Reviewed, UniProtKB/Swiss-Prot P50984 (CXAA_CONPE)

Names and origin

Protein names	Recommended name:     Alpha-conotoxin PnIA       Short name=Alpha-PnIA
Organism	Conus pennaceus (Feathered cone)
Taxonomic identifier	37335 [NCBI]
Taxonomic lineage	Eukaryota › Metazoa › Mollusca › Gastropoda › Orthogastropoda › Apogastropoda › Caenogastropoda › Sorbeoconcha › Hypsogastropoda › Neogastropoda › Conoidea › Conidae › Conus

Protein attributes

Sequence length	16 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin blocks mammalian nAChRs (alpha-3/beta-2 > alpha-7 > alpha-3/beta-4). Ref.1 Ref.3
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom duct.
Miscellaneous	PnIA[A10L] corresponds to PnIB[S55N], whereas PnIA[N11S] corresponds to PnIB[L54A].
Sequence similarities	Belongs to the conotoxin A superfamily. Alpha-type family.

Ontologies

Keywords
Cellular component	Secreted
Molecular function	Acetylcholine receptor inhibitor Neurotoxin Postsynaptic neurotoxin Toxin
PTM	Amidation Disulfide bond Sulfation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	pathogenesis Inferred from electronic annotation. Source: UniProtKB-KW synaptic transmission Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	acetylcholine receptor inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Peptide

1 – 16

16

Alpha-conotoxin PnIA

PRO_0000044462

Amino acid modifications

Modified residue

15

1

Sulfotyrosine

Modified residue

16

1

Cysteine amide Ref.1

Disulfide bond

2 ↔ 8

Ref.1 Ref.4

Disulfide bond

3 ↔ 16

Ref.1 Ref.4

Experimental info

Mutagenesis

10

1

A → L: Blocks nAChr alpha-7 subunits with higher potency than PnIA and PnIB. Blocks nAChR alpha-3/beta-2 subunits with a potency range between the potency of PnIA and PnIB. Ref.3

Mutagenesis

11

1

N → S: Blocks nAChR alpha-7 subunits with lower potency than PnIA and PnIB. Blocks nAChR alpha-3/beta-2 subunits with a potency range between the potency of PnIA and PnIB. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

16

Helix Strand Turn

Details...

Helix

2 – 4

3

Helix

6 – 11

6

Turn

13 – 15

3

Sequences

	Sequence		Length	Mass (Da)
	P50984-1 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 05310FF95EC99005	FASTA	16	1,628
	10 GCCSLPPCAA NNPDYC

References

[1]	"New mollusc-specific alpha-conotoxins block Aplysia neuronal acetylcholine receptors." Fainzilber M., Hasson A., Oren R., Burlingame A.L., Gordon D., Spira M.E., Zlotkin E. Biochemistry 33:9523-9529(1994) [PubMed: 8068627] [Abstract] Cited for: PROTEIN SEQUENCE, FUNCTION. Tissue: Venom.
[2]	"Identification of tyrosine sulfation in Conus pennaceus conotoxins alpha-PnIA and alpha-PnIB: further investigation of labile sulfo- and phosphopeptides by electrospray, matrix-assisted laser desorption/ionization (MALDI) and atmospheric pressure MALDI mass spectrometry." Wolfender J.L., Chu F., Ball H., Wolfender F., Fainzilber M., Baldwin M.A., Burlingame A.L. J. Mass Spectrom. 34:447-454(1999) [PubMed: 10226369] [Abstract] Cited for: SULFATION AT TYR-15.
[3]	"Single-residue alteration in alpha-conotoxin PnIA switches its nAChR subtype selectivity." Luo S., Nguyen T.A., Cartier G.E., Olivera B.M., Yoshikami D., McIntosh J.M. Biochemistry 38:14542-14548(1999) [PubMed: 10545176] [Abstract] Cited for: FUNCTION, SYNTHESIS, MUTAGENESIS OF ALA-10 AND ASN-11.
[4]	"The 1.1 A crystal structure of the neuronal acetylcholine receptor antagonist, alpha-conotoxin PnIA from Conus pennaceus." Hu S.-H., Gehrmann J., Guddat L.W., Alewood P.F., Craik D.J., Martin J.L. Structure 4:417-423(1996) [PubMed: 8740364] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS), DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

PIR

A54877.

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1PEN	X-ray	1.10	A	1-16	[»]
2BR8	X-ray	2.40	F/G/H/I/J	1-16	[»]

ModBase

Search...

Family and domain databases

InterPro

IPR018072. Conotoxin_a-typ_CS.
[Graphical view]

PROSITE

PS60014. ALPHA_CONOTOXIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

CXAA_CONPE

Accession

Primary (citable) accession number: P50984

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	June 16, 2009
This is version 56 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)