ID   ANTA_HIRME              Reviewed;          55 AA.
AC   P80302;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1994, sequence version 1.
DT   25-MAY-2022, entry version 98.
DE   RecName: Full=Hirustasin;
OS   Hirudo medicinalis (Medicinal leech).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Annelida; Clitellata;
OC   Hirudinea; Hirudinida; Hirudiniformes; Hirudinidae; Hirudo.
OX   NCBI_TaxID=6421;
RN   [1]
RP   PROTEIN SEQUENCE.
RX   PubMed=8112345; DOI=10.1111/j.1432-1033.1994.tb18575.x;
RA   Soellner C., Mentele R., Eckerskorn C., Fritz H., Sommerhoff C.P.;
RT   "Isolation and characterization of hirustasin, an antistasin-type serine-
RT   proteinase inhibitor from the medical leech Hirudo medicinalis.";
RL   Eur. J. Biochem. 219:937-943(1994).
RN   [2]
RP   X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF COMPLEX WITH KALLIKREIN.
RX   PubMed=9032072; DOI=10.1016/s0969-2126(97)00183-4;
RA   Mittl P.R.E., di Marco S., Fendrich G., Pohlig G., Heim J., Sommerhoff C.,
RA   Fritz H., Priestle J.P., Gruetter M.G.;
RT   "A new structural class of serine protease inhibitors revealed by the
RT   structure of the hirustasin-kallikrein complex.";
RL   Structure 5:253-264(1997).
RN   [3]
RP   ERRATUM OF PUBMED:9032072.
RA   Mittl P.R.E., di Marco S., Fendrich G., Pohlig G., Heim J., Sommerhoff C.,
RA   Fritz H., Priestle J.P., Grutter M.G.;
RL   Structure 5:585-585(1997).
RN   [4]
RP   X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS), AND DISULFIDE BONDS.
RX   PubMed=10368273; DOI=10.1016/s0969-2126(99)80009-4;
RA   Uson I., Sheldrick G.M., de La Fortelle E., Bricogne G., Di Marco S.,
RA   Priestle J.P., Gruetter M.G., Mittl P.R.;
RT   "The 1.2 A crystal structure of hirustasin reveals the intrinsic
RT   flexibility of a family of highly disulphide-bridged inhibitors.";
RL   Structure 7:55-63(1999).
CC   -!- FUNCTION: Acts as an inhibitor of tissue kallikrein, trypsin,
CC       chymotrypsin and neutrophil cathepsin G.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- SIMILARITY: Belongs to the protease inhibitor I15 (antistasin) family.
CC       {ECO:0000305}.
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DR   PDB; 1BX7; X-ray; 1.20 A; A=1-55.
DR   PDB; 1BX8; X-ray; 1.40 A; A=1-55.
DR   PDB; 1HIA; X-ray; 2.40 A; I/J=5-52.
DR   PDBsum; 1BX7; -.
DR   PDBsum; 1BX8; -.
DR   PDBsum; 1HIA; -.
DR   AlphaFoldDB; P80302; -.
DR   SMR; P80302; -.
DR   MEROPS; I15.001; -.
DR   EvolutionaryTrace; P80302; -.
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: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   Pfam; PF02822; Antistasin; 1.
DR   PRINTS; PR01706; ANTISTASIN.
DR   SUPFAM; SSF57262; SSF57262; 1.
DR   PROSITE; PS51252; ANTISTASIN; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; Disulfide bond; Heparin-binding;
KW   Protease inhibitor; Secreted; Serine protease inhibitor.
FT   CHAIN           1..55
FT                   /note="Hirustasin"
FT                   /id="PRO_0000155194"
FT   DOMAIN          24..50
FT                   /note="Antistasin-like"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00582"
FT   SITE            30..31
FT                   /note="Reactive bond"
FT   DISULFID        6..17
FT                   /evidence="ECO:0000269|PubMed:10368273"
FT   DISULFID        11..22
FT                   /evidence="ECO:0000269|PubMed:10368273"
FT   DISULFID        24..44
FT                   /evidence="ECO:0000269|PubMed:10368273"
FT   DISULFID        29..48
FT                   /evidence="ECO:0000269|PubMed:10368273"
FT   DISULFID        33..50
FT                   /evidence="ECO:0000269|PubMed:10368273"
FT   STRAND          7..9
FT                   /evidence="ECO:0007829|PDB:1BX8"
FT   STRAND          15..18
FT                   /evidence="ECO:0007829|PDB:1BX7"
FT   STRAND          21..24
FT                   /evidence="ECO:0007829|PDB:1BX7"
FT   STRAND          27..30
FT                   /evidence="ECO:0007829|PDB:1HIA"
FT   STRAND          37..39
FT                   /evidence="ECO:0007829|PDB:1HIA"
FT   STRAND          45..50
FT                   /evidence="ECO:0007829|PDB:1HIA"
SQ   SEQUENCE   55 AA;  5878 MW;  234226BEE3CC532E CRC64;
     TQGNTCGGET CSAAQVCLKG KCVCNEVHCR IRCKYGLKKD ENGCEYPCSC AKASQ