VM3HA_GLOHA
ID VM3HA_GLOHA Reviewed; 610 AA.
AC Q8AWI5;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=Zinc metalloproteinase-disintegrin-like halysase;
DE EC=3.4.24.-;
DE AltName: Full=Snake venom metalloproteinase;
DE Short=SVMP;
DE AltName: Full=Vascular apoptosis-inducing protein;
DE Short=VAP;
DE Flags: Precursor;
OS Gloydius halys (Chinese water mocassin) (Agkistrodon halys).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Gloydius.
OX NCBI_TaxID=8714;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 183-189; 194-208; 276-285
RP AND 488-502, FUNCTION, AND SUBUNIT.
RC TISSUE=Venom, and Venom gland;
RX PubMed=14688240; DOI=10.1093/jb/mvg202;
RA You W.-K., Seo H.-J., Chung K.-H., Kim D.-S.;
RT "A novel metalloprotease from Gloydius halys venom induces endothelial cell
RT apoptosis through its protease and disintegrin-like domains.";
RL J. Biochem. 134:739-749(2003).
RN [2]
RP FUNCTION.
RX PubMed=12963038; DOI=10.1016/j.bbrc.2003.08.049;
RA You W.-K., Jang Y.-J., Chung K.-H., Kim D.-S.;
RT "A novel disintegrin-like domain of a high molecular weight metalloprotease
RT inhibits platelet aggregation.";
RL Biochem. Biophys. Res. Commun. 309:637-642(2003).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RC TISSUE=Venom;
RX PubMed=16329990; DOI=10.1016/j.bbrc.2005.11.083;
RA You W.-K., Jang Y.-J., Chung K.-H., Jeon O.-H., Kim D.-S.;
RT "Functional roles of the two distinct domains of halysase, a snake venom
RT metalloprotease, to inhibit human platelet aggregation.";
RL Biochem. Biophys. Res. Commun. 339:964-970(2006).
CC -!- FUNCTION: Strongly inhibits the collagen-induced human platelet
CC aggregation (inhibition of alpha-2/beta-1 (ITGA2/ITGB1) integrin).
CC Hydrolyzes the Aalpha-chain of fibrinogen, without cleavage of
CC Bbeta- and gamma-chains. Degrades type IV collagen (but not types I, II
CC and V), fibronectin and vitronectin and also integrins alpha-1/beta-1
CC (ITGA1/ITGB1) and alpha-5/beta/1 (ITGA5/ITGB1) (but not alpha-V/beta-3
CC (ITGAV/ITGB3) and alpha-V/beta-5 (ITGAV/ITGB5) integrins). Both
CC metalloproteinase (peptidase M12B) and disintegrin-like domains
CC (recombinantly expressed and named halydin) play characteristic roles
CC to inhibit human platelet aggregation. Induces apoptosis and strongly
CC inhibits proliferation of endothelial cells as well as adhesion of the
CC cells to extracellular matrix proteins. The apoptosis is closely
CC associated with activation of caspase-3 and decreased level of Bcl-
CC X(L)/Bax. Apohalysase, which lacks metalloprotease activity, is also
CC able to induce the apoptosis. Cleaves insulin B chain at '34-His-|-Leu-
CC 35', '37-Glu-|-Ala-38', '38-Ala-|-Leu-39', '39-Leu-|-Tyr-40', '40-
CC Tyr-|-Leu-41', '47-Gly-|-Phe-48' and '48-Phe-|-Phe-49' bonds
CC (PubMed:16329990). {ECO:0000269|PubMed:12963038,
CC ECO:0000269|PubMed:14688240, ECO:0000269|PubMed:16329990}.
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: Inhibited by EDTA and EGTA. Not inhibited by PMSF,
CC antipain, pepstatin, and iodoacetamide. {ECO:0000269|PubMed:16329990}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:14688240}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-III
CC subfamily. P-IIIa sub-subfamily. {ECO:0000305}.
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DR EMBL; AY149647; AAN39540.1; -; mRNA.
DR AlphaFoldDB; Q8AWI5; -.
DR SMR; Q8AWI5; -.
DR MEROPS; M12.315; -.
DR PRIDE; Q8AWI5; -.
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:0006915; P:apoptotic process; 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; 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 Apoptosis; Calcium; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Hemorrhagic toxin; Hemostasis impairing toxin; Hydrolase;
KW Metal-binding; Metalloprotease; Platelet aggregation inhibiting toxin;
KW Protease; Secreted; Signal; Toxin; Zinc; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..182
FT /evidence="ECO:0000269|PubMed:14688240"
FT /id="PRO_0000329981"
FT CHAIN 183..610
FT /note="Zinc metalloproteinase-disintegrin-like halysase"
FT /id="PRO_0000329982"
FT DOMAIN 199..395
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 403..488
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT MOTIF 467..469
FT /note="D/ECD-tripeptide"
FT ACT_SITE 336
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
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 405
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 408
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 410
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 412
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 415
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 418
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT CARBOHYD 218
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..435
FT /evidence="ECO:0000250"
FT DISULFID 417..430
FT /evidence="ECO:0000250"
FT DISULFID 419..425
FT /evidence="ECO:0000250"
FT DISULFID 429..452
FT /evidence="ECO:0000250"
FT DISULFID 443..449
FT /evidence="ECO:0000250"
FT DISULFID 448..474
FT /evidence="ECO:0000250"
FT DISULFID 461..481
FT /evidence="ECO:0000250"
FT DISULFID 468..499
FT /evidence="ECO:0000250"
FT DISULFID 492..504
FT /evidence="ECO:0000250"
FT DISULFID 511..561
FT /evidence="ECO:0000250"
FT DISULFID 526..572
FT /evidence="ECO:0000250"
FT DISULFID 539..549
FT /evidence="ECO:0000250"
FT DISULFID 556..598
FT /evidence="ECO:0000250"
FT DISULFID 592..603
FT /evidence="ECO:0000250"
SQ SEQUENCE 610 AA; 67652 MW; F8AE9EC3C79EC13E CRC64;
MIQVLLVTIC LAVFPYQGSS IILESGNVND YEVVYPRKVP ALPKGAVQPK YEDAMQYEFK
VNGEPVVLHL EKNKGLFSED YSETHYSPDG REITTNPPVE DHCYYHGRIQ NDADSTASIS
ACNGLKGHFT LQGETYLIEP LKLPDSEAHA VFKYENVEKE DEAPKMCGVT QNWESYEPIK
KASQSNLTPE QQRYLNAKKY VKLVMVADYI MYLKYDRNLT TVRTRMYDIV NVINVIYQRM
NIHVALVGLE IWSNKDKFIL RSAADVTLKL FATWRETDLL KRKSHDNAQL LTGINFNGPT
AGLGYLGGIC NPMYSAGIVQ DHNKIHHLVA IAMAHEMGHN LGIDHDKDTC TCGAKSCVMA
GTLSCEASYL FSDCSRKEHQ AFLIKDMPQC ILKKPLKTDV VSPPVCGNYF VEVGEDCDCG
SPATCRDSCC DAATCKLRQG AQCAEGLCCD QCRFKGAGTE CRAATDECDM ADLCTGRSAE
CTDRFQRNGQ PCQNNNGYCY NGKCPIMTDQ CIALFGPNAA VSEDACFQFN LEGNHYGYCR
KEQNTKIACE PQNVKCGRLY CIDSSPANKN PCNIYYSPGD EDKGMVLPGT KCADGKACSN
GQCVDVNRAS
