VM3HA_PROFL
ID VM3HA_PROFL Reviewed; 609 AA.
AC Q8JIR2; Q9PSN8;
DT 13-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Zinc metalloproteinase/disintegrin-like HR1a;
DE EC=3.4.24.-;
DE AltName: Full=Snake venom metalloproteinase;
DE Short=SVMP;
DE Contains:
DE RecName: Full=Disintegrin-like 1a;
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] {ECO:0000305, ECO:0000312|EMBL:BAB92013.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=12220724; DOI=10.1016/s0041-0101(02)00179-4;
RA Kishimoto M., Takahashi T.;
RT "Molecular cloning of HR1a and HR1b, high molecular hemorrhagic factors,
RT from Trimeresurus flavoviridis venom.";
RL Toxicon 40:1369-1375(2002).
RN [2] {ECO:0000305}
RP PROTEIN SEQUENCE OF 401-609, AND GLYCOSYLATION AT ASN-520.
RC TISSUE=Venom {ECO:0000269|PubMed:8514736};
RX PubMed=8514736; DOI=10.1093/oxfordjournals.jbchem.a124069;
RA Takeya H., Nishida S., Nishino N., Makinose Y., Omori-Satoh T., Nikai T.,
RA Sugihara H., Iwanaga S.;
RT "Primary structures of platelet aggregation inhibitors (disintegrins)
RT autoproteolytically released from snake venom hemorrhagic
RT metalloproteinases and new fluorogenic peptide substrates for these
RT enzymes.";
RL J. Biochem. 113:473-483(1993).
RN [3]
RP FUNCTION, AND 3D-STRUCTURE MODELING.
RX PubMed=18061641; DOI=10.1016/j.toxicon.2007.10.009;
RA Morine N., Matsuda S., Terada K., Eto A., Ishida I., Oku H.;
RT "Neutralization of hemorrhagic snake venom metalloproteinase HR1a from
RT Protobothrops flavoviridis by human monoclonal antibody.";
RL Toxicon 51:345-352(2008).
RN [4]
RP CATALYTIC ACTIVITY.
RC STRAIN=Okinawa habu; TISSUE=Venom;
RX PubMed=18256489; DOI=10.1271/bbb.70540;
RA Morine N., Matsuda S., Terada K., Iwasaki H., Oku H.;
RT "The occurrence of HR1b in the venom of the snake Okinawa habu
RT (Protobothrops flavoviridis).";
RL Biosci. Biotechnol. Biochem. 72:591-594(2008).
CC -!- FUNCTION: [Zinc metalloproteinase/disintegrin-like HR1a]: Zinc protease
CC that induces hemorrhage and has proteolytic activity (PubMed:18061641).
CC Has preference for Ala, His, Pro, Met, and Tyr at the P1 position, in
CC descending order (in vitro). Predominantly prefers Val and Asp at the
CC P3 and P2 positions, respectively (PubMed:18256489).
CC {ECO:0000269|PubMed:18061641, ECO:0000269|PubMed:18256489}.
CC -!- FUNCTION: [Disintegrin-like 1a]: Inhibits platelet aggregation induced
CC by ADP, thrombin, platelet-activating factor and collagen. Acts by
CC inhibiting fibrinogen interaction with platelet receptors alpha-
CC IIb/beta-3 (ITGA2B/ITGB3) (By similarity). {ECO:0000250}.
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 -!- MISCELLANEOUS: The disintegrin domain belongs to the long disintegrin
CC subfamily.
CC -!- SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-III
CC subfamily. P-IIIb 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; AB074143; BAB92013.1; -; mRNA.
DR PIR; JX0266; JX0266.
DR AlphaFoldDB; Q8JIR2; -.
DR SMR; Q8JIR2; -.
DR MEROPS; M12.320; -.
DR iPTMnet; Q8JIR2; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0008237; F:metallopeptidase activity; IDA:UniProtKB.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; TAS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR CDD; cd04269; ZnMc_adamalysin_II_like; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR Gene3D; 4.10.70.10; -; 1.
DR InterPro; IPR006586; ADAM_Cys-rich.
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; PF08516; ADAM_CR; 1.
DR Pfam; PF00200; Disintegrin; 1.
DR Pfam; PF01562; Pep_M12B_propep; 1.
DR Pfam; PF01421; Reprolysin; 1.
DR PRINTS; PR00289; DISINTEGRIN.
DR SMART; SM00608; ACR; 1.
