VM2T3_PROMU
ID VM2T3_PROMU Reviewed; 481 AA.
AC O57413; Q7T1S1; Q91505; Q92119;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Zinc metalloproteinase/disintegrin;
DE Contains:
DE RecName: Full=Snake venom metalloproteinase TM-3 {ECO:0000303|PubMed:12071970, ECO:0000303|PubMed:12077431, ECO:0000303|PubMed:7488093, ECO:0000303|PubMed:8193588, ECO:0000303|PubMed:9703966};
DE Short=SVMP;
DE EC=3.4.24.-;
DE AltName: Full=Atrolysin e {ECO:0000312|EMBL:CAA62600.1};
DE AltName: Full=Fibrinlysin;
DE AltName: Full=Trimutase {ECO:0000303|Ref.2};
DE Contains:
DE RecName: Full=Disintegrin trimucrin {ECO:0000303|PubMed:8068721};
DE Flags: Precursor;
OS Protobothrops mucrosquamatus (Taiwan habu) (Trimeresurus mucrosquamatus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Protobothrops.
OX NCBI_TaxID=103944;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 411-442, FUNCTION,
RP PYROGLUTAMATE FORMATION AT GLU-190, SUBUNIT, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=7488093; DOI=10.1006/bbrc.1995.2614;
RA Huang K.F., Hung C.C., Pan F.M., Chow L.P., Tsugita A., Chiou S.H.;
RT "Characterization of multiple metalloproteinases with fibrinogenolytic
RT activity from the venom of Taiwan habu (Trimeresurus mucrosquamatus):
RT protein microsequencing coupled with cDNA sequence analysis.";
RL Biochem. Biophys. Res. Commun. 216:223-233(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RA Guo Y., Chang T., Lai C.;
RT "Cloning and expression of a trimutase gene from Taiwan habu (Trimeresurus
RT mucrosquamatus).";
RL Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=8068721; DOI=10.1016/0304-4165(94)90177-5;
RA Tsai I.H., Wang Y.M., Lee Y.H.;
RT "Characterization of a cDNA encoding the precursor of platelet aggregation
RT inhibition and metalloproteinase from Trimeresurus mucrosquamatus venom.";
RL Biochim. Biophys. Acta 1200:337-340(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 190-392.
RA Guo Y.-W., Ho P.-H.;
RT "Cloning and functional expression of a non-hemorrhagic thrombolytic enzyme
RT from Taiwan habu.";
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, ACTIVITY REGULATION, SUBUNIT, SUBCELLULAR LOCATION, AND
RP PYROGLUTAMATE FORMATION AT GLU-190.
RC TISSUE=Venom;
RX PubMed=8193588;
RA Huang K.-F., Hung C.C., Chiou S.-H.;
RT "Characterization of three fibrinogenolytic proteases isolated from the
RT venom of Taiwan habu (Trimeresurus mucrosquamatus).";
RL Biochem. Mol. Biol. Int. 31:1041-1050(1993).
RN [6]
RP ACTIVITY REGULATION.
RX PubMed=9703966; DOI=10.1006/bbrc.1998.9017;
RA Huang K.F., Hung C.C., Wu S.H., Chiou S.H.;
RT "Characterization of three endogenous peptide inhibitors for multiple
RT metalloproteinases with fibrinogenolytic activity from the venom of Taiwan
RT habu (Trimeresurus mucrosquamatus).";
RL Biochem. Biophys. Res. Commun. 248:562-568(1998).
RN [7] {ECO:0000312|PDB:1KUF}
RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 190-392, METAL-BINDING SITES, AND
RP DISULFIDE BONDS.
RX PubMed=12077431; DOI=10.1107/s090744490200656x;
RA Huang K.-F., Chiou S.-H., Ko T.-P., Yuann J.M., Wang A.H.-J.;
RT "The 1.35 A structure of cadmium-substituted TM-3, a snake-venom
RT metalloproteinase from Taiwan habu: elucidation of a TNFalpha-converting
RT enzyme-like active-site structure with a distorted octahedral geometry of
RT cadmium.";
RL Acta Crystallogr. D 58:1118-1128(2002).
