VM2FL_PROFL
ID VM2FL_PROFL Reviewed; 483 AA.
AC P18619; Q8JIS2;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 23-MAY-2003, sequence version 2.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Zinc metalloproteinase/disintegrin;
DE Contains:
DE RecName: Full=Snake venom metalloproteinase;
DE Short=SVMP;
DE EC=3.4.24.-;
DE Contains:
DE RecName: Full=Disintegrin flavoridin;
DE Flags: Precursor;
OS Protobothrops flavoviridis (Habu) (Trimeresurus flavoviridis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Protobothrops.
OX NCBI_TaxID=88087;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=12076658; DOI=10.1016/s0041-0101(02)00081-8;
RA Kishimoto M., Takahashi T.;
RT "Molecular cloning and sequence analysis of cDNA encoding flavoridin, a
RT disintegrin from the venom of Trimeresurus flavoviridis.";
RL Toxicon 40:1033-1040(2002).
RN [2]
RP PROTEIN SEQUENCE OF 414-483, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=2364514; DOI=10.1161/01.cir.82.1.261;
RA Musial J., Niewiarowski S., Rucinski B., Stewart G.J., Cook J.J.,
RA Williams J.A., Edmunds L.H. Jr.;
RT "Inhibition of platelet adhesion to surfaces of extracorporeal circuits by
RT disintegrins. RGD-containing peptides from viper venoms.";
RL Circulation 82:261-273(1990).
RN [3]
RP PROTEIN SEQUENCE OF 414-483, SUBCELLULAR LOCATION, AND DISULFIDE BONDS.
RC TISSUE=Venom;
RX PubMed=1516704; DOI=10.1016/0014-5793(92)80797-k;
RA Calvete J.J., Wang Y., Mann K., Schaefer W., Niewiarwoski S., Stewart G.J.;
RT "The disulfide bridge pattern of snake venom disintegrins, flavoridin and
RT echistatin.";
RL FEBS Lett. 309:316-320(1992).
RN [4]
RP DISULFIDE BONDS IN DISINTEGRIN FLAVORIDIN.
RX PubMed=8355276; DOI=10.1006/jmbi.1993.1438;
RA Klaus W., Broger C., Gerber P., Senn H.;
RT "Determination of the disulphide bonding pattern in proteins by local and
RT global analysis of nuclear magnetic resonance data. Application to
RT flavoridin.";
RL J. Mol. Biol. 232:897-906(1993).
RN [5]
RP STRUCTURE BY NMR OF 414-483, AND DISULFIDE BONDS.
RX PubMed=8355277; DOI=10.1006/jmbi.1993.1439;
RA Senn H., Klaus W.;
RT "The nuclear magnetic resonance solution structure of flavoridin, an
RT antagonist of the platelet GP IIb-IIIa receptor.";
RL J. Mol. Biol. 232:907-925(1993).
CC -!- FUNCTION: [Snake venom metalloproteinase]: Impairs hemostasis in the
CC envenomed animal. {ECO:0000250}.
CC -!- FUNCTION: [Disintegrin flavoridin]: Inhibits platelet aggregation
CC induced by ADP, thrombin, platelet-activating factor and collagen. Acts
CC by inhibiting fibrinogen interaction with platelet receptors
CC GPIIb/GPIIIa (ITGA2B/ITGB3) (By 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 -!- SUBUNIT: Monomeric (disintegrin). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1516704,
CC ECO:0000269|PubMed:2364514}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
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}.
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DR EMBL; AB052155; BAC00515.1; -; mRNA.
DR PIR; A58649; A58649.
DR PDB; 1FVL; NMR; -; A=414-483.
DR PDBsum; 1FVL; -.
DR AlphaFoldDB; P18619; -.
DR SMR; P18619; -.
DR MEROPS; M12.155; -.
DR EvolutionaryTrace; P18619; -.
