ID VSP1_PROFL Reviewed; 260 AA.
AC P05620; O13056;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-1998, sequence version 2.
DT 27-MAR-2024, entry version 109.
DE RecName: Full=Thrombin-like enzyme flavoxobin;
DE Short=SVTLE;
DE EC=3.4.21.74;
DE AltName: Full=Fibrinogen-clotting enzyme;
DE AltName: Full=Habutobin;
DE AltName: Full=Snake venom serine protease 1;
DE Short=SVSP;
DE Flags: Precursor;
GN Name=TLF1;
OS Protobothrops flavoviridis (Habu) (Trimeresurus flavoviridis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Protobothrops.
OX NCBI_TaxID=88087;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=8941719; DOI=10.1016/s0014-5793(96)01144-1;
RA Deshimaru M., Ogawa T., Nakashima K., Nobuhisa I., Chijiwa T.,
RA Shimohigashi Y., Fukumaki Y., Niwa M., Yamashina I., Hattori S., Ohno M.;
RT "Accelerated evolution of crotalinae snake venom gland serine proteases.";
RL FEBS Lett. 397:83-88(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 26-41.
RC TISSUE=Venom, and Venom gland;
RX PubMed=17803962; DOI=10.1016/j.bbrc.2007.08.103;
RA Sunagawa M., Nakamura M., Kosugi T.;
RT "Cloning of habutobin cDNA and antithrombotic activity of recombinant
RT protein.";
RL Biochem. Biophys. Res. Commun. 362:899-904(2007).
RN [3]
RP PROTEIN SEQUENCE OF 25-260.
RC TISSUE=Venom;
RX PubMed=3170503; DOI=10.1093/oxfordjournals.jbchem.a122313;
RA Shieh T.-C., Kawabata S., Kihara H., Ohno M., Iwanaga S.;
RT "Amino acid sequence of a coagulant enzyme, flavoxobin, from Trimeresurus
RT flavoviridis venom.";
RL J. Biochem. 103:596-605(1988).
RN [4]
RP PROTEIN SEQUENCE OF 25-49, AND FUNCTION AS C3 CONVERTASE-LIKE.
RC TISSUE=Venom;
RX PubMed=12225369; DOI=10.1046/j.1365-2567.2002.01490.x;
RA Yamamoto C., Tsuru D., Oda-Ueda N., Ohno M., Hattori S., Kim S.T.;
RT "Flavoxobin, a serine protease from Trimeresurus flavoviridis (habu snake)
RT venom, independently cleaves Arg726-Ser727 of human C3 and acts as a novel,
RT heterologous C3 convertase.";
RL Immunology 107:111-117(2002).
RN [5]
RP ERRATUM OF PUBMED:12225369.
RA Shieh T.-C., Kawabata S., Kihara H., Ohno M., Iwanaga S.;
RL J. Biochem. 103:900-900(1988).
RN [6]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=3910643; DOI=10.1093/oxfordjournals.jbchem.a135329;
RA Shieh T.C., Tanaka S., Kihara H., Ohno M., Makisumi S.;
RT "Purification and characterization of a coagulant enzyme from Trimeresurus
RT flavoviridis venom.";
RL J. Biochem. 98:713-721(1985).
RN [7]
RP FUNCTION.
RX PubMed=8585090; DOI=10.1016/0041-0101(95)00050-v;
RA Nakamura M., Kinjoh K., Miyagi C., Oka U., Sunagawa M., Yamashita S.,
RA Kosugi T.;
RT "Pharmacokinetics of habutobin in rabbits.";
RL Toxicon 33:1201-1206(1995).
RN [8]
RP FUNCTION.
RX PubMed=8817813; DOI=10.1016/0041-0101(95)00160-3;
RA Sunagawa M., Hanashiro K., Nakamura M., Kosugi T.;
RT "Habutobin releases plasminogen activator (U-PA) from bovine pulmonary
RT artery endothelial cells.";
RL Toxicon 34:691-699(1996).
RN [9]
RP ACTIVITY REGULATION.
RX PubMed=8875777; DOI=10.1016/0041-0101(96)00032-3;
RA Oka U., Nakamura M., Kinjoh K., Kosugi T.;
RT "Alpha 2-macroglobulin of rabbits inhibits the habutobin activity.";
RL Toxicon 34:903-912(1996).
RN [10]
RP FUNCTION.
RX PubMed=9241744;
RA Kinjoh K., Kosugi T., Nakamura M., Hanashiro K., Sunagawa M., Tokeshi Y.,
RA Eguchi Y.;
RT "Habutobin splits the Arg16-Gly17 bond in the A alpha chain of rabbit
RT fibrinogen.";
RL Thromb. Haemost. 77:1127-1128(1997).
