VSPHA_HYDHA
ID VSPHA_HYDHA Reviewed; 265 AA.
AC Q5MCS0;
DT 21-MAR-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 61.
DE RecName: Full=Serine protease harobin;
DE EC=3.4.21.-;
DE AltName: Full=Fibrin(ogen)olytic enzyme;
DE AltName: Full=Snake venom serine protease;
DE Short=SVSP;
DE Flags: Precursor;
OS Hydrophis hardwickii (Hardwick's spine-bellied seasnake) (Lapemis
OS hardwickii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Hydrophiidae; Hydrophis.
OX NCBI_TaxID=8781;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF CYS-106 AND CYS-152.
RC TISSUE=Venom gland;
RX PubMed=17544404; DOI=10.1016/j.febslet.2007.05.047;
RA He J., Chen S., Gu J.;
RT "Identification and characterization of Harobin, a novel fibrino(geno)lytic
RT serine protease from a sea snake (Lapemis hardwickii).";
RL FEBS Lett. 581:2965-2973(2007).
CC -!- FUNCTION: Serine protein with fibrinolytic and fibrinogenolytic
CC activities. Degrades Bbeta-chain (FGB) of fibrinogen first and then the
CC Aalpha-chain (FGA). Gamma-chain (FGG) are also digested on prolonged
CC incubation. In vitro, it cleaves high molecular weight (HMW) kininogen
CC (KNG) releasing bradykinin that promotes vasodilation. In vitro and in
CC vivo, it cleaves angiotensin-2 (AGT). This explains the reduction of
CC blood pressure in hypertensive rats. Has also antithrombotic effects on
CC thrombosis animal models. {ECO:0000269|PubMed:17544404}.
CC -!- ACTIVITY REGULATION: Inhibited by PMSF. {ECO:0000269|PubMed:17544404}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.39 mM for n-p-tosyl-gly-pro-arg p-nitroanilide
CC {ECO:0000269|PubMed:17544404};
CC pH dependence:
CC Optimum pH is 8.0. {ECO:0000269|PubMed:17544404};
CC Temperature dependence:
CC Optimum temperature is 65 degrees Celsius.
CC {ECO:0000269|PubMed:17544404};
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- PTM: Harobin contains three additional Cys residues than other snake
CC venom serine proteases, suggesting an additional disulfide bond. In
CC addition, it is more stable than other snake 6-disulfide-bond serine
CC proteases, since it is less sensitive to DTT.
CC -!- MISCELLANEOUS: Has no fibrinogen clotting ability. Is not a plasminogen
CC activator. Does not affect angiotensin-converting enzyme (ACE). In
CC vivo, does not show hemorrhagic activity in mice (PubMed:17544404).
CC {ECO:0000305|PubMed:17544404}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. Snake venom subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00274}.
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DR EMBL; AY835844; AAV98367.1; -; mRNA.
DR AlphaFoldDB; Q5MCS0; -.
DR SMR; Q5MCS0; -.
DR MEROPS; S01.481; -.
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 GO; GO:0008217; P:regulation of blood pressure; IEA:UniProtKB-KW.
DR GO; GO:0042311; P:vasodilation; IEA:UniProtKB-KW.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 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 InterPro; IPR033116; TRYPSIN_SER.
DR Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Fibrinogenolytic toxin; Fibrinolytic toxin; Glycoprotein;
KW Hemostasis impairing toxin; Hydrolase; Hypotensive agent; Protease;
KW Secreted; Serine protease; Signal; Toxin; Vasoactive; Vasodilator; Zymogen.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..33
FT /evidence="ECO:0000250"
FT /id="PRO_0000416022"
FT CHAIN 34..265
FT /note="Serine protease harobin"
FT /id="PRO_5000094349"
FT DOMAIN 34..257
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 74
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 119
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 212
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT CARBOHYD 112
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 130
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 40..172
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 59..75
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 106..152
FT /evidence="ECO:0000305"
FT DISULFID 107..264
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 151..218
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 183..197
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 208..233
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT MUTAGEN 106
FT /note="C->V: Is less stable than wild-type enzyme."
FT /evidence="ECO:0000269|PubMed:17544404"
FT MUTAGEN 152
FT /note="C->S: Is less stable than wild-type enzyme."
FT /evidence="ECO:0000269|PubMed:17544404"
SQ SEQUENCE 265 AA; 28996 MW; AA98538FF79BCE4A CRC64;
MPLIRVLASL LILQLSYGKS LDNGAKAITS LDRIIGGFEC NPSEHRSLVY LYNSAGFFCS
GTLLNHEWVL TAAHCNREDI QIRLGVHNVH VHYEDEQIRV PKEKLCCLST NNCTQFSQDI
MLIRLNSPVN YSEHIAPLSL PSNPPSMGSV CCVMGWGTIT SPEVTYPEVP HCVDINILHI
PVCQAAYPTM SGKNILCAGI LEGGKDSCKG DSGGPLICNG QIQGIVSWGR FPCAQFLEPG
IYTKVFDYKD WIEGIIAGNS NVICP
