VM2AE_CROAT
ID VM2AE_CROAT Reviewed; 478 AA.
AC P34182;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Zinc metalloproteinase/disintegrin;
DE Contains:
DE RecName: Full=Snake venom metalloproteinase atrolysin-E;
DE Short=SVMP;
DE EC=3.4.24.44;
DE AltName: Full=Hemorrhagic metalloproteinase HT-E;
DE AltName: Full=Hemorrhagic toxin E;
DE Contains:
DE RecName: Full=Disintegrin atrolysin-E;
DE AltName: Full=Atrolysin-E disintegrin;
DE Short=Atrolysin E/D;
DE Contains:
DE RecName: Full=Disintegrin atrolysin-E (4-73);
DE Contains:
DE RecName: Full=Disintegrin atrolysin-E (3-73);
DE Flags: Precursor;
OS Crotalus atrox (Western diamondback rattlesnake).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Crotalus.
OX NCBI_TaxID=8730;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=1378300; DOI=10.1021/bi00142a005;
RA Hite L.A., Shannon J.D., Bjarnason J.B., Fox J.W.;
RT "Sequence of a cDNA clone encoding the zinc metalloproteinase hemorrhagic
RT toxin e from Crotalus atrox: evidence for signal, zymogen, and disintegrin-
RT like structures.";
RL Biochemistry 31:6203-6211(1992).
RN [2]
RP SIMILARITY.
RC TISSUE=Venom;
RX PubMed=1515064; DOI=10.1515/bchm3.1992.373.2.381;
RA Hite L.A., Fox J.W., Bjarnason J.B.;
RT "A new family of proteinases is defined by several snake venom
RT metalloproteinases.";
RL Biol. Chem. Hoppe-Seyler 373:381-385(1992).
RN [3]
RP PROTEIN SEQUENCE OF 408-475 (DISINTEGRIN), FUNCTION, SYNTHESIS, MASS
RP SPECTROMETRY, AND SYNTHETIC CYCLIZATION.
RC TISSUE=Venom;
RX PubMed=9637732; DOI=10.1006/abbi.1998.0698;
RA Shimokawa K., Jia L.G., Shannon J.D., Fox J.W.;
RT "Isolation, sequence analysis, and biological activity of atrolysin E/D,
RT the non-RGD disintegrin domain from Crotalus atrox venom.";
RL Arch. Biochem. Biophys. 354:239-246(1998).
RN [4]
RP PROTEIN SEQUENCE OF 261-269; 277-297; 309-337; 408-444 AND 454-473, AND
RP MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=19371136; DOI=10.1021/pr900249q;
RA Calvete J.J., Fasoli E., Sanz L., Boschetti E., Righetti P.G.;
RT "Exploring the venom proteome of the western diamondback rattlesnake,
RT Crotalus atrox, via snake venomics and combinatorial peptide ligand library
RT approaches.";
RL J. Proteome Res. 8:3055-3067(2009).
RN [5]
RP FUNCTION.
RX PubMed=2817904; DOI=10.1016/0003-9861(89)90350-0;
RA Baramova E.N., Shannon J.D., Bjarnason J.B., Fox J.W.;
RT "Degradation of extracellular matrix proteins by hemorrhagic
RT metalloproteinases.";
RL Arch. Biochem. Biophys. 275:63-71(1989).
RN [6]
RP ACTIVATION OF ATROLYSIN-E.
RX PubMed=8914925; DOI=10.1006/abbi.1996.0509;
RA Shimokawa K., Jia L.G., Wang X.M., Fox J.W.;
RT "Expression, activation, and processing of the recombinant snake venom
RT metalloproteinase, pro-atrolysin E.";
RL Arch. Biochem. Biophys. 335:283-294(1996).
CC -!- FUNCTION: [Snake venom metalloproteinase atrolysin-E]: Snake venom zinc
CC metalloproteinase that causes hemorrhage by provoking the degradation
CC of the sub-endothelial matrix proteins (fibronectin, laminin, type IV
CC collagen, nidogen, and gelatins). {ECO:0000269|PubMed:2817904}.
