TERT_APIME
ID TERT_APIME Reviewed; 21 AA.
AC P56587;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-1998, sequence version 1.
DT 25-MAY-2022, entry version 73.
DE RecName: Full=Tertiapin {ECO:0000303|Ref.1};
DE Short=TPN {ECO:0000303|PubMed:10572003};
OS Apis mellifera (Honeybee).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Hymenoptera; Apocrita; Aculeata; Apoidea; Apidae;
OC Apis.
OX NCBI_TaxID=7460;
RN [1]
RP PROTEIN SEQUENCE, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RA Ovchinnikov Y.A., Miroshnikov A.I., Kudelin A.B., Kostina M.B.,
RA Boikov V.A., Magazanik L.G., Gotgilf I.M.;
RT "Structure and presynaptic activity of tertiapin-neurotoxin from bee venom
RT Apis mellifera.";
RL Bioorg. Khim. 6:359-365(1980).
RN [2]
RP PROTEIN SEQUENCE, SYNTHESIS, FUNCTION, MASS SPECTROMETRY, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Venom;
RX PubMed=9748337; DOI=10.1021/bi981178p;
RA Jin W., Lu Z.;
RT "A novel high-affinity inhibitor for inward-rectifier K+ channels.";
RL Biochemistry 37:13291-13299(1998).
RN [3]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=6091685;
RA Miroshnikov A.I., Boikov V.A., Snezhkova L.G., Severin S.E., Shvets V.I.;
RT "Interaction of tertiapin, a neurotoxin from bee venom, with calmodulin.";
RL Bioorg. Khim. 9:26-32(1983).
RN [4]
RP SYNTHESIS, SUSCEPTIBILITY TO OXIDATION, AND MUTAGENESIS OF MET-13.
RX PubMed=10572003; DOI=10.1021/bi991205r;
RA Jin W., Lu Z.;
RT "Synthesis of a stable form of tertiapin: a high-affinity inhibitor for
RT inward-rectifier K+ channels.";
RL Biochemistry 38:14286-14293(1999).
RN [5]
RP FUNCTION, SYNTHESIS, AND ALANINE-SCANNING MUTAGENESIS.
RX PubMed=10572004; DOI=10.1021/bi991206j;
RA Jin W., Klem A.M., Lewis J.H., Lu Z.;
RT "Mechanisms of inward-rectifier K+ channel inhibition by tertiapin-Q.";
RL Biochemistry 38:14294-14301(1999).
RN [6]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=11015309; DOI=10.1038/sj.bjp.0703611;
RA Drici M.D., Diochot S., Terrenoire C., Romey G., Lazdunski M.;
RT "The bee venom peptide tertiapin underlines the role of I(KACh) in
RT acetylcholine-induced atrioventricular blocks.";
RL Br. J. Pharmacol. 131:569-577(2000).
RN [7]
RP FUNCTION.
RX PubMed=10734170;
RA Kitamura H., Yokoyama M., Akita H., Matsushita K., Kurachi Y., Yamada M.;
RT "Tertiapin potently and selectively blocks muscarinic K(+) channels in
RT rabbit cardiac myocytes.";
RL J. Pharmacol. Exp. Ther. 293:196-205(2000).
RN [8]
RP MUTAGENESIS OF HIS-12 AND MET-13.
RX PubMed=11297426; DOI=10.1021/bi002584n;
RA Ramu Y., Klem A.M., Lu Z.;
RT "Titration of tertiapin-Q inhibition of ROMK1 channels by extracellular
RT protons.";
RL Biochemistry 40:3601-3605(2001).
RN [9]
RP SYNTHESIS, AND FUNCTION OF TERTIAPIN-Q.
RX PubMed=15947038; DOI=10.1124/jpet.105.085928;
RA Kanjhan R., Coulson E.J., Adams D.J., Bellingham M.C.;
RT "Tertiapin-Q blocks recombinant and native large conductance K+ channels in
RT a use-dependent manner.";
RL J. Pharmacol. Exp. Ther. 314:1353-1361(2005).
RN [10]
RP FUNCTION.
RX PubMed=16725344; DOI=10.1016/j.phrs.2006.03.021;
RA Hashimoto N., Yamashita T., Tsuruzoe N.;
RT "Tertiapin, a selective I(KACh) blocker, terminates atrial fibrillation
RT with selective atrial effective refractory period prolongation.";
RL Pharmacol. Res. 54:136-141(2006).
RN [11]
RP SYNTHESIS, AND MUTAGENESIS OF ALA-1; HIS-12 AND MET-13.
RX PubMed=16906771; DOI=10.1021/bi060509s;
RA Felix J.P., Liu J., Schmalhofer W.A., Bailey T., Bednarek M.A., Kinkel S.,
RA Weinglass A.B., Kohler M., Kaczorowski G.J., Priest B.T., Garcia M.L.;
RT "Characterization of Kir1.1 channels with the use of a radiolabeled
RT derivative of tertiapin.";
RL Biochemistry 45:10129-10139(2006).
RN [12]
RP STRUCTURE BY NMR, AND DISULFIDE BOND.
RC TISSUE=Venom;
RX PubMed=8265561; DOI=10.1002/prot.340170203;
RA Xu X., Nelson J.W.;
RT "Solution structure of tertiapin determined using nuclear magnetic
RT resonance and distance geometry.";
RL Proteins 17:124-137(1993).
CC -!- FUNCTION: Presynaptic neurotoxin that blocks the inwardly rectifying
CC Kir1.1/KCNJ1 and Kir3.1/3.4 (KCNJ3/KCNJ5) potassium channels with high
CC affinity by binding to the M1-M2 linker region of these channels in a
CC 1:1 stoichiometry. It may block the potassium channel pore by occluding
CC its alpha helix into the channel vestibule. Tertiapin-Q also inhibits
CC calcium-activated large conductance BK-type (KCNMA) potassium channels
CC in a concentration-, and voltage-dependent manner, in addition to
CC inhibiting Kir3.1/3.2 (KCNJ3/KCNJ6) heteromultimers potassium channels.
CC It can prevent dose-dependently acetylcholine(ACh)-induced
CC atrioventricular blocks in mammalian hearts, as KCNJ3/KCNJ5 channels
CC (also named I(KACh), because these channels are activated by ACh) are
CC found in mammalian myocytes. Interacts specifically with calmodulin in
CC the presence of calcium. {ECO:0000269|PubMed:10572004,
CC ECO:0000269|PubMed:10734170, ECO:0000269|PubMed:11015309,
CC ECO:0000269|PubMed:16725344, ECO:0000269|PubMed:6091685,
CC ECO:0000269|PubMed:9748337}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:9748337,
CC ECO:0000269|Ref.1}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:9748337, ECO:0000305|Ref.1}.
CC -!- PTM: Oxidation of Met-13 results in the loss of biological activity.
CC {ECO:0000269|PubMed:10572003}.
CC -!- PTM: An amidation at Lys-21 is suggested in Ref.1. {ECO:0000305|Ref.1}.
CC -!- MASS SPECTROMETRY: Mass=2458; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:9748337};
CC -!- MISCELLANEOUS: Tertiapin-Q is a stable (non-oxidizable) and
CC functionally similar derivative of tertiapin whose Met-13 residue is
CC replaced with a Gln residue.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Tertiapin entry;
CC URL="https://en.wikipedia.org/wiki/Tertiapin";
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DR PDB; 1TER; NMR; -; A=1-21.
DR PDBsum; 1TER; -.
DR AlphaFoldDB; P56587; -.
DR SMR; P56587; -.
DR EvolutionaryTrace; P56587; -.
DR Proteomes; UP000005203; Unplaced.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0015459; F:potassium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR035361; Bee_toxin.
DR Pfam; PF17454; Bee_toxin; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium-activated potassium channel impairing toxin;
KW Calmodulin-binding; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Neurotoxin; Oxidation;
KW Potassium channel impairing toxin; Presynaptic neurotoxin;
KW Reference proteome; Secreted; Toxin.
FT PEPTIDE 1..21
FT /note="Tertiapin"
FT /evidence="ECO:0000269|PubMed:9748337, ECO:0000269|Ref.1"
FT /id="PRO_0000044539"
FT SITE 12
FT /note="Is responsible of pH dependence of the channel
FT block"
FT SITE 13
FT /note="Susceptible to oxidation"
FT /evidence="ECO:0000269|PubMed:10572003"
FT DISULFID 3..14
FT /evidence="ECO:0000269|PubMed:8265561,
FT ECO:0000312|PDB:1TER"
FT DISULFID 5..18
FT /evidence="ECO:0000269|PubMed:8265561,
FT ECO:0000312|PDB:1TER"
FT MUTAGEN 1
FT /note="A->Y: Inhibits with high affinity rat but not human
FT Kir1.1 channels stably expressed in HEK293 cells; when
FT associated with K-12 and Q-13."
FT /evidence="ECO:0000269|PubMed:16906771"
FT MUTAGEN 12
FT /note="H->K: Eliminates the pH dependence of the channel
FT block; when associated with Q-13. Inhibits with high
FT affinity rat but not human Kir1.1 channels stably expressed
FT in HEK293 cells; when associated with Y-1 and Q-13."
FT /evidence="ECO:0000269|PubMed:11297426,
FT ECO:0000269|PubMed:16906771"
FT MUTAGEN 13
FT /note="M->Q: Stable fully functional peptide. Inhibits with
FT high affinity rat but not human Kir1.1 channels stably
FT expressed in HEK293 cells; when associated with Y-1 and K-
FT 12."
FT /evidence="ECO:0000269|PubMed:10572003,
FT ECO:0000269|PubMed:11297426, ECO:0000269|PubMed:16906771"
FT STRAND 7..9
FT /evidence="ECO:0007829|PDB:1TER"
FT HELIX 12..19
FT /evidence="ECO:0007829|PDB:1TER"
SQ SEQUENCE 21 AA; 2460 MW; 7B3C2D5A490339B8 CRC64;
ALCNCNRIII PHMCWKKCGK K
