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Protein

Disintegrin echistatin-alpha

Gene
N/A
Organism
Echis carinatus sochureki (Saw-scaled viper)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Potent inhibitor of ligand binding to the integrins alpha-V/beta-3 (ITGAV/ITGB3), alpha-5/beta-1 (ITGA5/ITGB1) and alpha-IIb/beta-3 (ITGA2B/ITGB3). Competition with fibrinogen for the RGD recognition sites on the alpha-IIb/beta-3 integrin (glyco-protein IIb/IIIa complex) results in the inhibition of platelet aggregation and other antithrombotic properties such as an ability to prevent coronary thrombosis in animal models. Is also a potent inhibitor of bone resorption. This results from the blocking of the interaction of alpha-V/beta-3 integrin on the surface of osteoclasts with bone extracellular matrix. In addition, interaction with alpha-V/beta-3 also inhibits adhesion of human umbilical vein endothelial cells (HUVEC) to immobilized vitronectin and fibronectin.3 Publications

Keywords - Molecular functioni

Cell adhesion impairing toxin, Hemostasis impairing toxin, Platelet aggregation inhibiting toxin, Toxin

Names & Taxonomyi

Protein namesi
Recommended name:
Disintegrin echistatin-alpha
Alternative name(s):
Carinatin
Platelet aggregation activation inhibitor
Cleaved into the following 2 chains:
OrganismiEchis carinatus sochureki (Saw-scaled viper)
Taxonomic identifieri124223 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiLepidosauriaSquamataBifurcataUnidentataEpisquamataToxicoferaSerpentesColubroideaViperidaeViperinaeEchis

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi24 – 241R → A: Does not react with alpha-IIb/beta-3 and alpha-V/beta-3. 1 Publication
Mutagenesisi27 – 271D → W: Shows increased binding to alpha-IIb/beta-3 and decreased binding to alpha-V/beta-3. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 4949Disintegrin echistatin-alpha-1PRO_0000007242Add
BLAST
Chaini1 – 4747Disintegrin echistatin-alpha-2PRO_0000007243Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11Pyrrolidone carboxylic acid; in form alpha-2
Disulfide bondi2 ↔ 11
Disulfide bondi7 ↔ 32
Disulfide bondi8 ↔ 37
Disulfide bondi20 ↔ 39

Keywords - PTMi

Disulfide bond, Pyrrolidone carboxylic acid

Expressioni

Tissue specificityi

Expressed by the venom gland.

Interactioni

Subunit structurei

Monomer.1 Publication

Structurei

Secondary structure

1
49
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi8 – 136Combined sources
Beta strandi15 – 217Combined sources
Turni23 – 253Combined sources
Beta strandi37 – 393Combined sources
Beta strandi44 – 463Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1RO3NMR-A1-49[»]
2ECHNMR-A2-49[»]
ProteinModelPortaliP17347.
SMRiP17347. Positions 1-49.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP17347.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 4747DisintegrinPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi24 – 263Cell attachment site

Sequence similaritiesi

Contains 1 disintegrin domain.PROSITE-ProRule annotation

Phylogenomic databases

HOVERGENiHBG005487.

Family and domain databases

Gene3Di4.10.70.10. 1 hit.
InterProiIPR018358. Disintegrin_CS.
IPR001762. Disintegrin_dom.
[Graphical view]
PRINTSiPR00289. DISINTEGRIN.
SMARTiSM00050. DISIN. 1 hit.
[Graphical view]
SUPFAMiSSF57552. SSF57552. 1 hit.
PROSITEiPS00427. DISINTEGRIN_1. 1 hit.
PS50214. DISINTEGRIN_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P17347-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40 
QCESGPCCRN CKFLKEGTIC KRARGDDMDD YCNGKTCDCP RNPHKGPAT
Length:49
Mass (Da):5,424
Last modified:February 1, 1994 - v2
Checksum:i04CC79B297A4F99F
GO

Sequence databases

PIRiA32029.
A35982.

Cross-referencesi

Sequence databases

PIRiA32029.
A35982.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1RO3NMR-A1-49[»]
2ECHNMR-A2-49[»]
ProteinModelPortaliP17347.
SMRiP17347. Positions 1-49.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

HOVERGENiHBG005487.

