[1]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. TISSUE=Venom gland; PubMed=1385408 [NCBI, ExPASy, EBI, Israel, Japan] Paine M.J.I., Desmond H.P., Theakston R.D.G., Crampton J.M.; "Purification, cloning, and molecular characterization of a high molecular weight hemorrhagic metalloprotease, jararhagin, from Bothrops jararaca venom. Insights into the disintegrin gene family."; J. Biol. Chem. 267:22869-22876(1992).
[2]	PROTEIN SEQUENCE OF 175-183; 236-242; 361-369; 423-448; 507-516; 520-534 AND 535-552, AND MISCELLANEOUS. DOI=10.1016/S0003-9861(02)00598-2; PubMed=12504907 [NCBI, ExPASy, EBI, Israel, Japan] Moura-da-Silva A.M., Della-Casa M.S., David A.S., Assakura M.T., Butera D., Lebrun I., Shannon J.D., Serrano S.M.T., Fox J.W.; "Evidence for heterogeneous forms of the snake venom metalloproteinase jararhagin: a factor contributing to snake venom variability."; Arch. Biochem. Biophys. 409:395-401(2003).
[3]	PROTEIN SEQUENCE OF 213-227; 373-393; 421-439 AND 503-521, AND CATALYTIC ACTIVITY. TISSUE=Venom; DOI=10.1016/S0041-0101(02)00116-2; PubMed=12165326 [NCBI, ExPASy, EBI, Israel, Japan] Maruyama M., Sugiki M., Anai K., Yoshida E.; "N-terminal amino acid sequences and some characteristics of fibrinolytic/hemorrhagic metalloproteinases purified from Bothrops jararaca venom."; Toxicon 40:1223-1226(2002).
[4]	PROTEIN SEQUENCE OF 360-571 (JARARHAGIN-C), AND FUNCTION OF JARARHAGIN-C. TISSUE=Venom; DOI=10.1006/bbrc.1994.1706; PubMed=8198592 [NCBI, ExPASy, EBI, Israel, Japan] Usami Y., Fujimura Y., Miura S., Shima H., Yoshida E., Yoshioka A., Hirano K., Suzuki M., Titani K.; "A 28 kDa-protein with disintegrin-like structure (jararhagin-C) purified from Bothrops jararaca venom inhibits collagen- and ADP-induced platelet aggregation."; Biochem. Biophys. Res. Commun. 201:331-339(1994).
[5]	FUNCTION. PubMed=7831660 [NCBI, ExPASy, EBI, Israel, Japan] Kamiguti A.S., Slupsky J.R., Zuzel M., Hay C.R.M.; "Properties of fibrinogen cleaved by Jararhagin, a metalloproteinase from the venom of Bothrops jararaca."; Thromb. Haemost. 72:244-249(1994).
[6]	PROTEIN SEQUENCE OF 360-375, FUNCTION, AND SUBUNIT (JARACETIN). TISSUE=Venom; DOI=10.1006/bbrc.1995.1081; PubMed=7530003 [NCBI, ExPASy, EBI, Israel, Japan] De Luca M., Ward C.M., Ohmori K., Andrews R.K., Berndt M.C.; "Jararhagin and jaracetin: novel snake venom inhibitors of the integrin collagen receptor, alpha 2 beta 1."; Biochem. Biophys. Res. Commun. 206:570-576(1995).
[7]	FUNCTION. PubMed=8973578 [NCBI, ExPASy, EBI, Israel, Japan] Kamiguti A.S., Hay C.R.M., Zuzel M.; "Inhibition of collagen-induced platelet aggregation as the result of cleavage of alpha 2 beta 1-integrin by the snake venom metalloproteinase jararhagin."; Biochem. J. 320:635-641(1996).
[8]	FUNCTION. DOI=10.1016/S0304-4165(96)00140-7; PubMed=9133658 [NCBI, ExPASy, EBI, Israel, Japan] Kamiguti A.S., Moura-da-Silva A.M., Laing G.D., Knapp T., Zuzel M., Crampton J.M., Theakston R.D.G.; "Collagen-induced secretion-dependent phase of platelet aggregation is inhibited by the snake venom metalloproteinase jararhagin."; Biochim. Biophys. Acta 1335:209-217(1997).
[9]	FUNCTION. DOI=10.1016/S0049-3848(01)00216-X; PubMed=11323026 [NCBI, ExPASy, EBI, Israel, Japan] Moura-da-Silva A.M., Marcinkiewicz C., Marcinkiewicz M., Niewiarowski S.; "Selective recognition of alpha2beta1 integrin by jararhagin, a metalloproteinase/disintegrin from Bothrops jararaca venom."; Thromb. Res. 102:153-159(2001).
[10]	FUNCTION. DOI=10.1074/jbc.M202049200; PubMed=12186858 [NCBI, ExPASy, EBI, Israel, Japan] Zigrino P., Kamiguti A.S., Eble J., Drescher C., Nischt R., Fox J.W., Mauch C.; "The reprolysin jararhagin, a snake venom metalloproteinase, functions as a fibrillar collagen agonist involved in fibroblast cell adhesion and signaling."; J. Biol. Chem. 277:40528-40535(2002).