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; Secreted; Signal; Toxin;
KW Zinc; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..190
FT /evidence="ECO:0000250"
FT /id="PRO_0000029017"
FT CHAIN 191..609
FT /note="Zinc metalloproteinase/disintegrin-like HR1a"
FT /id="PRO_0000029018"
FT PROPEP 397..400
FT /evidence="ECO:0000269|PubMed:8514736"
FT /id="PRO_0000029019"
FT CHAIN 401..609
FT /note="Disintegrin-like 1a"
FT /id="PRO_0000029020"
FT DOMAIN 200..396
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 404..490
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT MOTIF 468..470
FT /note="D/ECD-tripeptide"
FT ACT_SITE 337
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 203
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 287
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 336
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 340
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 346
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 391
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 394
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 406
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 409
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 411
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 413
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 416
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 419
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 470
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 473
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 485
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT CARBOHYD 298
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 350
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 374
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 520
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:8514736"
FT DISULFID 311..391
FT /note="In zinc metalloproteinase-disintegrin-like HR1a"
FT /evidence="ECO:0000250"
FT DISULFID 351..375
FT /note="In zinc metalloproteinase-disintegrin-like HR1a"
FT /evidence="ECO:0000250"
FT DISULFID 353..358
FT /note="In zinc metalloproteinase-disintegrin-like HR1a"
FT /evidence="ECO:0000250"
FT DISULFID 407..436
FT /note="In zinc metalloproteinase-disintegrin-like HR1a;
FT alternate"
FT /evidence="ECO:0000250"
FT DISULFID 407..426
FT /note="In disintegrin-like 1a; alternate"
FT /evidence="ECO:0000250"
FT DISULFID 418..436
FT /note="In disintegrin-like 1a; alternate"
FT /evidence="ECO:0000250"
FT DISULFID 418..431
FT /note="In zinc metalloproteinase-disintegrin-like HR1a;
FT alternate"
FT /evidence="ECO:0000250"
FT DISULFID 420..426
FT /note="In zinc metalloproteinase-disintegrin-like HR1a;
FT alternate"
FT /evidence="ECO:0000250"
FT DISULFID 430..453
FT /note="In zinc metalloproteinase-disintegrin-like HR1a"
FT /evidence="ECO:0000250"
FT DISULFID 444..450
FT /note="In zinc metalloproteinase-disintegrin-like HR1a"
FT /evidence="ECO:0000250"
FT DISULFID 449..475
FT /note="In zinc metalloproteinase-disintegrin-like HR1a"
FT /evidence="ECO:0000250"
FT DISULFID 462..482
FT /note="In both disintegrin-like 1a and zinc
FT metalloproteinase-disintegrin-like HR1a"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068,
FT ECO:0000255|PROSITE-ProRule:PRU00276"
FT DISULFID 469..501
FT /note="In zinc metalloproteinase-disintegrin-like HR1a;
FT alternate"
FT /evidence="ECO:0000250"
FT DISULFID 469..494
FT /note="In disintegrin-like 1a; alternate"
FT /evidence="ECO:0000250"
FT DISULFID 494..506
FT /note="In zinc metalloproteinase-disintegrin-like HR1a;
FT alternate"
FT /evidence="ECO:0000250"
FT DISULFID 501..506
FT /note="In disintegrin-like 1a"
FT /evidence="ECO:0000250"
FT DISULFID 513..563
FT /note="In zinc metalloproteinase-disintegrin-like HR1a;
FT alternate"
FT /evidence="ECO:0000250"
FT DISULFID 513..528
FT /note="In disintegrin-like 1a; alternate"
FT /evidence="ECO:0000250"
FT DISULFID 528..571
FT /note="In zinc metalloproteinase-disintegrin-like HR1a;
FT alternate"
FT /evidence="ECO:0000250"
FT DISULFID 541..551
FT /note="In zinc metalloproteinase-disintegrin-like HR1a;
FT alternate"
FT /evidence="ECO:0000250"
FT DISULFID 551..558
FT /note="In disintegrin-like 1a; alternate"
FT /evidence="ECO:0000250"
FT DISULFID 558..597
FT /note="In zinc metalloproteinase-disintegrin-like HR1a;
FT alternate"
FT /evidence="ECO:0000250"
FT DISULFID 563..571
FT /note="In disintegrin-like 1a"
FT /evidence="ECO:0000250"
FT DISULFID 591..602
FT /note="In zinc metalloproteinase-disintegrin-like HR1a;
FT alternate"
FT /evidence="ECO:0000250"
FT DISULFID 597..602
FT /note="In disintegrin-like 1a"
FT /evidence="ECO:0000250"
SQ SEQUENCE 609 AA; 68765 MW; E955A2369791D4FE CRC64;
MIQVLLVTIC LAVFPYQGSS IILGSGNVND YEVVYPRKVT AVPKGAVQPK YEDTMQYEFK
VNGEPVVLHL EKNKGLFSKD YSETHYSPDG REITTYPSVE DHCYYHGRIQ NDADSTASIS
ACNGLKGHFK LQGEMYLIEP LRFSDSEAHA VFKYENVEKE DEAPKMCGVT QTNWESDEPI
KKASKLVVTA EQQRYLNNFR FIELVIVADY RMFTKFNSNL NEVKTWVYEI VNTLNEIYRY
LYVRVALVAL EVWSNGDLSS VTLSAYDTLD SFGEWRKRDL LKRKSHDNAQ LLTAIDFNGT
IIGLAHVASM CDPKCSTGIV QDYSSRNLVV AVIMAHEMGH NLGIRHDREN CTCHANSCIM
SAVISDQPSK YFSNCSHVQY WNYINDDEPQ CILNEPLRTD IVSPPVCGNE LLEVGEECDC
GSPATCRYPC CDAATCKLHS WVECESGECC EQCRFRTAGT ECRARRSECD IAESCTGHSA
DCPTDRFHRN GQPCLHNFGY CYNGNCPIMY HQCYALWGAN ATVAKDSCFE DNQKGNDYGY
CRKENGRKIP CEPQDVKCGR LYCSLGNQLP CRFFYTPTDE NIGMVDTGTK CGDKKVCSNR
QCVDVNTAY
