P01501 (MEL_APIME) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Melittin

Alternative name(s):
Allergen Api m 3
Allergen Api m III
Allergen=Api m 4

Gene names

Name:

MELT

Organism

Apis mellifera (Honeybee) [Reference proteome]

Taxonomic identifier

7460 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Panarthropoda › Arthropoda › Mandibulata › Pancrustacea › Hexapoda › Insecta › Dicondylia › Pterygota › Neoptera › Endopterygota › Hymenoptera › Apocrita › Aculeata › Apoidea › Apidae › Apinae › Apini › Apis

Protein attributes

Sequence length	70 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	Melittin: Main toxin of bee venom with strong hemolytic activity. Forms a pore in the cell membrane by inserting into lipid bilayers in an alpha-helical conformation and has multiple effects, probably, as a result of its interaction with negatively charged phospholipids. It inhibits well known transport pumps such as the Na+-K+-ATPase and the H+-K+-ATPase. It increases the permeability of cell membranes to ions, particularly Na+ and indirectly Ca2+, because of the Na+-Ca2+-exchange. It acts synergistically with phospholipase A2. Ref.3 Melittin-S: 1.4-fold less hemolytic and adopts a less organized secondary structure than melittin. Ref.3
Subunit structure	Monomer and homotetramer.
Subcellular location	Secreted. Target cell membrane. Note: Forms a transmembrane alpha-helix in the target cell membrane. Forms a membrane channel in the prey.
Tissue specificity	Expressed by the venom gland.
Allergenic properties	Causes an allergic reaction in human.
Toxic dose	LC50 is 2.7 µg/ml against killifish. Ref.7
Miscellaneous	N-formyl-melittin major has 80% of the activity of melittin. Melittin: The secretion of this protein into venom follows a seasonal pattern. This variation is synchronized with phospholipase A2 variation, i.e. their production increase in the same months. Melittin-S: The secretion of this protein into venom follows a seasonal pattern, the maximum secretion occurring during the (southern) winter months.
Sequence similarities	Belongs to the melittin family.

Ontologies

Keywords
Biological process	Cytolysis Hemolysis Ion transport Transport
Cellular component	Membrane Secreted Target cell membrane Target membrane
Disease	Allergen
Domain	Signal Transmembrane
Molecular function	Toxin
PTM	Amidation Formylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cytolysis Inferred from electronic annotation. Source: UniProtKB-KW hemolysis in other organism Inferred from electronic annotation. Source: UniProtKB-KW ion transport Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of protein kinase activity Inferred from electronic annotation. Source: GOC
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW other organism cell membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	protein kinase inhibitor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Propeptide

22 – 43

22

Removed by a dipeptidylpeptidase

PRO_0000035148

Peptide

44 – 69

26

Melittin Ref.2 Ref.3 Ref.4

PRO_0000035149

Amino acid modifications

Modified residue

44

1

N-formylglycine; partial

Modified residue

69

1

Glutamine amide Ref.2

Natural variations

Natural variant

53

1

T → S in melittin-S.

Natural variant

64

1

K → S in melittin-2; possibly an artifact.

Natural variant

67 – 70

4

RQQG → KRQQ in melittin-2; possibly an artifact.

Secondary structure

1

.

.

.

.

.

70

Helix Strand Turn

Details...

Helix

45 – 53

9

Helix

55 – 68

14

Sequences

	Sequence		Length	Mass (Da)
	P01501 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 607F52C091C23BB6	FASTA	70	7,585
	10 20 30 40 50 60 MKFLVNVALV FMVVYISYIY AAPEPEPAPE PEAEADAEAD PEAGIGAVLK VLTTGLPALI 70 SWIKRKRQQG