RN [8] {ECO:0000312|PDB:1KUG, ECO:0000312|PDB:1KUI, ECO:0000312|PDB:1KUK}
RP X-RAY CRYSTALLOGRAPHY (1.37 ANGSTROMS) OF 190-392 IN COMPLEX WITH
RP ENDOGENOUS TRIPEPTIDE INHIBITORS, METAL-BINDING SITES, DISULFIDE BONDS, AND
RP ACTIVITY REGULATION.
RX PubMed=12071970; DOI=10.1046/j.1432-1033.2002.02982.x;
RA Huang K.-F., Chiou S.-H., Ko T.-P., Wang A.H.-J.;
RT "Determinants of the inhibition of a Taiwan habu venom metalloproteinase by
RT its endogenous inhibitors revealed by X-ray crystallography and synthetic
RT inhibitor analogues.";
RL Eur. J. Biochem. 269:3047-3056(2002).
CC -!- FUNCTION: [Snake venom metalloproteinase TM-3]: Potent fibrinogenolytic
CC protease which cleaves mainly the Aalpha chain of fibrinogen (FGA) and
CC slightly the Bbeta (FGB) and the gamma (FGG) chains (PubMed:8193588,
CC PubMed:7488093). May possess hemorrhagic activity (PubMed:7488093).
CC Compared to other SVMP, the substrate-binding pocket is relatively
CC shallow (PubMed:12077431). Is less susceptible to tripeptide inhibitors
CC than TM-1 (AC U3KRG1) and TM-2 (PubMed:9703966).
CC {ECO:0000269|PubMed:12077431, ECO:0000269|PubMed:7488093,
CC ECO:0000269|PubMed:8193588, ECO:0000269|PubMed:9703966}.
CC -!- FUNCTION: [Disintegrin trimucrin]: 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). {ECO:0000250|UniProtKB:P17349}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000305|PubMed:12071970, ECO:0000305|PubMed:12077431};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:12071970,
CC ECO:0000269|PubMed:12077431};
CC -!- ACTIVITY REGULATION: Inhibited by EDTA and 1,10-phenanthroline
CC (PubMed:8193588). Is also inhibited by endogenous tripeptide inhibitors
CC pyroGlu-Asn-Trp, pyroGlu-Gln-Trp, and pyroGlu-Lys-Trp (PubMed:9703966,
CC PubMed:12071970). {ECO:0000269|PubMed:12071970,
CC ECO:0000269|PubMed:8193588, ECO:0000269|PubMed:9703966}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:7488093,
CC ECO:0000269|PubMed:8193588}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:7488093,
CC ECO:0000269|PubMed:8193588}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:7488093, ECO:0000305|PubMed:8193588}.
CC -!- PTM: The N-terminus is blocked. {ECO:0000269|PubMed:7488093}.
CC -!- MISCELLANEOUS: This disintegrin is 100% identical to the disintegrin of
CC AC E9NW27, another disintegrin of the P-II subfamily of Protobothrops
CC mucrosquamatus.
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 -!- SEQUENCE CAUTION:
CC Sequence=CAA62600.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF011909; AAB94016.1; -; mRNA.
DR EMBL; X77089; CAA54364.1; -; mRNA.
DR EMBL; AF519177; AAP80728.1; -; mRNA.
DR EMBL; X91190; CAA62600.1; ALT_INIT; mRNA.
DR PIR; JC4342; JC4342.
DR PIR; S47570; S43125.
DR RefSeq; NP_001310177.1; NM_001323248.1.
DR PDB; 1KUF; X-ray; 1.35 A; A=190-392.
DR PDB; 1KUG; X-ray; 1.37 A; A=190-392.
DR PDB; 1KUI; X-ray; 1.50 A; A=190-392.
DR PDB; 1KUK; X-ray; 1.45 A; A=190-392.
DR PDBsum; 1KUF; -.
DR PDBsum; 1KUG; -.
DR PDBsum; 1KUI; -.
DR PDBsum; 1KUK; -.
DR AlphaFoldDB; O57413; -.
DR SMR; O57413; -.
DR MEROPS; M12.157; -.
DR MEROPS; M12.242; -.
DR GeneID; 107298299; -.
DR KEGG; pmur:107298299; -.
DR EvolutionaryTrace; O57413; -.
