VM2HA_PROFL
ID VM2HA_PROFL Reviewed; 478 AA.
AC P14530; P80949; Q90W25;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 3.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Zinc metalloproteinase/disintegrin;
DE Contains:
DE RecName: Full=Snake venom metalloproteinase HR2a {ECO:0000303|PubMed:10371209, ECO:0000303|PubMed:2753880};
DE Short=SVMP;
DE EC=3.4.24.53;
DE AltName: Full=Snake venom metalloproteinase HR2b {ECO:0000303|PubMed:7597726};
DE AltName: Full=Trimerelysin II;
DE Contains:
DE RecName: Full=Disintegrin flavostatin {ECO:0000303|PubMed:10371209, ECO:0000303|PubMed:9114455};
DE AltName: Full=Platelet aggregation activation inhibitor;
DE Flags: Precursor;
OS Protobothrops flavoviridis (Habu) (Trimeresurus flavoviridis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Protobothrops.
OX NCBI_TaxID=88087;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=10371209; DOI=10.1016/s0014-5793(99)00604-3;
RA Yamada D., Shin Y., Morita T.;
RT "Nucleotide sequence of a cDNA encoding a common precursor of disintegrin
RT flavostatin and hemorrhagic factor HR2a from the venom of Trimeresurus
RT flavoviridis.";
RL FEBS Lett. 451:299-302(1999).
RN [2]
RP PROTEIN SEQUENCE OF 191-392, DISULFIDE BONDS, PYROGLUTAMATE FORMATION AT
RP GLN-191, AND VARIANTS OKINAWA HABU 189-GLU--PHE-192 AND ASN-271.
RC STRAIN=Okinawa habu; TISSUE=Venom;
RX PubMed=7597726; DOI=10.1016/0041-0101(94)00147-z;
RA Iha M., Qi Z.Q., Kannki T., Tomihara Y., Yonaha K.;
RT "The primary structure of a hemorrhagic factor, HR2b, from the venom of
RT Okinawa habu (Trimeresurus flavoviridis).";
RL Toxicon 33:229-239(1995).
RN [3]
RP PROTEIN SEQUENCE OF 191-392, DISULFIDE BONDS, PYROGLUTAMATE FORMATION AT
RP GLN-191, AND ABSENCE OF GLYCOSYLATION.
RC STRAIN=Amami habu; TISSUE=Venom;
RX PubMed=2753880; DOI=10.1093/oxfordjournals.jbchem.a122756;
RA Miyata T., Takeya H., Ozeki Y., Arakawa M., Tokunaga F., Iwanaga S.,
RA Omori-Satoh T.;
RT "Primary structure of hemorrhagic protein, HR2a, isolated from the venom of
RT Trimeresurus flavoviridis.";
RL J. Biochem. 105:847-853(1989).
RN [4]
RP PROTEIN SEQUENCE OF 411-478, AND FUNCTION OF FLAVOSTATIN.
RC TISSUE=Venom;
RX PubMed=9114455; DOI=10.1016/s0196-9781(96)00259-8;
RA Maruyama K., Kawasaki T., Sakai Y., Taniuchi Y., Shimizu M., Kawashima H.,
RA Takenaka T.;
RT "Isolation and amino acid sequence of flavostatin, a novel disintegrin from
RT the venom of Trimeresurus flavoviridis.";
RL Peptides 18:73-78(1997).
CC -!- FUNCTION: [Snake venom metalloproteinase HR2a]: Zinc protease that
CC induces hemorrhage. {ECO:0000269|PubMed:9114455}.
CC -!- FUNCTION: [Disintegrin flavostatin]: Inhibits platelet aggregation
CC induced by ADP, thrombin, and collagen. Acts by inhibiting fibrinogen
CC interaction with platelet receptors GPIIb/GPIIIa (ITGA2B/ITGB3).
CC {ECO:0000269|PubMed:9114455}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleavage of 3-Asn-|-Gln-4, 10-His-|-Leu-11 and 14-Ala-|-Leu-15
CC in the insulin B chain, and the bond Z-Gly-Pro-|-Leu-Gly-Pro in a
CC small molecule substrate of microbial collagenase.; EC=3.4.24.53;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- PTM: Not N-glycosylated. {ECO:0000269|PubMed:2753880}.
CC -!- MISCELLANEOUS: The disintegrin belongs to the medium disintegrin
CC subfamily.
CC -!- SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-II
CC subfamily. P-IIa sub-subfamily. {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 EMBL; AY037808; AAK68850.1; -; mRNA.
DR PIR; JX0074; HYTVH2.
DR AlphaFoldDB; P14530; -.
DR SMR; P14530; -.
DR MEROPS; M12.156; -.
DR PRIDE; P14530; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd04269; ZnMc_adamalysin_II_like; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR Gene3D; 4.10.70.10; -; 1.