[11]	FUNCTION, AND ENZYME REGULATION. DOI=10.1016/S0041-008X(03)00337-5; PubMed=14613713 [NCBI, ExPASy, EBI, Israel, Japan] Escalante T., Nunez J., Moura-da-Silva A.M., Rucavado A., Theakston R.D.G., Gutierrez J.M.; "Pulmonary hemorrhage induced by jararhagin, a metalloproteinase from Bothrops jararaca snake venom."; Toxicol. Appl. Pharmacol. 193:17-28(2003).
[12]	FUNCTION. DOI=10.1016/S0041-0101(03)00237-X; PubMed=14602113 [NCBI, ExPASy, EBI, Israel, Japan] Maria D.A., Vassao R.C., Ruiz I.R.G.; "Haematopoietic effects induced in mice by the snake venom toxin jararhagin."; Toxicon 42:579-585(2003).
[13]	FUNCTION, AND ENZYME REGULATION. DOI=10.1016/j.toxicon.2004.08.009; PubMed=15530968 [NCBI, ExPASy, EBI, Israel, Japan] Costa E.P., Santos M.F.; "Jararhagin, a snake venom metalloproteinase-disintegrin, stimulates epithelial cell migration in an in vitro restitution model."; Toxicon 44:861-870(2004).
[14]	FUNCTION. DOI=10.1007/s10495-005-2945-1; PubMed=16133875 [NCBI, ExPASy, EBI, Israel, Japan] Tanjoni I., Weinlich R., Della-Casa M.S., Clissa P.B., Saldanha-Gama R.F., de Freitas M.S., Barja-Fidalgo C., Amarante-Mendes G.P., Moura-da-Silva A.M.; "Jararhagin, a snake venom metalloproteinase, induces a specialized form of apoptosis (anoikis) selective to endothelial cells."; Apoptosis 10:851-861(2005).
[15]	FUNCTION. DOI=10.1016/j.abb.2005.06.007; PubMed=16083850 [NCBI, ExPASy, EBI, Israel, Japan] Gallagher P., Bao Y., Serrano S.M.T., Laing G.D., Theakston R.D.G., Gutierrez J.M., Escalante T., Zigrino P., Moura-da-Silva A.M., Nischt R., Mauch C., Moskaluk C., Fox J.W.; "Role of the snake venom toxin jararhagin in proinflammatory pathogenesis: in vitro and in vivo gene expression analysis of the effects of the toxin."; Arch. Biochem. Biophys. 441:1-15(2005).
[16]	FUNCTION OF JARARHAGIN-C. DOI=10.1016/j.toxicon.2006.02.001; PubMed=16564063 [NCBI, ExPASy, EBI, Israel, Japan] Clissa P.B., Lopes-Ferreira M., Della-Casa M.S., Farsky S.H.P., Moura-da-Silva A.M.; "Importance of jararhagin disintegrin-like and cysteine-rich domains in the early events of local inflammatory response."; Toxicon 47:591-596(2006).
[17]	FUNCTION. DOI=10.1016/j.toxicon.2006.08.014; PubMed=17046041 [NCBI, ExPASy, EBI, Israel, Japan] Francisco G., Zara F.J., Maria D.A., Cruz-Neto A.P.; "Toxin jararhagin in low doses induces interstitial edema and increases the metabolic rate and red blood cells in mice."; Toxicon 48:1060-1067(2006).
[18]	FUNCTION. DOI=10.1016/j.biochi.2007.11.009; PubMed=18096518 [NCBI, ExPASy, EBI, Israel, Japan] Moura-da-Silva A.M., Ramos O.H.P., Baldo C., Niland S., Hansen U., Ventura J.S., Furlan S., Butera D., Della-Casa M.S., Tanjoni I., Clissa P.B., Fernandes I., Chudzinski-Tavassi A.M., Eble J.A.; "Collagen binding is a key factor for the hemorrhagic activity of snake venom metalloproteinases."; Biochimie 90:484-492(2008).
[19]	REVIEW. DOI=10.1016/j.toxicon.2005.02.013; PubMed=15922770 [NCBI, ExPASy, EBI, Israel, Japan] Laing G.D., Moura-da-Silva A.M.; "Jararhagin and its multiple effects on hemostasis."; Toxicon 45:987-996(2005).
[20]	CRYSTALLIZATION, AND 3D-STRUCTURE MODELING. DOI=10.1107/S090744490100614X; PubMed=11468397 [NCBI, ExPASy, EBI, Israel, Japan] Souza D.H.F., Selistre de Araujo H.S., Moura-da-Silva A.M., Della-Casa M.S., Oliva G., Garratt R.C.; "Crystallization and preliminary X-ray analysis of jararhagin, a metalloproteinase/disintegrin from Bothrops jararaca snake venom."; Acta Crystallogr. D 57:1135-1137(2001).

