ACRO_HUMAN
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 03-AUG-2022, entry version 211.
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).
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 -!- 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 -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
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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_001097.2.
DR AlphaFoldDB; P10323; -.
DR SMR; P10323; -.
DR BioGRID; 106565; 6.
DR IntAct; P10323; 5.
DR STRING; 9606.ENSP00000216139; -.
DR BindingDB; P10323; -.
DR ChEMBL; CHEMBL2738; -.
DR GuidetoPHARMACOLOGY; 2327; -.
DR MEROPS; S01.223; -.
DR GlyGen; P10323; 2 sites.
DR BioMuta; ACR; -.
DR DMDM; 115502349; -.
DR MassIVE; P10323; -.
DR PaxDb; P10323; -.
DR PeptideAtlas; P10323; -.
DR PRIDE; P10323; -.
DR ProteomicsDB; 52600; -.
DR Antibodypedia; 53952; 210 antibodies from 27 providers.
DR DNASU; 49; -.
DR Ensembl; ENST00000216139.10; ENSP00000216139.5; ENSG00000100312.11.
DR Ensembl; ENST00000636109.2; ENSP00000490828.1; ENSG00000283539.2.
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 CTD; 49; -.
DR DisGeNET; 49; -.
DR GeneCards; ACR; -.
DR HGNC; HGNC:126; ACR.
DR HPA; ENSG00000100312; Tissue enriched (testis).
DR MIM; 102480; gene.
DR neXtProt; NX_P10323; -.
DR OpenTargets; ENSG00000100312; -.
DR PharmGKB; PA24451; -.
DR VEuPathDB; HostDB:ENSG00000100312; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000162430; -.
DR InParanoid; P10323; -.
DR OMA; LMCRDNV; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; P10323; -.
DR TreeFam; TF335943; -.
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 BioGRID-ORCS; 49; 29 hits in 1069 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 84 other tissues.
DR ExpressionAtlas; P10323; baseline and differential.
DR Genevisible; P10323; HS.
DR GO; GO:0043159; C:acrosomal matrix; TAS:HGNC-UCL.
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:0003677; F:DNA binding; NAS:UniProtKB.
DR GO; GO:0042806; F:fucose binding; ISS:UniProtKB.
DR GO; GO:0005537; F:mannose binding; IDA: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:0007339; P:binding of sperm to zona pellucida; IEA:Ensembl.
DR GO; GO:0007341; P:penetration of zona pellucida; IEA:Ensembl.
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 Gene3D; 2.40.10.10; -; 2.
DR InterPro; IPR012267; Pept_S1A_acrosin.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR Pfam; PF00089; Trypsin; 1.
DR PIRSF; PIRSF001141; Acrosin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 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 Disulfide bond; Glycoprotein; Hydrolase; Protease; Reference proteome;
KW Serine protease; Signal; 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 302..316
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 327..375
FT /note="Pro residues"
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 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
