VM2L4_GLOBR
ID VM2L4_GLOBR Reviewed; 319 AA.
AC Q698K8;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2013, sequence version 3.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=Zinc metalloproteinase/disintegrin;
DE Contains:
DE RecName: Full=Snake venom metalloproteinase brevilysin L4;
DE Short=SVMP;
DE AltName: Full=Snake venom metalloproteinase hxl-1;
DE EC=3.4.24.-;
DE Contains:
DE RecName: Full=Disintegrin brevicaudin-1a;
DE Contains:
DE RecName: Full=Disintegrin brevicaudin-1b;
DE AltName: Full=Disintegrin adinbitor;
DE AltName: Full=Disintegrin halystatin;
DE Flags: Precursor; Fragment;
OS Gloydius brevicaudus (Korean slamosa snake) (Agkistrodon halys
OS brevicaudus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Gloydius.
OX NCBI_TaxID=259325;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 29-237, MASS SPECTROMETRY,
RP AND 3D-STRUCTURE MODELING.
RC TISSUE=Venom, and Venom gland;
RX PubMed=15777952; DOI=10.1016/j.toxicon.2004.12.005;
RA Deshimaru M., Ichihara M., Hattori T., Koba K., Terada S.;
RT "Primary structure of brevilysin L4, an enzymatically active fragment of a
RT disintegrin precursor from Gloydius halys brevicaudus venom.";
RL Toxicon 45:571-580(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 244-319, FUNCTION, AND ACTIVITY REGULATION.
RC TISSUE=Venom gland;
RX PubMed=15188058; DOI=10.1093/abbs/36.6.425;
RA Wang J.-H., Wu Y., Ren F., Lu L., Zhao B.-C.;
RT "Cloning and characterization of adinbitor, a novel disintegrin from the
RT snake venom of Agkistrodon halys brevicaudus stejneger.";
RL Acta Biochim. Biophys. Sin. 36:425-429(2004).
RN [3]
RP PROTEIN SEQUENCE OF 247-319, AND FUNCTION.
RC TISSUE=Venom;
RA Oshikawa K., Yasukouchi Y., Terada S.;
RT "Isolation and primary structures of platelet aggregation inhibitors from
RT Gloydius halys brevicaudus venom.";
RL Fukuoka Univ. Sci. Rep. 30:201-208(2000).
CC -!- FUNCTION: [Snake venom metalloproteinase brevilysin L4]:
CC metalloproteinase that impairs hemostasis in the envenomed animal (By
CC similarity). Shows autoproteolysis dependent on pH and temperature.
CC Does not show hemorrhagic activity. {ECO:0000250,
CC ECO:0000269|PubMed:15188058, ECO:0000269|Ref.3}.
CC -!- FUNCTION: [Disintegrin brevicaudin-1a]: Inhibits platelet aggregation
CC induced by ADP (IC(50) is 200 nM), collagen (IC(50) is 500 nM),
CC thrombin and epinephrin (IC(50) is 300 nM). Does not inhibit
CC aggregation induced by ristocetin.
CC -!- FUNCTION: [Disintegrin brevicaudin-1b]: Inhibits platelet aggregation
CC induced by ADP (IC(50) is 100 nM), collagen (IC(50) is 500 nM),
CC thrombin and epinephrin (IC(50) is 300 nM). Does not inhibit
CC aggregation induced by ristocetin. Significantly inhibits angiogenesis
CC both in vivo and in vitro.
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: Excess of calcium ions significantly suppress the
CC autoproteolysis of the enzyme. {ECO:0000269|PubMed:15188058}.
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- MASS SPECTROMETRY: [Snake venom metalloproteinase brevilysin L4]:
CC Mass=22752; Method=MALDI; Evidence={ECO:0000269|PubMed:15777952};
CC -!- MISCELLANEOUS: The disintegrins belong 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 -!- CAUTION: The metalloprotease is also encoded by another precursor (AC
CC Q90WC0). {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAT76292.1; Type=Erroneous termination; Note=Extended C-terminus.; Evidence={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; AY551929; AAT76292.1; ALT_TERM; mRNA.
DR PIR; A59410; A59410.
DR PIR; A59411; A59411.
DR AlphaFoldDB; Q698K8; -.
DR SMR; Q698K8; -.
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; IPR034027; Reprolysin_adamalysin.
DR Pfam; PF00200; Disintegrin; 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; Hemostasis impairing toxin; Hydrolase; Metal-binding;
KW Metalloprotease; Platelet aggregation inhibiting toxin; Protease; Secreted;
KW Toxin; Zinc; Zymogen.
FT PROPEP <1..28
FT /evidence="ECO:0000250"
FT /id="PRO_0000424444"
FT CHAIN 29..230
FT /note="Snake venom metalloproteinase brevilysin L4"
FT /id="PRO_0000424445"
FT PROPEP 231..246
FT /evidence="ECO:0000250"
FT /id="PRO_0000424446"
FT CHAIN 247..319
FT /note="Disintegrin brevicaudin-1b"
FT /id="PRO_0000318180"
FT CHAIN 249..319
FT /note="Disintegrin brevicaudin-1a"
FT /id="PRO_0000424447"
FT DOMAIN 34..230
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 238..319
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT MOTIF 297..299
FT /note="Cell attachment site"
FT ACT_SITE 171
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 37
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 121
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 170
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 174
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 180
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 225
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 228
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT DISULFID 145..225
FT /evidence="ECO:0000250"
FT DISULFID 185..209
FT /evidence="ECO:0000250"
FT DISULFID 187..192
FT /evidence="ECO:0000250"
FT DISULFID 252..261
FT /evidence="ECO:0000250"
FT DISULFID 254..262
FT /evidence="ECO:0000250"
FT DISULFID 267..281
FT /evidence="ECO:0000250"
FT DISULFID 275..305
FT /evidence="ECO:0000250"
FT DISULFID 280..284
FT /evidence="ECO:0000250"
FT DISULFID 293..312
FT /evidence="ECO:0000250"
FT CONFLICT 244..246
FT /note="ELL -> MHM (in Ref. 2; AAT76292)"
FT /evidence="ECO:0000305"
FT NON_TER 1
SQ SEQUENCE 319 AA; 35314 MW; 093F991FA589B1FA CRC64;
EDEAPKMCGV TQNWESYEPI KKASQSNLTP AHQRYIELVI VADHGMFTKY NGDSDKIREW
VRQMVNTVDE IYSYMYIDVA LAGLEIWSNE DLINVQPAAP HTLDSFGKWR ERDLLHRIHH
DNAMLLTAID FDGPTIGLAY VGTMCKPKGS TGVVQDHSTI NLRVAVTMAH EIGHNLGIHH
DTGSCSCGGY SCIMSPVISH EPSKYFSDCS YTQCWDFIMN QKPQCILNKP LRTDTVSTPV
SGNELLEAGE ECDCGSPGNP CCDAATCKLR QGAQCAEGLC CDQCRFMKKG TVCRIARGDD
MDDYCNGISA GCPRNPFHA
