P28891 (VMFIB_AGKCO) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Zinc metalloproteinase fibrolase EC=3.4.24.72 Alternative name(s): Fibrinolytic metalloproteinase Short name=Fibrinolytic proteinase INN=Alfimeprase
Organism	Agkistrodon contortrix contortrix (Southern copperhead)
Taxonomic identifier	8713 [NCBI]
Taxonomic lineage	Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Lepidosauria › Squamata › Scleroglossa › Serpentes › Colubroidea › Viperidae › Crotalinae › Agkistrodon

Protein attributes

Sequence length	203 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	This protein is a zinc protease from snake venom that acts in hemorrhage. It cleaves fibrinogen.
Catalytic activity	Hydrolysis of 14-Ala-|-Leu-15 in insulin B chain and 413-Lys-|-Leu-414 in alpha-chain of fibrinogen.
Cofactor	Binds 1 zinc ion per subunit Probable.
Enzyme regulation	Is inhibited by EDTA, o-phenanthroline and tetraethylenepentamine. Ref.2
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom gland.
Pharmaceutical use	Failed the phase III clinical trial for the treatment of arterial occlusive disease and acute ischemic stroke.
Sequence similarities	Belongs to the venom metalloproteinase family. P-I subfamily. Contains 1 peptidase M12B domain.

Ontologies

Keywords
Cellular component	Secreted
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease Toxin
PTM	Disulfide bond Pyrrolidone carboxylic acid
Technical term	Direct protein sequencing Pharmaceutical
Gene Ontology (GO)
Biological process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 203	203	Zinc metalloproteinase fibrolase		PRO_0000078197
Regions
	Domain	7 – 203	197	Peptidase M12B
Sites
	Active site	144	1	By similarity
	Metal binding	143	1	Zinc; catalytic Probable
	Metal binding	147	1	Zinc; catalytic Probable
	Metal binding	153	1	Zinc; catalytic Probable
Amino acid modifications
	Modified residue	1	1	Pyrrolidone carboxylic acid
	Disulfide bond	118 ↔ 198		Ref.3
	Disulfide bond	158 ↔ 182		Ref.3
	Disulfide bond	160 ↔ 165		Ref.3
Natural variations
	Natural variant	1	1	Missing in some of the chains.
	Natural variant	189	1	T → E.
	Natural variant	192	1	T → L.

Sequences

	Sequence		Length	Mass (Da)
	P28891 [UniParc]. Last modified February 1, 1994. Version 2. Checksum: 646EBE6F7F1EA191	FASTA	203	22,908
	10 20 30 40 50 60 QQRFPQRYVQ LVIVADHRMN TKYNGDSDKI RQWVHQIVNT INEIYRPLNI QFTLVGLEIW 70 80 90 100 110 120 SNQDLITVTS VSHDTLASFG NWRETDLLRR QRHDNAQLLT AIDFDGDTVG LAYVGGMCQL 130 140 150 160 170 180 KHSTGVIQDH SAINLLVALT MAHELGHNLG MNHDGNQCHC GANSCVMAAM LSDQPSKLFS 190 200 DCSKKDYQTF LTVNNPQCIL NKP

References

[1]	"Amino acid sequence of fibrolase, a direct-acting fibrinolytic enzyme from Agkistrodon contortrix contortrix venom." Randolph A., Chamberlain S.H., Chu H.L.C., Retzios A.D., Markland F.S. Jr., Masiarz F.R. Protein Sci. 1:590-600(1992) [PubMed: 1304358] [Abstract] Cited for: PROTEIN SEQUENCE, VARIANTS. Tissue: Venom.
[2]	"Purification and characterization of a fibrinolytic enzyme from venom of the southern copperhead snake (Agkistrodon contortrix contortrix)." Guan A.L., Retzios A.D., Henderson G.N., Markland F.S. Jr. Arch. Biochem. Biophys. 289:197-207(1991) [PubMed: 1898066] [Abstract] Cited for: PROTEIN SEQUENCE OF 141-151, ENZYME REGULATION. Tissue: Venom.
[3]	"Disulfide structure of alfimeprase: a recombinant analog of fibrolase." Jones G., Ronk M., Mori F., Zhang Z. Protein Sci. 10:1264-1267(2001) [PubMed: 11369866] [Abstract] Cited for: DISULFIDE BONDS.
[4]	"Clinical utility of novel agents in the treatment of central venous catheter occlusion." Reddy G.K. Support. Cancer Ther. 3:135-139(2006) [PubMed: 18632486] [Abstract] Cited for: PHARMACEUTICAL.
+	Additional computationally mapped references.

Cross-references

3D structure databases
ProteinModelPortal	P28891.
SMR	P28891. Positions 4-201.
ModBase	Search...
Protein family/group databases
MEROPS	M12.133.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Phylogenomic databases
HOVERGEN	HBG006978.
Enzyme and pathway databases
BRENDA	3.4.24.72. 192.
Family and domain databases
InterPro	IPR024079. MetalloPept_cat_dom. IPR001590. Peptidase_M12B. [Graphical view]
Gene3D	G3DSA:3.40.390.10. G3DSA:3.40.390.10. 1 hit.
Pfam	PF01421. Reprolysin. 1 hit. [Graphical view]
PROSITE	PS50215. ADAM_MEPRO. 1 hit. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

VMFIB_AGKCO

Accession

Primary (citable) accession number: P28891
Secondary accession number(s): Q9PS71

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	February 1, 1994
Last modified:	November 16, 2011
This is version 73 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Annotation program

Animal Toxin Annotation Program