GILX_HELHO
ID GILX_HELHO Reviewed; 230 AA.
AC P43685; E2I6G2;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 21-SEP-2011, sequence version 2.
DT 03-AUG-2022, entry version 87.
DE RecName: Full=Gilatoxin;
DE Short=GTX;
DE EC=3.4.21.-;
DE AltName: Full=Kallikrein-2;
OS Heloderma horridum horridum (Mexican beaded lizard).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Anguimorpha; Neoanguimorpha; Helodermatidae; Heloderma.
OX NCBI_TaxID=8552;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=20631207; DOI=10.1074/mcp.m110.001370;
RA Fry B.G., Winter K., Norman J.A., Roelants K., Nabuurs R.J., van Osch M.J.,
RA Teeuwisse W.M., van der Weerd L., McNaughtan J.E., Kwok H.F., Scheib H.,
RA Greisman L., Kochva E., Miller L.J., Gao F., Karas J., Scanlon D., Lin F.,
RA Kuruppu S., Shaw C., Wong L., Hodgson W.C.;
RT "Functional and structural diversification of the Anguimorpha lizard venom
RT system.";
RL Mol. Cell. Proteomics 9:2369-2390(2010).
RN [2]
RP PROTEIN SEQUENCE, FUNCTION, GLYCOSYLATION, AND TOXIC DOSE.
RC TISSUE=Venom;
RX PubMed=8408054; DOI=10.1016/s0021-9258(20)80636-x;
RA Utaisincharoen P., Mackessy S.P., Miller R.A., Tu A.T.;
RT "Complete primary structure and biochemical properties of gilatoxin, a
RT serine protease with kallikrein-like and angiotensin-degrading
RT activities.";
RL J. Biol. Chem. 268:21975-21983(1993).
RN [3]
RP PRELIMINARY PROTEIN SEQUENCE OF 1-37.
RC TISSUE=Venom;
RX PubMed=3395124; DOI=10.1016/0003-9861(88)90594-2;
RA Nikai T., Imai K., Sugihara H., Tu A.T.;
RT "Isolation and characterization of horridum toxin with arginine ester
RT hydrolase activity from Heloderma horridum (beaded lizard) venom.";
RL Arch. Biochem. Biophys. 264:270-280(1988).
CC -!- FUNCTION: Has kallikrein-like activity, releases bradykinin from
CC kininogen. Catalyzes the hydrolysis of various arginine ester
CC substrates for trypsin and thrombin and degrades both angiotensin I and
CC II by cleavage of the dipeptide Asp-Arg from the NH2-terminal end.
CC Fibrinogen is also degraded but a fibrin clot is not produced. May have
CC a potentiating effect on potent hemorrhagic toxins present in the
CC venom. {ECO:0000269|PubMed:8408054}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the mandibular venom gland.
CC -!- PTM: Extensively glycosylated, contains approximately 8 mol of
CC monosaccharide per mol of toxin. {ECO:0000269|PubMed:8408054}.
CC -!- TOXIC DOSE: LD(50) is 2.5 mg/kg of body weight by intravenous injection
CC into mice. {ECO:0000269|PubMed:8408054}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
CC -!- CAUTION: There is a significant difference between sequences of
CC PubMed:20631207 and PubMed:8408054. The sequence of PubMed:8408054 may
CC contain multiple errors since its last cysteine is absent from all
CC other lizard toxin sequences and an insertion of 6 amino acids is
CC present that is missing in other varanid lizard kallikrein toxins.
CC {ECO:0000305}.
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DR EMBL; HM437246; ADK55606.1; -; mRNA.
DR PIR; A48598; A48598.
DR AlphaFoldDB; P43685; -.
DR SMR; P43685; -.
DR MEROPS; S01.435; -.
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; -; 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 Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase;
KW Protease; Secreted; Serine protease; Toxin.
FT CHAIN 1..230
FT /note="Gilatoxin"
FT /id="PRO_0000088723"
FT DOMAIN 1..230
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 41
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 93
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 187
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT CARBOHYD 84
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 7..146
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 26..42
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 125..193
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 157..172
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 183..208
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT CONFLICT 26
FT /note="C -> W (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 33
FT /note="Q -> R (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 37
FT /note="V -> L (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 43..58
FT /note="FYLGELRIGLGVHNRR -> EELGPMKICFGMKNRN (in Ref. 2; AA
FT sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 63
FT /note="N -> D (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 67..71
FT /note="RVSAR -> KVAAV (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 80..94
FT /note="SIITNSSCSEYTDDI -> GTIYNCNYVNTVLMNNDLLKRELFP (in
FT Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 104..106
FT /note="EYT -> DYN (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 110
FT /note="R -> A (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 121
FT /note="E -> L (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 126..128
FT /note="TVM -> SVL (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 136
FT /note="P -> D (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 140..142
FT /note="YPA -> LPD (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 148
FT /note="R -> N (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 151..152
FT /note="ML -> IF (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 158..159
FT /note="EL -> QV (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 165..170
FT /note="NITDSV -> KFTNK (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 175..176
FT /note="TW -> VD (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 192..195
FT /note="ICRG -> VCDN (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 200
FT /note="I -> N (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 204
FT /note="Missing (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 207
FT /note="P -> N (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 211..224
FT /note="PLEYGVYTKVISFL -> GEKYGYIKLIKFN (in Ref. 2; AA
FT sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 229
FT /note="S -> N (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 230
FT /note="I -> IIQGGTTCP (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 230 AA; 25111 MW; B5816AC9F2EB1484 CRC64;
IIGGQECDET GHPWLALLHR SEGSTCSGVL LNQDWIVTAA HCFYLGELRI GLGVHNRRVL
RGNEQVRVSA RKKCYPATAS IITNSSCSEY TDDIMLIKLD SSVEYTERVR PLSLPTSPAS
EGAECTVMGW GTTTPPDVTY PAVPVCVRIE MLNNAVCELA RDLWNITDSV LCAGTWFGGK
DSCKGDSGGP LICRGQLTGI VSWGGFPCEQ PLEYGVYTKV ISFLFWIQSI
