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Protein

Astacin-like metalloendopeptidase

Gene

ASTL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Oocyte-specific oolemmal receptor involved in sperm and egg adhesion and fertilization. Plays a role in the polyspermy inhibition. Probably acts as a protease for the post-fertilization cleavage of ZP2. Cleaves the sperm-binding ZP2 at the surface of the zona pellucida after fertilization and cortical granule exocytosis, rendering the zona pellucida unable to support further sperm binding (By similarity).By similarity

Enzyme regulationi

Inhibited by wide spectrum metalloproteinase inhibitor batimastat (BB-94). Also inhibited by EDTA.1 Publication

Kineticsi

Enzymatic activity was assayed using synthetic quenched fluorescent substrates QF-24, QF-35 and QF-41. Astacin displayed the highest Kcat/KM value against QF-35.1 Publication

      pH dependencei

      Optimum pH is 7.5.1 Publication

      Sites

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Metal bindingi182 – 1821Zinc; catalyticPROSITE-ProRule annotation
      Active sitei183 – 1831PROSITE-ProRule annotationBy similarity
      Metal bindingi186 – 1861Zinc; catalyticPROSITE-ProRule annotation
      Metal bindingi192 – 1921Zinc; catalyticPROSITE-ProRule annotation

      GO - Molecular functioni

      • aspartic-type peptidase activity Source: UniProtKB
      • glutamic-type peptidase activity Source: UniProtKB
      • metalloendopeptidase activity Source: UniProtKB
      • peptidase activity Source: MGI
      • zinc ion binding Source: InterPro

      GO - Biological processi

      • cell adhesion Source: UniProtKB
      • fertilization Source: UniProtKB
      • negative regulation of binding of sperm to zona pellucida Source: UniProtKB
      • positive regulation of protein processing Source: UniProtKB
      • prevention of polyspermy Source: UniProtKB
      • proteolysis Source: MGI
      Complete GO annotation...

      Keywords - Molecular functioni

      Hydrolase, Metalloprotease, Protease

      Keywords - Biological processi

      Fertilization

      Keywords - Ligandi

      Metal-binding, Zinc

      Protein family/group databases

      MEROPSiM12.245.

      Names & Taxonomyi

      Protein namesi
      Recommended name:
      Astacin-like metalloendopeptidase (EC:3.4.-.-)
      Alternative name(s):
      Oocyte astacin
      Ovastacin
      Gene namesi
      Name:ASTLImported
      OrganismiHomo sapiens (Human)
      Taxonomic identifieri9606 [NCBI]
      Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
      ProteomesiUP000005640 Componenti: Chromosome 2

      Organism-specific databases

      HGNCiHGNC:31704. ASTL.

      Subcellular locationi

      • Cytoplasm By similarity
      • Cell membrane By similarity
      • Cytoplasmic granule By similarity
      • Cytoplasmic vesiclesecretory vesicle By similarity

      • Note: Secretory granules. Localizes to the peripheral cortical granules of ovulated eggs. Probably exocytosed from cortical granules during post-fertilization. Detected throughout the ooplasm of germinal vesicle stage oocytes in early bilaminar secondary follicles shortly after birth. Detected in the microvillar domain of the oolemma in arrested ovulated secondary oocytes and in the first polar body prior to fertilization. Upon fertilization, detected in the perivitelline space (PVS). Colocalizes with SPACA3 at the microvillar domain of the oolemma and in the perivitelline space (PVS) (By similarity).By similarity

      GO - Cellular componenti

      • cortical granule Source: UniProtKB
      • cytoplasm Source: UniProtKB
      • plasma membrane Source: UniProtKB
      • transport vesicle Source: UniProtKB-SubCell
      Complete GO annotation...

      Keywords - Cellular componenti

      Cell membrane, Cytoplasm, Cytoplasmic vesicle, Membrane

      Pathology & Biotechi

      Organism-specific databases

      PharmGKBiPA134922299.

      Polymorphism and mutation databases

      BioMutaiASTL.
      DMDMi317373556.

      PTM / Processingi

      Molecule processing

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Signal peptidei1 – 2323Sequence AnalysisAdd
      BLAST
      Chaini24 – 431408Astacin-like metalloendopeptidaseSequence AnalysisPRO_0000041964Add
      BLAST

      Keywords - PTMi

      Zymogen

      Proteomic databases

      PaxDbiQ6HA08.
      PRIDEiQ6HA08.

      PTM databases

      PhosphoSiteiQ6HA08.

      Expressioni

      Tissue specificityi

      Expressed in promyelocytic leukemia HL-60 cells, Burkitt's lymphoma Raji cells, and also in some ovarian carcinomas. Not detected in normal tissues.1 Publication

      Gene expression databases

      CleanExiHS_ASTL.

