ID   3SI1B_DENAN             Reviewed;          66 AA.
AC   P86419;
DT   05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT   05-OCT-2010, sequence version 1.
DT   25-MAY-2022, entry version 31.
DE   RecName: Full=Rho-elapitoxin-Da1b {ECO:0000305};
DE            Short=Rho-Da1b {ECO:0000303|PubMed:20659106, ECO:0000303|PubMed:21419153, ECO:0000303|PubMed:24793485};
DE            Short=Rho-EPTX-Da1b {ECO:0000305};
OS   Dendroaspis angusticeps (Eastern green mamba) (Naja angusticeps).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Elapidae; Elapinae; Dendroaspis.
OX   NCBI_TaxID=8618;
RN   [1]
RP   PROTEIN SEQUENCE, SYNTHESIS, FUNCTION, SUBCELLULAR LOCATION, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Venom;
RX   PubMed=20659106; DOI=10.1111/j.1476-5381.2010.00966.x;
RA   Rouget C., Quinton L., Maiga A., Gales C., Masuyer G., Malosse C.,
RA   Chamot-Rooke J., Thai R., Mourier G., De Pauw E., Gilles N., Servent D.;
RT   "Identification of a novel snake peptide toxin displaying high affinity and
RT   antagonist behaviour for the alpha2-adrenoceptors.";
RL   Br. J. Pharmacol. 161:1361-1374(2010).
RN   [2]
RP   PROTEIN SEQUENCE, FUNCTION, AND SYNTHESIS.
RX   PubMed=21419153; DOI=10.1016/j.toxicon.2011.03.009;
RA   Maiga A., Mourier G., Quinton L., Rouget C., Gales C., Denis C., Lluel P.,
RA   Senard J.M., Palea S., Servent D., Gilles N.;
RT   "G protein-coupled receptors, an unexploited animal toxin targets:
RT   exploration of green mamba venom for novel drug candidates active against
RT   adrenoceptors.";
RL   Toxicon 59:487-496(2012).
RN   [3]
RP   SYNTHESIS, AND FUNCTION.
RX   PubMed=24793485; DOI=10.1016/j.biochi.2014.04.009;
RA   Blanchet G., Collet G., Mourier G., Gilles N., Fruchart-Gaillard C.,
RA   Marcon E., Servent D.;
RT   "Polypharmacology profiles and phylogenetic analysis of three-finger toxins
RT   from mamba venom: case of aminergic toxins.";
RL   Biochimie 103:109-117(2014).
RN   [4]
RP   MUTAGENESIS OF ASP-7; GLN-15; ILE-26; ARG-28 AND THR-43.
RX   PubMed=28578406; DOI=10.1038/s41598-017-02953-0;
RA   Blanchet G., Alili D., Protte A., Upert G., Gilles N., Tepshi L.,
RA   Stura E.A., Mourier G., Servent D.;
RT   "Ancestral protein resurrection and engineering opportunities of the mamba
RT   aminergic toxins.";
RL   Sci. Rep. 7:2701-2701(2017).
CC   -!- FUNCTION: Non-competitive antagonist of alpha-2 adrenergic receptors
CC       (ADRA2) in smooth muscles, and partial antagonist of D3 dopamine
CC       receptors (DRD3) (inhibits 25% of methylspiperone binding to this
CC       receptor) (PubMed:20659106). Also shows a low antagonism on D2 dopamine
CC       receptors (DRD2) (short isoform) (PubMed:24793485). Shows high affinity
CC       to adrenergic receptors (Ki=14 nM (ADRA2A), Ki=73 nM (ADRA2B), and
CC       Ki=38 nM (ADRA2C)) (PubMed:20659106). Increases heart rate and blood
CC       catecholamine concentrations (PubMed:21419153).
CC       {ECO:0000269|PubMed:20659106, ECO:0000269|PubMed:21419153,
CC       ECO:0000269|PubMed:24793485}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:20659106}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:20659106}.
CC   -!- MASS SPECTROMETRY: Mass=7507.51; Method=Electrospray; Note=Monoisotopic
CC       mass.; Evidence={ECO:0000269|PubMed:20659106};
CC   -!- MISCELLANEOUS: Does not show interaction with adrenergic receptors
CC       (ADRA1A, ADRA1B, ADRA1D, ADRB1, ADRB2), dopaminergic receptors (DRD1,
CC       DRD2, DRD4, DRD5), histaminic receptors (HRH1, HRH3, HRH4), muscarinic
CC       receptors (CHRM1, CHRM2, CHRM3, CHRM4, CHRM5), and serotoninergic
CC       receptors (HTR1A, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7).