Comments

FUNCTION: Jararhagin causes hemorrhage. This is the result of the degradation of sub-endothelial matrix proteins leading to the disruption of the blood vessel endothelium, with accompanying disturbances in platelet function. It is able to degrade von Willebrand factor and it hydrolyzes the Aalpha-chain of fibrinogen while leaving the beta and gamma chains unaffected. It inhibits collagen-induced platelet aggregation though the binding of the molecule to the alpha-2 subunit I domain of the platelet surface alpha-2/beta-1 integrin (collagen receptor), and it cleaves the beta-1 subunit of the same integrin, inhibiting platelet interaction and ultimately causing impairment of signal transduction. It has inability to be affected by the plasma inhibitor alpha(2)-macroglobulin. In fibroblasts, it functions as a collagen-mimetic substrate and, in endothelial cells, it causes apoptosis and indirectly inhibits cell proliferation by release of angiostatin-like compounds. It induces a strong pro-inflammatory response characterized by intense leukocyte accumulation and release of cytokines at the site of the injection. Although hemorrhage and edema are a response to the direct effect of this toxin, jararhagin-induced inflammation and necrosis are dependent on macrophages and key pro-inflammatory cytokines or their receptors. It also possesses anti-tumorgenic properties.
FUNCTION: The monomer Jararhagin-C inhibits collagen- and ADP-induced platelet aggregation, but has no effect on glycoprotein Ib-IX-dependent platelet agglutination. Locally activates the early events of an acute inflammatory response as leukocyte rolling and pro-inflammatory cytokine release.
FUNCTION: Jaracetin is a dimer representing a differently processed form of jararhagin. It may be a dimeric form of Jararhagin-C. It modulates binding of von Willebrand Factor to the glycoprotein Ib-IX complex on platelets through a specific interaction with the von Willebrand Factor A1 domain. It potently induces platelet aggregation in citrated platelet-rich plasma.
CATALYTIC ACTIVITY: Cleavage of 10-His-|-Leu-11, 14-Ala-|-Leu-15, 16-Tyr-|-Leu-17 and 24-Phe-|-Phe-25 bonds in insulin B chain.
COFACTOR: Binds 1 zinc ion per subunit.
ENZYME REGULATION: Inhibited by EDTA, 1,10 phenanthroline and batimastat (a peptidomimetic MMP inhibitor).
SUBUNIT: Monomer (Jararhagin and Jararhagin-C) and dimer (Jaracetin).
SUBCELLULAR LOCATION: Secreted.
TISSUE SPECIFICITY: Expressed by the venom gland.
PTM: The N-terminus of Jararhagin is blocked.
MISCELLANEOUS: The metalloproteinase domain which is released from the cleavage of jararhagin-C is apparently unstable.
MISCELLANEOUS: A third form of jararhagin is obtained when the toxin is submitted to in vitro autolysis. The disintegrin-like/cysteine-rich domains appear to be disulfid-linked to a N-terminal portion of the metalloproteinase domain.
SIMILARITY: Belongs to the snake venom metalloproteinase family. P-III subfamily.
SIMILARITY: Contains 1 disintegrin domain.
SIMILARITY: Contains 1 peptidase M12B domain [view classification].

