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Q6HA08

- ASTL_HUMAN

UniProt

Q6HA08 - ASTL_HUMAN

Protein

Astacin-like metalloendopeptidase

Gene

ASTL

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 81 (01 Oct 2014)
      Sequence version 4 (11 Jan 2011)
      Previous versions | rss
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    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 – 1831By similarityPROSITE-ProRule annotation
      Metal bindingi186 – 1861Zinc; catalyticPROSITE-ProRule annotation
      Metal bindingi192 – 1921Zinc; catalyticPROSITE-ProRule annotation

      GO - Molecular functioni

      1. aspartic-type peptidase activity Source: UniProtKB
      2. glutamic-type peptidase activity Source: UniProtKB
      3. metalloendopeptidase activity Source: UniProtKB
      4. peptidase activity Source: MGI
      5. zinc ion binding Source: InterPro

      GO - Biological processi

      1. cell adhesion Source: UniProtKB
      2. fertilization Source: UniProtKB
      3. negative regulation of binding of sperm to zona pellucida Source: UniProtKB
      4. positive regulation of protein processing Source: UniProtKB
      5. prevention of polyspermy Source: UniProtKB
      6. proteolysis Source: MGI

      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: 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

      1. cortical granule Source: UniProtKB
      2. cytoplasm Source: UniProtKB
      3. plasma membrane Source: UniProtKB
      4. transport vesicle Source: UniProtKB-SubCell

      Keywords - Cellular componenti

      Cell membrane, Cytoplasm, Cytoplasmic vesicle, Membrane

      Pathology & Biotechi

      Organism-specific databases

      PharmGKBiPA134922299.

      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.
      GenevestigatoriQ6HA08.

      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. 1 interaction.
      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.
      HOGENOMiHOG000231483.
      HOVERGENiHBG080299.
      InParanoidiQ6HA08.
      KOiK08778.
      OMAiRWNLSAS.
      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

      MEGVGGLWPW VLGLLSLPGV ILGAPLASSC AGACGTSFPD GLTPEGTQAS    50
      GDKDIPAINQ GLILEETPES SFLIEGDIIR PSPFRLLSAT SNKWPMGGSG 100
      VVEVPFLLSS KYDEPSRQVI LEALAEFERS TCIRFVTYQD QRDFISIIPM 150
      YGCFSSVGRS GGMQVVSLAP TCLQKGRGIV LHELMHVLGF WHEHTRADRD 200
      RYIRVNWNEI LPGFEINFIK SQSSNMLTPY DYSSVMHYGR LAFSRRGLPT 250
      ITPLWAPSVH IGQRWNLSAS DITRVLKLYG CSPSGPRPRG RGSHAHSTGR 300
      SPAPASLSLQ RLLEALSAES RSPDPSGSSA GGQPVPAGPG ESPHGWESPA 350
      LKKLSAEASA RQPQTLASSP RSRPGAGAPG VAQEQSWLAG VSTKPTVPSS 400
      EAGIQPVPVQ GSPALPGGCV PRNHFKGMSE D 431
      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:
      EMBL
      GenBank
      DDBJ
      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.

      Polymorphism databases

      DMDMi317373556.

      Keywords - Coding sequence diversityi

      Polymorphism

      Cross-referencesi

      Web resourcesi

      Protein Spotlight

      Life's boundaries - Issue 141 of September2012

      Sequence databases

      Select the link destinations:
      EMBL
      GenBank
      DDBJ
      Links Updated
      AJ537600 mRNA. Translation: CAD61265.2 .
      AC012307 Genomic DNA. No translation available.
      BC107127 mRNA. Translation: AAI07128.1 .
      CCDSi CCDS33249.1.
      RefSeqi NP_001002036.3. NM_001002036.3.
      UniGenei Hs.447993.

      3D structure databases

      ProteinModelPortali Q6HA08.
      SMRi Q6HA08. Positions 52-284.
      ModBasei Search...
      MobiDBi Search...

      Protein-protein interaction databases

      BioGridi 136111. 1 interaction.
      STRINGi 9606.ENSP00000343674.

      Protein family/group databases

      MEROPSi M12.245.

      PTM databases

      PhosphoSitei Q6HA08.

      Polymorphism databases

      DMDMi 317373556.

      Proteomic databases

      PaxDbi Q6HA08.
      PRIDEi Q6HA08.

      Protocols and materials databases

      Structural Biology Knowledgebase Search...

      Genome annotation databases

      Ensembli ENST00000342380 ; ENSP00000343674 ; ENSG00000188886 .
      GeneIDi 431705.
      KEGGi hsa:431705.
      UCSCi uc010yui.2. human.

      Organism-specific databases

      CTDi 431705.
      GeneCardsi GC02M096789.
      H-InvDB HIX0029864.
      HGNCi HGNC:31704. ASTL.
      HPAi HPA015620.
      MIMi 608860. gene.
      neXtProti NX_Q6HA08.
      PharmGKBi PA134922299.
      GenAtlasi Search...

      Phylogenomic databases

      eggNOGi NOG330389.
      HOGENOMi HOG000231483.
      HOVERGENi HBG080299.
      InParanoidi Q6HA08.
      KOi K08778.
      OMAi RWNLSAS.
      OrthoDBi EOG73V6MT.
      PhylomeDBi Q6HA08.
      TreeFami TF315280.

      Miscellaneous databases

      GenomeRNAii 431705.
      NextBioi 108702.
      PROi Q6HA08.
      SOURCEi Search...

      Gene expression databases

      CleanExi HS_ASTL.
      Genevestigatori Q6HA08.

      Family and domain databases

      Gene3Di 3.40.390.10. 1 hit.
      InterProi IPR024079. MetalloPept_cat_dom.
      IPR001506. Peptidase_M12A.
      IPR006026. Peptidase_Metallo.
      [Graphical view ]
      Pfami PF01400. Astacin. 1 hit.
      [Graphical view ]
      PRINTSi PR00480. ASTACIN.
      SMARTi SM00235. ZnMc. 1 hit.
      [Graphical view ]
      PROSITEi PS00142. ZINC_PROTEASE. 1 hit.
      [Graphical view ]
      ProtoNeti Search...

      Publicationsi

      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: October 1, 2014
      This is version 81 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