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Protein

Disintegrin obtustatin

Gene
N/A
Organism
Macrovipera lebetina obtusa (Levant blunt-nosed viper) (Vipera lebetina obtusa)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Is a potent and selective inhibitor of alpha-1/beta-1 (ITGA1/ITGB1) integrin. It blocks the adhesion of alpha-1/beta-1-expressing K562 cells to immobilized collagens IV and I with IC50 of 2 and 0.5 nM, respectively. Potently inhibits angiogenesis in chicken and in mouse model and reduces tumor development by half. Is 25-fold less potent than viperistatin.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei22 – 221Indirectly maintains the active conformation of the loop

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Cell adhesion impairing toxin, Developmental protein, Toxin

Keywords - Biological processi

Angiogenesis, Differentiation

Names & Taxonomyi

Protein namesi
Recommended name:
Disintegrin obtustatin
OrganismiMacrovipera lebetina obtusa (Levant blunt-nosed viper) (Vipera lebetina obtusa)
Taxonomic identifieri209528 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiLepidosauriaSquamataBifurcataUnidentataEpisquamataToxicoferaSerpentesColubroideaViperidaeViperinaeMacrovipera

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi24 – 241L → R: Increase in inhibitory activity towards alpha-1/beta-1 integrin. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 4141Disintegrin obtustatinPRO_0000101814Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi1 ↔ 101 Publication
Disulfide bondi6 ↔ 291 Publication
Disulfide bondi7 ↔ 341 Publication
Disulfide bondi19 ↔ 361 Publication

Keywords - PTMi

Disulfide bond

Expressioni

Tissue specificityi

Expressed by the venom gland.1 Publication

Interactioni

Subunit structurei

Monomer.By similarity

Structurei

Secondary structure

1
41
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi3 – 53Combined sources
Turni8 – 103Combined sources
Beta strandi13 – 153Combined sources
Beta strandi23 – 253Combined sources
Beta strandi31 – 333Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1MPZNMR-A1-41[»]
ProteinModelPortaliP83469.
SMRiP83469. Positions 1-41.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP83469.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 4141DisintegrinAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi21 – 233Cell attachment site; atypical (KTS)

Sequence similaritiesi

Contains 1 disintegrin domain.Curated

Phylogenomic databases

HOVERGENiHBG005487.

Family and domain databases

Gene3Di4.10.70.10. 1 hit.
InterProiIPR001762. Disintegrin_dom.
[Graphical view]
PRINTSiPR00289. DISINTEGRIN.
SUPFAMiSSF57552. SSF57552. 1 hit.

Sequencei

Sequence statusi: Complete.

P83469-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40 
CTTGPCCRQC KLKPAGTTCW KTSLTSHYCT GKSCDCPLYP G
Length:41
Mass (Da):4,401
Last modified:November 1, 2002 - v1
Checksum:iAC81277E3E8DD536
GO

Cross-referencesi

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1MPZNMR-A1-41[»]
ProteinModelPortaliP83469.
SMRiP83469. Positions 1-41.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

HOVERGENiHBG005487.

Miscellaneous databases

EvolutionaryTraceiP83469.

Family and domain databases

Gene3Di4.10.70.10. 1 hit.
InterProiIPR001762. Disintegrin_dom.
[Graphical view]
PRINTSiPR00289. DISINTEGRIN.
SUPFAMiSSF57552. SSF57552. 1 hit.
ProtoNetiSearch...

Publicationsi

  1. "Amino acid sequence and homology modeling of obtustatin, a novel non-RGD-containing short disintegrin isolated from the venom of Vipera lebetina obtusa."
    Moreno-Murciano M.P., Monleon D., Calvete J.J., Celda B., Marcinkiewicz C.
    Protein Sci. 12:366-371(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    Tissue: Venom.
  2. "Obtustatin: a potent selective inhibitor of alpha1beta1 integrin in vitro and angiogenesis in vivo."
    Marcinkiewicz C., Weinreb P.H., Calvete J.J., Kisiel D.G., Mousa S.A., Tuszynski G.P., Lobb R.R.
    Cancer Res. 63:2020-2023(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
    Tissue: Venom.
  3. "Structural determinants of the selectivity of KTS-disintegrins for the alpha1beta1 integrin."
    Kisiel D.G., Calvete J.J., Katzhendler J., Fertala A., Lazarovici P., Marcinkiewicz C.
    FEBS Lett. 577:478-482(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: SYNTHESIS OF 19-29, MUTAGENESIS OF LEU-24.
    Tissue: Venom.
  4. "Concerted motions of the integrin-binding loop and the C-terminal tail of the non-RGD disintegrin obtustatin."
    Monleon D., Moreno-Murciano M.P., Kovacs H., Marcinkiewicz C., Calvete J.J., Celda B.
    J. Biol. Chem. 278:45570-45576(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR, SITE.
  5. Cited for: STRUCTURE BY NMR, DISULFIDE BONDS.

Entry informationi

Entry nameiDIS_MACLO
AccessioniPrimary (citable) accession number: P83469
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 2002
Last sequence update: November 1, 2002
Last modified: December 9, 2015
This is version 69 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Does not show inhibitory activity toward alpha-2/beta-1 (ITGA2/ITGB1), alpha-IIb/beta-3 (ITGA2B/ITGB3), alpha-V/beta-3 (ITGAV/ITGB3), alpha-4/beta-1 (ITGA4/ITGB1), alpha-5/beta-1 (ITGA5/ITGB1), alpha-6/beta-1 (ITGA6/ITGB1), and alpha-9/beta-1 (ITGA9/ITGB1), alpha-4/beta-7 (ITGA4/ITGB7) integrins.1 Publication

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.