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 22-FEB-2023, entry version 114. 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}; 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; 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 OrthoDB; 5406290at2759; -. 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; Collagenase (Catalytic Domain); 1. DR Gene3D; 4.10.70.10; Disintegrin domain; 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 PANTHER; PTHR11905; ADAM A DISINTEGRIN AND METALLOPROTEASE DOMAIN; 1. DR PANTHER; PTHR11905:SF32; DISINTEGRIN AND METALLOPROTEINASE DOMAIN-CONTAINING PROTEIN 28; 1. 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; Blood coagulation inhibitor (disintegrin); 1. DR SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 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 //