G9I930 (PA2HB_MICTN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Basic phospholipase A2 homolog Tx-beta Short name=svPLA2 homolog Alternative name(s): MitTx-beta
Organism	Micrurus tener tener (Texas coral snake)
Taxonomic identifier	1114302 [NCBI]
Taxonomic lineage	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Sauropsida › Sauria › Lepidosauria › Squamata › Scleroglossa › Serpentes › Colubroidea › Elapidae › Elapinae › Micrurus › Micrurus tener

Protein attributes

Sequence length	149 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	Heterodimer: snake venom phospholipase that potently activates mouse H+-gated sodium channel ASIC1/ACCN2 (acid-sensitive ion channel 1) expressed in Xenopus oocytes. Both alternatively spliced isoforms ASIC1a and ASIC1b are activated, with a higher potency for ASIC1a (EC50=9.4 nM) vs ASIC1b (EC50=23 nM). The ASIC3/ACCN3 subtype is also sensitive to the heterodimer, but with a lower potency (EC50=830 nM). On ASIC2a/ACCN1, the toxin shows a very weak activation, but produces a remarkable potentiation (>100-fold) of protons when the extracellular pH drops below neutrality. The toxin interacts with the extracellular region of the channel, since responses are only observed in the outside-out configuration. In vivo, the heterodimer elicits robust pain-related behavior in mice by activation of ASIC1/ACCN2 channels on capsaicin-sensitive nerve fibers. Ref.1 Monomer: does not have phospholipase A2 activity but may maintain some lipid-binding character from its PLA2 lineage, which could aid in effecting neuronal depolarization. Ref.1
Subunit structure	Heterodimer of an alpha and a beta chains. Ref.1
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom gland.
Miscellaneous	This toxin has been studied to probe molecular mechanisms underlying pain sensation. By targeting ASIC1/ACCN2, it reveals an unexpected contribution of this channel to nociception. The heterodimeric toxin does not affect ASIC2b/ACCN1, ASIC4/ACCN4, Kv2.1/KCNB1, Cav3.3/CACNA1I, ENaC/SCNN1A, TRPA1, TRPV1, TRPV3, TRPM8, P2X2/P2RX2, and 5-HT3/HTR3A channels (Ref.1).
Sequence similarities	Belongs to the phospholipase A2 family. Group I subfamily. K49 sub-subfamily.

Ontologies

Keywords
Cellular component	Secreted
Domain	Signal
Molecular function	Ion channel impairing toxin Neurotoxin Toxin
PTM	Disulfide bond
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological_process	lipid catabolic process Inferred from electronic annotation. Source: InterPro phospholipid metabolic process Inferred from electronic annotation. Source: InterPro
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro phospholipase A2 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 – 30	30
	Chain	31 – 149	119	Basic phospholipase A2 homolog Tx-beta		PRO_5000828218
Amino acid modifications
	Disulfide bond	41 ↔ 100		By similarity
	Disulfide bond	55 ↔ 148		By similarity
	Disulfide bond	57 ↔ 73		By similarity
	Disulfide bond	72 ↔ 130		By similarity
	Disulfide bond	79 ↔ 123		By similarity
	Disulfide bond	89 ↔ 116		By similarity
	Disulfide bond	109 ↔ 121		By similarity

Sequences

	Sequence		Length	Mass (Da)
	G9I930 [UniParc]. Last modified February 22, 2012. Version 1. Checksum: 4CF027CBCA751BE4	FASTA	149	16,793
	10 20 30 40 50 60 MDKMNPAHLL VLAAVCVSLL GASSIPPQAL NLNQFRLMIK CTNDRVWADF VDYGCYCVAR 70 80 90 100 110 120 DSNTPVDDLD RCCQAQKQCY DEAVKVHGCK PLVMFYSFEC RYLASDLDCS GNNTKCRNFV 130 140 CNCDRTATLC ILTATYNRNN HKIDPSRCQ

References

[1]

"A heteromeric Texas coral snake toxin targets acid-sensing ion channels to produce pain." Bohlen C.J., Chesler A.T., Sharif-Naeini R., Medzihradszky K.F., Zhou S., King D., Sanchez E.E., Burlingame A.L., Basbaum A.I., Julius D. Nature 479:410-414(2011) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE, OF N-TERMINUS FUNCTION, SUBUNIT. Tissue: Venom and Venom gland.

Web resources

Protein Spotlight

The poison in pain - Issue 140 of July 2012

Cross-references

Sequence databases
EMBL GenBank DDBJ	JN613326 mRNA. Translation: AET85560.1.
3D structure databases
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
Gene3D	1.20.90.10. 1 hit.
InterPro	IPR001211. PLipase_A2. IPR013090. PLipase_A2_AS. IPR016090. PLipase_A2_dom. [Graphical view]
PANTHER	PTHR11716. PTHR11716. 1 hit.
Pfam	PF00068. Phospholip_A2_1. 1 hit. [Graphical view]
PRINTS	PR00389. PHPHLIPASEA2.
SMART	SM00085. PA2c. 1 hit. [Graphical view]
SUPFAM	SSF48619. PhospholipaseA2. 1 hit.
PROSITE	PS00119. PA2_ASP. 1 hit. PS00118. PA2_HIS. False negative. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

PA2HB_MICTN

Accession

Primary (citable) accession number: G9I930

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 18, 2012
Last sequence update:	February 22, 2012
Last modified:	May 1, 2013
This is version 11 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program

Annotation program

Chordata Protein Annotation Program