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

X68251; CAA48323.1; -; Genomic_DNA.

[EMBL / GenBank / DDBJ] [CoDingSequence]

PIR

S24789; S24789.

3D structure databases

PDB

1C9G; Model; -; A=152-355.

[ExPASy / RCSB / EBI]

PDBsum

1C9G; -.

ModBase

P30431.

Protein family/group databases

MEROPS

M12.138; -.

Ontologies

GO:0005576;	Cellular component: extracellular region (inferred from electronic annotation from UniProtKB-KW).
GO:0004222;	Molecular function: metalloendopeptidase activity (inferred from electronic annotation from InterPro).
GO:0005515;	Molecular function: protein binding (inferred from electronic annotation from UniProtKB-KW).
GO:0008270;	Molecular function: zinc ion binding (inferred from electronic annotation from InterPro).
GO:0006915;	Biological process: apoptosis (inferred from electronic annotation from UniProtKB-KW).
GO:0007596;	Biological process: blood coagulation (inferred from electronic annotation from UniProtKB-KW).
GO:0007155;	Biological process: cell adhesion (inferred from electronic annotation from UniProtKB-KW).
GO:0009405;	Biological process: pathogenesis (inferred from electronic annotation from UniProtKB-KW).
GO:0006508;	Biological process: proteolysis (inferred from electronic annotation from InterPro).
QuickGo view.

Family and domain databases

InterPro

IPR006586; ADAM_cysteine.
IPR001762; Blood-coag_inhib_Disintegrin.
IPR006025; Pept_M_Zn_BS.
IPR001590; Peptidase_M12B.
IPR002870; Peptidase_M12B_N.
Graphical view of domain structure.

Gene3D

G3DSA:4.10.70.10; Blood-coag_inhib_Disintegrin; 1.

Pfam

PF08516; ADAM_CR; 1.
PF00200; Disintegrin; 1.
PF01562; Pep_M12B_propep; 1.
PF01421; Reprolysin; 1.
Pfam graphical view of domain structure.

PRINTS

PR00289; DISINTEGRIN.

ProDom

PD000664; Disintegrin; 1.
[Domain structure / List of seq. sharing at least 1 domain]

SMART

SM00608; ACR; 1.
SM00050; DISIN; 1.
SMART graphical view of domain structure.

PROSITE

PS50215; ADAM_MEPRO; 1.
PS00427; DISINTEGRIN_1; 1.
PS50214; DISINTEGRIN_2; 1.
PS00142; ZINC_PROTEASE; 1.
PROSITE graphical view of domain structure (profiles).

Phylogenomic databases

HOVERGEN

P30431; -.

