Reviewed, UniProtKB/Swiss-Prot P18619 (DISF_TRIFL)

Names and origin

Protein names	Recommended name:     Zinc metalloproteinase/disintegrin Cleaved into the following 2 chains:     1- Recommended name:             Metalloproteinase               EC=3.4.24.-     2- Recommended name:             Disintegrin flavoridin
Organism	Trimeresurus flavoviridis (Habu) (Protobothrops flavoviridis)
Taxonomic identifier	88087 [NCBI]
Taxonomic lineage	Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Lepidosauria › Squamata › Scleroglossa › Serpentes › Colubroidea › Viperidae › Crotalinae › Trimeresurus

Protein attributes

Sequence length	483 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	The metalloproteinase is a probable venom zinc protease that acts in hemorrhage By similarity. The disintegrin inhibits fibrinogen interaction with platelet receptors expressed on glycoprotein IIb-IIIa complex. Acts by binding to the glycoprotein IIb-IIIa receptor on the platelet surface and inhibits aggregation induced by ADP, thrombin, platelet-activating factor and collagen.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom gland.
Sequence similarities	Belongs to the venom metalloproteinase family. P-II subfamily. Contains 1 disintegrin domain. Contains 1 peptidase M12B domain.

Ontologies

Keywords
Biological process	Blood coagulation Cell adhesion
Cellular component	Secreted
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease Toxin
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	blood coagulation Inferred from electronic annotation. Source: UniProtKB-KW cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW pathogenesis Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from electronic annotation. Source: UniProtKB-KW zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
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 – 190

170

By similarity

PRO_0000028996

Chain

191 – 395

205

Metalloproteinase

PRO_0000028997

Propeptide

396 – 413

18

Ref.2

PRO_0000028998

Chain

414 – 483

70

Disintegrin flavoridin

PRO_0000028999

Regions

Domain

197 – 395

199

Peptidase M12B

Domain

403 – 483

81

Disintegrin

Motif

462 – 464

3

Cell attachment site

Sites

Active site

334

1

By similarity

Metal binding

333

1

Zinc; catalytic Probable

Metal binding

337

1

Zinc; catalytic Probable

Metal binding

343

1

Zinc; catalytic Probable

Amino acid modifications

Glycosylation

263

1

N-linked (GlcNAc...) Potential

Glycosylation

293

1

N-linked (GlcNAc...) Potential

Disulfide bond

308 ↔ 390

By similarity

Disulfide bond

352 ↔ 374

By similarity

Disulfide bond

354 ↔ 357

By similarity

Disulfide bond

417 ↔ 432

Ref.3 Ref.4

Disulfide bond

419 ↔ 427

Ref.3 Ref.4

Disulfide bond

426 ↔ 449

Ref.3 Ref.4

Disulfide bond

440 ↔ 446

Ref.3 Ref.4

Disulfide bond

445 ↔ 470

Ref.3 Ref.4

Disulfide bond

458 ↔ 477

Ref.3 Ref.4

Experimental info

Sequence conflict

455 – 456

2

RT → TG AA sequence Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

483

Helix Strand Turn

Details...

