ASTL_HUMAN
ID ASTL_HUMAN Reviewed; 431 AA.
AC Q6HA08; Q3KNT0;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 4.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Astacin-like metalloendopeptidase;
DE EC=3.4.-.-;
DE AltName: Full=Oocyte astacin;
DE AltName: Full=Ovastacin;
DE AltName: Full=ZP2-proteinase {ECO:0000305};
DE Flags: Precursor;
GN Name=ASTL {ECO:0000312|HGNC:HGNC:31704};
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ARG-222 AND GLN-277.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP RETRACTED PAPER.
RX PubMed=15087446; DOI=10.1074/jbc.m401588200;
RA Quesada V., Sanchez J., Alvarez J., Lopez-Otin C.;
RT "Identification and characterization of human and mouse ovastacin, a novel
RT metalloproteinase similar to hatching enzymes from arthropods, birds,
RT amphibians, and fish.";
RL J. Biol. Chem. 279:26627-26634(2004).
RN [4]
RP RETRACTION NOTICE OF PUBMED:15087446.
RX PubMed=30808003; DOI=10.1074/jbc.w118.007326;
RA Quesada V., Sanchez L.M., Alvarez J., Lopez-Otin C.;
RT "Withdrawal: Identification and characterization of human and mouse
RT ovastacin: A novel metalloproteinase similar to hatching enzymes from
RT arthropods, birds, amphibians, and fish.";
RL J. Biol. Chem. 294:1432-1432(2019).
CC -!- FUNCTION: Oocyte-specific oolemmal receptor involved in sperm and egg
CC adhesion and fertilization. Plays a role in the polyspermy inhibition.
CC Probably acts as a protease for the post-fertilization cleavage of ZP2.
CC Cleaves the sperm-binding ZP2 at the surface of the zona pellucida
CC after fertilization and cortical granule exocytosis, rendering the zona
CC pellucida unable to support further sperm binding.
CC {ECO:0000250|UniProtKB:Q6HA09}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU01211};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|PROSITE-
CC ProRule:PRU01211};
CC -!- SUBUNIT: Interacts (via N-terminal domain) with SPACA3; the interaction
CC occurs during fertilization. {ECO:0000250|UniProtKB:Q6HA09}.
CC -!- INTERACTION:
CC Q6HA08; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-11998350, EBI-3867333;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q6HA09}. Cell
CC membrane {ECO:0000250|UniProtKB:Q6HA09}. Cytoplasmic vesicle, secretory
CC vesicle, Cortical granule {ECO:0000250|UniProtKB:Q6HA09}. Note=Probably
CC exocytosed from cortical granules during post-fertilization. Detected
CC throughout the ooplasm of germinal vesicle stage oocytes in early
CC bilaminar secondary follicles at postnatal (PN) day 3. Detected in the
CC microvillar domain of the oolemma in arrested ovulated secondary
CC oocytes and in the first polar body prior to fertilization. Upon
CC fertilization, detected in the perivitelline space (PVS) and
CC occasionally on the oolemma in 2-cell through morulae stages.
CC Colocalizes with SPACA3 at the microvillar domain of the oolemma and in
CC the perivitelline space (PVS). {ECO:0000250|UniProtKB:Q6HA09}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Life's boundaries - Issue
CC 141 of September2012;
CC URL="https://web.expasy.org/spotlight/back_issues/141";
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DR EMBL; AC012307; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC107127; AAI07128.1; -; mRNA.
DR EMBL; AJ537600; CAD61265.2; -; mRNA.
DR CCDS; CCDS33249.1; -.
DR RefSeq; NP_001002036.3; NM_001002036.3.
DR AlphaFoldDB; Q6HA08; -.
DR SMR; Q6HA08; -.
DR BioGRID; 136111; 10.
DR IntAct; Q6HA08; 4.
DR STRING; 9606.ENSP00000343674; -.
DR MEROPS; M12.245; -.
DR iPTMnet; Q6HA08; -.
DR PhosphoSitePlus; Q6HA08; -.
DR BioMuta; ASTL; -.
DR DMDM; 317373556; -.
DR MassIVE; Q6HA08; -.
DR PaxDb; Q6HA08; -.
DR PeptideAtlas; Q6HA08; -.
DR PRIDE; Q6HA08; -.
DR Antibodypedia; 2745; 60 antibodies from 18 providers.
DR DNASU; 431705; -.
DR Ensembl; ENST00000342380.3; ENSP00000343674.2; ENSG00000188886.4.
DR GeneID; 431705; -.
DR KEGG; hsa:431705; -.