Other

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Apoptosis; Blood coagulation; Cell adhesion; Direct protein sequencing; Glycoprotein; Hydrolase; Metal-binding; Metalloprotease; Protease; Secreted; Toxin; Zinc; Zymogen.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`PROPEP`	`<1 150`	`>150`	`By similarity.`	`PRO_0000029009`
`CHAIN`	`151 571`	`421`	`Zinc metalloproteinase-disintegrin jararhagin.`	`PRO_0000029010`
`CHAIN`	`360 571`	`212`	`Disintegrin jararhagin-C.`	`PRO_0000029011`
`DOMAIN`	`159 355`	`197`	`Peptidase M12B.`
`DOMAIN`	`363 449`	`87`	`Disintegrin.`
`MOTIF`	`427 429`	`3`	`D/ECD-tripeptide.`
`COMPBIAS`	`450 571`	`122`	`Cys-rich.`
`ACT_SITE`	`296 296`		`By similarity.`
`METAL`	`295 295`		`Zinc; catalytic (Probable).`
`METAL`	`299 299`		`Zinc; catalytic (Probable).`
`METAL`	`305 305`		`Zinc; catalytic (Probable).`
`SITE`	`339 339`	`1`	`Necessary, but not sufficient, for proteolytic processing.`
`CARBOHYD`	`333 333`		`N-linked (GlcNAc...) (Potential).`
`DISULFID`	`270 350`		`By similarity.`
`DISULFID`	`310 334`		`By similarity.`
`DISULFID`	`312 317`		`By similarity.`
`DISULFID`	`377 395`		`By similarity.`
`DISULFID`	`379 390`		`By similarity.`
`DISULFID`	`389 412`		`By similarity.`
`DISULFID`	`403 409`		`By similarity.`
`DISULFID`	`408 434`		`By similarity.`
`DISULFID`	`421 441`		`By similarity.`
`NON_TER`	`1 1`
`STRAND`	`159 167`	`9`
`HELIX`	`169 174`	`6`
`TURN`	`175 177`	`3`
`HELIX`	`179 197`	`19`
`HELIX`	`198 200`	`3`
`STRAND`	`202 211`	`10`
`HELIX`	`224 238`	`15`
`TURN`	`239 241`	`3`
`STRAND`	`246 252`	`7`
`STRAND`	`262 264`	`3`
`TURN`	`272 274`	`3`
`STRAND`	`275 280`	`6`
`HELIX`	`286 300`	`15`
`STRAND`	`311 317`	`7`
`HELIX`	`333 346`	`14`
`HELIX`	`350 352`	`3`

Sequence information

Length: 571 AA [This is the length of the partial sequence of the unprocessed precursor]

Molecular weight: 63983 Da [This is the MW of the partial sequence of the unprocessed precursor]

CRC64: F5E549F8BF61177B [This is a checksum on the sequence]

        10         20         30         40         50         60 
ATRPKGAVQP KYEDAMQYEF KVNGEPVVLH LEKNKGLFSK DYSEIHYSPD GREITTYPPV 

        70         80         90        100        110        120 
EDHCYYHGRI ENDADSTASI SACNGLKGYF KLQRETYFIE PLKLPDSEAH AVFKYENVEK 

       130        140        150        160        170        180 
EDEAPKMCGV TQNWKSYEPI KKASQLAFTA EQQRYDPYKY IEFFVVVDQG TVTKNNGDLD 

       190        200        210        220        230        240 
KIKARMYELA NIVNEIFRYL YMHVALVGLE IWSNGDKITV KPDVDYTLNS FAEWRKTDLL 

       250        260        270        280        290        300 
TRKKHDNAQL LTAIDFNGPT IGYAYIGSMC HPKRSVGIVQ DYSPINLVVA VIMAHEMGHN 

       310        320        330        340        350        360 
LGIHHDTGSC SCGDYPCIMG PTISNEPSKF FSNCSYIQCW DFIMNHNPEC IINEPLGTDI 

       370        380        390        400        410        420 
ISPPVCGNEL LEVGEECDCG TPENCQNECC DAATCKLKSG SQCGHGDCCE QCKFSKSGTE 

       430        440        450        460        470        480 
CRASMSECDP AEHCTGQSSE CPADVFHKNG QPCLDNYGYC YNGNCPIMYH QCYALFGADV 

       490        500        510        520        530        540 
YEAEDSCFKD NQKGNYYGYC RKENGKKIPC APEDVKCGRL YCKDNSPGQN NPCKMFYSND 

       550        560        570 
DEHKGMVLPG TKCADGKVCS NGHCVDVATA Y

P30431 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools