CA18_CONMR
ID CA18_CONMR Reviewed; 69 AA.
AC F5C3U4;
DT 03-SEP-2014, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 1.
DT 25-MAY-2022, entry version 29.
DE RecName: Full=Alpha-conotoxin Mr1.7a;
DE AltName: Full=Conotoxin Mr1.8;
DE Contains:
DE RecName: Full=Alpha-conotoxin MrIC;
DE AltName: Full=Mr1.7c;
DE Contains:
DE RecName: Full=Alpha-conotoxin Mr1.7b;
DE AltName: Full=Mr002;
DE Flags: Precursor;
OS Conus marmoreus (Marble cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Conus.
OX NCBI_TaxID=42752;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom duct;
RX PubMed=22781954; DOI=10.1016/j.toxicon.2012.06.011;
RA Liu Z., Li H., Liu N., Wu C., Jiang J., Yue J., Jing Y., Dai Q.;
RT "Diversity and evolution of conotoxins in Conus virgo, Conus eburneus,
RT Conus imperialis and Conus marmoreus from the South China Sea.";
RL Toxicon 60:982-989(2012).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND IDENTIFICATION BY MASS SPECTROMETRY OF
RP MR1.7B.
RC TISSUE=Venom, and Venom duct;
RX PubMed=23152539; DOI=10.1074/mcp.m112.021469;
RA Dutertre S., Jin A.H., Kaas Q., Jones A., Alewood P.F., Lewis R.J.;
RT "Deep venomics reveals the mechanism for expanded peptide diversity in cone
RT snail venom.";
RL Mol. Cell. Proteomics 12:312-329(2013).
RN [3]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY OF MR1.7A; MR1.7B AND MRIC,
RP SYNTHESIS OF 51-69; 52-68 AND 53-68, AND HYDROXYLATION AT PRO-52 AND
RP PRO-58.
RC TISSUE=Venom, and Venom duct;
RX PubMed=24351107; DOI=10.1021/bi400882s;
RA Jin A.H., Vetter I., Dutertre S., Abraham N., Emidio N.B., Inserra M.,
RA Murali S.S., Christie M.J., Alewood P.F., Lewis R.J.;
RT "MrIC, a novel alpha-conotoxin agonist in the presence of PNU at endogenous
RT alpha7 nicotinic acetylcholine receptors.";
RL Biochemistry 53:1-3(2014).
CC -!- FUNCTION: [Alpha-conotoxin MrIC]: Acts as a co-agonist with PNU (an
CC alpha-7 nAChR-selective allosteric modulator) at the endogenous alpha-
CC 7/CHRNA7 nicotinic acetylcholine receptors (nAChR) when tested in human
CC SH-SY5Y neuroblastoma cells. Is the third alpha-conotoxin that acts as
CC an agonist (after alpha-conotoxin SrIA/SrIB). Also acts as an
CC antagonist at human alpha-7 nAChRs heterologously expressed in Xenopus
CC oocytes (PubMed:24351107). Has possibly a distinct nAChR binding mode
CC from other alpha-conotoxins, due to a different three residue motif
CC (lacks the Ser-Xaa-Pro motif) (By similarity).
CC {ECO:0000250|UniProtKB:Q2I2R8, ECO:0000269|PubMed:24351107}.
CC -!- FUNCTION: [Alpha-conotoxin Mr1.7a]: Acts as a weak partial agonist at
CC alpha-7/CHRNA7 nicotinic acetylcholine receptors (nAChR) when tested in
CC human SH-SY5Y neuroblastoma cells (PubMed:24351107). Has possibly a
CC distinct nAChR binding mode from other alpha-conotoxins, due to a
CC different three residue motif (lacks the Ser-Xaa-Pro motif) (By
CC similarity). {ECO:0000250|UniProtKB:Q2I2R8,
CC ECO:0000269|PubMed:24351107}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:24351107}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:24351107}.
CC -!- DOMAIN: The cysteine framework is I (CC-C-C). Alpha4/7 pattern.
CC {ECO:0000305}.
CC -!- PTM: Two 4-hydroxyprolines have been detected by MS but the assignment
CC of which of the three prolines is modified is uncertain
CC (PubMed:23152539, and PubMed:24351107).
CC -!- MISCELLANEOUS: Neither MrIC, Mr1.7b, nor Mr1.7a inhibit alpha-7/CHRNA7,
CC alpha-3-beta-2/CHRNA3-CHRNB2 and alpha-3-beta-4/CHRNA3-CHRNB4 nAChRs
CC endogenously expressed in human SH-SY5Y neuroblastoma cells. MrIC does
CC not activate alpha-3-beta-2/CHRNA3-CHRNB2 and alpha-3-beta-4/CHRNA3-
CC CHRNB4 endogenously expressed in human SH-SY5Y neuroblastoma cells.
CC Mr1.7b does not activate alpha-7 endogenously expressed in human SH-
CC SY5Y neuroblastoma cells (PubMed:24351107).
CC {ECO:0000305|PubMed:24351107}.
CC -!- SIMILARITY: Belongs to the conotoxin A superfamily. {ECO:0000305}.
CC -!- CAUTION: The cDNA sequence of this peptide has been submitted (EMBL
CC entry JF460791) and described in PubMed:22781954 under the name Mr1.8.
CC {ECO:0000305}.
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DR EMBL; JF460791; ADZ99331.1; -; mRNA.
DR AlphaFoldDB; F5C3U4; -.
DR SMR; F5C3U4; -.
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:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR009958; Conotoxin_a-typ.
DR Pfam; PF07365; Toxin_8; 1.
PE 1: Evidence at protein level;
KW Acetylcholine receptor inhibiting toxin; Amidation;
KW Cleavage on pair of basic residues; Disulfide bond; Hydroxylation;
KW Neurotoxin; Postsynaptic neurotoxin; Secreted; Signal; Toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..49
FT /id="PRO_0000430174"
FT PEPTIDE 51..69
FT /note="Alpha-conotoxin Mr1.7b"
FT /id="PRO_0000430175"
FT PEPTIDE 52..68
FT /note="Alpha-conotoxin MrIC"
FT /id="PRO_0000430176"
FT PEPTIDE 53..68
FT /note="Alpha-conotoxin Mr1.7a"
FT /id="PRO_0000430177"
FT REGION 56..58
FT /note="Lacks the Ser-Xaa-Pro motif that is crucial for
FT potent interaction with nAChR"
FT /evidence="ECO:0000305"
FT MOD_RES 52
FT /note="4-hydroxyproline; in Mr1.7b"
FT /evidence="ECO:0000269|PubMed:24351107"
FT MOD_RES 58
FT /note="4-hydroxyproline; in Mr1.7b"
FT /evidence="ECO:0000269|PubMed:24351107"
FT MOD_RES 68
FT /note="Cysteine amide"
FT /evidence="ECO:0000250"
FT DISULFID 54..60
FT /evidence="ECO:0000250|UniProtKB:P56636"
FT DISULFID 55..68
FT /evidence="ECO:0000250|UniProtKB:P56636"
FT VARIANT 69
FT /note="G -> S (in Mr1.7b)"
SQ SEQUENCE 69 AA; 7580 MW; B818681272597A55 CRC64;
MGMRMMFTVF LLVVLATTVV SFTSNRVLDP AFRRRNAAAK ASDLIALNAR RPECCTHPAC
HVSNPELCG
