ID   VM3AD_AGKCL             Reviewed;         620 AA.
AC   O42138; C9E1R4;
DT   18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   08-NOV-2023, entry version 114.
DE   RecName: Full=Zinc metalloproteinase-disintegrin-like ACLD;
DE            EC=3.4.24.-;
DE   AltName: Full=Snake venom metalloproteinase;
DE            Short=SVMP;
DE   AltName: Full=VMP-III;
DE            Short=AclVMP-III;
DE   Flags: Precursor;
OS   Agkistrodon contortrix laticinctus (Broad-banded copperhead) (Agkistrodon
OS   mokasen laticinctus).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Viperidae; Crotalinae; Agkistrodon.
OX   NCBI_TaxID=37195;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom gland;
RX   PubMed=9392519; DOI=10.1016/s0167-4838(97)00111-8;
RA   Selistre de Araujo H.S., de Souza D.H.F., Ownby C.L.;
RT   "Analysis of a cDNA sequence encoding a novel member of the snake venom
RT   metalloproteinase, disintegrin-like, cysteine-rich (MDC) protein family
RT   from Agkistrodon contortrix laticinctus.";
RL   Biochim. Biophys. Acta 1342:109-115(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom gland;
RX   PubMed=19799929; DOI=10.1016/j.toxicon.2009.09.016;
RA   Jia Y., Perez J.C.;
RT   "Molecular cloning and characterization of cDNAs encoding
RT   metalloproteinases from snake venom glands.";
RL   Toxicon 55:462-469(2010).
CC   -!- FUNCTION: Is a potent activator of prothrombin (F2). Does not elicit
CC       any hemorrhagic response. Barely inhibits collagen-induced platelet
CC       aggregation. Binds neither collagen, nor the jararhagin-monoclonal
CC       antibody MAJar3. Hydrolyzes the Aalpha-chain of fibrin and fibrinogen,
CC       without affecting the Bbeta- and gamma-chains. Is capable of triggering
CC       endothelial pro-inflammatory and procoagulant cell responses, but fails
CC       to trigger apoptosis. Induces von Willebrand factor release, and the
CC       expression of both ICAM1 and E-selectin (SELE) (without increase in
CC       VCAM1) in endothelial cells (HUVEC). Is also able to up-regulate the
CC       synthesis of the coagulation factor TF (F3). Enhances nitric oxide (NO)
CC       generation, prostacyclin production and interleukin-8 release (By
CC       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   -!- ACTIVITY REGULATION: Inhibited by EDTA and O-phenanthroline. Not
CC       inhibited by PMSF, benzamidine, irreversible serine-proteinase
CC       inhibitors and cysteine proteinase inhibitor E-64 (By similarity).
CC       {ECO:0000250}.
CC   -!- SUBUNIT: Monomer. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
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; U86634; AAC18911.1; -; mRNA.
DR   EMBL; GQ451435; ACV83929.1; -; mRNA.
DR   AlphaFoldDB; O42138; -.
DR   SMR; O42138; -.
DR   MEROPS; M12.142; -.
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:0016504; F:peptidase activator activity; IEA:UniProtKB-KW.
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; Collagenase (Catalytic Domain); 1.
DR   Gene3D; 4.10.70.10; Disintegrin domain; 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   PANTHER; PTHR11905; ADAM A DISINTEGRIN AND METALLOPROTEASE DOMAIN; 1.
DR   PANTHER; PTHR11905:SF32; DISINTEGRIN AND METALLOPROTEINASE DOMAIN-CONTAINING PROTEIN 28; 1.
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; Blood coagulation inhibitor (disintegrin); 1.
DR   SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 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   2: Evidence at transcript level;
KW   Blood coagulation cascade activating toxin; Calcium;
KW   Cell adhesion impairing toxin; Disulfide bond; Glycoprotein;
KW   Hemostasis impairing toxin; Hydrolase; Metal-binding; Metalloprotease;
KW   Platelet aggregation inhibiting toxin; Protease; Prothrombin activator;
KW   Secreted; Signal; Toxin; Zinc; Zymogen.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   PROPEP          21..189
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000326416"
FT   CHAIN           190..620
FT                   /note="Zinc metalloproteinase-disintegrin-like ACLD"
FT                   /id="PRO_0000326417"
FT   DOMAIN          199..395
FT                   /note="Peptidase M12B"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT   DOMAIN          403..489
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         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         410
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   CARBOHYD        259
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        265
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        373
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        396
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        502
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        536
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..500
FT                   /evidence="ECO:0000250"
FT   DISULFID        493..505
FT                   /evidence="ECO:0000250"
FT   DISULFID        512..562
FT                   /evidence="ECO:0000250"
FT   DISULFID        527..573
FT                   /evidence="ECO:0000250"
FT   DISULFID        540..550
FT                   /evidence="ECO:0000250"
FT   DISULFID        557..599
FT                   /evidence="ECO:0000250"
FT   DISULFID        593..604
FT                   /evidence="ECO:0000250"
FT   CONFLICT        96
FT                   /note="Y -> H (in Ref. 2; ACV83929)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        139
FT                   /note="D -> E (in Ref. 2; ACV83929)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        268
FT                   /note="S -> L (in Ref. 2; ACV83929)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        306
FT                   /note="M -> K (in Ref. 2; ACV83929)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        463
FT                   /note="Q -> A (in Ref. 2; ACV83929)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   620 AA;  69512 MW;  9016AFEB5AE0BB87 CRC64;
     MIQVLLVTLC LAVFPYQGSS IILESGNVND YEVVYPRKVT VLPKGAVQPK YEDAMQYEFK
     VNGEPVVLHL EKNKQLFSKD YSETHYSPDG REITTYPLVE DHCYYHGRIE NDADSTASIS
     ACNGLKGHFK LQGEMYLIDP LKLPDSEAHA VFKYENVEKE DEAPKMCGVT QNWESYEPIK
     KASQLNLTPE QQAYLDAKKY VEFVVVLDHG MYTKYKDNLD KIKTRIFEIV NTMNEMFIPL
     NIRVALICLE IWSDKDKFNM TSAANVTSIS FRNWRATDLL KRKSHDNAQL LTVIDFDGPT
     IGKAYMASMC DPKRSVGIIQ DHSTINLMMA VTMAHEMGHN LGMDHDEKYC TCGAKSCVMA
     KALSRQPSKL FSNCSQEDYR KYLIKRRPKC ILNEPNGTDI VSPPVCGNEL LEVGEECDCG
     SPTNCQNPCC DAATCKLTPG SQCADGVCCD QCRFTRAGTE CRQAKDDCDM ADLCTGQSAE
     CPTDRFQRNG HPCLNDNGYC YNRTCPTLKN QCIYFFGPNA AVAKDSCFKG NQKSNNHTYC
     RKENGKKIPC APQDIKCGRL YCFRNLPGKK NICSVIYTPT DEDIGMVLPG TKCEDGKVCS
     NGHCVDVNIA YKSTTGFSQI
//