VM3AH_DEIAC
ID VM3AH_DEIAC Reviewed; 610 AA.
AC Q9W6M5; C7E3Q3; Q6Q274;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2012, sequence version 2.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=Zinc metalloproteinase-disintegrin-like acurhagin;
DE Short=Acur;
DE EC=3.4.24.-;
DE AltName: Full=Acutolysin e2;
DE AltName: Full=Snake venom metalloproteinase;
DE Short=SVMP;
DE AltName: Full=Zinc metalloproteinase-disintegrin-like acutolysin-E;
DE Flags: Precursor;
OS Deinagkistrodon acutus (Hundred-pace snake) (Agkistrodon acutus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Deinagkistrodon.
OX NCBI_TaxID=36307;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, ACTIVITY
RP REGULATION, AND SUBUNIT.
RC TISSUE=Venom gland;
RX PubMed=16023283; DOI=10.1016/j.biochi.2005.06.002;
RA Wang W.J., Shih C.H., Huang T.F.;
RT "Primary structure and antiplatelet mechanism of a snake venom
RT metalloproteinase, acurhagin, from Agkistrodon acutus venom.";
RL Biochimie 87:1065-1077(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland {ECO:0000312|EMBL:AAD27891.1};
RA Liu Q.D., Qian Y.W., Xu W.H., Liu J.;
RT "Purification and molecular cloning of acutin, a disintegrin-like/cysteine-
RT rich two-domain protein which is the proteolytic product of a large
RT hemorrhagic metalloproteinase (acutolysin e) from Agkistrodon acutus.";
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-584.
RA Gao Y.X., Zhu Z.Q., Teng M.K.;
RT "Molecular cloning of acutolysin e2, a P-III type hemorrhagic
RT metalloproteinase from Agkistrodon acutus.";
RL Submitted (JUN-2009) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, ACTIVITY REGULATION, SUBUNIT, AND MASS
RP SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=12008947;
RA Wang W.J., Huang T.F.;
RT "Purification and characterization of a novel metalloproteinase, acurhagin,
RT from Agkistrodon acutus venom.";
RL Thromb. Haemost. 87:641-650(2002).
RN [5]
RP BIOPHYSICOCHEMICAL PROPERTIES.
RC TISSUE=Venom;
RX PubMed=18554518; DOI=10.1016/j.biochi.2008.05.012;
RA Chen H.-S., Tsai H.-Y., Wang Y.-M., Tsai I.-H.;
RT "P-III hemorrhagic metalloproteinases from Russell's viper venom: cloning,
RT characterization, phylogenetic and functional site analyses.";
RL Biochimie 90:1486-1498(2008).
CC -!- FUNCTION: Snake venom zinc metalloprotease that causes hemorrhage and
CC dose-dependently inhibits platelet aggregation triggered by collagen.
CC This inhibition is due to its binding to glycoprotein VI (GP6) and
CC collagen. The binding to GP6 results in inhibition of the signaling
CC pathway (decrease of tyrosine phosphorylation of signaling proteins
CC such as Syk, LAT, PI3-K and PLCgamma2). Preferentially cleaves alpha
CC chain (FGA) of fibrinogen, followed by beta chain (FGB). Also degrades
CC the extracellular matrix protein fibronectin (FN1), and cleaves
CC collagen and von Willebrand factor (VWF). {ECO:0000269|PubMed:12008947,
CC ECO:0000269|PubMed:16023283}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q9PW35};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q9PW35};
CC -!- ACTIVITY REGULATION: The proteinase activity is slightly enhanced by
CC Ca(2+) and Mg(2+), but is completely inhibited by Zn(2+). Is completely
CC inhibited by phenanthroline and EDTA. Not inhibited by PMSF.
CC {ECO:0000269|PubMed:12008947, ECO:0000269|PubMed:16023283}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=9.4 uM for NFF-2 (fluorogenic substrates with cleavage at Ala-Nva)
CC {ECO:0000269|PubMed:18554518};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:12008947,
CC ECO:0000269|PubMed:16023283}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- PTM: N-glycosylated.
CC -!- MASS SPECTROMETRY: Mass=48133; Method=Unknown;
CC Evidence={ECO:0000269|PubMed:12008947};
CC -!- MISCELLANEOUS: Does not degrade gamma chain of fibrinogen
CC (PubMed:12008947). Does not inhibit collagen-induced platelet
CC aggregation by activating alpha-2/beta-1 integrin (ITGA2/ITGB1), or by
CC inhibiting alpha-IIb/beta-3 (ITGA2B/ITGB3) interaction with fibrinogen.
CC Does not cleave platelet membrane glycoproteins, including glycoprotein
CC VI (GP6), GPIbalpha (GP1BA) and beta-3 integrin (ITGB3)
CC (PubMed:12008947). {ECO:0000305|PubMed:12008947}.
CC -!- SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-III
CC subfamily. P-IIIa sub-subfamily. {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; AY566610; AAS57937.1; -; mRNA.
DR EMBL; AF141379; AAD27891.1; -; mRNA.
