LV1B_MESMA
ID LV1B_MESMA Reviewed; 94 AA.
AC Q95P90; A1YAC9; A2ICL8; Q3HM34;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 15-JUN-2010, sequence version 2.
DT 25-MAY-2022, entry version 54.
DE RecName: Full=HMG-CoA reductase inhibitor bumarsin;
DE AltName: Full=JCH2;
DE AltName: Full=Lipolysis-activating peptide 1-beta chain;
DE Short=BmLVP1-beta;
DE Short=LVP1-beta;
DE AltName: Full=Neurotoxin KITx;
DE Short=BmKITx;
DE AltName: Full=Putative toxin BmKTXLP2;
DE Flags: Precursor;
OS Mesobuthus martensii (Manchurian scorpion) (Buthus martensii).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Mesobuthus.
OX NCBI_TaxID=34649;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 23-52, SUBUNIT, VARIANT
RP GLU-94, IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=22575281; DOI=10.1016/j.toxicon.2012.04.352;
RA Chai S.C., Armugam A., Strong P.N., Jeyaseelan K.;
RT "Characterization of bumarsin, a 3-hydroxy-3-methylglutaryl-coenzyme
RT reductase inhibitor from Mesobuthus martensii Karsch venom.";
RL Toxicon 60:272-279(2012).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLU-94.
RC TISSUE=Venom gland;
RX PubMed=11923087; DOI=10.1016/s1096-4959(02)00020-9;
RA Zhu S.-Y., Li W.-X.;
RT "Precursors of three unique cysteine-rich peptides from the scorpion Buthus
RT martensii Karsch.";
RL Comp. Biochem. Physiol. 131B:749-756(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], RNA EDITING OF POSITION 34, AND VARIANTS SER-56
RP AND GLU-94.
RC TISSUE=Venom gland;
RX PubMed=16513212; DOI=10.1016/j.peptides.2006.01.012;
RA Zeng X.-C., Luo F., Li W.-X.;
RT "Molecular dissection of venom from Chinese scorpion Mesobuthus martensii:
RT identification and characterization of four novel disulfide-bridged venom
RT peptides.";
RL Peptides 27:1745-1754(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND RNA EDITING OF POSITION 34.
RX PubMed=17141763; DOI=10.1016/j.febslet.2006.11.040;
RA Zhu S., Gao B.;
RT "Molecular characterization of a new scorpion venom lipolysis activating
RT peptide: evidence for disulfide bridge-mediated functional switch of
RT peptides.";
RL FEBS Lett. 580:6825-6836(2006).
CC -!- FUNCTION: The homodimer inhibits HMG-CoA reductase (HMGCR) (32% of
CC inhibition produced by 0.6 uM), a glycoprotein involved in the control
CC of cholesterol biosynthesis. The inhibitory effects of bumarsin are
CC seen at much lower concentrations (0.6 uM) than that for statins such
CC as atorvastatin (5 mM) and simvastatin (10 uM). In addition to
CC inhibition of HMG-CoA reductase, this protein lowers cholesterol levels
CC by inducing steroid hormone synthesis via StAR, and by increasing
CC reverse cholesterol transport mediated by the induction of ABCA1 and
CC APOA1. {ECO:0000269|PubMed:22575281}.
CC -!- FUNCTION: The heterodimer non-edited LVP1 induces lipolysis in rat
CC adipocytes. Induction of lipolysis by LVP1 appears to be mediated
CC through the beta-2 adrenergic receptor pathway (ADRB2) (By similarity).
CC {ECO:0000250|UniProtKB:P84809}.
CC -!- FUNCTION: The monomer edited version, named BmKITx, similar to alpha-
CC toxins, may modulate voltage-gated sodium channels (Nav) and may block
CC voltage-gated potassium channels (Kv). {ECO:0000305}.
CC -!- SUBUNIT: Homodimer; disulfide-linked or monomer (edited version) or
CC heterodimer of an alpha chain (AC Q6WJF5) and this beta chain (non-
CC edited version). {ECO:0000269|PubMed:22575281}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:22575281}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:22575281}.
CC -!- RNA EDITING: Modified_positions=34 {ECO:0000269|PubMed:16513212,
CC ECO:0000269|PubMed:17141763}; Note=Partially edited. RNA editing at
CC this position consists of an insertion of three nucleotides, restoring
CC the first Cys residue that forms a disulfide bond with Cys-89, giving a
CC monomeric toxin with 4 disulfide bonds.;
CC -!- SIMILARITY: Belongs to the long (3 C-C) scorpion toxin superfamily.
CC {ECO:0000305}.
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DR EMBL; DQ872674; ABJ09778.1; -; Genomic_DNA.
DR EMBL; AF155368; AAK61818.1; -; mRNA.
DR EMBL; DQ208932; ABA61321.1; -; mRNA.
DR EMBL; EF193809; ABM73369.1; -; mRNA.
DR AlphaFoldDB; Q95P90; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0015459; F:potassium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0019871; F:sodium channel inhibitor activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-KW.
DR Gene3D; 3.30.30.10; -; 1.
DR InterPro; IPR044062; LCN-type_CS_alpha_beta_dom.
DR InterPro; IPR036574; Scorpion_toxin-like_sf.
DR InterPro; IPR002061; Scorpion_toxinL/defensin.
DR Pfam; PF00537; Toxin_3; 1.
DR SUPFAM; SSF57095; SSF57095; 1.
PE 1: Evidence at protein level;
KW Cholesterol biosynthesis; Cholesterol metabolism;
KW Direct protein sequencing; Disulfide bond;
KW G-protein coupled receptor impairing toxin; Ion channel impairing toxin;
KW Lipid biosynthesis; Lipid metabolism; Neurotoxin;
KW Potassium channel impairing toxin; RNA editing; Secreted; Signal;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism; Toxin; Voltage-gated potassium channel impairing toxin;
KW Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:22575281"
FT CHAIN 23..94
FT /note="HMG-CoA reductase inhibitor bumarsin"
FT /id="PRO_0000035363"
FT SITE 44
FT /note="Important for blocking potassium channels"
FT /evidence="ECO:0000250"
FT SITE 47
FT /note="Important for blocking potassium channels"
FT /evidence="ECO:0000250"
FT DISULFID 37..59
FT /evidence="ECO:0000250"
FT DISULFID 45..69
FT /evidence="ECO:0000250"
FT DISULFID 49..71
FT /evidence="ECO:0000250"
FT DISULFID 89
FT /note="Interchain (with C-90 in BmLVP1 chain alpha)"
FT /evidence="ECO:0000305"
FT VARIANT 34
FT /note="Y -> CD (in RNA edited version)"
FT VARIANT 56
FT /note="G -> S"
FT /evidence="ECO:0000269|PubMed:16513212"
FT VARIANT 94
FT /note="G -> E"
FT /evidence="ECO:0000269|PubMed:11923087,
FT ECO:0000269|PubMed:16513212, ECO:0000269|PubMed:22575281"
FT CONFLICT 7
FT /note="I -> F (in Ref. 3; ABA61321)"
FT /evidence="ECO:0000305"
FT CONFLICT 14
FT /note="V -> L (in Ref. 3; ABA61321)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 94 AA; 10477 MW; F232AE78BE2FF7E0 CRC64;
MVKMQVIFIA FIAVIACSMV YGDSLSPWNE GDTYYGCQRQ TDEFCNKICK LHLASGGSCQ
QPAPFVKLCT CQGIDYDNSF FFGALEKQCP KLRG
