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Q6HA08

- ASTL_HUMAN

UniProt

Q6HA08 - ASTL_HUMAN

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Protein

Astacin-like metalloendopeptidase

Gene

ASTL

Organism
Homo sapiens (Human)
Status
Reviewed - 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 – 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
    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: 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
    Complete GO annotation...

    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. 6 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.
    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

            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:
    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. 6 interactions.
    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.
    GeneTreei ENSGT00760000119227.
    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

    « 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: October 29, 2014
    This is version 82 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