DR EMBL; GQ245980; ACT33415.1; -; mRNA.
DR AlphaFoldDB; Q9W6M5; -.
DR SMR; Q9W6M5; -.
DR MEROPS; M12.334; -.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
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 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..191
FT /evidence="ECO:0000250"
FT /id="PRO_0000330010"
FT CHAIN 192..610
FT /note="Zinc metalloproteinase-disintegrin-like acurhagin"
FT /id="PRO_0000235853"
FT DOMAIN 198..394
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 402..488
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT MOTIF 466..468
FT /note="D/ECD-tripeptide"
FT ACT_SITE 335
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 201
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 285
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 334
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 338
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 344
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 389
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 392
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 407
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 409
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 411
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 414
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 417
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 468
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 469
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 471
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 483
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 484
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT MOD_RES 192
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000250"
FT CARBOHYD 372
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 309..389
FT /evidence="ECO:0000250|UniProtKB:O93523"
FT DISULFID 349..373
FT /evidence="ECO:0000250|UniProtKB:O93523"
FT DISULFID 351..356
FT /evidence="ECO:0000250|UniProtKB:O93523"
FT DISULFID 405..434
FT /evidence="ECO:0000250|UniProtKB:O93523"
FT DISULFID 416..429
FT /evidence="ECO:0000250|UniProtKB:O93523"
FT DISULFID 418..424
FT /evidence="ECO:0000250|UniProtKB:O93523"
FT DISULFID 428..451
FT /evidence="ECO:0000250|UniProtKB:O93523"
FT DISULFID 442..448
FT /evidence="ECO:0000250|UniProtKB:O93523"
FT DISULFID 447..473
FT /evidence="ECO:0000250|UniProtKB:O93523"
FT DISULFID 460..480
FT /evidence="ECO:0000250|UniProtKB:O93523"
FT DISULFID 467..499
FT /evidence="ECO:0000250|UniProtKB:O93523"
FT DISULFID 492..504
FT /evidence="ECO:0000250|UniProtKB:O93523"
FT DISULFID 511..561
FT /evidence="ECO:0000250|UniProtKB:O93523"
FT DISULFID 526..572
FT /evidence="ECO:0000250|UniProtKB:O93523"
FT DISULFID 539..549
FT /evidence="ECO:0000250|UniProtKB:O93523"
FT DISULFID 556..598
FT /evidence="ECO:0000250|UniProtKB:O93523"
FT DISULFID 592..603
FT /evidence="ECO:0000250|UniProtKB:O93523"
FT CONFLICT 160
FT /note="Missing (in Ref. 2; AAD27891 and 3; ACT33415)"
FT /evidence="ECO:0000305"
FT CONFLICT 182
FT /note="I -> V (in Ref. 3; ACT33415)"
FT /evidence="ECO:0000305"
FT CONFLICT 204
FT /note="V -> F (in Ref. 3; ACT33415)"
FT /evidence="ECO:0000305"
FT CONFLICT 222
FT /note="K -> I (in Ref. 2; AAD27891)"
FT /evidence="ECO:0000305"
FT CONFLICT 427
FT /note="E -> P (in Ref. 3; ACT33415)"
FT /evidence="ECO:0000305"
FT CONFLICT 446
FT /note="D -> K (in Ref. 2; AAD27891 and 3; ACT33415)"
FT /evidence="ECO:0000305"
FT CONFLICT 518..519
FT /note="DI -> EV (in Ref. 2; AAD27891)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 610 AA; 68542 MW; 23E208CF1DCFDF0F CRC64;
MIQVLLVTIC LAAFPYQGSS IILESGDVND YEVVYPRKVT ALPKGAVQQK YEDAMQYEFK
VNGEPVVLHL EKNKHLFSKD YSETHYSPDG REITINPPVE DHCYYHGRIE NDGDSTASIS
ACNGLKGNFK LQGETYLIEP MKLSDSEAHA VFKYENVEKE DEAPKMCGVT QKWKSYEPIK
KISQLNLIPE QQIYDPFKYV ETVVVVDKAM VTKYNGDLDK IKTKMYEAAN NMNEMYRYMF
FRVVMVGLII WTEEDKITVK PDVDYTLNAF AEWRKTYLLA EKKHDNAQLI TGIDFRGSII
GYAYIGSMCH PKRSVGIIQD YSPINLVLAV IMAHEMGHNL GIHHDDGYCY CGGYPCIMGP
SISPEPSKFF SNCSYIQCWD FIMNHNPECI DNEPLGTDII SPPLCGNELL EVGEECDCGT
PENCQNECCD AATCKLKSGS QCGHGDCCEQ CKFRTSGTEC RASMSECDPA EHCTGQSSEC
PADVFHKNGE PCLDNYGYCY NGNCPIMYHQ CYALFGADIY EAEDSCFESN KKGNYYGYCR
KENGKKIPCA SEDVKCGRLY CKDDSPGQNN PCKMFYSNDD EHKGMVLPGT KCADGKVCSN
GHCVDVTTAY