RN [11]
RP FUNCTION.
RX PubMed=10708795; DOI=10.1016/s0041-0101(99)00215-9;
RA Nejime T., Kinjoh K., Nakamura M., Hanashiro K., Sunagawa M., Eguchi Y.,
RA Kosugi T.;
RT "Habutobin recognizes Thr(7) in the sequence of fibrinopeptide A of rabbit
RT fibrinogen.";
RL Toxicon 38:1029-1041(2000).
CC -!- FUNCTION: Thrombin-like snake venom serine protease that clots
CC fibrinogen (FGA) by releasing fibrinopeptide A. According to
CC PubMed:8585090, only cleaves rabbit fibrinogen, whereas no specificity
CC is described in PubMed:3910643 (tests done on bovine fibrinogen). Also
CC acts as a C3 convertase that independently cleaves human C3 and kick-
CC starts the complement cascade. Also increases urokinase-type
CC plasminogen activator (PLAU) and plasminogen activator inhibitor
CC (SERPINE1) in cultured bovine pulmonary artery endothelial cells. Dose-
CC dependently inhibits collagen-induced platelet aggregation.
CC {ECO:0000269|PubMed:10708795, ECO:0000269|PubMed:12225369,
CC ECO:0000269|PubMed:3910643, ECO:0000269|PubMed:8585090,
CC ECO:0000269|PubMed:8817813, ECO:0000269|PubMed:9241744}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Selective cleavage of Arg-|-Xaa bond in fibrinogen, to form
CC fibrin, and release fibrinopeptide A. The specificity of further
CC degradation of fibrinogen varies with species origin of the enzyme.;
CC EC=3.4.21.74;
CC -!- ACTIVITY REGULATION: Inhibited by alpha(2)-macroglobulin,
CC diisopropylfluorophosphate (DFP) and PMSF. Low inhibition by tosyl-L-
CC lysine chloromethyl ketone. {ECO:0000269|PubMed:3910643,
CC ECO:0000269|PubMed:8875777}.
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- MISCELLANEOUS: Negative results: does not affect fibrinogen of human,
CC monkey, bovine, dog, rat and guinea-pig. Does not release
CC fibrinopeptide B (PubMed:9241744). {ECO:0000305|PubMed:9241744}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. Snake venom subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00274}.
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DR EMBL; D67078; BAA19976.1; -; mRNA.
DR PIR; A41456; A41456.
DR AlphaFoldDB; P05620; -.
DR SMR; P05620; -.
DR MEROPS; S01.347; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR PANTHER; PTHR24264:SF15; RIKEN CDNA 2210010C04 GENE; 1.
DR PANTHER; PTHR24264; TRYPSIN-RELATED; 1.
DR Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
PE 1: Evidence at protein level;
KW Blood coagulation cascade activating toxin;
KW Complement system impairing toxin; Direct protein sequencing;
KW Disulfide bond; Hemostasis impairing toxin; Hydrolase;
KW Platelet aggregation inhibiting toxin; Protease; Secreted; Serine protease;
KW Signal; Toxin; Zymogen.
FT SIGNAL 1..18
FT /evidence="ECO:0000250"
FT PROPEP 19..24
FT /evidence="ECO:0000269|PubMed:12225369,
FT ECO:0000269|PubMed:3170503"
FT /id="PRO_0000028385"
FT CHAIN 25..260
FT /note="Thrombin-like enzyme flavoxobin"
FT /id="PRO_0000028386"
FT DOMAIN 25..251
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 67
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 112
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 206
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT DISULFID 31..165
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 52..68
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 100..258
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 144..212
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 176..191
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 202..227
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT CONFLICT 31
FT /note="Missing (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 35..37
FT /note="EHP -> HR (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 41
FT /note="A -> V (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 82
FT /note="K -> Q (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 106
FT /note="D -> T (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 221..222
FT /note="SY -> YI (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 224
FT /note="G -> S (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 259
FT /note="L -> P (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 260 AA; 28398 MW; A6594CA045EDE4EE CRC64;
MVLIRVLANL LILQLSYAQK SSELVIGGDE CNINEHPFLV ALYDAWSGRF LCGGTLINPE
WVLTAAHCDS KNFKMKLGAH SKKVLNEDEQ IRNPKEKFIC PNKKNDEVLD KDIMLIKLDS
PVSYSEHIAP LSLPSSPPSV GSVCRIMGWG SITPVEETFP DVPHCANINL LDDVECKPGY
PELLPEYRTL CAGVLQGGID TCGFDSGTPL ICNGQFQGIV SYGGHPCGQS RKPGIYTKVF
DYNAWIQSII AGNTAATCLP
//
