PA2HB_MICTN
ID PA2HB_MICTN Reviewed; 149 AA.
AC G9I930;
DT 18-APR-2012, integrated into UniProtKB/Swiss-Prot.
DT 22-FEB-2012, sequence version 1.
DT 25-MAY-2022, entry version 36.
DE RecName: Full=Basic phospholipase A2 homolog MitTx-beta {ECO:0000303|PubMed:22094702};
DE Short=svPLA2 homolog {ECO:0000305};
DE Flags: Precursor;
OS Micrurus tener tener (Texas coral snake).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Elapinae; Micrurus.
OX NCBI_TaxID=1114302;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 31-46, FUNCTION, SUBUNIT,
RP 3D-STRUCTURE MODELING, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=22094702; DOI=10.1038/nature10607;
RA Bohlen C.J., Chesler A.T., Sharif-Naeini R., Medzihradszky K.F., Zhou S.,
RA King D., Sanchez E.E., Burlingame A.L., Basbaum A.I., Julius D.;
RT "A heteromeric Texas coral snake toxin targets acid-sensing ion channels to
RT produce pain.";
RL Nature 479:410-414(2011).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (2.07 ANGSTROMS) OF 31-148 IN COMPLEX MITTX-ALPHA AND
RP THE CHICKEN ASIC1 IN AN OPEN STATE, DISULFIDE BONDS, AND FUNCTION.
RX PubMed=24507937; DOI=10.1016/j.cell.2014.01.011;
RA Baconguis I., Bohlen C.J., Goehring A., Julius D., Gouaux E.;
RT "X-ray structure of acid-sensing ion channel 1-snake toxin complex reveals
RT open state of a Na(+)-selective channel.";
RL Cell 156:717-729(2014).
CC -!- FUNCTION: Heterodimer: MitTx, a heteromeric complex between Kunitz- and
CC phospholipase-A2-like proteins, potently, persistently and selectively
CC activates rat and chicken acid-sensing ion channel ASIC1
CC (PubMed:22094702, PubMed:24507937). Both alternatively spliced rat
CC isoforms ASIC1a and ASIC1b are activated, with a higher potency for
CC ASIC1a (EC(50)=9.4 nM) vs ASIC1b (EC(50)=23 nM) (PubMed:22094702). The
CC rat ASIC3 subtype is also sensitive to the heterodimer, but with a
CC lower potency (EC(50)=830 nM) (PubMed:22094702). On rat ASIC2a, the
CC toxin shows a very weak activation, but produces a remarkable
CC potentiation (>100-fold) of protons when the extracellular pH drops
CC below neutrality (PubMed:22094702). Moderate and weak activations are
CC also observed on the heterotrimers Asic1a-Asic2a and Asic1a-Asic3
CC (expressed in CHO cells), respectively (PubMed:22094702). The binding
CC sites of the beta subunit of MitTx and the spider psalmotoxin-1 toxin
CC overlap, explaining why these toxins are mutually exclusive
CC (PubMed:22094702. PubMed:24507937). In vivo, the heterodimer elicits
CC robust pain-related behavior in mice by activation of ASIC1 channels on
CC capsaicin-sensitive nerve fibers (PubMed:22094702).
CC {ECO:0000269|PubMed:22094702, ECO:0000269|PubMed:24507937}.
CC -!- FUNCTION: Monomer: does not have phospholipase A2 activity but may
CC maintain some lipid-binding character from its PLA2 lineage, which
CC could aid in effecting neuronal depolarization.
CC {ECO:0000305|PubMed:22094702}.
CC -!- SUBUNIT: Heterodimer of an alpha (Kunitz-type) and a beta
CC (phospholipase A2 homolog) chains; non-covalently-linked.
CC {ECO:0000269|PubMed:22094702}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:22094702}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:22094702}.
CC -!- DOMAIN: The toxin-channel complex has a triskelion-like shape with one
CC toxin heterodimer radiating from each ASIC1 subunit. Toxin subunits
CC protrude from the edges of the channel trimer, with each heterodimer
CC interacting almost exclusively with a single subunit.
CC {ECO:0000269|PubMed:24507937}.
CC -!- MISCELLANEOUS: The heterodimeric toxin does not affect ASIC2b, ASIC4,
CC Kv2.1/KCNB1, Cav3.3/CACNA1I, ENaC alpha/beta/gamma
CC (SCNN1A/SCNN1B/SCNN1G), TRPA1, TRPV1, TRPV3, TRPM8, P2X2/P2RX2, and 5-
CC HT3/HTR3A channels. {ECO:0000305|PubMed:22094702}.
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. Group I subfamily.
CC K49 sub-subfamily. {ECO:0000305}.
CC -!- CAUTION: Does not bind calcium as one of the calcium-binding sites is
CC lost (Asp->Lys in position 77, which corresponds to 'Lys-49' in the
CC current nomenclature). {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=The poison in pain - Issue
CC 140 of July 2012;
CC URL="https://web.expasy.org/spotlight/back_issues/140";
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DR EMBL; JN613326; AET85560.1; -; mRNA.