      Organism-specific databases

      HPAiHPA015620.

      Interactioni

      Subunit structurei

      Interacts (via N-terminal domain) with SPACA3; the interaction occurs during fertilization.By similarity

      Protein-protein interaction databases

      BioGridi136111. 3 interactions.
      STRINGi9606.ENSP00000343674.

      Structurei

      3D structure databases

      ProteinModelPortaliQ6HA08.
      SMRiQ6HA08. Positions 52-284.
      ModBaseiSearch...
      MobiDBiSearch...

      Family & Domainsi

      Sequence similaritiesi

      Belongs to the peptidase M12A family.Sequence Analysis

      Keywords - Domaini

      Signal

      Phylogenomic databases

      eggNOGiNOG330389.
      GeneTreeiENSGT00760000119227.
      HOGENOMiHOG000231483.
      HOVERGENiHBG080299.
      InParanoidiQ6HA08.
      KOiK08778.
      OMAiISIIPMY.
      OrthoDBiEOG73V6MT.
      PhylomeDBiQ6HA08.
      TreeFamiTF315280.

      Family and domain databases

      Gene3Di3.40.390.10. 1 hit.
      InterProiIPR024079. MetalloPept_cat_dom.
      IPR001506. Peptidase_M12A.
      IPR006026. Peptidase_Metallo.
      [Graphical view]
      PfamiPF01400. Astacin. 1 hit.
      [Graphical view]
      PRINTSiPR00480. ASTACIN.
      SMARTiSM00235. ZnMc. 1 hit.
      [Graphical view]
      PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
      [Graphical view]

      Sequencei

      Sequence statusi: Complete.

      Sequence processingi: The displayed sequence is further processed into a mature form.

      Q6HA08-1 [UniParc]FASTAAdd to basket

      « Hide

              10         20         30         40         50
      MEGVGGLWPW VLGLLSLPGV ILGAPLASSC AGACGTSFPD GLTPEGTQAS
      60 70 80 90 100
      GDKDIPAINQ GLILEETPES SFLIEGDIIR PSPFRLLSAT SNKWPMGGSG
      110 120 130 140 150
      VVEVPFLLSS KYDEPSRQVI LEALAEFERS TCIRFVTYQD QRDFISIIPM
      160 170 180 190 200
      YGCFSSVGRS GGMQVVSLAP TCLQKGRGIV LHELMHVLGF WHEHTRADRD
      210 220 230 240 250
      RYIRVNWNEI LPGFEINFIK SQSSNMLTPY DYSSVMHYGR LAFSRRGLPT
      260 270 280 290 300
      ITPLWAPSVH IGQRWNLSAS DITRVLKLYG CSPSGPRPRG RGSHAHSTGR
      310 320 330 340 350
      SPAPASLSLQ RLLEALSAES RSPDPSGSSA GGQPVPAGPG ESPHGWESPA
      360 370 380 390 400
      LKKLSAEASA RQPQTLASSP RSRPGAGAPG VAQEQSWLAG VSTKPTVPSS
      410 420 430
      EAGIQPVPVQ GSPALPGGCV PRNHFKGMSE D
      Length:431
      Mass (Da):45,936
      Last modified:January 11, 2011 - v4
      Checksum:i6E1FD4653506AFC1
      GO

      Experimental Info

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Sequence conflicti90 – 901T → A in CAD61265 (PubMed:15087446).Curated
      Sequence conflicti300 – 3001R → K in CAD61265 (PubMed:15087446).Curated

      Natural variant

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Natural varianti204 – 2041R → H.
      Corresponds to variant rs56238667 [ dbSNP | Ensembl ].
      VAR_061734
      Natural varianti222 – 2221Q → R.2 Publications
      Corresponds to variant rs749458 [ dbSNP | Ensembl ].
      VAR_033491
      Natural varianti277 – 2771K → Q.1 Publication
      Corresponds to variant rs1657502 [ dbSNP | Ensembl ].
      VAR_057063

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      AJ537600 mRNA. Translation: CAD61265.2.
      AC012307 Genomic DNA. No translation available.
      BC107127 mRNA. Translation: AAI07128.1.
      CCDSiCCDS33249.1.
      RefSeqiNP_001002036.3. NM_001002036.3.
      UniGeneiHs.447993.

      Genome annotation databases

      EnsembliENST00000342380; ENSP00000343674; ENSG00000188886.
      GeneIDi431705.
      KEGGihsa:431705.
      UCSCiuc010yui.2. human.

