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Protein

Zinc metalloproteinase-disintegrin-like alternagin

Gene
N/A
Organism
Bothrops alternatus (Urutu) (Rhinocerophis alternatus)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Zinc metalloproteinase-disintegrin-like alternagin: hemorrhagic protease that acts as a potent inhibitor of collagen-induced adhesion by blockage of alpha-2/beta-1 (ITGA2/ITGB1) integrin. Cleaves at Leu-|-Met bonds (PubMed:11368322).1 Publication
Disintegrin alternagin-C: potent inhibitor of the collagen binding to alpha-2/beta-1 (ITGA2/ITGB1) integrin. Has a chemotactic activity on neutrophils and this effect involves actin cytoskeleton rearrangement, FAK, PI3-kinase and Erk-2 activities. Induces endothelial cell proliferation, and these effects are mediated at least in part by an increased expression of vascular endothelial growth factor (VEGF). In injured muscles, reduces both MMP-2 mRNA and gelatinolytic activity, suggesting that it changes the overall balance of extracellular matrix protein turnover during muscle regeneration. In low concentrations, induces formation of new vessels and up-regulates the expression of VEGF receptor 2 (KDR) without affecting VEGF receptor 1 (FLT1) expression. In high concentrations, strongly inhibits angiogenesis, and the expression of both receptors is down-regulated. Has very low plasma clotting activity.

Miscellaneous

Zinc metalloproteinase-disintegrin-like alternagin: does not present any fibrinogen-clotting activity and does not bind to alpha-IIb/beta-3 (ITGA2B/ITGB3), alpha-1/beta-1 (ITGA1/ITGB1), alpha-5/beta-1 (ITGA5/ITGB1), alpha-4/beta-1 (ITGA4/ITGB1), alpha-V/beta-3 (ITGAV/ITGB3) and alpha-9/beta-1 (ITGA9/ITGB1) integrins.1 Publication

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Activity regulationi

Inhibited by EDTA.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi6Calcium 1; via carbonyl oxygenBy similarity1
Metal bindingi9Calcium 1By similarity1
Metal bindingi11Calcium 1; via carbonyl oxygenBy similarity1
Metal bindingi13Calcium 1By similarity1
Metal bindingi16Calcium 1By similarity1
Metal bindingi19Calcium 1By similarity1
Metal bindingi70Calcium 2By similarity1
Metal bindingi71Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi73Calcium 2By similarity1
Metal bindingi85Calcium 2By similarity1
Metal bindingi86Calcium 2; via carbonyl oxygenBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCell adhesion impairing toxin, Developmental protein, Hemorrhagic toxin, Hemostasis impairing toxin, Hydrolase, Metalloprotease, Protease, Toxin
Biological processAngiogenesis, Chemotaxis, Differentiation
LigandCalcium, Metal-binding

Protein family/group databases

MEROPSiM12.335

Names & Taxonomyi

Protein namesi
Recommended name:
Zinc metalloproteinase-disintegrin-like alternagin (EC:3.4.24.-)
Alternative name(s):
Snake venom metalloproteinase
Short name:
SVMP
Cleaved into the following chain:
OrganismiBothrops alternatus (Urutu) (Rhinocerophis alternatus)
Taxonomic identifieri64174 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiLepidosauriaSquamataBifurcataUnidentataEpisquamataToxicoferaSerpentesColubroideaViperidaeCrotalinaeBothrops

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000326269‹1 – ›196Zinc metalloproteinase-disintegrin-like alternaginAdd BLAST›196
ChainiPRO_00003262701 – ›196Disintegrin-like alternagin-CAdd BLAST›196