DR PDB; 4NTW; X-ray; 2.07 A; C=31-148.
DR PDB; 4NTX; X-ray; 2.27 A; C=31-148.
DR PDB; 4NTY; X-ray; 2.65 A; C=31-148.
DR PDBsum; 4NTW; -.
DR PDBsum; 4NTX; -.
DR PDBsum; 4NTY; -.
DR AlphaFoldDB; G9I930; -.
DR SMR; G9I930; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0099106; F:ion channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0004623; F:phospholipase A2 activity; IEA:InterPro.
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:InterPro.
DR GO; GO:0006644; P:phospholipid metabolic process; IEA:InterPro.
DR CDD; cd00125; PLA2c; 1.
DR Gene3D; 1.20.90.10; -; 1.
DR InterPro; IPR001211; PLipase_A2.
DR InterPro; IPR033112; PLipase_A2_Asp_AS.
DR InterPro; IPR016090; PLipase_A2_dom.
DR InterPro; IPR036444; PLipase_A2_dom_sf.
DR PANTHER; PTHR11716; PTHR11716; 1.
DR Pfam; PF00068; Phospholip_A2_1; 1.
DR PRINTS; PR00389; PHPHLIPASEA2.
DR SMART; SM00085; PA2c; 1.
DR SUPFAM; SSF48619; SSF48619; 1.
DR PROSITE; PS00119; PA2_ASP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Proton-gated sodium channel impairing toxin;
KW Secreted; Signal; Toxin.
FT SIGNAL 1..30
FT /evidence="ECO:0000269|PubMed:22094702"
FT CHAIN 31..149
FT /note="Basic phospholipase A2 homolog MitTx-beta"
FT /evidence="ECO:0000305|PubMed:22094702"
FT /id="PRO_5000828218"
FT DISULFID 41..100
FT /evidence="ECO:0000269|PubMed:24507937,
FT ECO:0000312|PDB:4NTW, ECO:0000312|PDB:4NTX,
FT ECO:0000312|PDB:4NTY"
FT DISULFID 55..148
FT /evidence="ECO:0000269|PubMed:24507937,
FT ECO:0000312|PDB:4NTW, ECO:0000312|PDB:4NTX,
FT ECO:0000312|PDB:4NTY"
FT DISULFID 57..73
FT /evidence="ECO:0000269|PubMed:24507937,
FT ECO:0000312|PDB:4NTW, ECO:0000312|PDB:4NTX,
FT ECO:0000312|PDB:4NTY"
FT DISULFID 72..130
FT /evidence="ECO:0000269|PubMed:24507937,
FT ECO:0000312|PDB:4NTW, ECO:0000312|PDB:4NTX,
FT ECO:0000312|PDB:4NTY"
FT DISULFID 79..123
FT /evidence="ECO:0000269|PubMed:24507937,
FT ECO:0000312|PDB:4NTW, ECO:0000312|PDB:4NTX,
FT ECO:0000312|PDB:4NTY"
FT DISULFID 89..116
FT /evidence="ECO:0000269|PubMed:24507937,
FT ECO:0000312|PDB:4NTW, ECO:0000312|PDB:4NTX,
FT ECO:0000312|PDB:4NTY"
FT DISULFID 109..121
FT /evidence="ECO:0000269|PubMed:24507937,
FT ECO:0000312|PDB:4NTW, ECO:0000312|PDB:4NTX,
FT ECO:0000312|PDB:4NTY"
FT HELIX 32..40
FT /evidence="ECO:0007829|PDB:4NTW"
FT HELIX 47..49
FT /evidence="ECO:0007829|PDB:4NTW"
FT TURN 50..52
FT /evidence="ECO:0007829|PDB:4NTW"
FT TURN 54..56
FT /evidence="ECO:0007829|PDB:4NTW"
FT HELIX 68..87
FT /evidence="ECO:0007829|PDB:4NTW"
FT TURN 91..93
FT /evidence="ECO:0007829|PDB:4NTW"
FT HELIX 104..106
FT /evidence="ECO:0007829|PDB:4NTW"
FT HELIX 115..133
FT /evidence="ECO:0007829|PDB:4NTW"
FT HELIX 138..140
FT /evidence="ECO:0007829|PDB:4NTX"
FT HELIX 145..147
FT /evidence="ECO:0007829|PDB:4NTW"
SQ SEQUENCE 149 AA; 16793 MW; 4CF027CBCA751BE4 CRC64;
MDKMNPAHLL VLAAVCVSLL GASSIPPQAL NLNQFRLMIK CTNDRVWADF VDYGCYCVAR
DSNTPVDDLD RCCQAQKQCY DEAVKVHGCK PLVMFYSFEC RYLASDLDCS GNNTKCRNFV
CNCDRTATLC ILTATYNRNN HKIDPSRCQ
