LYSF_TABYA
ID LYSF_TABYA Reviewed; 255 AA.
AC F8QQG5;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 21-SEP-2011, sequence version 1.
DT 03-AUG-2022, entry version 45.
DE RecName: Full=Tablysin 15 {ECO:0000303|PubMed:21475772};
DE AltName: Full=Disintegrin {ECO:0000303|PubMed:21475772};
DE Flags: Precursor;
OS Tabanus yao (Horsefly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Tabanomorpha; Tabanoidea;
OC Tabanidae; Tabanus.
OX NCBI_TaxID=485572;
RN [1] {ECO:0000312|EMBL:ADK94760.1}
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 24-39; 80-88; 92-100;
RP 187-200; 205-216 AND 241-252, FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND RECOMBINANT EXPRESSION.
RC TISSUE=Salivary gland;
RX PubMed=21475772; DOI=10.1160/th11-01-0029;
RA Ma D., Xu X., An S., Liu H., Yang X., Andersen J.F., Wang Y., Tokumasu F.,
RA Ribeiro J.M., Francischetti I.M., Lai R.;
RT "A novel family of RGD-containing disintegrins (Tablysin-15) from the
RT salivary gland of the horsefly Tabanus yao targets alphaIIbbeta3 or
RT alphaVbeta3 and inhibits platelet aggregation and angiogenesis.";
RL Thromb. Haemost. 105:1032-1045(2011).
RN [2] {ECO:0007744|PDB:3U3L, ECO:0007744|PDB:3U3N}
RP X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF 24-255, FUNCTION, DISULFIDE
RP BONDS, BINDING TO LEUKOTRIENE C4, AND MUTAGENESIS OF 32-ARG--ASP-34.
RX PubMed=22311975; DOI=10.1074/jbc.m112.340471;
RA Xu X., Francischetti I.M., Lai R., Ribeiro J.M., Andersen J.F.;
RT "Structure of protein having inhibitory disintegrin and leukotriene
RT scavenging functions contained in single domain.";
RL J. Biol. Chem. 287:10967-10976(2012).
CC -!- FUNCTION: Anti-inflammatory scavenger of eicosanoids and antithrombotic
CC protein that inhibits platelets aggregation induced by collagen, ADP
CC and convulxin (GPVI agonist) (PubMed:21475772, PubMed:22311975).
CC Exhibits high affinity binding for glycoprotein IIb-IIIa receptor
CC (ITGA2B/ITGB3) and endothelial cell alphaVbeta3 (ITGAV/ITGB3)
CC integrins, but not for alpha-5/beta-1 or alpha-2/beta-1
CC (PubMed:21475772). Accordingly, it blocks endothelial cell adhesion to
CC vitronectin (IC(50)~1 nM) and marginally to fibronectin (IC(50)~1 uM),
CC but not to collagen (PubMed:21475772). It also inhibits fibroblast
CC growth factor (FGF)-induced endothelial cell proliferation, and
CC attenuates tube formation in vitro (PubMed:21475772). In addition, it
CC dose-dependently attenuates thrombus formation to collagen under flow
CC (PubMed:21475772). Also binds proinflammatory cysteinyl leukotrienes
CC (leukotrienes C4 (LTC4), D4 (LTD4) and E4 (LTE4)) with submicromolar
CC affinities (PubMed:22311975). {ECO:0000269|PubMed:21475772,
CC ECO:0000269|PubMed:22311975}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:21475772}.
CC -!- TISSUE SPECIFICITY: Expressed in salivary glands.
CC {ECO:0000269|PubMed:21475772}.
CC -!- SIMILARITY: Belongs to the CRISP family. {ECO:0000305}.
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DR EMBL; GU363426; ADK94760.1; -; mRNA.
DR PDB; 3U3L; X-ray; 1.57 A; C=24-255.
DR PDB; 3U3N; X-ray; 1.65 A; C=24-255.
DR PDB; 3U3U; X-ray; 2.50 A; C=24-255.
DR PDBsum; 3U3L; -.
DR PDBsum; 3U3N; -.
DR PDBsum; 3U3U; -.
DR SMR; F8QQG5; -.
DR Gene3D; 3.40.33.10; -; 1.
DR InterPro; IPR014044; CAP_domain.
DR InterPro; IPR035940; CAP_sf.
DR InterPro; IPR001283; CRISP-related.
DR InterPro; IPR034763; P14a_insect.
DR PANTHER; PTHR10334; PTHR10334; 1.
DR Pfam; PF00188; CAP; 1.
DR PIRSF; PIRSF038921; P14a; 1.
DR SMART; SM00198; SCP; 1.
DR SUPFAM; SSF55797; SSF55797; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond;
KW Hemostasis impairing toxin; Platelet aggregation inhibiting toxin;
KW Secreted; Signal; Toxin.
FT SIGNAL 1..23
FT /evidence="ECO:0000255, ECO:0000305|PubMed:21475772"
FT CHAIN 24..255
FT /note="Tablysin 15"
FT /id="PRO_5003377418"
FT DOMAIN 67..211
FT /note="SCP"
FT /evidence="ECO:0000255"
FT MOTIF 32..34
FT /note="Cell attachment site"
FT /evidence="ECO:0000269|PubMed:22311975"
FT BINDING 82
FT /ligand="leukotriene E4"
FT /ligand_id="ChEBI:CHEBI:57462"
FT /evidence="ECO:0000269|PubMed:22311975"
FT BINDING 153
FT /ligand="leukotriene E4"
FT /ligand_id="ChEBI:CHEBI:57462"
FT /evidence="ECO:0000269|PubMed:22311975"
FT BINDING 156
FT /ligand="leukotriene E4"
FT /ligand_id="ChEBI:CHEBI:57462"
FT /evidence="ECO:0000269|PubMed:22311975"
FT DISULFID 27..40
FT /evidence="ECO:0000269|PubMed:22311975,
FT ECO:0007744|PDB:3U3L, ECO:0007744|PDB:3U3N"
FT DISULFID 31..117
FT /evidence="ECO:0000269|PubMed:22311975,
FT ECO:0007744|PDB:3U3L, ECO:0007744|PDB:3U3N"
FT DISULFID 49..110
FT /evidence="ECO:0000269|PubMed:22311975,
FT ECO:0007744|PDB:3U3L, ECO:0007744|PDB:3U3N"
FT DISULFID 192..209
FT /evidence="ECO:0000269|PubMed:22311975,
FT ECO:0007744|PDB:3U3L, ECO:0007744|PDB:3U3N"
FT DISULFID 232..243
FT /evidence="ECO:0000269|PubMed:22311975,
FT ECO:0007744|PDB:3U3L, ECO:0007744|PDB:3U3N"
FT MUTAGEN 32..34
FT /note="RGD->AGA: Loss of ability to inhibit platelet
FT aggregation induced by collagen and convulxin."
FT /evidence="ECO:0000269|PubMed:22311975"
SQ SEQUENCE 255 AA; 28220 MW; 3450921998A570AE CRC64;
MTSIPVSSFL LAALVLQYAT SDAVNYCRLP CRGDNYHVGC GEPAYAQECG QSPRTRELLK
EHRNEILSKI NDVRDHVAKG SWGLPVAARM KVVVWDAELA GLAKRHTKGC VGETHACRNT
ERFWLPGQLN FKYSGDKLPR IKELIDDAVK KGHLQKHNIT REIIGNYREN GPNGDVKELA
LAISDRVTAV GCGLTTWQDG AKARALLTCN FSSQNTRGRP VYKIGNSPGE KCIEKDETYK
NLCPATEPID PNKSN
