VKTA_MICTN
ID VKTA_MICTN Reviewed; 84 AA.
AC G9I929;
DT 18-APR-2012, integrated into UniProtKB/Swiss-Prot.
DT 22-FEB-2012, sequence version 1.
DT 25-MAY-2022, entry version 34.
DE RecName: Full=Kunitz-type neurotoxin MitTx-alpha {ECO:0000303|PubMed:22094702};
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 25-50 AND 59-67, FUNCTION,
RP SUBUNIT, AND PYROGLUTAMATE FORMATION AT GLN-25.
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 25-84 IN COMPLEX WITH MITTX-BETA
RP AND 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: 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
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 -!- 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 Asic2a-Asic3 heterotrimer, Kv2.1/KCNB1, Cav3.3/CACNA1I, ENaC
CC alpha/beta/gamma (SCNN1A/SCNN1B/SCNN1G), TRPA1, TRPV1, TRPV3, TRPM8,
CC P2X2/P2RX2, and 5-HT3/HTR3A channels. {ECO:0000305|PubMed:22094702}.
CC -!- SIMILARITY: Belongs to the venom Kunitz-type family. {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; JN613325; AET85559.1; -; mRNA.
DR PDB; 4NTW; X-ray; 2.07 A; B=25-84.
DR PDB; 4NTX; X-ray; 2.27 A; B=25-84.
DR PDB; 4NTY; X-ray; 2.65 A; B=25-84.
DR PDBsum; 4NTW; -.
DR PDBsum; 4NTX; -.
DR PDBsum; 4NTY; -.
DR AlphaFoldDB; G9I929; -.
DR SMR; G9I929; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0099106; F:ion channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR Gene3D; 4.10.410.10; -; 1.
DR InterPro; IPR002223; Kunitz_BPTI.
DR InterPro; IPR036880; Kunitz_BPTI_sf.
DR Pfam; PF00014; Kunitz_BPTI; 1.
DR SMART; SM00131; KU; 1.
DR SUPFAM; SSF57362; SSF57362; 1.
DR PROSITE; PS50279; BPTI_KUNITZ_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Protease inhibitor;
KW Proton-gated sodium channel impairing toxin; Pyrrolidone carboxylic acid;
KW Secreted; Serine protease inhibitor; Signal; Toxin.
FT SIGNAL 1..24
FT /evidence="ECO:0000269|PubMed:22094702"
FT CHAIN 25..84
FT /note="Kunitz-type neurotoxin MitTx-alpha"
FT /evidence="ECO:0000305|PubMed:22094702"
FT /id="PRO_5000828217"
FT DOMAIN 31..82
FT /note="BPTI/Kunitz inhibitor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT MOD_RES 25
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:22094702"
FT DISULFID 31..82
FT /evidence="ECO:0000269|PubMed:24507937,
FT ECO:0000312|PDB:4NTW, ECO:0000312|PDB:4NTX,
FT ECO:0000312|PDB:4NTY"
FT DISULFID 41..65
FT /evidence="ECO:0000269|PubMed:24507937,
FT ECO:0000312|PDB:4NTW, ECO:0000312|PDB:4NTX,
FT ECO:0000312|PDB:4NTY"
FT DISULFID 57..78
FT /evidence="ECO:0000269|PubMed:24507937,
FT ECO:0000312|PDB:4NTW, ECO:0000312|PDB:4NTX,
FT ECO:0000312|PDB:4NTY"
FT HELIX 29..32
FT /evidence="ECO:0007829|PDB:4NTW"
FT STRAND 45..51
FT /evidence="ECO:0007829|PDB:4NTW"
FT TURN 52..55
FT /evidence="ECO:0007829|PDB:4NTW"
FT STRAND 56..62
FT /evidence="ECO:0007829|PDB:4NTW"
FT STRAND 67..69
FT /evidence="ECO:0007829|PDB:4NTW"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:4NTW"
FT HELIX 75..83
FT /evidence="ECO:0007829|PDB:4NTW"
SQ SEQUENCE 84 AA; 9498 MW; 7D5C274A6ABDA89D CRC64;
MSSGGLLLLL GLLTLCAELT PVSSQIRPAF CYEDPPFFQK CGAFVDSYYF NRSRITCVHF
FYGQCDVNQN HFTTMSECNR VCHG
