ID   VMPAR_HIPPR             Reviewed;          19 AA.
AC   P85975;
DT   02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT   02-SEP-2008, sequence version 1.
DT   03-AUG-2022, entry version 30.
DE   RecName: Full=Zinc metalloproteinase partitagin {ECO:0000303|PubMed:17555860};
DE            EC=3.4.24.-;
DE   Flags: Fragment;
OS   Hippasa partita (Funnel-web spider) (Hippasa deserticola).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC   Araneomorphae; Entelegynae; Lycosoidea; Lycosidae; Hippasa.
OX   NCBI_TaxID=547193;
RN   [1] {ECO:0000305}
RP   PROTEIN SEQUENCE, FUNCTION, COFACTOR, ACTIVITY REGULATION,
RP   BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP   AND MASS SPECTROMETRY.
RC   TISSUE=Venom {ECO:0000269|PubMed:17555860};
RX   PubMed=17555860; DOI=10.1016/j.biochi.2007.04.005;
RA   Nagaraju S., Girish K.S., Fox J.W., Kemparaju K.;
RT   "'Partitagin' a hemorrhagic metalloprotease from Hippasa partita spider
RT   venom: role in tissue necrosis.";
RL   Biochimie 89:1322-1331(2007).
RN   [2]
RP   FUNCTION, ACTIVITY REGULATION, AND TOXIC DOSE.
RC   TISSUE=Venom;
RX   PubMed=21150580; DOI=10.1097/mbc.0b013e32833fcc15;
RA   Shivaiah N., Kempaiah K.;
RT   "'Partitagin', a unique beta, gamma-fibrinogenase that inhibits platelet
RT   aggregation from Hippasa partita spider venom.";
RL   Blood Coagul. Fibrinolysis 22:24-28(2011).
CC   -!- FUNCTION: Zinc metalloproteinase that causes hemorrhage in mice
CC       following intradermal injection and impairs hemostasis in its prey. In
CC       skin tissues, it degrades components of the basement membrane
CC       surrounding blood vessels and capillaries. In muscle tissue, it
CC       degrades the extracellular matrix, thus causing muscle necrosis.
CC       However, it lacks direct toxicity on myocytes. Hydrolyzes alpha-2 chain
CC       (COL4A2) of type IV collagen more slowly than the alpha-1 chain
CC       (COL4A1). Hydrolyzes fibronectin (FN1). It also impairs hemostasis by
CC       acting on fibrin(ogen) and platelets. Shows fibrinolytic activity, with
CC       a selective degradation of gamma-dimer (FGG). Shows fibrinogenolytic
CC       activity by preferentially cleaving the Bbeta chain, and later gamma-
CC       chain. Aalpha-chain remains resistant to proteolytic digestion. Weakly
CC       inhibits collagen-triggered platelet aggregation of human plasma rich
CC       platelet. {ECO:0000269|PubMed:17555860, ECO:0000269|PubMed:21150580}.
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000269|PubMed:17555860};
CC       Note=Binds 3 Zn(2+) ions per subunit. {ECO:0000269|PubMed:17555860};
CC   -!- ACTIVITY REGULATION: Inhibited by EDTA, 1,10-phenanthroline, cyanide,
CC       and serum alpha2-microglobulin. Not inhibited by EGTA, PMSF, leupeptin,
CC       pepstatin and aprotinin. {ECO:0000269|PubMed:17555860,
CC       ECO:0000269|PubMed:21150580}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 7.6. {ECO:0000269|PubMed:17555860};
CC       Temperature dependence:
CC         Optimum temperature is 37 degrees Celsius.
CC         {ECO:0000269|PubMed:17555860};
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17555860}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000269|PubMed:17555860}.
CC   -!- MASS SPECTROMETRY: Mass=29129; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:17555860};
CC   -!- TOXIC DOSE: Dose that inhibits collagen-triggered platelet aggregation
CC       of human plasma rich platelet (IC(50)) is 1.3 mmol/l.
CC       {ECO:0000269|PubMed:21150580}.
CC   -!- SIMILARITY: Belongs to the venom metalloproteinase (M12B) family.
CC       {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   AlphaFoldDB; P85975; -.
DR   ArachnoServer; AS001205; Partitagin-1-Hippasa partita.
DR   GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR   GO; GO:0004222; F:metalloendopeptidase activity; IDA:UniProtKB.
DR   GO; GO:0008237; F:metallopeptidase activity; IDA:UniProtKB.
DR   GO; GO:0090729; F:toxin activity; IDA:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR   GO; GO:0044482; P:envenomation resulting in blood vessel extracellular matrix damage, causing hemorrhagic damage in another organism; IDA:UniProtKB.
DR   GO; GO:0035899; P:negative regulation of blood coagulation in another organism; IDA:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Fibrinogenolytic toxin; Fibrinolytic toxin;
KW   Hemostasis impairing toxin; Hydrolase; Metal-binding; Metalloprotease;
KW   Platelet aggregation inhibiting toxin; Protease; Secreted; Toxin; Zinc.
FT   CHAIN           1..>19
FT                   /note="Zinc metalloproteinase partitagin"
FT                   /id="PRO_0000349128"
FT   NON_TER         19
FT                   /evidence="ECO:0000303|PubMed:17555860"
SQ   SEQUENCE   19 AA;  2334 MW;  BE63CFFC4899AF0C CRC64;
     AYDPDPYKRY SAEHTFFLL