DIS_PROJR
ID DIS_PROJR Reviewed; 110 AA.
AC Q7ZZM2;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 25-MAY-2022, entry version 71.
DE RecName: Full=Disintegrin jerdostatin;
DE Flags: Precursor;
OS Protobothrops jerdonii (Jerdon's pitviper) (Trimeresurus jerdonii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Protobothrops.
OX NCBI_TaxID=242841;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SYNTHESIS OF 68-110, AND MUTAGENESIS
RP OF ARG-88.
RC TISSUE=Venom gland;
RX PubMed=16215260; DOI=10.1074/jbc.m509738200;
RA Sanz L., Chen R.-Q., Perez A., Hilario R., Juarez P., Marcinkiewicz C.,
RA Monleon D., Celda B., Xiong Y.-L., Perez-Paya E., Calvete J.J.;
RT "cDNA cloning and functional expression of jerdostatin, a novel RTS-
RT disintegrin from Trimeresurus jerdonii and a specific antagonist of the
RT alpha1beta1 integrin.";
RL J. Biol. Chem. 280:40714-40722(2005).
RN [2]
RP STRUCTURE BY NMR OF 68-110, FUNCTION, DISULFIDE BONDS, AND MUTAGENESIS OF
RP ARG-88 AND GLY-108.
RX PubMed=21656569; DOI=10.1002/prot.23076;
RA Carbajo R.J., Sanz L., Mosulen S., Perez A., Marcinkiewicz C.,
RA Pineda-Lucena A., Calvete J.J.;
RT "NMR structure and dynamics of recombinant wild type and mutated
RT jerdostatin, a selective inhibitor of integrin alpha1beta1.";
RL Proteins 79:2530-2542(2011).
CC -!- FUNCTION: Recombinant protein inhibits the adhesion of alpha-1/beta-1-
CC K562 (ITGA1/ITGB1) cells to collagen IV with an IC(50) of 80 nM.
CC {ECO:0000269|PubMed:16215260, ECO:0000269|PubMed:21656569}.
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:16215260}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:21656569}.
CC -!- PTM: Two conformers are found, they may differ by their disulfide bond
CC connectivities. Conformer 2 is 33 times less active than conformer 1.
CC Conformer 2 may represent a non-native protein (PubMed:16215260).
CC {ECO:0000269|PubMed:16215260}.
CC -!- PTM: The C-terminal dipeptide may be post-translationally removed, as
CC seen in disintegrins that possess a KTS integrin-binding motif.
CC -!- MISCELLANEOUS: Does not show inhibitory activity toward alpha-IIb/beta-
CC 3 (ITGA2B/ITGB3), alpha-V/beta-3 (ITGAV/ITGB3), alpha-2/beta-1
CC (ITGA2/ITGB1), alpha-5/beta-1 (ITGA5/ITGB1), alpha-4/beta-1
CC (ITGA4/ITGB1), alpha-6/beta-1 (ITGA6/ITGB1), and alpha-9/beta-1
CC (ITGA9/ITGB1). {ECO:0000305|PubMed:16215260}.
CC -!- SIMILARITY: Belongs to the disintegrin family. Short disintegrin
CC subfamily. {ECO:0000305}.
CC -!- CAUTION: The mature sequence shown is shorter than the sequence
CC proposed in PubMed:16215260 and PubMed:21656569. A comparison of
CC jerdostatin with KTS-disintegrins and a higher potency (IC(50) of 80 nM
CC compared to 180 nM) suggest that the C-terminal dipeptide is post-
CC translationally removed. {ECO:0000305}.
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DR EMBL; AY262730; AAP20878.1; -; mRNA.
DR PDB; 2W9O; NMR; -; A=68-110.
DR PDB; 2W9U; NMR; -; A=68-110.
DR PDB; 2W9V; NMR; -; A=68-108.
DR PDB; 2W9W; NMR; -; A=68-108.
DR PDBsum; 2W9O; -.
DR PDBsum; 2W9U; -.
DR PDBsum; 2W9V; -.
DR PDBsum; 2W9W; -.
DR AlphaFoldDB; Q7ZZM2; -.
DR BMRB; Q7ZZM2; -.
DR SMR; Q7ZZM2; -.
DR EvolutionaryTrace; Q7ZZM2; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR Gene3D; 4.10.70.10; -; 1.
DR InterPro; IPR036436; Disintegrin_dom_sf.
DR SUPFAM; SSF57552; SSF57552; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell adhesion impairing toxin; Disulfide bond; Secreted;
KW Signal; Toxin.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..67
FT /evidence="ECO:0000250"
FT /id="PRO_0000322603"
FT CHAIN 68..110
FT /note="Disintegrin jerdostatin"
FT /evidence="ECO:0000305|PubMed:16215260,
FT ECO:0000305|PubMed:21656569"
FT /id="PRO_0000007246"
FT DOMAIN 27..110
FT /note="Disintegrin"
FT MOTIF 88..90
FT /note="Cell attachment site; atypical (RTS)"
FT DISULFID 68..77
FT /evidence="ECO:0000269|PubMed:21656569"
FT DISULFID 73..96
FT /evidence="ECO:0000269|PubMed:21656569"
FT DISULFID 74..101
FT /evidence="ECO:0000269|PubMed:21656569"
FT DISULFID 86..103
FT /evidence="ECO:0000269|PubMed:21656569"
FT MUTAGEN 88
FT /note="R->K: Decrease in inhibitory activity towards
FT ITGA1/ITGB1 integrin (IC(50) is 300 nM). Decrease in
FT inhibitory activity towards ITGA1/ITGB1 integrin (IC(50) of
FT 703 nM) (IC(50) is 703 nM); when associated with G-108."
FT /evidence="ECO:0000269|PubMed:16215260,
FT ECO:0000269|PubMed:21656569"
FT MUTAGEN 108
FT /note="G->GNG: Decrease in inhibitory activity towards
FT ITGA1/ITGB1 integrin (IC(50) is 180 nM). Decrease in
FT inhibitory activity towards ITGA1/ITGB1 integrin (IC(50) is
FT 703 nM); when associated with R-88."
FT /evidence="ECO:0000269|PubMed:21656569"
FT STRAND 71..77
FT /evidence="ECO:0007829|PDB:2W9O"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:2W9O"
FT STRAND 89..91
FT /evidence="ECO:0007829|PDB:2W9O"
FT STRAND 92..95
FT /evidence="ECO:0007829|PDB:2W9V"
SQ SEQUENCE 110 AA; 11849 MW; C14C5D7986C9F5E7 CRC64;
MIQVLLVTIC LAVFPYQVSS KTLKSGSVNE YEVVNPGTVT GLPKGAVKQP EKKHEPMKGN
TLQKLPLCTT GPCCRQCKLK PAGTTCWRTS VSSHYCTGRS CECPSYPGNG
