ASTL_MOUSE
ID ASTL_MOUSE Reviewed; 435 AA.
AC Q6HA09; A2AHU0; A2AHU1; G7Z016; G7Z017; G7Z018; G7Z019; Q8BMA1;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2005, sequence version 3.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Astacin-like metalloendopeptidase {ECO:0000305};
DE EC=3.4.-.-;
DE AltName: Full=Oocyte astacin;
DE AltName: Full=Ovastacin;
DE AltName: Full=Sperm acrosomal SLLP1-binding protein;
DE Flags: Precursor;
GN Name=Astl {ECO:0000312|MGI:MGI:3046414}; Synonyms=Sas1b;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4; 5 AND 6), FUNCTION IN
RP FERTILIZATION, TOPOLOGY, ENZYME ACTIVITY, INTERACTION WITH SPACA3,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Swiss Webster; TISSUE=Ovary;
RX PubMed=22206759; DOI=10.1016/j.ydbio.2011.12.021;
RA Sachdev M., Mandal A., Mulders S., Digilio L.C., Panneerdoss S.,
RA Suryavathi V., Pires E., Klotz K.L., Hermens L., Herrero M.B.,
RA Flickinger C.J., van Duin M., Herr J.C.;
RT "Oocyte specific oolemmal SAS1B involved in sperm binding through intra-
RT acrosomal SLLP1 during fertilization.";
RL Dev. Biol. 363:40-51(2012).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Egg;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Egg;
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 [5]
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 [6]
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).
RN [7]
RP DEVELOPMENTAL STAGE.
RX PubMed=22275110; DOI=10.1002/dvdy.23737;
RA Acloque H., Lavial F., Pain B.;
RT "Astacin-like metallo-endopeptidase is dynamically expressed in embryonic
RT stem cells and embryonic epithelium during morphogenesis.";
RL Dev. Dyn. 241:574-582(2012).
RN [8]
RP FUNCTION IN POLYSPERMY INHIBITION, CLEAVAGE OF ZP2, SUBCELLULAR LOCATION,
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=22472438; DOI=10.1083/jcb.201112094;
RA Burkart A.D., Xiong B., Baibakov B., Jimenez-Movilla M., Dean J.;
RT "Ovastacin, a cortical granule protease, cleaves ZP2 in the zona pellucida
RT to prevent polyspermy.";
RL J. Cell Biol. 197:37-44(2012).
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:0000269|PubMed:22206759, ECO:0000269|PubMed:22472438}.
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 -!- ACTIVITY REGULATION: Inhibited by wide spectrum metalloproteinase
CC inhibitor batimastat (BB-94). Also inhibited by EDTA (By similarity).
CC {ECO:0000250|UniProtKB:Q6HA08}.
CC -!- SUBUNIT: Interacts (via N-terminal domain) with SPACA3; the interaction
CC occurs during fertilization. {ECO:0000269|PubMed:22206759}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22206759,
CC ECO:0000269|PubMed:22472438}. Cell membrane
CC {ECO:0000269|PubMed:22206759}. Cytoplasmic vesicle, secretory vesicle,
CC Cortical granule {ECO:0000269|PubMed:22472438}. 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:0000269|PubMed:22472438}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1; Synonyms=V1;
CC IsoId=Q6HA09-1; Sequence=Displayed;
CC Name=2 {ECO:0000305}; Synonyms=V2;
CC IsoId=Q6HA09-2; Sequence=VSP_051832;
CC Name=3; Synonyms=V6;
CC IsoId=Q6HA09-3; Sequence=VSP_043998;
CC Name=4; Synonyms=V4;
CC IsoId=Q6HA09-4; Sequence=VSP_043997;
CC Name=5; Synonyms=V5;
CC IsoId=Q6HA09-5; Sequence=VSP_051832, VSP_043999;
CC Name=6; Synonyms=V3;
CC IsoId=Q6HA09-6; Sequence=VSP_051832, VSP_043997;
CC -!- TISSUE SPECIFICITY: Ovary-specific. Expressed in secondary, antral and
CC Graafian follicle oocytes. Expressed in the egg cells. Not detected in
CC two-cell embryos. Not detected in naked oocytes, oocytes in primordial
CC or unilaminar primary follicles, or in any other ovarian cells at pre-
CC pubertal, pubertal or adult stages (at protein level). Ovary-specific.
