DIS_MACLO
ID DIS_MACLO Reviewed; 41 AA.
AC P83469;
DT 01-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-2002, sequence version 1.
DT 25-MAY-2022, entry version 81.
DE RecName: Full=Disintegrin obtustatin;
OS Macrovipera lebetina obtusa (Levant blunt-nosed viper) (Vipera lebetina
OS obtusa).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Viperinae; Macrovipera.
OX NCBI_TaxID=209528;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Venom;
RX PubMed=12538900; DOI=10.1110/ps.0230203;
RA Moreno-Murciano M.P., Monleon D., Calvete J.J., Celda B., Marcinkiewicz C.;
RT "Amino acid sequence and homology modeling of obtustatin, a novel non-RGD-
RT containing short disintegrin isolated from the venom of Vipera lebetina
RT obtusa.";
RL Protein Sci. 12:366-371(2003).
RN [2]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=12727812;
RA Marcinkiewicz C., Weinreb P.H., Calvete J.J., Kisiel D.G., Mousa S.A.,
RA Tuszynski G.P., Lobb R.R.;
RT "Obtustatin: a potent selective inhibitor of alpha1beta1 integrin in vitro
RT and angiogenesis in vivo.";
RL Cancer Res. 63:2020-2023(2003).
RN [3]
RP SYNTHESIS OF 19-29, AND MUTAGENESIS OF LEU-24.
RC TISSUE=Venom;
RX PubMed=15556632; DOI=10.1016/j.febslet.2004.10.050;
RA Kisiel D.G., Calvete J.J., Katzhendler J., Fertala A., Lazarovici P.,
RA Marcinkiewicz C.;
RT "Structural determinants of the selectivity of KTS-disintegrins for the
RT alpha1beta1 integrin.";
RL FEBS Lett. 577:478-482(2004).
RN [4]
RP STRUCTURE BY NMR, AND SITE.
RX PubMed=12947085; DOI=10.1074/jbc.m307030200;
RA Monleon D., Moreno-Murciano M.P., Kovacs H., Marcinkiewicz C.,
RA Calvete J.J., Celda B.;
RT "Concerted motions of the integrin-binding loop and the C-terminal tail of
RT the non-RGD disintegrin obtustatin.";
RL J. Biol. Chem. 278:45570-45576(2003).
RN [5]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=12742023; DOI=10.1016/s0022-2836(03)00371-1;
RA Moreno-Murciano M.P., Monleon D., Marcinkiewicz C., Calvete J.J., Celda B.;
RT "NMR solution structure of the non-RGD disintegrin obtustatin.";
RL J. Mol. Biol. 329:135-145(2003).
CC -!- FUNCTION: Is a potent and selective inhibitor of alpha-1/beta-1
CC (ITGA1/ITGB1) integrin. It blocks the adhesion of alpha-1/beta-1-
CC expressing K562 cells to immobilized collagens IV and I with IC(50) of
CC 2 and 0.5 nM, respectively. Potently inhibits angiogenesis in chicken
CC and in mouse model and reduces tumor development by half. Is 25-fold
CC less potent than viperistatin. {ECO:0000269|PubMed:12538900,
CC ECO:0000269|PubMed:12727812}.
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12538900}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000269|PubMed:12538900}.
CC -!- MISCELLANEOUS: Does not show inhibitory activity toward alpha-2/beta-1
CC (ITGA2/ITGB1), alpha-IIb/beta-3 (ITGA2B/ITGB3), alpha-V/beta-3
CC (ITGAV/ITGB3), alpha-4/beta-1 (ITGA4/ITGB1), alpha-5/beta-1
CC (ITGA5/ITGB1), alpha-6/beta-1 (ITGA6/ITGB1), and alpha-9/beta-1
CC (ITGA9/ITGB1), alpha-4/beta-7 (ITGA4/ITGB7) integrins.
CC {ECO:0000305|PubMed:12727812}.
CC -!- SIMILARITY: Belongs to the disintegrin family. Short disintegrin
CC subfamily. {ECO:0000305}.
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DR PDB; 1MPZ; NMR; -; A=1-41.
DR PDBsum; 1MPZ; -.
DR AlphaFoldDB; P83469; -.
DR SMR; P83469; -.
DR EvolutionaryTrace; P83469; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR Gene3D; 4.10.70.10; -; 1.
DR InterPro; IPR001762; Disintegrin_dom.
DR InterPro; IPR036436; Disintegrin_dom_sf.
DR PRINTS; PR00289; DISINTEGRIN.
DR SUPFAM; SSF57552; SSF57552; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Angiogenesis; Cell adhesion impairing toxin;
KW Developmental protein; Differentiation; Direct protein sequencing;
KW Disulfide bond; Secreted; Toxin.
FT CHAIN 1..41
FT /note="Disintegrin obtustatin"
FT /id="PRO_0000101814"
FT DOMAIN 1..41
FT /note="Disintegrin"
FT MOTIF 21..23
FT /note="Cell attachment site; atypical (KTS)"
FT SITE 22
FT /note="Indirectly maintains the active conformation of the
FT loop"
FT DISULFID 1..10
FT /evidence="ECO:0000269|PubMed:12742023"
FT DISULFID 6..29
FT /evidence="ECO:0000269|PubMed:12742023"
FT DISULFID 7..34
FT /evidence="ECO:0000269|PubMed:12742023"
FT DISULFID 19..36
FT /evidence="ECO:0000269|PubMed:12742023"
FT MUTAGEN 24
FT /note="L->R: Increase in inhibitory activity towards alpha-
FT 1/beta-1 integrin."
FT /evidence="ECO:0000269|PubMed:15556632"
FT STRAND 3..5
FT /evidence="ECO:0007829|PDB:1MPZ"
FT TURN 8..10
FT /evidence="ECO:0007829|PDB:1MPZ"
FT STRAND 13..15
FT /evidence="ECO:0007829|PDB:1MPZ"
FT STRAND 23..25
FT /evidence="ECO:0007829|PDB:1MPZ"
FT STRAND 31..33
FT /evidence="ECO:0007829|PDB:1MPZ"
SQ SEQUENCE 41 AA; 4401 MW; AC81277E3E8DD536 CRC64;
CTTGPCCRQC KLKPAGTTCW KTSLTSHYCT GKSCDCPLYP G
