Reviewed, UniProtKB/Swiss-Prot P50985 (CXAB_CONPE)

Names and origin

Protein names	Recommended name:     Alpha-conotoxin PnIB
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	61 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
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-7 > alpha-3/beta-2). Ref.3
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom duct.
Miscellaneous	PnIB[L54A] corresponds to PnIA[N11S], whereas PnIB[S55N] corresponds to PnIA[A10L].
Sequence similarities	Belongs to the conotoxin A superfamily. Alpha-type family.

Ontologies

Keywords
Cellular component	Secreted
Domain	Signal
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

Signal peptide

1 – 21

21

Potential

Propeptide

22 – 44

23

Ref.2

PRO_0000034883

Peptide

45 – 60

16

Alpha-conotoxin PnIB

PRO_0000034884

Sites

Site

54

1

Direct interaction with nAChR alpha-7 subunit

Amino acid modifications

Modified residue

59

1

Sulfotyrosine

Modified residue

60

1

Cysteine amide

Disulfide bond

46 ↔ 52

Ref.5

Disulfide bond

47 ↔ 60

Ref.5

Experimental info

Mutagenesis

54

1

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

Mutagenesis

55

1

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

Secondary structure

1

.

.

.

.

.

.

.

61

Helix Strand Turn

Details...

Helix

46 – 48

3

Helix

50 – 55

6

Turn

57 – 59

3

Sequences

	Sequence		Length	Mass (Da)
	P50985-1 [UniParc]. Last modified January 16, 2004. Version 2. Checksum: 42E0033324D66922	FASTA	61	6,363
	10 20 30 40 50 60 MGMRMMFTVF LLVVLATTVV SFTSDRASDD GNAAASDLIA LTIKGCCSLP PCALSNPDYC G

References

[1]	"Mechanisms for evolving hypervariability: the case of conopeptides." Conticello S.G., Gilad Y., Avidan N., Ben-Asher E., Levy Z., Fainzilber M. Mol. Biol. Evol. 18:120-131(2001) [PubMed: 11158371] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"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 OF 45-60. Tissue: Venom.
[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 LEU-54 AND SER-55.
[4]	"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-59.
[5]	"Crystal structure at 1.1-A resolution of alpha-conotoxin PnIB: comparison with alpha-conotoxins PnIA and GI." Hu S.H., Gehrmann J., Alewood P.F., Craik D.J., Martin J.L. Biochemistry 36:11323-11330(1997) [PubMed: 9298951] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.1 ANGSTROMS) OF 45-60, DISULFIDE BONDS.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF215088 mRNA. Translation: AAG60509.1.

PIR

B54877.

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AKG	X-ray	1.10	A	45-60	[»]

ModBase

Search...

Family and domain databases

InterPro

IPR009958. Conotoxin_a-typ.
IPR018072. Conotoxin_a-typ_CS.
[Graphical view]

Pfam

PF07365. Toxin_8. 1 hit.
[Graphical view]

PROSITE

PS60014. ALPHA_CONOTOXIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

CXAB_CONPE

Accession

Primary (citable) accession number: P50985
Secondary accession number(s): Q9BP57

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	January 16, 2004
Last modified:	June 16, 2009
This is version 64 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)