CC -!- FUNCTION: [Disintegrin atrolysin-E]: Potent inhibitor of both
CC collagen- (IC(50)=4 nM) and ADP-induced (IC(50)=8 nM) platelet
CC aggregation. May act by binding to the platelet receptor GPIIb/GPIIIa
CC (ITGA2B/ITGB3). {ECO:0000269|PubMed:9637732}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleavage of 3-Asn-|-Gln-4, 9-Ser-|-His-10 and 14-Ala-|-Leu-15
CC bonds in insulin B chain and 14-Tyr-|-Gln-15 and 8-Thr-|-Ser-9 in A
CC chain. Cleaves type IV collagen at 73-Ala-|-Gln-74 in alpha1-(IV) and
CC at 7-Gly-|-Leu-8 in alpha2-(IV).; EC=3.4.24.44;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000305};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000305};
CC -!- SUBUNIT: Monomer (disintegrin). {ECO:0000250|UniProtKB:Q90WC0}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- MASS SPECTROMETRY: [Disintegrin atrolysin-E]: Mass=7392; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:9637732};
CC -!- MASS SPECTROMETRY: [Disintegrin atrolysin-E (3-73)]: Mass=7641.4;
CC Method=Unknown; Note=Average mass.;
CC Evidence={ECO:0000269|PubMed:19371136};
CC -!- MASS SPECTROMETRY: [Disintegrin atrolysin-E (4-73)]: Mass=7584.6;
CC Method=Unknown; Note=Average mass.;
CC Evidence={ECO:0000269|PubMed:19371136};
CC -!- MISCELLANEOUS: Pro-atrolysin-E can be enzymatically activated by venom,
CC atrolysin-A and atrolysin-E itself.
CC -!- MISCELLANEOUS: The disintegrin belongs 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: See also the NCBI entry AAB23201 which has been created from
CC PubMed:1515064. {ECO:0000305}.
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DR EMBL; M89784; AAB00731.1; -; mRNA.
DR PIR; A43296; A43296.
DR AlphaFoldDB; P34182; -.
DR SMR; P34182; -.
DR MEROPS; M12.145; -.
DR BRENDA; 3.4.24.1; 1710.
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:0030574; P:collagen catabolic 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; 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; PF00200; Disintegrin; 1.
DR Pfam; PF01562; Pep_M12B_propep; 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 Cell adhesion impairing toxin; Collagen degradation;
KW Direct protein sequencing; Disulfide bond; Hemorrhagic toxin;
KW Hemostasis impairing toxin; Hydrolase; Metal-binding; Metalloprotease;
KW Platelet aggregation inhibiting toxin; Protease; Secreted; Signal; Toxin;
KW Zinc; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..187
FT /evidence="ECO:0000250"
FT /id="PRO_0000029003"
FT CHAIN 188..389
FT /note="Snake venom metalloproteinase atrolysin-E"
FT /id="PRO_0000029004"
FT PROPEP 390..407
FT /evidence="ECO:0000269|PubMed:19371136,
FT ECO:0000269|PubMed:9637732"
FT /id="PRO_0000407579"
FT CHAIN 408..478
FT /note="Disintegrin atrolysin-E (3-73)"
FT /id="PRO_0000407580"
FT CHAIN 408..475
FT /note="Disintegrin atrolysin-E"
FT /id="PRO_0000029005"
FT CHAIN 409..478
FT /note="Disintegrin atrolysin-E (4-73)"
FT /id="PRO_0000407581"
FT DOMAIN 193..389
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 397..478
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT MOTIF 456..458
FT /note="Cell attachment site; atypical (MVD)"
FT ACT_SITE 330
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 329
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT BINDING 333
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT BINDING 339
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DISULFID 304..384
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DISULFID 344..368
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DISULFID 346..351
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DISULFID 411..420
FT /evidence="ECO:0000250|UniProtKB:Q90WC0"
FT DISULFID 413..421
FT /evidence="ECO:0000250|UniProtKB:Q90WC0"
FT DISULFID 426..440
FT /evidence="ECO:0000250|UniProtKB:Q90WC0"
FT DISULFID 434..464
FT /evidence="ECO:0000250|UniProtKB:Q90WC0"
FT DISULFID 439..443
FT /evidence="ECO:0000250|UniProtKB:Q90WC0"
FT DISULFID 452..471
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT CONFLICT 296
FT /note="Missing (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 478 AA; 53638 MW; 02B2724F38D9D686 CRC64;
MIQVLLVTIC LAAFPYQGSS IILESGNVND YEVIYPRKVT ALPKGAVQPK YEDTMQYELK
VNGEPVVLHL EKNKGLFSKD YSETHYSFDG RKITTNPSVE DHCYYHGRIE NDADSTASIS
ACNGLKGHFK LQGEMYLIEP LKLSDSEAHA VFKLKNVEKE DEAPKMCGVT QNWESYEPIK
KASDLNLNPE HQRYVELFIV VDHGMYTKYN GDSDKIRQRV HQMVNIMKES YTYMYIDILL
AGIEIWSNGD LINVQPASPN TLNSFGEWRE TDLLKRKSHD NAQLLTSIAF DEQIIGRAYI
GGICDPKRST GVVQDHSEIN LRVAVTMTHE LGHNLGIHHD TDSCSCGGYS CIMSPVISDE
PSKYFSDCSY IQCWEFIMNQ KPQCILKKPL RTDTVSTPVS GNELLEAGIE CDCGSLENPC
CYATTCKMRP GSQCAEGLCC DQCRFMKKGT VCRVSMVDRN DDTCTGQSAD CPRNGLYG
