PA2_HETLA
ID PA2_HETLA Reviewed; 167 AA.
AC P0DMI6;
DT 14-MAY-2014, integrated into UniProtKB/Swiss-Prot.
DT 14-MAY-2014, sequence version 1.
DT 03-AUG-2022, entry version 24.
DE RecName: Full=Phospholipase A2 heteromtoxin {ECO:0000303|PubMed:23142507};
DE Short=HmTx {ECO:0000303|PubMed:23142507};
DE Contains:
DE RecName: Full=Heteromtoxin large subunit {ECO:0000303|PubMed:23142507};
DE EC=3.1.1.4;
DE Contains:
DE RecName: Full=Heteromtoxin small subunit {ECO:0000303|PubMed:23142507};
DE Flags: Precursor;
OS Heterometrus laoticus (Thai giant scorpion).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Iurida; Scorpionoidea; Scorpionidae; Heterometrinae;
OC Heterometrus.
OX NCBI_TaxID=217256;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 62-77, MASS SPECTROMETRY,
RP CATALYTIC ACTIVITY, AND 3D-STRUCTURE MODELING.
RC TISSUE=Venom, and Venom gland;
RX PubMed=23142507; DOI=10.1016/j.toxicon.2012.10.012;
RA Incamnoi P., Patramanon R., Thammasirirak S., Chaveerach A., Uawonggul N.,
RA Sukprasert S., Rungsa P., Daduang J., Daduang S.;
RT "Heteromtoxin (HmTx), a novel heterodimeric phospholipase A(2) from
RT Heterometrus laoticus scorpion venom.";
RL Toxicon 61:62-71(2013).
CC -!- FUNCTION: Phospholipase toxin, which catalyzes the calcium-dependent
CC hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides. Inhibits
CC both skeletal (RYR1) and cardiac (RYR2) ryanodine receptors (calcium
CC release channels). Probably blocks ryanodine receptors by generating a
CC lipid product (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-
CC glycero-3-phosphocholine + a fatty acid + H(+); Xref=Rhea:RHEA:15801,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868,
CC ChEBI:CHEBI:57643, ChEBI:CHEBI:58168; EC=3.1.1.4;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10035,
CC ECO:0000269|PubMed:23142507};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC Note=Binds 1 Ca(2+) ion. {ECO:0000250};
CC -!- SUBUNIT: Heterodimer composed of a large and a small subunits;
CC disulfide-linked.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- MASS SPECTROMETRY: Mass=14018.4; Mass_error=23.2; Method=MALDI;
CC Note=The measured ranges are 32-135, 141-167.;
CC Evidence={ECO:0000269|PubMed:23142507};
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. Group III
CC subfamily. {ECO:0000305}.
CC -!- CAUTION: In contrast to other phospholipases, it lacks the typical Asp
CC active site (Asp->Glu in position 93). {ECO:0000305}.
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DR AlphaFoldDB; P0DMI6; -.
DR SMR; P0DMI6; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005246; F:calcium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004623; F:phospholipase A2 activity; IEA:UniProtKB-EC.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0050482; P:arachidonic acid secretion; IEA:InterPro.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006644; P:phospholipid metabolic process; IEA:InterPro.
DR Gene3D; 1.20.90.10; -; 1.
DR InterPro; IPR016090; PLipase_A2_dom.
DR InterPro; IPR036444; PLipase_A2_dom_sf.
DR InterPro; IPR033113; PLipase_A2_His_AS.
DR Pfam; PF05826; Phospholip_A2_2; 1.
DR SUPFAM; SSF48619; SSF48619; 1.
DR PROSITE; PS00118; PA2_HIS; 1.
PE 1: Evidence at protein level;
KW Calcium; Calcium channel impairing toxin; Direct protein sequencing;
KW Disulfide bond; Hydrolase; Ion channel impairing toxin; Lipid degradation;
KW Lipid metabolism; Metal-binding; Neurotoxin;
KW Ryanodine-sensitive calcium-release channel impairing toxin; Secreted;
KW Signal; Toxin; Zymogen.
FT SIGNAL 1..?
FT PROPEP ?..31
FT /id="PRO_0000429182"
FT CHAIN 32..135
FT /note="Heteromtoxin large subunit"
FT /id="PRO_0000429183"
FT PROPEP 136..140
FT /id="PRO_0000429184"
FT CHAIN 141..167
FT /note="Heteromtoxin small subunit"
FT /id="PRO_0000429185"
FT ACT_SITE 64
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10035"
FT BINDING 38
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P00630"
FT BINDING 40
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P00630"
FT BINDING 42
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P00630"
FT BINDING 65
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P00630"
FT DISULFID 39..61
FT /evidence="ECO:0000250|UniProtKB:Q6T178"
FT DISULFID 60..99
FT /evidence="ECO:0000250|UniProtKB:Q6T178"
FT DISULFID 67..92
FT /evidence="ECO:0000250|UniProtKB:Q6T178"
FT DISULFID 90..127
FT /evidence="ECO:0000250|UniProtKB:Q6T178"
FT DISULFID 132..144
FT /note="Interchain (between large and small chains)"
FT /evidence="ECO:0000250|UniProtKB:Q6T178"
FT CONFLICT 72
FT /note="A -> S (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 74
FT /note="E -> Q (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 167 AA; 18200 MW; 4747FD93B690A038 CRC64;
MHTPKHAIRR MSKGEMEFFE GRCQRMGEAE RTVWGTKWCG SGNEATSGID LGYFKNLDSC
CRTHDHCDNI PAGETKYGLT NEGIYTMMNC KCESVFKQCL KDVTGVFEGP AAAAVRKIYF
DLYGNGCYSV QCPAGGRSAR TGGCPNGVAT YTGETGYGAW LLNKANG
