CA1B_CONPE
ID CA1B_CONPE Reviewed; 61 AA.
AC P50985; Q9BP57;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 16-JAN-2004, sequence version 2.
DT 25-MAY-2022, entry version 102.
DE RecName: Full=Alpha-conotoxin PnIB {ECO:0000303|PubMed:10226369, ECO:0000303|PubMed:10545176, ECO:0000303|PubMed:8068627, ECO:0000303|PubMed:9298951};
DE Flags: Precursor;
OS Conus pennaceus (Feathered cone) (Conus episcopus).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Darioconus.
OX NCBI_TaxID=37335;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11158371; DOI=10.1093/oxfordjournals.molbev.a003786;
RA Conticello S.G., Gilad Y., Avidan N., Ben-Asher E., Levy Z., Fainzilber M.;
RT "Mechanisms for evolving hypervariability: the case of conopeptides.";
RL Mol. Biol. Evol. 18:120-131(2001).
RN [2]
RP PROTEIN SEQUENCE OF 45-60, AND AMIDATION AT CYS-60.
RC TISSUE=Venom;
RX PubMed=8068627; DOI=10.1021/bi00198a018;
RA Fainzilber M., Hasson A., Oren R., Burlingame A.L., Gordon D., Spira M.E.,
RA Zlotkin E.;
RT "New mollusc-specific alpha-conotoxins block Aplysia neuronal acetylcholine
RT receptors.";
RL Biochemistry 33:9523-9529(1994).
RN [3]
RP FUNCTION, SYNTHESIS OF 45-60, AND MUTAGENESIS OF LEU-54 AND SER-55.
RX PubMed=10545176; DOI=10.1021/bi991252j;
RA Luo S., Nguyen T.A., Cartier G.E., Olivera B.M., Yoshikami D.,
RA McIntosh J.M.;
RT "Single-residue alteration in alpha-conotoxin PnIA switches its nAChR
RT subtype selectivity.";
RL Biochemistry 38:14542-14548(1999).
RN [4]
RP SULFATION AT TYR-59.
RX PubMed=10226369;
RX DOI=10.1002/(sici)1096-9888(199904)34:4<447::aid-jms801>3.0.co;2-1;
RA Wolfender J.L., Chu F., Ball H., Wolfender F., Fainzilber M., Baldwin M.A.,
RA Burlingame A.L.;
RT "Identification of tyrosine sulfation in Conus pennaceus conotoxins alpha-
RT PnIA and alpha-PnIB: further investigation of labile sulfo- and
RT phosphopeptides by electrospray, matrix-assisted laser
RT desorption/ionization (MALDI) and atmospheric pressure MALDI mass
RT spectrometry.";
RL J. Mass Spectrom. 34:447-454(1999).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.1 ANGSTROMS) OF 45-60, AND DISULFIDE BONDS.
RX PubMed=9298951; DOI=10.1021/bi9713052;
RA Hu S.H., Gehrmann J., Alewood P.F., Craik D.J., Martin J.L.;
RT "Crystal structure at 1.1-A resolution of alpha-conotoxin PnIB: comparison
RT with alpha-conotoxins PnIA and GI.";
RL Biochemistry 36:11323-11330(1997).
CC -!- FUNCTION: Alpha-conotoxins act on postsynaptic membranes, they bind to
CC the nicotinic acetylcholine receptors (nAChR) and thus inhibit them.
CC This toxin blocks mammalian nAChRs (alpha-7 > alpha-3/beta-2).
CC {ECO:0000269|PubMed:10545176}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC -!- DOMAIN: The cysteine framework is I (CC-C-C). Alpha4/7 pattern.
CC -!- SIMILARITY: Belongs to the conotoxin A superfamily. {ECO:0000305}.
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DR EMBL; AF215088; AAG60509.1; -; mRNA.
DR PIR; B54877; B54877.
DR PDB; 1AKG; X-ray; 1.10 A; A=45-60.
DR PDBsum; 1AKG; -.
DR AlphaFoldDB; P50985; -.
DR SMR; P50985; -.
DR ConoServer; 36; PnIB precursor.
DR EvolutionaryTrace; P50985; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0035792; C:host cell postsynaptic membrane; IEA:UniProtKB-KW.
DR GO; GO:0030550; F:acetylcholine receptor inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0099106; F:ion channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR009958; Conotoxin_a-typ.
DR InterPro; IPR018072; Conotoxin_a-typ_CS.
DR Pfam; PF07365; Toxin_8; 1.
DR PROSITE; PS60014; ALPHA_CONOTOXIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylcholine receptor inhibiting toxin; Amidation;
KW Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Neurotoxin; Postsynaptic neurotoxin; Secreted; Signal; Sulfation; Toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..44
FT /evidence="ECO:0000269|PubMed:8068627"
FT /id="PRO_0000034883"
FT PEPTIDE 45..60
FT /note="Alpha-conotoxin PnIB"
FT /evidence="ECO:0000269|PubMed:8068627"
FT /id="PRO_0000034884"
FT REGION 48..50
FT /note="Ser-Xaa-Pro motif, crucial for potent interaction
FT with nAChR"
FT /evidence="ECO:0000250|UniProtKB:P56636"
FT SITE 54
FT /note="Important in inhibition of nAChR alpha-7 subunit"
FT /evidence="ECO:0000305|PubMed:10545176"
FT MOD_RES 59
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000269|PubMed:10226369"
FT MOD_RES 60
FT /note="Cysteine amide"
FT /evidence="ECO:0000269|PubMed:8068627"
FT DISULFID 46..52
FT /evidence="ECO:0000269|PubMed:9298951"
FT DISULFID 47..60
FT /evidence="ECO:0000269|PubMed:9298951"
FT MUTAGEN 54
FT /note="L->A: 28-fold decrease in inhibition potency of
FT nAChr alpha-7 subunits and 8-fold increase in inhibition
FT potency of nAChr alpha-3-beta-2 subunits."
FT /evidence="ECO:0000269|PubMed:10545176"
FT MUTAGEN 55
FT /note="S->N: 5-fold increase in inhibition potency of nAChr
FT alpha-7 subunits and 20-fold increase in inhibition potency
FT of nAChr alpha-3-beta-2 subunits."
FT /evidence="ECO:0000269|PubMed:10545176"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:1AKG"
FT HELIX 50..55
FT /evidence="ECO:0007829|PDB:1AKG"
FT TURN 57..59
FT /evidence="ECO:0007829|PDB:1AKG"
SQ SEQUENCE 61 AA; 6363 MW; 42E0033324D66922 CRC64;
MGMRMMFTVF LLVVLATTVV SFTSDRASDD GNAAASDLIA LTIKGCCSLP PCALSNPDYC
G