CC {ECO:0000269|PubMed:22206759, ECO:0000269|PubMed:22472438}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryonic stem cells.
CC {ECO:0000269|PubMed:22275110}.
CC -!- DISRUPTION PHENOTYPE: Absence of cortical granules exocytosis during
CC post-fertilization. Multiple capacitated sperm binding to eggs and two-
CC cell embryos are not prevented. Post-fertilization cleavage of ZP2 does
CC not occur. {ECO:0000269|PubMed:22206759, ECO:0000269|PubMed:22472438}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Life's boundaries - Issue
CC 141 of September 2012;
CC URL="https://web.expasy.org/spotlight/back_issues/141";
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DR EMBL; FJ187790; ACN71160.1; -; mRNA.
DR EMBL; FJ187791; ACN71161.1; -; mRNA.
DR EMBL; FJ187792; ACN71162.1; -; mRNA.
DR EMBL; FJ187793; ACN71163.1; -; mRNA.
DR EMBL; FJ187794; ACN71164.1; -; mRNA.
DR EMBL; FJ187795; ACN71165.1; -; mRNA.
DR EMBL; AK033037; BAC28134.1; -; mRNA.
DR EMBL; AL731836; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL845368; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC064729; AAH64729.2; -; mRNA.
DR EMBL; AJ537599; CAD61264.2; -; mRNA.
DR CCDS; CCDS16700.1; -. [Q6HA09-2]
DR CCDS; CCDS71138.1; -. [Q6HA09-1]
DR RefSeq; NP_001277932.1; NM_001291003.1. [Q6HA09-1]
DR RefSeq; NP_766127.1; NM_172539.3. [Q6HA09-2]
DR AlphaFoldDB; Q6HA09; -.
DR SMR; Q6HA09; -.
DR STRING; 10090.ENSMUSP00000054456; -.
DR MEROPS; M12.245; -.
DR iPTMnet; Q6HA09; -.
DR PhosphoSitePlus; Q6HA09; -.
DR PaxDb; Q6HA09; -.
DR PRIDE; Q6HA09; -.
DR ProteomicsDB; 281855; -. [Q6HA09-1]
DR ProteomicsDB; 281856; -. [Q6HA09-2]
DR ProteomicsDB; 281857; -. [Q6HA09-3]
DR ProteomicsDB; 281858; -. [Q6HA09-4]
DR ProteomicsDB; 281859; -. [Q6HA09-5]
DR ProteomicsDB; 281860; -. [Q6HA09-6]
DR Antibodypedia; 2745; 60 antibodies from 18 providers.
DR DNASU; 215095; -.
DR Ensembl; ENSMUST00000059839; ENSMUSP00000054456; ENSMUSG00000050468. [Q6HA09-2]
DR Ensembl; ENSMUST00000089673; ENSMUSP00000087102; ENSMUSG00000050468. [Q6HA09-1]
DR Ensembl; ENSMUST00000179618; ENSMUSP00000135987; ENSMUSG00000050468. [Q6HA09-2]
DR GeneID; 215095; -.
DR KEGG; mmu:215095; -.
DR UCSC; uc008mfg.2; mouse. [Q6HA09-1]
DR UCSC; uc029uen.2; mouse. [Q6HA09-3]
DR CTD; 431705; -.
DR MGI; MGI:3046414; Astl.
DR VEuPathDB; HostDB:ENSMUSG00000050468; -.
DR eggNOG; KOG3714; Eukaryota.
