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Q6HA08 (ASTL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 78. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Astacin-like metalloendopeptidase

EC=3.4.-.-
Alternative name(s):
Oocyte astacin
Ovastacin
Gene names
Name:ASTL
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length431 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Enzyme regulation

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

Subunit structure

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

Subcellular location

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.

Tissue specificity

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

Sequence similarities

Belongs to the peptidase M12A family.

Biophysicochemical properties

Kinetic parameters:

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. Ref.1

pH dependence:

Optimum pH is 7.5. Ref.1

Ontologies

Keywords
   Biological processFertilization
   Cellular componentCell membrane
Cytoplasm
Cytoplasmic vesicle
Membrane
   Coding sequence diversityPolymorphism
   DomainSignal
   LigandMetal-binding
Zinc
   Molecular functionHydrolase
Metalloprotease
Protease
   PTMZymogen
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell adhesion

Inferred from sequence or structural similarity PubMed 22206759. Source: UniProtKB

fertilization

Inferred from sequence or structural similarity PubMed 22206759. Source: UniProtKB

negative regulation of binding of sperm to zona pellucida

Inferred from sequence or structural similarity PubMed 22472438. Source: UniProtKB

positive regulation of protein processing

Inferred from sequence or structural similarity PubMed 22472438. Source: UniProtKB

prevention of polyspermy

Inferred from sequence or structural similarity PubMed 22472438. Source: UniProtKB

proteolysis

Inferred from direct assay Ref.1. Source: MGI

   Cellular_componentcortical granule

Inferred from sequence or structural similarity PubMed 22472438. Source: UniProtKB

cytoplasm

Inferred from sequence or structural similarity PubMed 22206759. Source: UniProtKB

plasma membrane

Inferred from sequence or structural similarity PubMed 22206759. Source: UniProtKB

transport vesicle

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionaspartic-type peptidase activity

Inferred from sequence or structural similarity PubMed 22472438. Source: UniProtKB

glutamic-type peptidase activity

Inferred from sequence or structural similarity PubMed 22472438. Source: UniProtKB

metalloendopeptidase activity

Inferred from direct assay Ref.1. Source: UniProtKB

peptidase activity

Inferred from direct assay Ref.1. Source: MGI

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Potential
Chain24 – 431408Astacin-like metalloendopeptidase
PRO_0000041964

Sites

Active site1831 By similarity UniProtKB P07584
Metal binding1821Zinc; catalytic By similarity UniProtKB P07584
Metal binding1861Zinc; catalytic By similarity UniProtKB P07584
Metal binding1921Zinc; catalytic By similarity UniProtKB P07584

Natural variations

Natural variant2041R → H.
Corresponds to variant rs56238667 [ dbSNP | Ensembl ].
VAR_061734
Natural variant2221Q → R. Ref.1 Ref.3
Corresponds to variant rs749458 [ dbSNP | Ensembl ].
VAR_033491
Natural variant2771K → Q. Ref.3
Corresponds to variant rs1657502 [ dbSNP | Ensembl ].
VAR_057063

Experimental info

Sequence conflict901T → A in CAD61265. Ref.1
Sequence conflict3001R → K in CAD61265. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q6HA08 [UniParc].

Last modified January 11, 2011. Version 4.
Checksum: 6E1FD4653506AFC1

FASTA43145,936
        10         20         30         40         50         60 
MEGVGGLWPW VLGLLSLPGV ILGAPLASSC AGACGTSFPD GLTPEGTQAS GDKDIPAINQ 

        70         80         90        100        110        120 
GLILEETPES SFLIEGDIIR PSPFRLLSAT SNKWPMGGSG VVEVPFLLSS KYDEPSRQVI 

       130        140        150        160        170        180 
LEALAEFERS TCIRFVTYQD QRDFISIIPM YGCFSSVGRS GGMQVVSLAP TCLQKGRGIV 

       190        200        210        220        230        240 
LHELMHVLGF WHEHTRADRD RYIRVNWNEI LPGFEINFIK SQSSNMLTPY DYSSVMHYGR 

       250        260        270        280        290        300 
LAFSRRGLPT ITPLWAPSVH IGQRWNLSAS DITRVLKLYG CSPSGPRPRG RGSHAHSTGR 

       310        320        330        340        350        360 
SPAPASLSLQ RLLEALSAES RSPDPSGSSA GGQPVPAGPG ESPHGWESPA LKKLSAEASA 

       370        380        390        400        410        420 
RQPQTLASSP RSRPGAGAPG VAQEQSWLAG VSTKPTVPSS EAGIQPVPVQ GSPALPGGCV 

       430 
PRNHFKGMSE D 

« Hide

References

« Hide 'large scale' references
[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: Ovary.
[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. expand/collapse author list , 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.
+Additional computationally mapped references.

Web resources

Protein Spotlight

Life's boundaries - Issue 141 of September2012

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ537600 mRNA. Translation: CAD61265.2.
AC012307 Genomic DNA. No translation available.
BC107127 mRNA. Translation: AAI07128.1.
RefSeqNP_001002036.3. NM_001002036.3.
UniGeneHs.447993.

3D structure databases

ProteinModelPortalQ6HA08.
SMRQ6HA08. Positions 52-284.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid136111. 1 interaction.
STRING9606.ENSP00000343674.

Protein family/group databases

MEROPSM12.245.

PTM databases

PhosphoSiteQ6HA08.

Polymorphism databases

DMDM317373556.

Proteomic databases

PaxDbQ6HA08.
PRIDEQ6HA08.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000342380; ENSP00000343674; ENSG00000188886.
GeneID431705.
KEGGhsa:431705.
UCSCuc010yui.2. human.

Organism-specific databases

CTD431705.
GeneCardsGC02M096789.
H-InvDBHIX0029864.
HGNCHGNC:31704. ASTL.
HPAHPA015620.
MIM608860. gene.
neXtProtNX_Q6HA08.
PharmGKBPA134922299.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG330389.
HOGENOMHOG000231483.
HOVERGENHBG080299.
InParanoidQ6HA08.
KOK08778.
OMARWNLSAS.
OrthoDBEOG73V6MT.
PhylomeDBQ6HA08.
TreeFamTF315280.

Gene expression databases

CleanExHS_ASTL.
GenevestigatorQ6HA08.

Family and domain databases

Gene3D3.40.390.10. 1 hit.
InterProIPR024079. MetalloPept_cat_dom.
IPR001506. Peptidase_M12A.
IPR006026. Peptidase_Metallo.
[Graphical view]
PfamPF01400. Astacin. 1 hit.
[Graphical view]
PRINTSPR00480. ASTACIN.
SMARTSM00235. ZnMc. 1 hit.
[Graphical view]
PROSITEPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi431705.
NextBio108702.
PROQ6HA08.
SOURCESearch...

Entry information

Entry nameASTL_HUMAN
AccessionPrimary (citable) accession number: Q6HA08
Secondary accession number(s): Q3KNT0
Entry history
Integrated into UniProtKB/Swiss-Prot: September 27, 2005
Last sequence update: January 11, 2011
Last modified: April 16, 2014
This is version 78 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM