ANTA_HAEOF
ID ANTA_HAEOF Reviewed; 136 AA.
AC P15358; Q9TWQ8; Q9TX45;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 2.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Antistasin;
DE Short=ATS;
DE AltName: Full=Blood coagulation factor Xa/proclotting enzyme inhibitor;
DE Flags: Precursor;
OS Haementeria officinalis (Mexican leech).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Annelida; Clitellata;
OC Hirudinea; Rhynchobdellida; Glossiphoniidae; Haementeria.
OX NCBI_TaxID=6410;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2470652; DOI=10.1016/0378-1119(89)90382-x;
RA Han J.H., Law S.W., Keller P.M., Kniskern P.J., Silberklang M., Tung J.S.,
RA Gasic T.B., Gasic G.J., Friedman P.A., Ellis R.W.;
RT "Cloning and expression of cDNA encoding antistasin, a leech-derived
RT protein having anti-coagulant and anti-metastatic properties.";
RL Gene 75:47-57(1989).
RN [2]
RP PROTEIN SEQUENCE OF 18-136, AND PYROGLUTAMATE FORMATION AT GLN-18.
RC TISSUE=Saliva;
RX PubMed=3164720; DOI=10.1016/s0021-9258(19)81491-6;
RA Nutt E., Gasic T., Rodkey J., Gasic G.J., Jacobs J.W., Friedman P.A.,
RA Simpson E.;
RT "The amino acid sequence of antistasin. A potent inhibitor of factor Xa
RT reveals a repeated internal structure.";
RL J. Biol. Chem. 263:10162-10167(1988).
RN [3]
RP PROTEIN SEQUENCE OF 18-136.
RC TISSUE=Saliva;
RX PubMed=8271959; DOI=10.1016/0076-6879(93)23052-o;
RA Dunwiddie C.T., Waxman L., Vlasuk G.P., Friedman P.A.;
RT "Purification and characterization of inhibitors of blood coagulation
RT factor Xa from hematophagous organisms.";
RL Methods Enzymol. 223:291-312(1993).
RN [4]
RP REACTIVE SITE.
RX PubMed=2777803; DOI=10.1016/s0021-9258(19)84761-0;
RA Dunwiddie C., Thornberry N.A., Bull H.G., Sardana M., Friedman P.A.,
RA Jacobs J.W., Simpson E.;
RT "Antistasin, a leech-derived inhibitor of factor Xa. Kinetic analysis of
RT enzyme inhibition and identification of the reactive site.";
RL J. Biol. Chem. 264:16694-16699(1989).
RN [5]
RP SULFATIDE-BINDING.
RX PubMed=2745433; DOI=10.1016/s0021-9258(18)63831-1;
RA Holt G.D., Krivan H.C., Gasic G.J., Ginsburg V.;
RT "Antistasin, an inhibitor of coagulation and metastasis, binds to sulfatide
RT (Gal(3-SO4) beta 1-1Cer) and has a sequence homology with other proteins
RT that bind sulfated glycoconjugates.";
RL J. Biol. Chem. 264:12138-12140(1989).
RN [6]
RP MUTAGENESIS.
RX PubMed=1445252; DOI=10.1042/bj2870943;
RA Hofmann K.J., Nutt E.M., Dunwiddie C.;
RT "Site-directed mutagenesis of the leech-derived factor Xa inhibitor
RT antistasin. Probing of the reactive site.";
RL Biochem. J. 287:943-949(1992).
RN [7]
RP MUTAGENESIS.
RX PubMed=8073407; DOI=10.1016/0049-3848(94)90138-4;
RA Theunissen H.J., Dijkema R., Swinkels J.C., de Poorter T.L., Vink P.M.,
RA van Dinther T.G.;
RT "Mutational analysis of antistasin, an inhibitor of blood coagulation
RT factor Xa derived from the Mexican leech Haementeria officinalis.";
RL Thromb. Res. 75:41-50(1994).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 24-127.
RX PubMed=9311976; DOI=10.1093/emboj/16.17.5151;
RA Lapatto R., Krengel U., Schreuder H.A., Arkema A., de Boer B., Kalk K.H.,
RA Hol W.G.J., Grootenhuis P.D.J., Mulders J.W.M., Dijkema R.,
RA Theunissen H.J.M., Dijkstra B.W.;
RT "X-ray structure of antistasin at 1.9-A resolution and its modelled complex
RT with blood coagulation factor Xa.";
RL EMBO J. 16:5151-5161(1997).
