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Protein

Astacin-like metalloendopeptidase

Gene

ASTL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Cofactori

Zn2+PROSITE-ProRule annotationNote: Binds 1 zinc ion per subunit.PROSITE-ProRule annotation

Activity 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)DescriptionActionsGraphical viewLength
      Metal bindingi182Zinc; via tele nitrogen; catalyticPROSITE-ProRule annotation1
      Active sitei183PROSITE-ProRule annotation1
      Metal bindingi186Zinc; via tele nitrogen; catalyticPROSITE-ProRule annotation1
      Metal bindingi192Zinc; via tele nitrogen; catalyticPROSITE-ProRule annotation1

      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

      Keywordsi

      Molecular functionHydrolase, Metalloprotease, Protease
      Biological processFertilization
      LigandMetal-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
      Proteomesi
      • UP000005640 Componenti: Chromosome 2

      Organism-specific databases

      EuPathDBiHostDB:ENSG00000188886.3
      HGNCiHGNC:31704 ASTL
      MIMi608860 gene
      neXtProtiNX_Q6HA08

      Subcellular locationi

      Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

      Keywords - Cellular componenti

      Cell membrane, Cytoplasm, Cytoplasmic vesicle, Membrane

      Pathology & Biotechi

      Organism-specific databases

      OpenTargetsiENSG00000188886
      PharmGKBiPA134922299

      Polymorphism and mutation databases

      BioMutaiASTL
      DMDMi317373556

      PTM / Processingi

      Molecule processing

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Signal peptidei1 – 23Sequence analysisAdd BLAST23
      ChainiPRO_000004196424 – 431Astacin-like metalloendopeptidaseSequence analysisAdd BLAST408

      Amino acid modifications

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Disulfide bondi132 ↔ 281PROSITE-ProRule annotation
      Disulfide bondi153 ↔ 172PROSITE-ProRule annotation

      Keywords - PTMi

      Disulfide bond, Zymogen

      Proteomic databases

      PaxDbiQ6HA08
      PeptideAtlasiQ6HA08
      PRIDEiQ6HA08
      ProteomicsDBi66354

      PTM databases

      iPTMnetiQ6HA08
      PhosphoSitePlusiQ6HA08

      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

      BgeeiENSG00000188886 Expressed in 55 organ(s), highest expression level in urinary bladder
      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, 6 interactors
      IntActiQ6HA08, 1 interactor
      STRINGi9606.ENSP00000343674

      Structurei

      3D structure databases

      ProteinModelPortaliQ6HA08
      SMRiQ6HA08
      ModBaseiSearch...
      MobiDBiSearch...

      Family & Domainsi

      Domains and Repeats

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Domaini85 – 282Peptidase M12APROSITE-ProRule annotationAdd BLAST198

      Keywords - Domaini

      Signal

      Phylogenomic databases

      eggNOGiKOG3714 Eukaryota
      ENOG410ZPX7 LUCA
      GeneTreeiENSGT00760000119227
      HOGENOMiHOG000231483
      HOVERGENiHBG080299
      InParanoidiQ6HA08
      KOiK08778
      OMAiISIIPMY
      OrthoDBiEOG091G009U
      PhylomeDBiQ6HA08
      TreeFamiTF315280

      Family and domain databases

      Gene3Di3.40.390.10, 1 hit
      InterProiView protein in InterPro
      IPR024079 MetalloPept_cat_dom_sf
      IPR001506 Peptidase_M12A
      IPR006026 Peptidase_Metallo
      PfamiView protein in Pfam
      PF01400 Astacin, 1 hit
      PRINTSiPR00480 ASTACIN
      SMARTiView protein in SMART
      SM00235 ZnMc, 1 hit
      PROSITEiView protein in PROSITE
      PS51864 ASTACIN, 1 hit
      PS00142 ZINC_PROTEASE, 1 hit

      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)DescriptionActionsGraphical viewLength
      Sequence conflicti90T → A in CAD61265 (PubMed:15087446).Curated1
      Sequence conflicti300R → K in CAD61265 (PubMed:15087446).Curated1

      Natural variant

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Natural variantiVAR_061734204R → H. Corresponds to variant dbSNP:rs41320144Ensembl.1
      Natural variantiVAR_033491222Q → R2 PublicationsCorresponds to variant dbSNP:rs749458Ensembl.1
      Natural variantiVAR_057063277K → Q1 PublicationCorresponds to variant dbSNP:rs1657502Ensembl.1

      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

      Similar proteinsi

      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
      ModBaseiSearch...
      MobiDBiSearch...

      Protein-protein interaction databases

      BioGridi136111, 6 interactors
      IntActiQ6HA08, 1 interactor
      STRINGi9606.ENSP00000343674

      Protein family/group databases

      MEROPSiM12.245

      PTM databases

      iPTMnetiQ6HA08
      PhosphoSitePlusiQ6HA08

      Polymorphism and mutation databases

      BioMutaiASTL
      DMDMi317373556

      Proteomic databases

      PaxDbiQ6HA08
      PeptideAtlasiQ6HA08
      PRIDEiQ6HA08
      ProteomicsDBi66354

      Protocols and materials databases

      Structural Biology KnowledgebaseSearch...

      Genome annotation databases

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

      Organism-specific databases

      CTDi431705
      EuPathDBiHostDB:ENSG00000188886.3
      GeneCardsiASTL
      H-InvDBiHIX0029864
      HGNCiHGNC:31704 ASTL
      HPAiHPA015620
      MIMi608860 gene
      neXtProtiNX_Q6HA08
      OpenTargetsiENSG00000188886
      PharmGKBiPA134922299
      GenAtlasiSearch...

      Phylogenomic databases

      eggNOGiKOG3714 Eukaryota
      ENOG410ZPX7 LUCA
      GeneTreeiENSGT00760000119227
      HOGENOMiHOG000231483
      HOVERGENiHBG080299
      InParanoidiQ6HA08
      KOiK08778
      OMAiISIIPMY
      OrthoDBiEOG091G009U
      PhylomeDBiQ6HA08
      TreeFamiTF315280

      Miscellaneous databases

      GenomeRNAii431705
      PROiPR:Q6HA08
      SOURCEiSearch...

      Gene expression databases

      BgeeiENSG00000188886 Expressed in 55 organ(s), highest expression level in urinary bladder
      CleanExiHS_ASTL

      Family and domain databases

      Gene3Di3.40.390.10, 1 hit
      InterProiView protein in InterPro
      IPR024079 MetalloPept_cat_dom_sf
      IPR001506 Peptidase_M12A
      IPR006026 Peptidase_Metallo
      PfamiView protein in Pfam
      PF01400 Astacin, 1 hit
      PRINTSiPR00480 ASTACIN
      SMARTiView protein in SMART
      SM00235 ZnMc, 1 hit
      PROSITEiView protein in PROSITE
      PS51864 ASTACIN, 1 hit
      PS00142 ZINC_PROTEASE, 1 hit
      ProtoNetiSearch...

      Entry informationi

      Entry nameiASTL_HUMAN
      AccessioniPrimary (citable) accession number: Q6HA08
      Secondary accession number(s): Q3KNT0
      Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 27, 2005
      Last sequence update: January 11, 2011
      Last modified: November 7, 2018
      This is version 104 of the entry and version 4 of the sequence. See 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
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