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; Cell adhesion impairing toxin; Direct protein sequencing;
KW Disulfide bond; Fibrinogenolytic toxin; Fibrinolytic toxin;
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..189
FT /id="PRO_0000322612"
FT CHAIN 190..392
FT /note="Snake venom metalloproteinase TM-3"
FT /id="PRO_5000053304"
FT PROPEP 393..410
FT /evidence="ECO:0000250"
FT /id="PRO_0000322613"
FT CHAIN 411..481
FT /note="Disintegrin trimucrin"
FT /evidence="ECO:0000305|PubMed:8068721"
FT /id="PRO_0000322614"
FT DOMAIN 197..392
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 400..481
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT MOTIF 459..461
FT /note="Cell attachment site"
FT ACT_SITE 334
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT BINDING 296..299
FT /ligand="an L-amino acid tripeptide"
FT /ligand_id="ChEBI:CHEBI:155837"
FT /ligand_note="endogenous tripeptide inhibitor"
FT /evidence="ECO:0000269|PubMed:12071970,
FT ECO:0007744|PDB:1KUG, ECO:0007744|PDB:1KUK"
FT BINDING 333
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:12071970,
FT ECO:0000269|PubMed:12077431, ECO:0007744|PDB:1KUF,
FT ECO:0007744|PDB:1KUG, ECO:0007744|PDB:1KUI,
FT ECO:0007744|PDB:1KUK"
FT BINDING 337
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:12071970,
FT ECO:0000269|PubMed:12077431, ECO:0007744|PDB:1KUF,
FT ECO:0007744|PDB:1KUG, ECO:0007744|PDB:1KUI,
FT ECO:0007744|PDB:1KUK"
FT BINDING 343
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:12071970,
FT ECO:0000269|PubMed:12077431, ECO:0007744|PDB:1KUF,
FT ECO:0007744|PDB:1KUG, ECO:0007744|PDB:1KUI,
FT ECO:0007744|PDB:1KUK"
FT BINDING 357
FT /ligand="an L-amino acid tripeptide"
FT /ligand_id="ChEBI:CHEBI:155837"
FT /ligand_note="endogenous tripeptide inhibitor"
FT /evidence="ECO:0000269|PubMed:12071970,
FT ECO:0007744|PDB:1KUG, ECO:0007744|PDB:1KUK"
FT MOD_RES 190
FT /note="Pyrrolidone carboxylic acid (Glu)"
FT /evidence="ECO:0000305|PubMed:7488093,
FT ECO:0000305|PubMed:8193588"
FT DISULFID 308..387
FT /evidence="ECO:0000269|PubMed:12071970,
FT ECO:0000269|PubMed:12077431, ECO:0007744|PDB:1KUF,
FT ECO:0007744|PDB:1KUG, ECO:0007744|PDB:1KUI,
FT ECO:0007744|PDB:1KUK"
FT DISULFID 349..371
FT /evidence="ECO:0000269|PubMed:12071970,
FT ECO:0000269|PubMed:12077431, ECO:0007744|PDB:1KUF,
FT ECO:0007744|PDB:1KUG, ECO:0007744|PDB:1KUI,
FT ECO:0007744|PDB:1KUK"
FT DISULFID 351..354
FT /evidence="ECO:0000269|PubMed:12071970,
FT ECO:0000269|PubMed:12077431, ECO:0007744|PDB:1KUF,
FT ECO:0007744|PDB:1KUG, ECO:0007744|PDB:1KUI,
FT ECO:0007744|PDB:1KUK"
FT DISULFID 414..429
FT /evidence="ECO:0000250"
FT DISULFID 416..424
FT /evidence="ECO:0000250"
FT DISULFID 423..446
FT /evidence="ECO:0000250"
FT DISULFID 437..443
FT /evidence="ECO:0000250"
FT DISULFID 442..467
FT /evidence="ECO:0000250"
