IDA:UniProtKB.
DR   GO; GO:0007341; P:penetration of zona pellucida; IEA:Ensembl.
DR   GO; GO:0030163; P:protein catabolic process; IBA:GO_Central.
DR   GO; GO:0006508; P:proteolysis; IEA:InterPro.
DR   GO; GO:0048545; P:response to steroid hormone; IEA:Ensembl.
DR   GO; GO:0007338; P:single fertilization; ISS:UniProtKB.
DR   CDD; cd00190; Tryp_SPc; 1.
DR   FunFam; 2.40.10.10:FF:000003; Transmembrane serine protease 3; 1.
DR   Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2.
DR   InterPro; IPR012267; Pept_S1A_acrosin.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR001314; Peptidase_S1A.
DR   InterPro; IPR001254; Trypsin_dom.
DR   InterPro; IPR018114; TRYPSIN_HIS.
DR   InterPro; IPR033116; TRYPSIN_SER.
DR   PANTHER; PTHR24252:SF8; ACROSIN; 1.
DR   PANTHER; PTHR24252; ACROSIN-RELATED; 1.
DR   Pfam; PF00089; Trypsin; 1.
DR   PIRSF; PIRSF001141; Acrosin; 1.
DR   PRINTS; PR00722; CHYMOTRYPSIN.
DR   SMART; SM00020; Tryp_SPc; 1.
DR   SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR   PROSITE; PS50240; TRYPSIN_DOM; 1.
DR   PROSITE; PS00134; TRYPSIN_HIS; 1.
DR   PROSITE; PS00135; TRYPSIN_SER; 1.
PE   1: Evidence at protein level;
KW   Disease variant; Disulfide bond; Glycoprotein; Hydrolase; Protease;
KW   Proteomics identification; Reference proteome; Serine protease; Signal;
KW   Zymogen.
FT   SIGNAL          1..19
FT   CHAIN           20..421
FT                   /note="Acrosin"
FT                   /id="PRO_0000027518"
FT   CHAIN           20..42
FT                   /note="Acrosin light chain"
FT                   /id="PRO_0000027519"
FT   CHAIN           43..343
FT                   /note="Acrosin heavy chain"
FT                   /id="PRO_0000027520"
FT   PROPEP          344..421
FT                   /note="Pro-rich"
FT                   /evidence="ECO:0000305"
FT                   /id="PRO_0000027521"
FT   DOMAIN          43..290
FT                   /note="Peptidase S1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   REGION          297..316
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          327..383
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          397..421
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        301..316
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        328..372
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        397..409
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        412..421
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        88
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        142
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        240
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        22
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        210
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000250"
FT   DISULFID        25..154
FT                   /note="Interchain (between light and heavy chains)"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        29..162
FT                   /note="Interchain (between light and heavy chains)"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        73..89
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        177..246
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        209..225
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        236..266
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   VARIANT         56..421
FT                   /note="Missing (in SPGF87; likely pathogenic; loss of
FT                   protein expression in patient sperm)"
FT                   /evidence="ECO:0000269|PubMed:37004249"
FT                   /id="VAR_088987"
FT   VARIANT         120
FT                   /note="L -> V (in dbSNP:rs1064734)"
FT                   /id="VAR_011650"
FT   VARIANT         166
FT                   /note="F -> L (in dbSNP:rs1064735)"
FT                   /id="VAR_011651"
FT   CONFLICT        64
FT                   /note="T -> R (in Ref. 2 and 4)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        226
FT                   /note="A -> V (in Ref. 3)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        268
FT                   /note="R -> L (in Ref. 2 and 4)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        296
FT                   /note="M -> V (in Ref. 6; CAG30252)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        345
FT                   /note="R -> P (in Ref. 2, 3 and 4)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   421 AA;  45847 MW;  7A2F7ECEC98008FA CRC64;
     MVEMLPTAIL LVLAVSVVAK DNATCDGPCG LRFRQNPQGG VRIVGGKAAQ HGAWPWMVSL
     QIFTYNSHRY HTCGGSLLNS RWVLTAAHCF VGKNNVHDWR LVFGAKEITY GNNKPVKAPL
     QERYVEKIII HEKYNSATEG NDIALVEITP PISCGRFIGP GCLPHFKAGL PRGSQSCWVA
     GWGYIEEKAP RPSSILMEAR VDLIDLDLCN STQWYNGRVQ PTNVCAGYPV GKIDTCQGDS
     GGPLMCKDSK ESAYVVVGIT SWGVGCARAK RPGIYTATWP YLNWIASKIG SNALRMIQSA
     TPPPPTTRPP PIRPPFSHPI SAHLPWYFQP PPRPLPPRPP AAQPRPPPSP PPPPPPPASP
     LPPPPPPPPP TPSSTTKLPQ GLSFAKRLQQ LIEVLKGKTY SDGKNHYDME TTELPELTST
     S
//