VM2H1_BOTLA
ID VM2H1_BOTLA Reviewed; 484 AA.
AC U5PZ28;
DT 19-MAR-2014, integrated into UniProtKB/Swiss-Prot.
DT 22-JAN-2014, sequence version 1.
DT 03-AUG-2022, entry version 24.
DE RecName: Full=Zinc metalloproteinase-disintegrin BlatH1;
DE EC=3.4.24.-;
DE AltName: Full=Snake venom metalloproteinase;
DE Short=SVMP;
DE Flags: Precursor;
OS Bothriechis lateralis (Side-striped palm pitviper).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Bothriechis.
OX NCBI_TaxID=44727;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 437-452, FUNCTION, ACTIVITY
RP REGULATION, SUBUNIT, TOXIC DOSE, MASS SPECTROMETRY, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC TISSUE=Venom, and Venom gland;
RX PubMed=24457155; DOI=10.1016/j.biochi.2014.01.008;
RA Camacho E., Villalobos E., Sanz L., Perez A., Escalante T., Lomonte B.,
RA Calvete J.J., Gutierrez J.M., Rucavado A.;
RT "Understanding structural and functional aspects of PII snake venom
RT metalloproteinases: Characterization of BlatH1, a hemorrhagic dimeric
RT enzyme from the venom of Bothriechis lateralis.";
RL Biochimie 101:145-155(2014).
CC -!- FUNCTION: Snake venom zinc metalloprotease-disintegrin that hydrolyzes
CC azocasein, gelatin and fibrinogen (Aalpha and Bbeta chains and
CC partially gamma-chain), and exerts a potent local and systemic
CC hemorrhagic activity in mice. It inhibits ADP- and collagen-induced
CC human platelet aggregation (IC(50) = 0.3 uM and 0.7 uM for ADP and
CC collagen, respectively). This inhibition is dependent of protease
CC activity, and probably occurs through the degradation of an unknown
CC platelet receptor. {ECO:0000269|PubMed:24457155}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Platelet aggregation in inhibited by the
CC metalloproteinase inhibitors EDTA and Batimastat. The hemorrhagic
CC activity is not inhibited by the plasma proteinase inhibitor alpha2-
CC macroglobulin, although the SVMP is able to cleave this plasma
CC inhibitor, generating a 90 kDa product. {ECO:0000269|PubMed:24457155}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:24457155}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- PTM: The N-terminus is blocked.
CC -!- MASS SPECTROMETRY: Mass=83644; Mass_error=63; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:24457155};
CC -!- TOXIC DOSE: LD(50) is 7.2 mg/kg by intravenous injection into mice.
CC {ECO:0000269|PubMed:24457155}.
CC -!- MISCELLANEOUS: The disintegrin domain belongs to the long disintegrin
CC subfamily.
CC -!- SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-II
CC subfamily. P-IIc sub-subfamily. {ECO:0000305}.
CC -!- CAUTION: This protein does not undergo proteolytic processing to
CC release the disintegrin domain. {ECO:0000305}.
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DR EMBL; KF309674; AGY49227.1; -; mRNA.
DR AlphaFoldDB; U5PZ28; -.
DR SMR; U5PZ28; -.
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; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Hemorrhagic toxin; Hemostasis impairing toxin; Hydrolase; Metal-binding;
KW Metalloprotease; 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:0000250"
FT /id="PRO_0000425968"
FT CHAIN 191..484
FT /note="Zinc metalloproteinase-disintegrin BlatH1"
FT /id="PRO_0000425969"
FT DOMAIN 199..395
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 403..484
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT MOTIF 465..467
FT /note="TDN-tripeptide"
FT ACT_SITE 336
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 202
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 286
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 335
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 339
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 345
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 390
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 393
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 405
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 408
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 412
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 415
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 418
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT MOD_RES 191
FT /note="Pyrrolidone carboxylic acid (Glu)"
FT /evidence="ECO:0000250"
FT CARBOHYD 259
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 297
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 373
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 310..390
FT /evidence="ECO:0000250"
FT DISULFID 350..374
FT /evidence="ECO:0000250"
FT DISULFID 352..357
FT /evidence="ECO:0000250"
FT DISULFID 406..425
FT /evidence="ECO:0000255"
FT DISULFID 417..435
FT /evidence="ECO:0000250"
FT DISULFID 419..430
FT /evidence="ECO:0000250"
FT DISULFID 421
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068,
FT ECO:0000255|PROSITE-ProRule:PRU00276"
FT DISULFID 429..452
FT /evidence="ECO:0000250"
FT DISULFID 443..449
FT /evidence="ECO:0000250"
FT DISULFID 448..473
FT /evidence="ECO:0000250"
FT DISULFID 461..480
FT /evidence="ECO:0000250"
SQ SEQUENCE 484 AA; 54298 MW; 1B7A2A5BE79CA370 CRC64;
MIQVLLVTIC LAALPYQGSS IILESGNVND YEVVYPRKVT ALPKGAGQPK YEDAMQYEFK
VNGEPVVLHL EKNKGLFSKD YSETHYSSDG RKITTNPPVE DHCYYHGRIE NDADSTGSIS
ACNGLKGHFK LQGEMYLIEP LKLSDSEAHA IYKYENVEKE DEAPKMCGVT ETNWESYEPI
KKASQSNLTP EQQRFNPFKY VELVIVADHR MFTKYNGDLE KIRIKIYEIV NILNEMFRYL
YIRIALVDLE IWSNRDLINV TSVAGDTLDS FGNWRETDLL KRKSHDNAQL LTGIDFNGTT
IGIAYIASMC NPYLSVGIVQ DHSEINFLIA VTMAHEMGHN LGMRHDTDYC TCGGYSCIMC
AVLSDQPSKF FSNCSYIQYG KFIMNQNSQC ILNEPLGTDI VSPPVCGNEI LEVGEECDCG
CPTNCQDPCC NAATCKQYSW VQCESGECCE QCRFRAAGTV CRRATDNDMD NRCTGQSADC
PSNG
