CA12A_CONRE
ID CA12A_CONRE Reviewed; 66 AA.
AC P85013; S0BDZ3;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-2017, sequence version 2.
DT 25-MAY-2022, entry version 48.
DE RecName: Full=Alpha-conotoxin RegIIA {ECO:0000303|PubMed:22108175};
DE AltName: Full=Reg2a {ECO:0000303|PubMed:17153339};
DE Flags: Precursor;
OS Conus regius (Crown cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Stephanoconus.
OX NCBI_TaxID=101314;
RN [1]
RP PROTEIN SEQUENCE, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND AMIDATION
RP AT CYS-65.
RC TISSUE=Venom;
RX PubMed=17153339; DOI=10.1007/978-3-540-30880-5_4;
RA Franco A., Pisarewicz K., Moller C., Mora D., Fields G.B., Mari F.;
RT "Hyperhydroxylation: a new strategy for neuronal targeting by venomous
RT marine molluscs.";
RL Prog. Mol. Subcell. Biol. 43:83-103(2006).
RN [2]
RP PROTEIN SEQUENCE OF 50-65, NUCLEOTIDE SEQUENCE [GENOMIC DNA], SYNTHESIS OF
RP 50-65, FUNCTION, STRUCTURE BY NMR OF 50-65, DISULFIDE BOND, AMIDATION AT
RP CYS-65, AND MASS SPECTROMETRY.
RC TISSUE=Venom, and Venom duct;
RX PubMed=22108175; DOI=10.1016/j.bcp.2011.11.006;
RA Franco A., Kompella S.N., Akondi K.B., Melaun C., Daly N.L., Luetje C.W.,
RA Alewood P.F., Craik D.J., Adams D.J., Mari F.;
RT "RegIIA: an alpha4/7-conotoxin from the venom of Conus regius that potently
RT blocks alpha3beta4 nAChRs.";
RL Biochem. Pharmacol. 83:419-426(2012).
RN [3]
RP FUNCTION, AND SYNTHESIS OF 50-65.
RX PubMed=27646000; DOI=10.1074/jbc.m116.730804;
RA Cuny H., Kompella S.N., Tae H.S., Yu R., Adams D.J.;
RT "Key Structural Determinants in the Agonist Binding Loops of Human beta2
RT and beta4 Nicotinic Acetylcholine Receptor Subunits Contribute to
RT alpha3beta4 Subtype Selectivity of alpha-Conotoxins.";
RL J. Biol. Chem. 291:23779-23792(2016).
RN [4]
RP FUNCTION ON ALPHA-7/CHRNA7 NACHR, MUTAGENESIS OF HIS-54, 3D-STRUCTURE
RP MODELING, AND SYNTHESIS OF 50-65.
RX PubMed=30025921; DOI=10.1016/j.neuropharm.2018.07.019;
RA Yu J., Zhu X., Zhang L., Kudryavtsev D., Kasheverov I., Lei Y.,
RA Zhangsun D., Tsetlin V., Luo S.;
RT "Species specificity of rat and human alpha7 nicotinic acetylcholine
RT receptors towards different classes of peptide and protein antagonists.";
RL Neuropharmacology 139:226-237(2018).
CC -!- FUNCTION: Alpha-conotoxins act on postsynaptic membranes, they bind to
CC the nicotinic acetylcholine receptors (nAChR) and thus inhibit them.
CC This toxin inhibits alpha-3 containing subunit nAChR (alpha-beta-
CC 2/CHRNA3-CHRNB2 with IC(50)=33 nM (rat)/132.4 nM (human)), and alpha-3-
CC beta-4/CHRNA3-CHRNB4 with IC(50)=97 nM (rat)/45.6 nM (human)
CC (PubMed:22108175, PubMed:27646000). In addition, it also inhibits
CC alpha-7/CHRNA7 nAChR with IC(50)=103-210 nM (human)/41 nM (rat) nAChRs
CC (PubMed:22108175, PubMed:30025921). {ECO:0000269|PubMed:22108175,
CC ECO:0000269|PubMed:27646000, ECO:0000269|PubMed:30025921}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17153339}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000269|PubMed:17153339}.
CC -!- DOMAIN: The cysteine framework is I (CC-C-C). Alpha4/7 pattern.
CC {ECO:0000305}.
CC -!- MASS SPECTROMETRY: Mass=1664.9; Method=MALDI; Note=Monoisotopic mass.;
CC Evidence={ECO:0000269|PubMed:22108175};
CC -!- MISCELLANEOUS: Does not inhibit muscle (alpha-beta-gamma-delta) and
CC neuronal alpha-4-beta-2 and alpha-9-alpha-10 nAChRs.
CC {ECO:0000269|PubMed:22108175}.
CC -!- SIMILARITY: Belongs to the conotoxin A superfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CCB84446.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; FR871900; CCB84446.1; ALT_TERM; Genomic_DNA.
DR AlphaFoldDB; P85013; -.
DR BMRB; P85013; -.
DR ConoServer; 32; RegIIA.
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 Acetylcholine receptor inhibiting toxin; Amidation;
KW Cleavage on pair of basic residues; Direct protein sequencing;
KW Disulfide bond; Ion channel impairing toxin; Neurotoxin;
KW Postsynaptic neurotoxin; Secreted; Signal; Toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..49
FT /evidence="ECO:0000269|PubMed:17153339"
FT /id="PRO_0000439620"
FT PEPTIDE 50..65
FT /note="Alpha-conotoxin RegIIA"
FT /evidence="ECO:0000269|PubMed:17153339"
FT /id="PRO_0000259389"
FT REGION 53..55
FT /note="Ser-Xaa-Pro motif, crucial for potent interaction
FT with nAChR"
FT /evidence="ECO:0000250|UniProtKB:P56636"
FT MOD_RES 65
FT /note="Cysteine amide"
FT /evidence="ECO:0000269|PubMed:17153339,
FT ECO:0000269|PubMed:22108175"
FT DISULFID 51..57
FT /evidence="ECO:0000269|PubMed:22108175"
FT DISULFID 52..65
FT /evidence="ECO:0000269|PubMed:22108175"
FT MUTAGEN 54
FT /note="H->D: Decrease in inhibition potency of AChR alpha-
FT 7/CHRNA7 (2.5-fold on rat receptor and 65-fold on human
FT receptor)."
FT /evidence="ECO:0000269|PubMed:30025921"
SQ SEQUENCE 66 AA; 7038 MW; 439508E036B7A6BA CRC64;
MGMRMMFTVF LLVVLTTTVV SSTSVRASDG RNAAADNRAS DLIAQIVRRG CCSHPACNVN
NPHICG
