VM1AD_CROAT
ID VM1AD_CROAT Reviewed; 414 AA.
AC P15167;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 3.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Snake venom metalloproteinase atrolysin-D;
DE Short=SVMP;
DE EC=3.4.24.42;
DE AltName: Full=Hemorrhagic metalloproteinase atrolysin D;
DE AltName: Full=Hemorrhagic toxin D;
DE Short=HT-D;
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=8311451; DOI=10.1006/abbi.1994.1026;
RA Hite L.A., Jia L.-G., Bjarnason J.B., Fox J.W.;
RT "cDNA sequences for four snake venom metalloproteinases: structure,
RT classification, and their relationship to mammalian reproductive
RT proteins.";
RL Arch. Biochem. Biophys. 308:182-191(1994).
RN [2]
RP PROTEIN SEQUENCE OF 191-393, AND PYROGLUTAMATE FORMATION AT GLN-191.
RC TISSUE=Venom;
RX PubMed=2745407; DOI=10.1016/s0021-9258(18)80102-8;
RA Shannon J.D., Baramova E.N., Bjarnason J.B., Fox J.W.;
RT "Amino acid sequence of a Crotalus atrox venom metalloproteinase which
RT cleaves type IV collagen and gelatin.";
RL J. Biol. Chem. 264:11575-11583(1989).
RN [3]
RP PROTEIN SEQUENCE OF 367-379.
RX DOI=10.1016/0167-4838(87)90077-X;
RA Bjarnason J.B., Fox J.W.;
RT "Characterization of two hemorrhagic zinc proteinases, toxin c and toxin d,
RT from western diamondback rattlesnake (Crotalus atrox) venom.";
RL Biochim. Biophys. Acta 911:356-363(1987).
RN [4]
RP PROTEIN SEQUENCE OF 188-197 AND 224-236, AND IDENTIFICATION BY MASS
RP 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 X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 191-393 IN COMPLEX WITH ZINC ION
RP AND CALCIUM ION, METAL-BINDING SITES, AND DISULFIDE BONDS.
RC TISSUE=Venom;
RX PubMed=8078901; DOI=10.1073/pnas.91.18.8447;
RA Zhang D., Botos I., Gomis-Rueth F.-X., Doll R., Blood C., Njoroge F.G.,
RA Fox J.W., Bode W., Meyer E.F.;
RT "Structural interaction of natural and synthetic inhibitors with the venom
RT metalloproteinase, atrolysin C (form d).";
RL Proc. Natl. Acad. Sci. U.S.A. 91:8447-8451(1994).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 191-393 IN COMPLEX WITH ZINC ION
RP AND CALCIUM ION, DISULFIDE BONDS, AND METAL-BINDING SITES.
RX PubMed=8610113; DOI=10.1073/pnas.93.7.2749;
RA Botos I., Scapozza L., Zhang D., Liotta L.A., Meyer E.F.;
RT "Batimastat, a potent matrix metalloproteinase inhibitor, exhibits an
RT unexpected mode of binding.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:2749-2754(1996).
CC -!- FUNCTION: Snake venom zinc metalloproteinase that causes hemorrhage by
CC provoking the degradation of the sub-endothelial matrix proteins
CC (fibronectin, laminin, type IV collagen, nidogen, and gelatins).
CC {ECO:0000269|PubMed:2817904}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleavage of 5-His-|-Leu-6, 10-His-|-Leu-11, 14-Ala-|-Leu-15,
CC 16-Tyr-|-Leu-17 and 23-Gly-|-Phe-24 of insulin B chain. With small
CC molecule substrates prefers hydrophobic residue at P2' and small
CC residue such as Ala, Gly at P1.; EC=3.4.24.42;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- PTM: The N-terminus is blocked.
CC -!- SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-I
CC 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; U01237; AAA03352.1; -; mRNA.
DR PIR; S41610; HYRSAC.
DR PDB; 1ATL; X-ray; 1.80 A; A/B=192-393.
DR PDB; 1DTH; X-ray; 2.00 A; A/B=191-393.
DR PDB; 1HTD; X-ray; 2.10 A; A/B=192-393.
DR PDBsum; 1ATL; -.
DR PDBsum; 1DTH; -.
DR PDBsum; 1HTD; -.