      Keywords - Coding sequence diversityi

      Polymorphism

      Cross-referencesi

      Web resourcesi

      Protein Spotlight

      Life's boundaries - Issue 141 of September2012

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      AJ537600 mRNA. Translation: CAD61265.2.
      AC012307 Genomic DNA. No translation available.
      BC107127 mRNA. Translation: AAI07128.1.
      CCDSiCCDS33249.1.
      RefSeqiNP_001002036.3. NM_001002036.3.
      UniGeneiHs.447993.

      3D structure databases

      ProteinModelPortaliQ6HA08.
      SMRiQ6HA08. Positions 52-284.
      ModBaseiSearch...
      MobiDBiSearch...

      Protein-protein interaction databases

      BioGridi136111. 3 interactions.
      STRINGi9606.ENSP00000343674.

      Protein family/group databases

      MEROPSiM12.245.

      PTM databases

      PhosphoSiteiQ6HA08.

      Polymorphism and mutation databases

      BioMutaiASTL.
      DMDMi317373556.

      Proteomic databases

      PaxDbiQ6HA08.
      PRIDEiQ6HA08.

      Protocols and materials databases

      Structural Biology KnowledgebaseSearch...

      Genome annotation databases

      EnsembliENST00000342380; ENSP00000343674; ENSG00000188886.
      GeneIDi431705.
      KEGGihsa:431705.
      UCSCiuc010yui.2. human.

      Organism-specific databases

      CTDi431705.
      GeneCardsiGC02M096789.
      H-InvDBHIX0029864.
      HGNCiHGNC:31704. ASTL.
      HPAiHPA015620.
      MIMi608860. gene.
      neXtProtiNX_Q6HA08.
      PharmGKBiPA134922299.
      GenAtlasiSearch...

      Phylogenomic databases

      eggNOGiNOG330389.
      GeneTreeiENSGT00760000119227.
      HOGENOMiHOG000231483.
      HOVERGENiHBG080299.
      InParanoidiQ6HA08.
      KOiK08778.
      OMAiISIIPMY.
      OrthoDBiEOG73V6MT.
      PhylomeDBiQ6HA08.
      TreeFamiTF315280.

      Miscellaneous databases

      GenomeRNAii431705.
      NextBioi108702.
      PROiQ6HA08.
      SOURCEiSearch...

      Gene expression databases

      CleanExiHS_ASTL.

      Family and domain databases

      Gene3Di3.40.390.10. 1 hit.
      InterProiIPR024079. MetalloPept_cat_dom.
      IPR001506. Peptidase_M12A.
      IPR006026. Peptidase_Metallo.
      [Graphical view]
      PfamiPF01400. Astacin. 1 hit.
      [Graphical view]
      PRINTSiPR00480. ASTACIN.
      SMARTiSM00235. ZnMc. 1 hit.
      [Graphical view]
      PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
      [Graphical view]
      ProtoNetiSearch...

      Publicationsi

      « Hide 'large scale' publications
      1. "Identification and characterization of human and mouse ovastacin, a novel metalloproteinase similar to hatching enzymes from arthropods, birds, amphibians, and fish."
        Quesada V., Sanchez J., Alvarez J., Lopez-Otin C.
        J. Biol. Chem. 279:26627-26634(2004) [PubMed] [Europe PMC] [Abstract]
        Cited for: NUCLEOTIDE SEQUENCE [MRNA], ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, VARIANT ARG-222.
        Tissue: Ovary1 Publication.
      2. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
        Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
        , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
        Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
        Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
        The MGC Project Team
        Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
        Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ARG-222 AND GLN-277.

      Entry informationi

      Entry nameiASTL_HUMAN
      AccessioniPrimary (citable) accession number: Q6HA08
      Secondary accession number(s): Q3KNT0
      Entry historyi
      Integrated into UniProtKB/Swiss-Prot: September 27, 2005
      Last sequence update: January 11, 2011
      Last modified: July 22, 2015
      This is version 86 of the entry and version 4 of the sequence. [Complete history]
      Entry statusiReviewed (UniProtKB/Swiss-Prot)
      Annotation programChordata Protein Annotation Program
      DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

      Miscellaneousi

      Keywords - Technical termi

      Complete proteome, Reference proteome

      Documents

      1. Human chromosome 2
        Human chromosome 2: entries, gene names and cross-references to MIM
      2. Human entries with polymorphisms or disease mutations
        List of human entries with polymorphisms or disease mutations
      3. Human polymorphisms and disease mutations
        Index of human polymorphisms and disease mutations
      4. MIM cross-references
        Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
      5. Peptidase families
        Classification of peptidase families and list of entries
      6. SIMILARITY comments
        Index of protein domains and families

      External Data

      Dasty 3

      Similar proteinsi

      Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
      100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
      90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
      50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.