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi7 ↔ 36In zinc metalloproteinase-disintegrin-like alternagin; alternatePROSITE-ProRule annotation
Disulfide bondi7 ↔ 26In disintegrin-like alternagin-C; alternatePROSITE-ProRule annotation
Disulfide bondi18 ↔ 36In disintegrin-like alternagin-C; alternatePROSITE-ProRule annotation
Disulfide bondi18 ↔ 31In zinc metalloproteinase-disintegrin-like alternagin; alternatePROSITE-ProRule annotation
Disulfide bondi20 ↔ 26In zinc metalloproteinase-disintegrin-like alternagin; alternatePROSITE-ProRule annotation
Disulfide bondi30 ↔ 53In zinc metalloproteinase-disintegrin-like alternaginPROSITE-ProRule annotation
Disulfide bondi44 ↔ 50In zinc metalloproteinase-disintegrin-like alternaginPROSITE-ProRule annotation
Disulfide bondi49 ↔ 75In zinc metalloproteinase-disintegrin-like alternaginPROSITE-ProRule annotation
Disulfide bondi62 ↔ 82In both disintegrin-like alternagin-C and zinc metalloproteinase-disintegrin-like alternaginPROSITE-ProRule annotation
Disulfide bondi69 ↔ 101In zinc metalloproteinase-disintegrin-like alternagin; alternatePROSITE-ProRule annotation
Disulfide bondi69 ↔ 94In disintegrin-like alternagin-C; alternatePROSITE-ProRule annotation
Disulfide bondi94 ↔ 106In zinc metalloproteinase-disintegrin-like alternagin; alternatePROSITE-ProRule annotation
Disulfide bondi101 ↔ 106In disintegrin-like alternagin-CPROSITE-ProRule annotation
Disulfide bondi114 ↔ 164In zinc metalloproteinase-disintegrin-like alternagin; alternatePROSITE-ProRule annotation
Disulfide bondi114 ↔ 129In disintegrin-like alternagin-C; alternatePROSITE-ProRule annotation
Disulfide bondi129 ↔ 175In zinc metalloproteinase-disintegrin-like alternagin; alternatePROSITE-ProRule annotation
Disulfide bondi142 ↔ 152In zinc metalloproteinase-disintegrin-like alternagin; alternatePROSITE-ProRule annotation
Disulfide bondi152 ↔ 159In disintegrin-like alternagin-C; alternatePROSITE-ProRule annotation
Disulfide bondi164 ↔ 175In disintegrin-like alternagin-CPROSITE-ProRule annotation

Post-translational modificationi

The N-terminus of alternagin is blocked.

Keywords - PTMi

Disulfide bond

Proteomic databases

PRIDEiP0C6R9

Expressioni

Tissue specificityi

Expressed by the venom gland.

Interactioni

Subunit structurei

Monomer.By similarity

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 90DisintegrinPROSITE-ProRule annotationAdd BLAST87

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi68 – 70D/ECD-tripeptide3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi91 – ›196Cys-richAdd BLAST›106

Sequence similaritiesi

Family and domain databases

Gene3Di4.10.70.10, 1 hit
InterProiView protein in InterPro
IPR006586 ADAM_Cys-rich
IPR001762 Disintegrin_dom
IPR036436 Disintegrin_dom_sf
PfamiView protein in Pfam
PF08516 ADAM_CR, 1 hit
PF00200 Disintegrin, 1 hit
PRINTSiPR00289 DISINTEGRIN
SMARTiView protein in SMART
SM00608 ACR, 1 hit
SM00050 DISIN, 1 hit
SUPFAMiSSF57552 SSF57552, 1 hit
PROSITEiView protein in PROSITE
PS50214 DISINTEGRIN_2, 1 hit

Sequencei

Sequence statusi: Fragment.

Sequence processingi: The displayed sequence is further processed into a mature form.

P0C6R9-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
IISPPVCGNE LLEVGEECDC GTPENCQNXC CDAATCKLKS GSQCGHXDCC
60 70 80 90 100
EQCKFTKSGT ECRASMSECD PAEHCTGQSX XCXXDVFHKN GQPCLDNYGY
110 120 130 140 150
CYNGNCPIMY HAQCYALFGA DVYEAEDSCF KDNQKGNYYG YCRKENXXXX
160 170 180 190
XCXXXDVKCG RLYCKDNSPK QNNPCKMFYS NDDEHKGNVL PGTKCE
Length:196
Mass (Da):21,731
Last modified:December 11, 2013 - v2
Checksum:iD7031E021D1479C2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Non-terminal residuei11
Sequence uncertaintyi30 – 31Assigned by comparison with orthologs2
Sequence uncertaintyi82Assigned by comparison with orthologs1
Sequence uncertaintyi152Assigned by comparison with orthologs1
Non-terminal residuei1961

Similar proteinsi

Cross-referencesi

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

MEROPSiM12.335

Proteomic databases

PRIDEiP0C6R9

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Family and domain databases

Gene3Di4.10.70.10, 1 hit
InterProiView protein in InterPro
IPR006586 ADAM_Cys-rich
IPR001762 Disintegrin_dom
IPR036436 Disintegrin_dom_sf
PfamiView protein in Pfam
PF08516 ADAM_CR, 1 hit
PF00200 Disintegrin, 1 hit
PRINTSiPR00289 DISINTEGRIN
SMARTiView protein in SMART
SM00608 ACR, 1 hit
SM00050 DISIN, 1 hit
SUPFAMiSSF57552 SSF57552, 1 hit
PROSITEiView protein in PROSITE
PS50214 DISINTEGRIN_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiVM3A_BOTAL
AccessioniPrimary (citable) accession number: P0C6R9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: December 11, 2013
Last modified: September 12, 2018
This is version 48 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Direct protein sequencing

Documents

  1. SIMILARITY comments
    Index of protein domains and families
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Main funding by: National Institutes of Health

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