References

[1]	"Nucleotide sequence of cloned cDNA coding for honeybee prepromelittin." Vlasak R., Unger-Ullmann C., Kreil G., Frischauf A.-M. Eur. J. Biochem. 135:123-126(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Sequence analysis of melittin from tryptic and peptic degradation products." Habermann E., Jentsch J. Hoppe-Seyler's Z. Physiol. Chem. 348:37-50(1967) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 44-69 (MELITTIN AND MELITTIN-2), AMIDATION AT GLN-69.
[3]	"Identification of a novel melittin isoform from Africanized Apis mellifera venom." Sciani J.M., Marques-Porto R., Lourenco A. Jr., Orsi R.D., Junior R.S., Barraviera B., Pimenta D.C. Peptides 31:1473-1479(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 44-69 (MELITTIN-S), FUNCTION, MASS SPECTROMETRY, SEASONAL VARIATION, 3D-STRUCTURE MODELING. Strain: Africanized honey bee. Tissue: Venom.
[4]	"Africanized honey bee (Apis mellifera) venom profiling: Seasonal variation of melittin and phospholipase A(2) levels." Ferreira Junior R.S., Sciani J.M., Marques-Porto R., Junior A.L., Orsi R.D., Barraviera B., Pimenta D.C. Toxicon 56:355-362(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 44-69 (MELITTIN), MASS SPECTROMETRY, SEASONAL VARIATION. Strain: Africanized honey bee. Tissue: Venom.
[5]	"Haemolytic activity and action on the surface tension of aqueous solutions of synthetic melittins and their derivatives." Schroeder E., Luebke K., Lehmann M., Beetz I. Experientia 27:764-765(1971) [PubMed] [Europe PMC] [Abstract] Cited for: SYNTHESIS OF 44-69.
[6]	"Isolation and structure of N 1-formyl melittin." Luebke K., Matthes S., Kloss G. Experientia 27:765-767(1971) [PubMed] [Europe PMC] [Abstract] Cited for: SYNTHESIS OF 44-69.
[7]	"Isolation and structures of grammistins, peptide toxins from the skin secretion of the soapfish Grammistes sexlineatus." Shiomi K., Igarashi T., Yokota H., Nagashima Y., Ishida M. Toxicon 38:91-103(2000) [PubMed] [Europe PMC] [Abstract] Cited for: LETHAL CONCENTRATION.
[8]	"The structure of melittin. II. Interpretation of the structure." Terwilliger T.C., Eisenberg D. J. Biol. Chem. 257:6016-6022(1982) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 44-69.
[9]	Barnham K.J., Hewish D., Werkmeister J., Curtain C., Kirkpatrick A., Bartone N., Norton R., Rivett D. Submitted (JUN-1998) to the PDB data bank Cited for: STRUCTURE BY NMR OF 44-69.
[10]	"The actions of melittin on membranes." Dempsey C.E. Biochim. Biophys. Acta 1031:143-161(1990) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
+	Additional computationally mapped references.

Web resources

Protein Spotlight

Why Pooh luvvs hunny - Issue 12 of July 2001

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X02007 mRNA. Translation: CAA26038.1.

PIR

MPHB1. A91133.

RefSeq

NP_001011607.1. NM_001011607.1.

UniGene

Ame.1212.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BH1	NMR	-	A	44-69	[»]
2MLT	X-ray	2.00	A/B	44-69	[»]
3QRX	X-ray	2.20	B	44-69	[»]

ProteinModelPortal

P01501.

SMR

P01501. Positions 44-69.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48928N.

STRING

7460.P01501.

Protein family/group databases

Allergome

3091. Api m 4.0101.
48. Api m 4.

TCDB

1.C.18.1.1. melittin family.

Proteomic databases

PaxDb

P01501.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblMetazoa

GB10355-RA; GB10355-PA; GB10355.

GeneID

406130.

KEGG

ame:406130.

Organism-specific databases

CTD

38785.

Family and domain databases

InterPro

IPR002116. Melittin/Api_allergen.
[Graphical view]

Pfam

PF01372. Melittin. 1 hit.
[Graphical view]

ProDom

PD014636. Melittin/Api_allergen. 1 hit.
[Graphical view] [Entries sharing at least one domain]

ProtoNet

Search...

Other

EvolutionaryTrace

P01501.

PMAP-CutDB

P01501.

Entry information

Entry name

MEL_APIME

Accession

Primary (citable) accession number: P01501
Secondary accession number(s): P01503

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	April 3, 2013
This is version 108 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program