Reviewed, UniProtKB/Swiss-Prot P28891 (FIBR_AGKCO)

Names and origin

Protein names	Recommended name:     Zinc metalloproteinase fibrolase     EC=3.4.24.72 Alternative name(s):     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.
Sequence processing	The displayed sequence is not processed.
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.
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom gland.
Pharmaceutical use	Is currently used in a clinical trial for the treatment of peripheral arterial occlusion.
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	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 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
	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.2
	Disulfide bond	158 ↔ 182		Ref.2
	Disulfide bond	160 ↔ 165		Ref.2
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)
	P28891-1 [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]	"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.

Cross-references

3D structure databases
HSSP	HSSP built from PDB template 4AIG based on UniProtKB P34179.
ModBase	Search...
Protein family/group databases
MEROPS	M12.133.
Phylogenomic databases
HOVERGEN	P28891.
Enzyme and pathway databases
BRENDA	3.4.24.72. 19148.
Family and domain databases
InterPro	IPR006025. Pept_M_Zn_BS. IPR001590. Peptidase_M12B. [Graphical view]
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

FIBR_AGKCO

Accession

Primary (citable) accession number: P28891

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	February 1, 1994
Last modified:	June 16, 2009
This is version 63 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Tox-Prot (Toxin Annotation Project)