Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
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)DescriptionActionsGraphical viewLength
      Metal bindingi182Zinc; catalyticPROSITE-ProRule annotation1
      Active sitei183PROSITE-ProRule annotationBy similarity1
      Metal bindingi186Zinc; catalyticPROSITE-ProRule annotation1
      Metal bindingi192Zinc; 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

      • 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

      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

      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

      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

      Keywords - PTMi

      Zymogen

      Proteomic databases

      PaxDbiQ6HA08.
      PeptideAtlasiQ6HA08.
      PRIDEiQ6HA08.

      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.
      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

      Sequence similaritiesi

      Belongs to the peptidase M12A family.Sequence analysis

      Keywords - Domaini

      Signal

      Phylogenomic databases

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

      Family and domain databases

      Gene3Di3.40.390.10. 1 hit.
      InterProiView protein in InterPro
      IPR024079. MetalloPept_cat_dom.
      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
      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

      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: August 30, 2017
      This is version 98 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
      5. Peptidase families
        Classification of peptidase families and list of entries
      6. SIMILARITY comments
        Index of protein domains and families