ID   LUFX_LUTLO              Reviewed;         301 AA.
AC   Q5WPU8;
DT   03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT   23-NOV-2004, sequence version 1.
DT   03-AUG-2022, entry version 16.
DE   RecName: Full=Lufaxin {ECO:0000303|PubMed:22796577};
DE   AltName: Full=32.4 kDa salivary protein {ECO:0000312|EMBL:AAS05319.1};
DE   AltName: Full=Lutzomyia longipalpis FXa inhibitor {ECO:0000303|PubMed:22796577};
DE   Flags: Precursor;
OS   Lutzomyia longipalpis (Sand fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Diptera; Nematocera; Psychodoidea; Psychodidae;
OC   Lutzomyia; Lutzomyia.
OX   NCBI_TaxID=7200;
RN   [1] {ECO:0000312|EMBL:AAS05319.1}
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Salivary gland;
RX   PubMed=15371479; DOI=10.1242/jeb.01185;
RA   Valenzuela J.G., Garfield M., Rowton E.D., Pham V.M.;
RT   "Identification of the most abundant secreted proteins from the salivary
RT   glands of the sand fly Lutzomyia longipalpis, vector of Leishmania
RT   chagasi.";
RL   J. Exp. Biol. 207:3717-3729(2004).
RN   [2]
RP   FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, RECOMBINANT PROTEIN,
RP   BIOASSAY, AND PROBABLE GLYCOSYLATION AT ASN-262.
RX   PubMed=22796577; DOI=10.1161/atvbaha.112.253906;
RA   Collin N., Assumpcao T.C., Mizurini D.M., Gilmore D.C., Dutra-Oliveira A.,
RA   Kotsyfakis M., Sa-Nunes A., Teixeira C., Ribeiro J.M., Monteiro R.Q.,
RA   Valenzuela J.G., Francischetti I.M.;
RT   "Lufaxin, a novel factor Xa inhibitor from the salivary gland of the sand
RT   fly Lutzomyia longipalpis blocks protease-activated receptor 2 activation
RT   and inhibits inflammation and thrombosis in vivo.";
RL   Arterioscler. Thromb. Vasc. Biol. 32:2185-2198(2012).
RN   [3]
RP   FUNCTION, SUBUNIT, AND RECOMBINANT EXPRESSION.
RX   PubMed=28912782; DOI=10.3389/fimmu.2017.01065;
RA   Mendes-Sousa A.F., do Vale V.F., Silva N.C.S., Guimaraes-Costa A.B.,
RA   Pereira M.H., Sant'Anna M.R.V., Oliveira F., Kamhawi S., Ribeiro J.M.C.,
RA   Andersen J.F., Valenzuela J.G., Araujo R.N.;
RT   "The sand fly salivary protein lufaxin inhibits the early steps of the
RT   alternative pathway of complement by direct binding to the proconvertase
RT   C3b-B.";
RL   Front. Immunol. 8:1065-1065(2017).
CC   -!- FUNCTION: Sand fly salivary protein with antithrombotic, and anti-
CC       complement (alternative pathway) activities (PubMed:22796577,
CC       PubMed:28912782). Is a slow, tight, non-competitive, and reversible
CC       inhibitor of factor Xa (FXa, F10) (PubMed:22796577). Is specific for
CC       FXa (Kd=3.86 nM) and does not interact with non-activated FX, or all
CC       other enzymes tested (PubMed:22796577). In addition, it blocks
CC       prothrombinase and increases both prothrombin time and activated
CC       partial thromboplastin time (PubMed:22796577). It also prevents
CC       protease-activated receptor 2 (F2RL1, PAR2) activation by FXa
CC       (PubMed:22796577). In vivo, it abrogates edema formation triggered by
CC       injection of FXa in the paw of mice (PubMed:22796577). Moreover, it
CC       prevents FeCl3-induced carotid artery thrombus formation and prolongs
CC       activated partial thromboplastin time ex vivo, implying that it works
CC       as an anticoagulant in vivo (PubMed:22796577). It also inhibits the
CC       early steps of the alternative pathway of complement by direct binding
CC       to the proconvertase C3b-B complex, by inhibiting activation of factor
CC       B and consequently the formation of the C3 convertase
CC       (PubMed:28912782). {ECO:0000269|PubMed:22796577,
CC       ECO:0000269|PubMed:28912782}.
CC   -!- SUBUNIT: Interacts with factor Xa (PubMed:22796577). Interacts with
CC       complement proconvertase C3b-B complex (PubMed:28912782).
CC       {ECO:0000269|PubMed:22796577, ECO:0000269|PubMed:28912782}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:22796577}.
CC   -!- TISSUE SPECIFICITY: Expressed in salivary glands.
CC       {ECO:0000269|PubMed:22796577}.
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DR   EMBL; AY445936; AAS05319.1; -; mRNA.
DR   VEuPathDB; VectorBase:LLOJ001514; -.
DR   Proteomes; UP000092461; Unplaced.
PE   1: Evidence at protein level;
KW   Blood coagulation cascade inhibiting toxin;
KW   Complement system impairing toxin; Glycoprotein;
KW   Hemostasis impairing toxin; Secreted; Signal; Toxin.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   CHAIN           24..301
FT                   /note="Lufaxin"
FT                   /id="PRO_5004263472"
FT   CARBOHYD        262
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT                   ECO:0000305|PubMed:22796577"
SQ   SEQUENCE   301 AA;  34951 MW;  F098EAFE12FB1129 CRC64;
     MNSINFLSIV GLISFGFIVA VKCDGDEYFI GKYKEKDETL FFASYGLKRD PCQIVLGYKC
     SNNQTHFVLN FKTNKKSCIS AIKLTSYPKI NQNSDLTKNL YCQTGGIGTD NCKLVFKKRK
     RQIAANIEIY GIPAKKCSFK DRYIGADPLH VDSYGLPYQF DQEHGWNVER YNIFKDTRFS
     TEVFYHKNGL FNTQITYLAE EDSFSEAREI TAKDIKKKFS IILPNEEYKR ISFLDVYWFQ
     ETMRKKPKYP YIHYNGECSN ENKTCELVFD TDELMTYALV KVFTNPESDG SRLKEEDLGR
     G