Turn

429 – 432

4

Beta strand

444 – 446

3

Beta strand

448 – 451

4

Beta strand

457 – 459

3

Beta strand

462 – 465

4

Sequences

	Sequence		Length	Mass (Da)
	P18619-1 [UniParc]. Last modified May 23, 2003. Version 2. Checksum: 3B943C81E6C7E1C3	FASTA	483	54,514
	10 20 30 40 50 60 MIQVLLVTIC LAVFPYQGSS IILESGNVND YEVVYPRKVT ALPKRAVQQK YEDAMQYELK 70 80 90 100 110 120 VNGEPVVLHL EKNKGLFSED YSETHYSPDG REITTYPSVE DHCYYHGRIH NDADSTASIS 130 140 150 160 170 180 ACDGLKGYFK LQGETYLIEP LKLSDSEAHA VYKYENIEKE DEAPKMCGVT QNWESDESIK 190 200 210 220 230 240 KASQLYLTPE QQRFPQRYIE LAIVVDHGMY KKYNHDSDKI KVRVHQMVNH INEMYRPLNI 250 260 270 280 290 300 AITLSLLQIW SNKDLITVKS ASNVTLNLFG NWRETVLLKR RSHDCAHLLT DINFTGNIIG 310 320 330 340 350 360 LAYKQGMCNP KLSVGLVQDY SSNVFVVAVI MTHELGHNLG MEHDEEKNGK KCNCKTCIMS 370 380 390 400 410 420 PAISDPPAQL FSDCSKNDYH TFLTNRNPQC ILNAPLRTDT VSTPVSGNEF LEAGEECDCG 430 440 450 460 470 480 SPSNPCCDAA TCKLRPGAQC ADGLCCDQCR FKKKRTICRI ARGDFPDDRC TGLSNDCPRW NDL

References

[1]	"Molecular cloning and sequence analysis of cDNA encoding flavoridin, a disintegrin from the venom of Trimeresurus flavoviridis." Kishimoto M., Takahashi T. Toxicon 40:1033-1040(2002) [PubMed: 12076658] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Venom gland.
[2]	"Inhibition of platelet adhesion to surfaces of extracorporeal circuits by disintegrins. RGD-containing peptides from viper venoms." Musial J., Niewiarowski S., Rucinski B., Stewart G.J., Cook J.J., Williams J.A., Edmunds L.H. Jr. Circulation 82:261-273(1990) [PubMed: 2364514] [Abstract] Cited for: PROTEIN SEQUENCE OF 414-483. Tissue: Venom.
[3]	"The disulfide bridge pattern of snake venom disintegrins, flavoridin and echistatin." Calvete J.J., Wang Y., Mann K., Schaefer W., Niewiarwoski S., Stewart G.J. FEBS Lett. 309:316-320(1992) [PubMed: 1516704] [Abstract] Cited for: PROTEIN SEQUENCE OF DISINTEGRIN FLAVORIDIN, DISULFIDE BONDS. Tissue: Venom.
[4]	"Determination of the disulphide bonding pattern in proteins by local and global analysis of nuclear magnetic resonance data. Application to flavoridin." Klaus W., Broger C., Gerber P., Senn H. J. Mol. Biol. 232:897-906(1993) [PubMed: 8355276] [Abstract] Cited for: DISULFIDE BONDS IN DISINTEGRIN FLAVORIDIN.
[5]	"The nuclear magnetic resonance solution structure of flavoridin, an antagonist of the platelet GP IIb-IIIa receptor." Senn H., Klaus W. J. Mol. Biol. 232:907-925(1993) [PubMed: 8355277] [Abstract] Cited for: STRUCTURE BY NMR OF 414-483.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AB052155 mRNA. Translation: BAC00515.1.

PIR

A58649.

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FVL	NMR	-	A	414-483	[»]

SMR

P18619. Positions 194-394.

ModBase

Search...

Protein family/group databases

MEROPS

M12.155.

Phylogenomic databases

HOVERGEN

P18619.

Family and domain databases

InterPro

IPR001762. Blood-coag_inhib_Disintegrin.
IPR018358. Disintegrin_CS.
IPR006025. Pept_M_Zn_BS.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view]

Gene3D

G3DSA:4.10.70.10. Blood-coag_inhib_Disintegrin. 1 hit.

Pfam

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

PRINTS

PR00289. DISINTEGRIN.

ProDom

PD000664. Disintegrin. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00050. DISIN. 1 hit.
[Graphical view]

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...

Entry information

Entry name

DISF_TRIFL

Accession

Primary (citable) accession number: P18619
Secondary accession number(s): Q8JIS2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	May 23, 2003
Last modified:	June 16, 2009
This is version 76 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Tox-Prot (Toxin Annotation Project)