DR InterPro; IPR018358; Disintegrin_CS.
DR InterPro; IPR001762; Disintegrin_dom.
DR InterPro; IPR036436; Disintegrin_dom_sf.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001590; Peptidase_M12B.
DR InterPro; IPR002870; Peptidase_M12B_N.
DR InterPro; IPR034027; Reprolysin_adamalysin.
DR Pfam; PF00200; Disintegrin; 1.
DR Pfam; PF01562; Pep_M12B_propep; 1.
DR Pfam; PF01421; Reprolysin; 1.
DR PRINTS; PR00289; DISINTEGRIN.
DR SMART; SM00050; DISIN; 1.
DR SUPFAM; SSF57552; SSF57552; 1.
DR PROSITE; PS50215; ADAM_MEPRO; 1.
DR PROSITE; PS00427; DISINTEGRIN_1; 1.
DR PROSITE; PS50214; DISINTEGRIN_2; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Calcium; Cell adhesion impairing toxin; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Hemorrhagic toxin;
KW Hemostasis impairing toxin; Hydrolase; Metal-binding; Metalloprotease;
KW Platelet aggregation inhibiting toxin; Protease;
KW Pyrrolidone carboxylic acid; Secreted; Signal; Toxin; Zinc; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..190
FT /evidence="ECO:0000305"
FT /id="PRO_0000029013"
FT CHAIN 191..392
FT /note="Snake venom metalloproteinase HR2a"
FT /evidence="ECO:0000269|PubMed:2753880"
FT /id="PRO_0000029014"
FT PROPEP 393..410
FT /evidence="ECO:0000305"
FT /id="PRO_0000029015"
FT CHAIN 411..478
FT /note="Disintegrin flavostatin"
FT /evidence="ECO:0000269|PubMed:9114455"
FT /id="PRO_0000029016"
FT DOMAIN 197..392
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 400..478
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT REGION 459..478
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 459..461
FT /note="Cell attachment site"
FT ACT_SITE 334
FT BINDING 200
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 284
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 333
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 337
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 343
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 387
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 390
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT SITE 293
FT /note="Not glycosylated"
FT /evidence="ECO:0000269|PubMed:2753880"
FT MOD_RES 191
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:2753880,
FT ECO:0000269|PubMed:7597726"
FT DISULFID 308..387
FT /evidence="ECO:0000269|PubMed:2753880,
FT ECO:0000269|PubMed:7597726"
FT DISULFID 349..371
FT /evidence="ECO:0000269|PubMed:2753880,
FT ECO:0000269|PubMed:7597726"
FT DISULFID 351..354
FT /evidence="ECO:0000269|PubMed:2753880,
FT ECO:0000269|PubMed:7597726"
FT DISULFID 414..423
FT /evidence="ECO:0000250"
FT DISULFID 416..424
FT /evidence="ECO:0000250"
FT DISULFID 429..443
FT /evidence="ECO:0000250"
FT DISULFID 437..467
FT /evidence="ECO:0000250"
FT DISULFID 442..446
FT /evidence="ECO:0000250"
FT DISULFID 455..474
FT /evidence="ECO:0000250"
FT VARIANT 189..192
FT /note="PEQQ -> EQRF (in Okinawa habu)"
FT /evidence="ECO:0000269|PubMed:7597726"
FT VARIANT 192
FT /note="Missing (in 50% of the chains)"
FT VARIANT 271
FT /note="D -> N (in Okinawa habu)"
FT /evidence="ECO:0000269|PubMed:7597726"
SQ SEQUENCE 478 AA; 53646 MW; 6C8FF7F184F1B85F CRC64;
MIEVLLVTIC LAVFPYPGSS IILESGNVDD YEVVYPQKLT ALPKGAVQPK YEDAMQYEFK
VNGEPVVLHL EKNKGLFSED YSETHYSPDG REITTYPSVE DHCYYHGRIQ NDADSTASIS
ACDGLKGYFK LQGETYLIEP LELSDSEAHA VFKYENVEKE DEAPKMCGVT QNWESDESIK
KASQLYLTPE QQRFPQRYIE LAIVVDHGMY TKYSSNFKKI RKRVHQMVNN INEMYRPLNI
AITLSLLDVW SEKDLITMQA VAPTTARLFG DWRETVLLKQ KDHDHAQLLT DINFTGNTIG
WAYMGGMCNA KNSVGIVKDH SSNVFMVAVT MTHEIGHNLG MEHDDKDKCK CEACIMSAVI
SDKPSKLFSD CSKDYYQTFL TNSKPQCIIN APLRTDTVST PVSGNEFLEA GEECDCGSPS
NPCCDAATCK LRPGAQCADG LCCDQCRFKK KRTICRRARG DNPDDRCTGQ SADCPRNS
