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G9I930

- PA2HB_MICTN

UniProt

G9I930 - PA2HB_MICTN

Protein

Basic phospholipase A2 homolog Tx-beta

Gene
N/A
Organism
Micrurus tener tener (Texas coral snake)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli
  1. Functioni

    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 (EC(50)=9.4 nM) vs ASIC1b (EC(50)=23 nM). The ASIC3/ACCN3 subtype is also sensitive to the heterodimer, but with a lower potency (EC(50)=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.1 Publication
    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.1 Publication

    GO - Molecular functioni

    1. calcium ion binding Source: InterPro
    2. phospholipase A2 activity Source: InterPro

    GO - Biological processi

    1. lipid catabolic process Source: InterPro
    2. phospholipid metabolic process Source: InterPro

    Keywords - Molecular functioni

    Ion channel impairing toxin, Neurotoxin, Toxin

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Basic phospholipase A2 homolog Tx-beta
    Short name:
    svPLA2 homolog
    Alternative name(s):
    MitTx-beta
    OrganismiMicrurus tener tener (Texas coral snake)
    Taxonomic identifieri1114302 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiLepidosauriaSquamataBifurcataUnidentataEpisquamataToxicoferaSerpentesColubroideaElapidaeElapinaeMicrurus

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular region Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Secreted

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 30301 PublicationAdd
    BLAST
    Chaini31 – 149119Basic phospholipase A2 homolog Tx-betaPRO_5000828218Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi41 ↔ 100By similarity
    Disulfide bondi55 ↔ 148By similarity
    Disulfide bondi57 ↔ 73By similarity
    Disulfide bondi72 ↔ 130By similarity
    Disulfide bondi79 ↔ 123By similarity
    Disulfide bondi89 ↔ 116By similarity
    Disulfide bondi109 ↔ 121By similarity

    Keywords - PTMi

    Disulfide bond

    Expressioni

    Tissue specificityi

    Expressed by the venom gland.

    Interactioni

    Subunit structurei

    Heterodimer of an alpha and a beta chains.1 Publication

    Structurei

    Secondary structure

    1
    149
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi32 – 409
    Helixi47 – 493
    Turni50 – 523
    Turni54 – 563
    Helixi68 – 8720
    Turni91 – 933
    Helixi104 – 1063
    Helixi115 – 13319
    Helixi138 – 1403
    Helixi145 – 1473

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4NTWX-ray2.07C31-149[»]
    4NTXX-ray2.27C31-149[»]
    4NTYX-ray2.65C31-149[»]
    ProteinModelPortaliG9I930.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Signal

    Family and domain databases

    Gene3Di1.20.90.10. 1 hit.
    InterProiIPR001211. PLipase_A2.
    IPR013090. PLipase_A2_AS.
    IPR016090. PLipase_A2_dom.
    [Graphical view]
    PANTHERiPTHR11716. PTHR11716. 1 hit.
    PfamiPF00068. Phospholip_A2_1. 1 hit.
    [Graphical view]
    PRINTSiPR00389. PHPHLIPASEA2.
    SMARTiSM00085. PA2c. 1 hit.
    [Graphical view]
    SUPFAMiSSF48619. SSF48619. 1 hit.
    PROSITEiPS00119. PA2_ASP. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    G9I930-1 [UniParc]FASTAAdd to Basket

    « Hide

    MDKMNPAHLL VLAAVCVSLL GASSIPPQAL NLNQFRLMIK CTNDRVWADF    50
    VDYGCYCVAR DSNTPVDDLD RCCQAQKQCY DEAVKVHGCK PLVMFYSFEC 100
    RYLASDLDCS GNNTKCRNFV CNCDRTATLC ILTATYNRNN HKIDPSRCQ 149
    Length:149
    Mass (Da):16,793
    Last modified:February 22, 2012 - v1
    Checksum:i4CF027CBCA751BE4
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    JN613326 mRNA. Translation: AET85560.1.

    Cross-referencesi

    Web resourcesi

    Protein Spotlight

    The poison in pain - Issue 140 of July 2012

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    JN613326 mRNA. Translation: AET85560.1 .

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4NTW X-ray 2.07 C 31-149 [» ]
    4NTX X-ray 2.27 C 31-149 [» ]
    4NTY X-ray 2.65 C 31-149 [» ]
    ProteinModelPortali G9I930.
    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Family and domain databases

    Gene3Di 1.20.90.10. 1 hit.
    InterProi IPR001211. PLipase_A2.
    IPR013090. PLipase_A2_AS.
    IPR016090. PLipase_A2_dom.
    [Graphical view ]
    PANTHERi PTHR11716. PTHR11716. 1 hit.
    Pfami PF00068. Phospholip_A2_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00389. PHPHLIPASEA2.
    SMARTi SM00085. PA2c. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48619. SSF48619. 1 hit.
    PROSITEi PS00119. PA2_ASP. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.

    Entry informationi

    Entry nameiPA2HB_MICTN
    AccessioniPrimary (citable) accession number: G9I930
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 18, 2012
    Last sequence update: February 22, 2012
    Last modified: October 1, 2014
    This is version 18 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programAnimal Toxin Annotation Program
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    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.1 Publication

    Keywords - Technical termi

    3D-structure, Direct protein sequencing

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. Protein Spotlight
      Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3