VM3AD_AGKCL
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 03-AUG-2022, entry version 110.
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 PRIDE; O42138; -.
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; -; 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 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