CC       {ECO:0000269|PubMed:24793485}.
CC   -!- SIMILARITY: Belongs to the snake three-finger toxin family. Short-chain
CC       subfamily. Aminergic toxin sub-subfamily.
CC       {ECO:0000305|PubMed:24793485}.
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DR   AlphaFoldDB; P86419; -.
DR   SMR; P86419; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   CDD; cd00206; snake_toxin; 1.
DR   Gene3D; 2.10.60.10; -; 1.
DR   InterPro; IPR003571; Snake_3FTx.
DR   InterPro; IPR045860; Snake_toxin-like_sf.
DR   InterPro; IPR018354; Snake_toxin_con_site.
DR   SUPFAM; SSF57302; SSF57302; 1.
DR   PROSITE; PS00272; SNAKE_TOXIN; 1.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Disulfide bond;
KW   G-protein coupled receptor impairing toxin; Secreted; Toxin.
FT   CHAIN           1..66
FT                   /note="Rho-elapitoxin-Da1b"
FT                   /evidence="ECO:0000269|PubMed:20659106,
FT                   ECO:0000269|PubMed:21419153"
FT                   /id="PRO_0000398129"
FT   DISULFID        3..24
FT                   /evidence="ECO:0000250|UniProtKB:Q8QGR0"
FT   DISULFID        17..42
FT                   /evidence="ECO:0000250|UniProtKB:Q8QGR0"
FT   DISULFID        46..58
FT                   /evidence="ECO:0000250|UniProtKB:Q8QGR0"
FT   DISULFID        59..64
FT                   /evidence="ECO:0000250|UniProtKB:Q8QGR0"
FT   MUTAGEN         7
FT                   /note="D->N: In AncTx5; 3-4-fold increase in inhibition
FT                   potency on alpha-2A adrenergic receptor and D3 dopamine
FT                   receptor, 28-fold increase in inhibition potency on alpha-
FT                   2B adrenergic receptor, and 10-fold increase in inhibition
FT                   potency on ADRA2C adrenergic receptor."
FT                   /evidence="ECO:0000269|PubMed:28578406"
FT   MUTAGEN         15
FT                   /note="Q->E: In AncTx5; 3-4-fold increase in inhibition
FT                   potency on alpha-2A adrenergic receptor and D3 dopamine
FT                   receptor, 28-fold increase in inhibition potency on alpha-
FT                   2B adrenergic receptor, and 10-fold increase in inhibition
FT                   potency on ADRA2C adrenergic receptor."
FT                   /evidence="ECO:0000269|PubMed:28578406"
FT   MUTAGEN         26
FT                   /note="I->K: In AncTx5; 3-4-fold increase in inhibition
FT                   potency on alpha-2A adrenergic receptor and D3 dopamine
FT                   receptor, 28-fold increase in inhibition potency on alpha-
FT                   2B adrenergic receptor, and 10-fold increase in inhibition
FT                   potency on ADRA2C adrenergic receptor."
FT                   /evidence="ECO:0000269|PubMed:28578406"
FT   MUTAGEN         28
FT                   /note="R->W: In AncTx5; 3-4-fold increase in inhibition
FT                   potency on alpha-2A adrenergic receptor and D3 dopamine
FT                   receptor, 28-fold increase in inhibition potency on alpha-
FT                   2B adrenergic receptor, and 10-fold increase in inhibition
FT                   potency on ADRA2C adrenergic receptor."
FT                   /evidence="ECO:0000269|PubMed:28578406"
FT   MUTAGEN         43
FT                   /note="T->A: In AncTx5; 3-4-fold increase in inhibition
FT                   potency on alpha-2A adrenergic receptor and D3 dopamine
FT                   receptor, 28-fold increase in inhibition potency on alpha-
FT                   2B adrenergic receptor, and 10-fold increase in inhibition
FT                   potency on ADRA2C adrenergic receptor."
FT                   /evidence="ECO:0000269|PubMed:28578406"
SQ   SEQUENCE   66 AA;  7521 MW;  7C1BB301805EA667 CRC64;
     LTCVTKDTIF GITTQNCPAG QNLCFIRRHY INHRYTEITR GCTATCPKPT NVRETIHCCN
     TDKCNE