FT DISULFID 455..474
FT /evidence="ECO:0000250"
FT CONFLICT 3
FT /note="E -> Q (in Ref. 1; CAA62600 and 3; CAA54364)"
FT /evidence="ECO:0000305"
FT CONFLICT 7
FT /note="V -> M (in Ref. 3; CAA54364)"
FT /evidence="ECO:0000305"
FT CONFLICT 20
FT /note="S -> C (in Ref. 1; CAA62600)"
FT /evidence="ECO:0000305"
FT CONFLICT 29
FT /note="N -> D (in Ref. 1; CAA62600 and 3; CAA54364)"
FT /evidence="ECO:0000305"
FT CONFLICT 37
FT /note="R -> A (in Ref. 3; CAA54364)"
FT /evidence="ECO:0000305"
FT CONFLICT 40
FT /note="S -> T (in Ref. 1; CAA62600 and 3; CAA54364)"
FT /evidence="ECO:0000305"
FT CONFLICT 64
FT /note="E -> G (in Ref. 1; CAA62600)"
FT /evidence="ECO:0000305"
FT CONFLICT 137
FT /note="P -> L (in Ref. 1; CAA62600)"
FT /evidence="ECO:0000305"
FT CONFLICT 200
FT /note="K -> E (in Ref. 1; CAA62600)"
FT /evidence="ECO:0000305"
FT CONFLICT 210
FT /note="Y -> H (in Ref. 1; CAA62600)"
FT /evidence="ECO:0000305"
FT CONFLICT 231
FT /note="I -> M (in Ref. 1; CAA62600)"
FT /evidence="ECO:0000305"
FT CONFLICT 358
FT /note="A -> P (in Ref. 1; CAA62600)"
FT /evidence="ECO:0000305"
FT CONFLICT 368
FT /note="F -> S (in Ref. 3; CAA54364)"
FT /evidence="ECO:0000305"
FT CONFLICT 467
FT /note="C -> S (in Ref. 1; CAA62600)"
FT /evidence="ECO:0000305"
FT STRAND 197..205
FT /evidence="ECO:0007829|PDB:1KUF"
FT HELIX 207..212
FT /evidence="ECO:0007829|PDB:1KUF"
FT TURN 213..215
FT /evidence="ECO:0007829|PDB:1KUF"
FT HELIX 217..235
FT /evidence="ECO:0007829|PDB:1KUF"
FT HELIX 236..238
FT /evidence="ECO:0007829|PDB:1KUF"
FT STRAND 240..249
FT /evidence="ECO:0007829|PDB:1KUF"
FT HELIX 262..275
FT /evidence="ECO:0007829|PDB:1KUF"
FT HELIX 277..280
FT /evidence="ECO:0007829|PDB:1KUF"
FT STRAND 284..290
FT /evidence="ECO:0007829|PDB:1KUF"
FT HELIX 295..297
FT /evidence="ECO:0007829|PDB:1KUF"
FT STRAND 300..302
FT /evidence="ECO:0007829|PDB:1KUF"
FT TURN 310..312
FT /evidence="ECO:0007829|PDB:1KUF"
FT STRAND 313..318
FT /evidence="ECO:0007829|PDB:1KUF"
FT HELIX 324..338
FT /evidence="ECO:0007829|PDB:1KUF"
FT TURN 346..348
FT /evidence="ECO:0007829|PDB:1KUF"
FT STRAND 352..354
FT /evidence="ECO:0007829|PDB:1KUF"
FT HELIX 370..382
FT /evidence="ECO:0007829|PDB:1KUF"
FT HELIX 386..389
FT /evidence="ECO:0007829|PDB:1KUF"
SQ SEQUENCE 481 AA; 54178 MW; C38714924F6091DF CRC64;
MIEVLLVTIC LAVFPYQGSS IILESGNVND YEVVYPRKVS ALPKGAVQPK YEDAMQYEFK
VNGEAVVLHL EKNKGLFSED YSETHYSPDG REITTYPSVE DHCYYHGRIH NDADSTASIS
ACDGLKGYFK LQGETYPIEP LELSDSEAHA VFKYENVEKE DEAPKMCGVT QNWESDESIK
KASQLYLTPE QQRFPQRYIK LAIVVDHGMY TKYSSNFKKI RKRVHQMVSN INEMCRPLNI
AITLALLDVW SEKDFITVQA DAPTTAGLFG DWRERVLLKK KNHDHAQLLT DTNFARNTIG
WAYVGRMCDE KYSVAVVKDH SSKVFMVAVT MTHELGHNLG MEHDDKDKCK CDTCIMSAVI
SDKQSKLFSD CSKDYYQTFL TNDNPQCILN APLRTDTVST PVSGNEFLEA GEECDCGSPE
NPCCDAATCK LRPGAQCAEG LCCDQCRFKK KRTICRRARG DNPDDRCTGQ SADCPRNGLY
G