DR MANE-Select; ENST00000342380.3; ENSP00000343674.2; NM_001002036.4; NP_001002036.3.
DR UCSC; uc010yui.2; human.
DR CTD; 431705; -.
DR DisGeNET; 431705; -.
DR GeneCards; ASTL; -.
DR HGNC; HGNC:31704; ASTL.
DR HPA; ENSG00000188886; Group enriched (bone marrow, brain).
DR MIM; 608860; gene.
DR neXtProt; NX_Q6HA08; -.
DR OpenTargets; ENSG00000188886; -.
DR PharmGKB; PA134922299; -.
DR VEuPathDB; HostDB:ENSG00000188886; -.
DR eggNOG; KOG3714; Eukaryota.
DR GeneTree; ENSGT00940000154856; -.
DR HOGENOM; CLU_640213_0_0_1; -.
DR InParanoid; Q6HA08; -.
DR OMA; KWPTGGG; -.
DR OrthoDB; 681837at2759; -.
DR PhylomeDB; Q6HA08; -.
DR TreeFam; TF315280; -.
DR BRENDA; 3.4.24.21; 2681.
DR PathwayCommons; Q6HA08; -.
DR SignaLink; Q6HA08; -.
DR BioGRID-ORCS; 431705; 16 hits in 1066 CRISPR screens.
DR GenomeRNAi; 431705; -.
DR Pharos; Q6HA08; Tbio.
DR PRO; PR:Q6HA08; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q6HA08; protein.
DR Bgee; ENSG00000188886; Expressed in bone marrow and 75 other tissues.
DR GO; GO:0060473; C:cortical granule; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0070001; F:aspartic-type peptidase activity; ISS:UniProtKB.
DR GO; GO:0070002; F:glutamic-type peptidase activity; ISS:UniProtKB.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0007155; P:cell adhesion; ISS:UniProtKB.
DR GO; GO:0009566; P:fertilization; ISS:UniProtKB.
DR GO; GO:2000360; P:negative regulation of binding of sperm to zona pellucida; ISS:UniProtKB.
DR GO; GO:0010954; P:positive regulation of protein processing; ISS:UniProtKB.
DR GO; GO:0060468; P:prevention of polyspermy; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001506; Peptidase_M12A.
DR InterPro; IPR006026; Peptidase_Metallo.
DR Pfam; PF01400; Astacin; 1.
DR PRINTS; PR00480; ASTACIN.
DR SMART; SM00235; ZnMc; 1.
DR PROSITE; PS51864; ASTACIN; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasm; Cytoplasmic vesicle; Disulfide bond;
KW Fertilization; Hydrolase; Membrane; Metal-binding; Metalloprotease;
KW Protease; Reference proteome; Signal; Zinc; Zymogen.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..431
FT /note="Astacin-like metalloendopeptidase"
FT /evidence="ECO:0000255"
FT /id="PRO_0000041964"
FT DOMAIN 85..282
FT /note="Peptidase M12A"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT REGION 283..304
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 317..431
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 386..406
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 183
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT BINDING 182
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT BINDING 186
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT BINDING 192
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT DISULFID 132..281
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT DISULFID 153..172
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT VARIANT 204
FT /note="R -> H (in dbSNP:rs41320144)"
FT /id="VAR_061734"
FT VARIANT 222
FT /note="Q -> R (in dbSNP:rs749458)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_033491"
FT VARIANT 277
FT /note="K -> Q (in dbSNP:rs1657502)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_057063"
SQ SEQUENCE 431 AA; 45936 MW; 6E1FD4653506AFC1 CRC64;
MEGVGGLWPW VLGLLSLPGV ILGAPLASSC AGACGTSFPD GLTPEGTQAS GDKDIPAINQ
GLILEETPES SFLIEGDIIR PSPFRLLSAT SNKWPMGGSG VVEVPFLLSS KYDEPSRQVI
LEALAEFERS TCIRFVTYQD QRDFISIIPM YGCFSSVGRS GGMQVVSLAP TCLQKGRGIV
LHELMHVLGF WHEHTRADRD RYIRVNWNEI LPGFEINFIK SQSSNMLTPY DYSSVMHYGR
LAFSRRGLPT ITPLWAPSVH IGQRWNLSAS DITRVLKLYG CSPSGPRPRG RGSHAHSTGR
SPAPASLSLQ RLLEALSAES RSPDPSGSSA GGQPVPAGPG ESPHGWESPA LKKLSAEASA
RQPQTLASSP RSRPGAGAPG VAQEQSWLAG VSTKPTVPSS EAGIQPVPVQ GSPALPGGCV
PRNHFKGMSE D
