O57413 (VM2T3_PROMU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Zinc metalloproteinase/disintegrin Cleaved into the following 2 chains: Snake venom metalloproteinase TM-3 Short name=SVMP EC=3.4.24.- Alternative name(s): Fibrinlysin Trimutase Disintegrin trimucrin
Organism	Protobothrops mucrosquamatus (Taiwan habu) (Trimeresurus mucrosquamatus)
Taxonomic identifier	103944 [NCBI]
Taxonomic lineage	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Sauropsida › Sauria › Lepidosauria › Squamata › Scleroglossa › Serpentes › Colubroidea › Viperidae › Crotalinae › Protobothrops

Protein attributes

Sequence length	481 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Metalloproteinase TM-3: fibrin(ogen)olytic protease which cleaves the Aalpha chain of fibrinogen (FGA) first followed by the Bbeta chain (FGB) and shows relatively low activity on the gamma chain (FGG). Ref.2 Ref.4 Disintegrin trimucrin: inhibits platelet aggregation induced by ADP, thrombin, platelet-activating factor and collagen. Acts by inhibiting fibrinogen interaction with platelet receptors GPIIb/GPIIIa (ITGA2B/ITGB3). Ref.2 Ref.4
Cofactor	Binds 1 zinc ion per subunit By similarity.
Enzyme regulation	Inhibited by EDTA and 1,10-phenanthroline. Ref.4
Subunit structure	Monomer. Ref.4
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom gland.
Sequence similarities	Belongs to the venom metalloproteinase (M12B) family. P-II subfamily. Contains 1 disintegrin domain. Contains 1 peptidase M12B domain.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Secreted
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Fibrinogenolytic toxin Fibrinolytic toxin Hemostasis impairing toxin Hydrolase Metalloprotease Platelet aggregation inhibiting toxin Protease Toxin
PTM	Disulfide bond Zymogen
Technical term	3D-structure
Gene Ontology (GO)
Biological_process	cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

Potential

Propeptide

21 – 189

169

PRO_0000322612

Chain

190 – 392

203

Snake venom metalloproteinase TM-3

PRO_5000053304

Propeptide

393 – 408

16

By similarity

PRO_0000322613

Chain

409 – 481

73

Disintegrin trimucrin By similarity

PRO_0000322614

Regions

Domain

197 – 392

196

Peptidase M12B

Domain

400 – 481

82

Disintegrin

Motif

459 – 461

3

Cell attachment site By similarity

Sites

Active site

334

1

Metal binding

333

1

Zinc; catalytic

Metal binding

337

1

Zinc; catalytic

Metal binding

343

1

Zinc; catalytic

Amino acid modifications

Disulfide bond

308 ↔ 387

Ref.5 Ref.6

Disulfide bond

349 ↔ 371

Ref.5 Ref.6

Disulfide bond

351 ↔ 354

Ref.5 Ref.6

Disulfide bond

414 ↔ 429

By similarity

Disulfide bond

416 ↔ 424

By similarity

Disulfide bond

423 ↔ 446

By similarity

Disulfide bond

437 ↔ 443

By similarity

Disulfide bond

442 ↔ 467

By similarity

Disulfide bond

455 ↔ 474

By similarity

Experimental info

Sequence conflict

3

1

E → Q in CAA54364. Ref.2

Sequence conflict

7

1

V → M in CAA54364. Ref.2

Sequence conflict

29

1

N → D in CAA54364. Ref.2

Sequence conflict

37

1

R → A in CAA54364. Ref.2

Sequence conflict

40

1

S → T in CAA54364. Ref.2

Sequence conflict

200

1

K → E Ref.5

Sequence conflict

200

1

K → E Ref.6

Sequence conflict

368

1

F → S in CAA54364. Ref.2

Secondary structure

1

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481

Helix Strand Turn

Details...