Miscellaneous databases

EvolutionaryTraceiP17347.

Family and domain databases

Gene3Di4.10.70.10. 1 hit.
InterProiIPR018358. Disintegrin_CS.
IPR001762. Disintegrin_dom.
[Graphical view]
PRINTSiPR00289. DISINTEGRIN.
SMARTiSM00050. DISIN. 1 hit.
[Graphical view]
SUPFAMiSSF57552. SSF57552. 1 hit.
PROSITEiPS00427. DISINTEGRIN_1. 1 hit.
PS50214. DISINTEGRIN_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Echistatin. A potent platelet aggregation inhibitor from the venom of the viper, Echis carinatus."
    Gan Z.R., Gould R.J., Jacobs J.W., Friedman P.A., Polokoff M.A.
    J. Biol. Chem. 263:19827-19832(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE, FUNCTION, SUBUNIT.
    Tissue: Venom.
  2. "Platelet glycoprotein IIb-IIIa protein antagonists from snake venoms: evidence for a family of platelet-aggregation inhibitors."
    Dennis M.S., Henzel W.J., Pitti R.M., Lipari M.T., Napier M.A., Deisher T.A., Bunting S., Lazarus R.A.
    Proc. Natl. Acad. Sci. U.S.A. 87:2471-2475(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE, FUNCTION.
    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] [Europe PMC] [Abstract]
    Cited for: DISULFIDE BONDS.
  4. "Significance of RGD loop and C-terminal domain of echistatin for recognition of alphaIIb beta3 and alpha(v) beta3 integrins and expression of ligand-induced binding site."
    Marcinkiewicz C., Vijay-Kumar S., McLane M.A., Niewiarowski S.
    Blood 90:1565-1575(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF ARG-24 AND ASP-27.
  5. Cited for: REVIEW.
  6. "1H NMR studies of echistatin in solution. Sequential resonance assignments and secondary structure."
    Dalvit C., Widmer H., Bovermann G., Breckenridge R., Metternich R.
    Eur. J. Biochem. 202:315-321(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR.
  7. "Nuclear magnetic resonance studies of the snake toxin echistatin. 1H resonance assignments and secondary structure."
    Cooke R.M., Carter B.G., Martin D.M.A., Murray-Rust P., Weir M.P.
    Eur. J. Biochem. 202:323-328(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR.
  8. "The secondary structure of echistatin from 1H-NMR, circular-dichroism and Raman spectroscopy."
    Saudek V., Atkinson R.A., Lepage P., Pelton J.T.
    Eur. J. Biochem. 202:329-338(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR.
  9. "Three-dimensional structure of echistatin, the smallest active RGD protein."
    Saudek V., Atkinson R.A., Pelton J.T.
    Biochemistry 30:7369-7372(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR.
  10. "Proton NMR assignments and secondary structure of the snake venom protein echistatin."
    Chen Y., Pitzenberger S.M., Garsky V.M., Lumma P.K., Sanyal G., Baum J.
    Biochemistry 30:11625-11636(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR.
  11. "Echistatin: the refined structure of a disintegrin in solution by 1H NMR and restrained molecular dynamics."
    Atkinson R.A., Saudek V., Pelton J.T.
    Int. J. Pept. Protein Res. 43:563-572(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 2-49, DISULFIDE BOND.
  12. "Conformation and concerted dynamics of the integrin-binding site and the C-terminal region of echistatin revealed by homonuclear NMR."
    Monleon D., Esteve V., Kovacs H., Calvete J.J., Celda B.
    Biochem. J. 387:57-66(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 2-49, DISULFIDE BOND.

Entry informationi

Entry nameiVM2EA_ECHCS
AccessioniPrimary (citable) accession number: P17347
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: February 1, 1994
Last modified: May 11, 2016
This is version 102 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
Annotation programAnimal Toxin Annotation Program

Miscellaneousi

Miscellaneous

This peptide has served as a model to produce tirofiban (Aggrastat), a nonpeptide drug available in the market as antiplatelet agent.1 Publication
The disintegrin belongs to the short disintegrin subfamily.

Keywords - Technical termi

3D-structure, Direct protein sequencing

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.