CC -!- FUNCTION: This highly disulfide-bonded protein is a potent inhibitor of
CC factor Xa. May have therapeutic utility as an anticoagulant. Also
CC exhibits a strong metastatic activity.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- MISCELLANEOUS: Binds to heparin-agarose, binds to sulfated
CC glycoconjugates.
CC -!- MISCELLANEOUS: At least four isoforms of antistasin have been
CC identified in leech salivary gland extracts, which differ by 1 or 2
CC amino-acid residues.
CC -!- SIMILARITY: Belongs to the protease inhibitor I15 (antistasin) family.
CC {ECO:0000305}.
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DR EMBL; M24422; AAA29192.1; -; mRNA.
DR EMBL; M24423; AAA29193.1; -; mRNA.
DR PIR; A28806; A28806.
DR PIR; A34398; A34398.
DR PIR; JS0209; JS0209.
DR PIR; S13904; S13904.
DR PDB; 1SKZ; X-ray; 1.90 A; A=20-136.
DR PDBsum; 1SKZ; -.
DR AlphaFoldDB; P15358; -.
DR SMR; P15358; -.
DR MEROPS; I15.007; -.
DR EvolutionaryTrace; P15358; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0007596; P:blood coagulation; IEA:UniProtKB-KW.
DR GO; GO:0050819; P:negative regulation of coagulation; IEA:InterPro.
DR InterPro; IPR004094; Antistasin-like.
DR InterPro; IPR011061; Hirudin/antistatin.
DR InterPro; IPR008086; Prot_inh_I15_antistasin_leech.
DR PRINTS; PR01706; ANTISTASIN.
DR SUPFAM; SSF57262; SSF57262; 2.
DR PROSITE; PS51252; ANTISTASIN; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Blood coagulation; Direct protein sequencing; Disulfide bond;
KW Hemostasis; Heparin-binding; Protease inhibitor;
KW Pyrrolidone carboxylic acid; Repeat; Secreted; Serine protease inhibitor;
KW Signal.
FT SIGNAL 1..17
FT /evidence="ECO:0000269|PubMed:3164720,
FT ECO:0000269|PubMed:8271959"
FT CHAIN 18..136
FT /note="Antistasin"
FT /id="PRO_0000001700"
FT DOMAIN 45..70
FT /note="Antistasin-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00582"
FT DOMAIN 100..125
FT /note="Antistasin-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00582"
FT BINDING 114..117
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000255"
FT BINDING 128..135
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000255"
FT SITE 51..52
FT /note="Reactive bond"
FT SITE 106..107
FT /note="Reactive bond"
FT MOD_RES 18
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:3164720"
FT DISULFID 25..36
FT DISULFID 30..43
FT DISULFID 45..65
FT DISULFID 50..68
FT DISULFID 54..70
FT DISULFID 79..90
FT DISULFID 84..97
FT DISULFID 99..120
FT DISULFID 105..123
FT DISULFID 109..125
FT VARIANT 22
FT /note="G -> R (in isoform B)"
FT VARIANT 47
FT /note="G -> E"
FT VARIANT 52
FT /note="M -> V"
FT VARIANT 71
FT /note="R -> I"
FT HELIX 25..28
FT /evidence="ECO:0007829|PDB:1SKZ"
FT TURN 38..40
FT /evidence="ECO:0007829|PDB:1SKZ"
FT STRAND 58..60
FT /evidence="ECO:0007829|PDB:1SKZ"
FT STRAND 66..70
FT /evidence="ECO:0007829|PDB:1SKZ"
FT HELIX 81..83
FT /evidence="ECO:0007829|PDB:1SKZ"
FT TURN 92..94
FT /evidence="ECO:0007829|PDB:1SKZ"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:1SKZ"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:1SKZ"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:1SKZ"
FT STRAND 121..125
FT /evidence="ECO:0007829|PDB:1SKZ"
SQ SEQUENCE 136 AA; 15225 MW; 582AF009ED9A0291 CRC64;
MIKLAILLLF TVAIVRCQGP FGPGCEEAGC PEGSACNIIT DRCTCSGVRC RMHCPHGFQR
SRYGCEFCKC RLEPMKATCD ISECPEGMMC SRLTNKCDCK IDINCRKTCP NGLKRDKLGC
EYCECRPKRK LIPRLS