Beta strand

197 – 205

9

Helix

207 – 212

6

Turn

213 – 215

3

Helix

217 – 235

19

Helix

236 – 238

3

Beta strand

240 – 249

10

Helix

262 – 275

14

Helix

277 – 280

4

Beta strand

284 – 290

7

Helix

295 – 297

3

Beta strand

300 – 302

3

Turn

310 – 312

3

Beta strand

313 – 318

6

Helix

324 – 338

15

Turn

346 – 348

3

Beta strand

352 – 354

3

Helix

370 – 382

13

Helix

386 – 389

4

Sequences

	Sequence		Length	Mass (Da)
	O57413 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: C38714924F6091DF	FASTA	481	54,178
	10 20 30 40 50 60 MIEVLLVTIC LAVFPYQGSS IILESGNVND YEVVYPRKVS ALPKGAVQPK YEDAMQYEFK 70 80 90 100 110 120 VNGEAVVLHL EKNKGLFSED YSETHYSPDG REITTYPSVE DHCYYHGRIH NDADSTASIS 130 140 150 160 170 180 ACDGLKGYFK LQGETYPIEP LELSDSEAHA VFKYENVEKE DEAPKMCGVT QNWESDESIK 190 200 210 220 230 240 KASQLYLTPE QQRFPQRYIK LAIVVDHGMY TKYSSNFKKI RKRVHQMVSN INEMCRPLNI 250 260 270 280 290 300 AITLALLDVW SEKDFITVQA DAPTTAGLFG DWRERVLLKK KNHDHAQLLT DTNFARNTIG 310 320 330 340 350 360 WAYVGRMCDE KYSVAVVKDH SSKVFMVAVT MTHELGHNLG MEHDDKDKCK CDTCIMSAVI 370 380 390 400 410 420 SDKQSKLFSD CSKDYYQTFL TNDNPQCILN APLRTDTVST PVSGNEFLEA GEECDCGSPE 430 440 450 460 470 480 NPCCDAATCK LRPGAQCAEG LCCDQCRFKK KRTICRRARG DNPDDRCTGQ SADCPRNGLY G

References

[1]	"Cloning and expression of a trimutase gene from Taiwan habu (Trimeresurus mucrosquamatus)." Guo Y., Chang T., Lai C. Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Venom gland.
[2]	"Characterization of a cDNA encoding the precursor of platelet aggregation inhibition and metalloproteinase from Trimeresurus mucrosquamatus venom." Tsai I.H., Wang Y.M., Lee Y.H. Biochim. Biophys. Acta 1200:337-340(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION. Tissue: Venom gland.
[3]	"Cloning and functional expression of a non-hemorrhagic thrombolytic enzyme from Taiwan habu." Guo Y.-W., Ho P.-H. Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 190-392.
[4]	"Characterization of three fibrinogenolytic proteases isolated from the venom of Taiwan habu (Trimeresurus mucrosquamatus)." Huang K.-F., Hung C.C., Chiou S.-H. Biochem. Mol. Biol. Int. 31:1041-1050(1993) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, SUBUNIT. Tissue: Venom.
[5]	"The 1.35 A structure of cadmium-substituted TM-3, a snake-venom metalloproteinase from Taiwan habu: elucidation of a TNFalpha-converting enzyme-like active-site structure with a distorted octahedral geometry of cadmium." Huang K.-F., Chiou S.-H., Ko T.-P., Yuann J.M., Wang A.H.-J. Acta Crystallogr. D 58:1118-1128(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 190-392, METAL-BINDING SITES, DISULFIDE BONDS.
[6]	"Determinants of the inhibition of a Taiwan habu venom metalloproteinase by its endogenous inhibitors revealed by X-ray crystallography and synthetic inhibitor analogues." Huang K.-F., Chiou S.-H., Ko T.-P., Wang A.H.-J. Eur. J. Biochem. 269:3047-3056(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.37 ANGSTROMS) OF 190-392, METAL-BINDING SITES, DISULFIDE BONDS.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF011909 mRNA. Translation: AAB94016.1.
X77089 mRNA. Translation: CAA54364.1.
AF519177 mRNA. Translation: AAP80728.1.

PIR

S43125. S47570.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1KUF	X-ray	1.35	A	190-392	[»]
1KUG	X-ray	1.37	A	190-392	[»]
1KUI	X-ray	1.50	A	190-392	[»]
1KUK	X-ray	1.45	A	190-392	[»]

ProteinModelPortal

O57413.

SMR

O57413. Positions 192-392, 411-476.

ModBase

Search...

Protein family/group databases

MEROPS

M12.157.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Phylogenomic databases

HOVERGEN

HBG006978.

Family and domain databases

Gene3D

3.40.390.10. 1 hit.
4.10.70.10. 1 hit.

InterPro

IPR001762. Blood-coag_inhib_Disintegrin.
IPR018358. Disintegrin_CS.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view]

Pfam

PF00200. Disintegrin. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
[Graphical view]

PRINTS

PR00289. DISINTEGRIN.

SMART

SM00050. DISIN. 1 hit.
[Graphical view]

SUPFAM

SSF57552. Disintegrin. 1 hit.

PROSITE

PS50215. ADAM_MEPRO. 1 hit.
PS00427. DISINTEGRIN_1. 1 hit.
PS50214. DISINTEGRIN_2. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O57413.

Entry information

Entry name

VM2T3_PROMU

Accession

Primary (citable) accession number: O57413
Secondary accession number(s): Q7T1S1, Q91505

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 26, 2008
Last sequence update:	June 1, 1998
Last modified:	April 3, 2013
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program

Annotation program

Chordata Protein Annotation Program