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: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 3D-structure; Calcium; Cell adhesion impairing toxin;
KW Direct protein sequencing; Disulfide bond; Glycoprotein;
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..190
FT /evidence="ECO:0000250"
FT /id="PRO_0000028996"
FT CHAIN 191..395
FT /note="Snake venom metalloproteinase"
FT /id="PRO_0000028997"
FT PROPEP 396..413
FT /evidence="ECO:0000305|PubMed:1516704,
FT ECO:0000305|PubMed:2364514"
FT /id="PRO_0000028998"
FT CHAIN 414..483
FT /note="Disintegrin flavoridin"
FT /evidence="ECO:0000269|PubMed:1516704,
FT ECO:0000269|PubMed:2364514"
FT /id="PRO_0000028999"
FT DOMAIN 197..395
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 403..483
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT MOTIF 462..464
FT /note="Cell attachment site"
FT ACT_SITE 334
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 200
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 284
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 333
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305"
FT BINDING 337
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305"
FT BINDING 343
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305"
FT BINDING 390
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 393
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT CARBOHYD 263
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 293
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 308..390
FT /evidence="ECO:0000250"
FT DISULFID 352..374
FT /evidence="ECO:0000250"
FT DISULFID 354..357
FT /evidence="ECO:0000250"
FT DISULFID 417..432
FT /evidence="ECO:0000269|PubMed:1516704,
FT ECO:0000269|PubMed:8355276, ECO:0000269|PubMed:8355277,
FT ECO:0007744|PDB:1FVL"
FT DISULFID 419..427
FT /evidence="ECO:0000269|PubMed:1516704,
FT ECO:0000269|PubMed:8355276, ECO:0000269|PubMed:8355277,
FT ECO:0007744|PDB:1FVL"
FT DISULFID 426..449
FT /evidence="ECO:0000269|PubMed:1516704,
FT ECO:0000269|PubMed:8355276, ECO:0000269|PubMed:8355277,
FT ECO:0007744|PDB:1FVL"
FT DISULFID 440..446
FT /evidence="ECO:0000269|PubMed:1516704,
FT ECO:0000269|PubMed:8355276, ECO:0000269|PubMed:8355277,
FT ECO:0007744|PDB:1FVL"
FT DISULFID 445..470
FT /evidence="ECO:0000269|PubMed:1516704,
FT ECO:0000269|PubMed:8355276, ECO:0000269|PubMed:8355277,
FT ECO:0007744|PDB:1FVL"
FT DISULFID 458..477
FT /evidence="ECO:0000269|PubMed:1516704,
FT ECO:0000269|PubMed:8355276, ECO:0000269|PubMed:8355277,
FT ECO:0007744|PDB:1FVL"
FT CONFLICT 455..456
FT /note="RT -> TG (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT TURN 429..432
FT /evidence="ECO:0007829|PDB:1FVL"
FT STRAND 444..446
FT /evidence="ECO:0007829|PDB:1FVL"
FT STRAND 448..451
FT /evidence="ECO:0007829|PDB:1FVL"
FT STRAND 457..459
FT /evidence="ECO:0007829|PDB:1FVL"
FT STRAND 462..465
FT /evidence="ECO:0007829|PDB:1FVL"
SQ SEQUENCE 483 AA; 54514 MW; 3B943C81E6C7E1C3 CRC64;
MIQVLLVTIC LAVFPYQGSS IILESGNVND YEVVYPRKVT ALPKRAVQQK YEDAMQYELK
VNGEPVVLHL EKNKGLFSED YSETHYSPDG REITTYPSVE DHCYYHGRIH NDADSTASIS
ACDGLKGYFK LQGETYLIEP LKLSDSEAHA VYKYENIEKE DEAPKMCGVT QNWESDESIK
KASQLYLTPE QQRFPQRYIE LAIVVDHGMY KKYNHDSDKI KVRVHQMVNH INEMYRPLNI
AITLSLLQIW SNKDLITVKS ASNVTLNLFG NWRETVLLKR RSHDCAHLLT DINFTGNIIG
LAYKQGMCNP KLSVGLVQDY SSNVFVVAVI MTHELGHNLG MEHDEEKNGK KCNCKTCIMS
PAISDPPAQL FSDCSKNDYH TFLTNRNPQC ILNAPLRTDT VSTPVSGNEF LEAGEECDCG
SPSNPCCDAA TCKLRPGAQC ADGLCCDQCR FKKKRTICRI ARGDFPDDRC TGLSNDCPRW
NDL