DR AlphaFoldDB; P15167; -.
DR SMR; P15167; -.
DR MEROPS; M12.144; -.
DR KEGG; ag:AAA03352; -.
DR BRENDA; 3.4.24.42; 1710.
DR EvolutionaryTrace; P15167; -.
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 InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001590; Peptidase_M12B.
DR InterPro; IPR002870; Peptidase_M12B_N.
DR InterPro; IPR034027; Reprolysin_adamalysin.
DR Pfam; PF01562; Pep_M12B_propep; 1.
DR Pfam; PF01421; Reprolysin; 1.
DR PROSITE; PS50215; ADAM_MEPRO; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Collagen degradation; Direct protein sequencing;
KW Disulfide bond; Hemorrhagic toxin; Hemostasis impairing toxin; Hydrolase;
KW Metal-binding; Metalloprotease; Protease; Pyrrolidone carboxylic acid;
KW Secreted; Signal; Toxin; Zinc; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..190
FT /evidence="ECO:0000269|PubMed:2745407"
FT /id="PRO_0000029000"
FT CHAIN 191..393
FT /note="Snake venom metalloproteinase atrolysin-D"
FT /id="PRO_0000029001"
FT PROPEP 394..414
FT /id="PRO_0000029002"
FT DOMAIN 197..393
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT ACT_SITE 334
FT BINDING 200
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 284
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 333
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 337
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 343
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 388
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 391
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT MOD_RES 191
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:2745407"
FT DISULFID 308..388
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000269|PubMed:2745407"
FT DISULFID 348..355
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000269|PubMed:2745407"
FT VARIANT 191
FT /note="Missing (in some chains)"
FT STRAND 197..205
FT /evidence="ECO:0007829|PDB:1ATL"
FT HELIX 207..212
FT /evidence="ECO:0007829|PDB:1ATL"
FT TURN 213..215
FT /evidence="ECO:0007829|PDB:1ATL"
FT HELIX 217..235
FT /evidence="ECO:0007829|PDB:1ATL"
FT HELIX 236..238
FT /evidence="ECO:0007829|PDB:1ATL"
FT STRAND 240..249
FT /evidence="ECO:0007829|PDB:1ATL"
FT HELIX 262..275
FT /evidence="ECO:0007829|PDB:1ATL"
FT HELIX 277..280
FT /evidence="ECO:0007829|PDB:1ATL"
FT STRAND 284..290
FT /evidence="ECO:0007829|PDB:1ATL"
FT STRAND 295..297
FT /evidence="ECO:0007829|PDB:1ATL"
FT TURN 310..312
FT /evidence="ECO:0007829|PDB:1ATL"
FT STRAND 313..318
FT /evidence="ECO:0007829|PDB:1ATL"
FT HELIX 324..338
FT /evidence="ECO:0007829|PDB:1ATL"
FT STRAND 353..355
FT /evidence="ECO:0007829|PDB:1ATL"
FT STRAND 358..360
FT /evidence="ECO:0007829|PDB:1DTH"
FT HELIX 371..384
FT /evidence="ECO:0007829|PDB:1ATL"
FT HELIX 388..390
FT /evidence="ECO:0007829|PDB:1ATL"
SQ SEQUENCE 414 AA; 46845 MW; 0B41F26C9E450031 CRC64;
MIEVLLVTIC LAVFPYQGSS IILESGNVND YEVVYPRKVT ALPKGAVQPK YEDAMQYELK
VNGEPVVLHL EKNKELFSKD YSETHYSPDG RKITTNPSVE DHCYYRGRIE NDADSTASIS
ACNGLKGHFK LQGEMYLIEP LELSDSEAHA VFKLENVEKE DEAPKMCGVT QNWESYEPIK
KASDLNLNPD QQNLPQRYIE LVVVADHRVF MKYNSDLNTI RTRVHEIVNF INGFYRSLNI
HVSLTDLEIW SNEDQINIQS ASSDTLNAFA EWRETDLLNR KSHDNAQLLT AIELDEETLG
LAPLGTMCDP KLSIGIVQDH SPINLLMGVT MAHELGHNLG MEHDGKDCLR GASLCIMRPG
LTKGRSYEFS DDSMHYYERF LKQYKPQCIL NKPLRIDPVS TPVSGNELLE AGEE