DR GeneTree; ENSGT00940000154856; -.
DR HOGENOM; CLU_640213_0_0_1; -.
DR InParanoid; Q6HA09; -.
DR OMA; KWPTGGG; -.
DR OrthoDB; 681837at2759; -.
DR PhylomeDB; Q6HA09; -.
DR TreeFam; TF315280; -.
DR BioGRID-ORCS; 215095; 2 hits in 72 CRISPR screens.
DR PRO; PR:Q6HA09; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q6HA09; protein.
DR Bgee; ENSMUSG00000050468; Expressed in primary oocyte and 8 other tissues.
DR ExpressionAtlas; Q6HA09; baseline and differential.
DR Genevisible; Q6HA09; MM.
DR GO; GO:0060473; C:cortical granule; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0070001; F:aspartic-type peptidase activity; IDA:UniProtKB.
DR GO; GO:0070002; F:glutamic-type peptidase activity; IDA:UniProtKB.
DR GO; GO:0004222; F:metalloendopeptidase activity; ISS:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0007155; P:cell adhesion; IMP:UniProtKB.
DR GO; GO:0009566; P:fertilization; IMP:UniProtKB.
DR GO; GO:2000360; P:negative regulation of binding of sperm to zona pellucida; IDA:UniProtKB.
DR GO; GO:0010954; P:positive regulation of protein processing; IDA:UniProtKB.
DR GO; GO:0060468; P:prevention of polyspermy; IDA: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 Alternative splicing; Cell membrane; Cytoplasm; Cytoplasmic vesicle;
KW Disulfide bond; Fertilization; Hydrolase; Membrane; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Signal; Zinc; Zymogen.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..435
FT /note="Astacin-like metalloendopeptidase"
FT /evidence="ECO:0000255"
FT /id="PRO_0000041965"
FT DOMAIN 85..282
FT /note="Peptidase M12A"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT REGION 318..356
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 318..351
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 VAR_SEQ 1..21
FT /note="Missing (in isoform 2, isoform 5 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:16141072,
FT ECO:0000303|PubMed:22206759"
FT /id="VSP_051832"
FT VAR_SEQ 72..105
FT /note="Missing (in isoform 4 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:22206759"
FT /id="VSP_043997"
FT VAR_SEQ 82..113
FT /note="SPFRLLSVTNNKWPKGVGGFVEIPFLLSRKYD -> GVSHGVSFPN (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:22206759"
FT /id="VSP_043998"
FT VAR_SEQ 82..112
FT /note="SPFRLLSVTNNKWPKGVGGFVEIPFLLSRKY -> GVSHGVSFP (in
FT isoform 5)"
FT /evidence="ECO:0000303|PubMed:22206759"
FT /id="VSP_043999"
SQ SEQUENCE 435 AA; 47455 MW; 8530CC0E5B3B1350 CRC64;
MGIMGSLWPW ILTMLSLLGL SMGAPSASRC SGVCSTSVPE GFTPEGSPVF QDKDIPAINQ
GLISEETPES SFLVEGDIIR PSPFRLLSVT NNKWPKGVGG FVEIPFLLSR KYDELSRRVI
MDAFAEFERF TCIRFVAYHG QRDFVSILPM AGCFSGVGRS GGMQVVSLAP TCLRKGRGIV
LHELMHVLGF WHEHSRADRD RYIQVNWNEI LPGFEINFIK SRSTNMLVPY DYSSVMHYGR
FAFSWRGQPT IIPLWTSSVH IGQRWNLSTS DITRVCRLYN CSRSVPDSHG RGFEAQSDGS
SLTPASISRL QRLLEALSEE SGSSAPSGSR TGGQSIAGLG NSQQGWEHPP QSTFSVGALA
RPPQMLADAS KSGPGAGADS LSLEQFQLAQ APTVPLALFP EARDKPAPIQ DAFERLAPLP
GGCAPGSHIR EVPRD
