RP33_RHIDO
ID RP33_RHIDO Reviewed; 33 AA.
AC P0DTU2;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 17-JUN-2020, sequence version 1.
DT 25-MAY-2022, entry version 3.
DE RecName: Full=Rhinophrynin-33 {ECO:0000303|PubMed:28951157, ECO:0000303|PubMed:31639404};
DE Short=RP-33 {ECO:0000303|PubMed:31639404};
DE Contains:
DE RecName: Full=Rhinophrynin-27 {ECO:0000303|PubMed:28951157, ECO:0000303|PubMed:31639404};
DE Short=RP-27 {ECO:0000303|PubMed:31639404};
OS Rhinophrynus dorsalis (Mexican burrowing toad).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Rhinophrynidae; Rhinophrynus.
OX NCBI_TaxID=43566;
RN [1]
RP PROTEIN SEQUENCE, MASS SPECTROMETRY, SYNTHESIS OF 1-27, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Skin secretion;
RX PubMed=28951157; DOI=10.1016/j.peptides.2017.09.012;
RA Conlon J.M., Guilhaudis L., Leprince J., Coquet L., Mangoni M.L.,
RA Attoub S., Jouenne T., King J.D.;
RT "Peptidomic analysis of skin secretions of the Mexican burrowing toad
RT Rhinophrynus dorsalis (Rhinophrynidae): insight into the origin of host-
RT defense peptides within the Pipidae and characterization of a proline-
RT arginine-rich peptide.";
RL Peptides 97:22-28(2017).
RN [2]
RP FUNCTION, AND MUTAGENESIS OF GLU-1; GLU-6; ALA-8; GLU-13; ALA-17 AND
RP ALA-23.
RX PubMed=31639404; DOI=10.1016/j.biochi.2019.10.007;
RA Scorciapino M.A., Carta P., Pantic J., Lukic M.L., Lukic A., Musale V.,
RA Abdel-Wahab Y.H.A., Conlon J.M.;
RT "Conformational analysis and in vitro immunomodulatory and insulinotropic
RT properties of the frog skin host-defense peptide rhinophrynin-27 and
RT selected analogs.";
RL Biochimie 167:198-206(2019).
CC -!- FUNCTION: [Rhinophrynin-27]: Non-cytotoxic peptide with
CC immunosuppressive and insulinotropic effects (PubMed:31639404). Induces
CC an increased production of the anti-inflammatory cytokine IL-10 and
CC inhibits production of the pro-inflammatory cytokines TNF-alpha and IL-
CC 1beta, when incubated with mouse peritoneal cells (PubMed:31639404).
CC Does not display growth-inhibitory activity against the Gram-positive
CC S.epidermidis and Gram-negative E.coli bacteria and against the
CC opportunistic yeast pathogen C.parapsilosis (MIC>128 uM)
CC (PubMed:28951157). In addition, it lacks cytotoxic activity against
CC mouse erythrocytes (LC(50)>500 uM) and A549 human non-small cell lung
CC adenocarcinoma cells (LC(50)>100 uM) (PubMed:28951157). Moderately
CC stimulates insulin release from rat clonal beta-cells and mouse
CC pancreatic islets (PubMed:31639404). {ECO:0000269|PubMed:28951157,
CC ECO:0000269|PubMed:31639404}.
CC -!- FUNCTION: [Rhinophrynin-33]: Non-cytotoxic peptide with
CC immunosuppressive but without insulinotropic effects (PubMed:31639404).
CC Inhibits production of the pro-inflammatory cytokines TNF-alpha, but
CC has no effect on IL-10 and IL-1beta production, when incubated with
CC mouse peritoneal cells (PubMed:31639404). Has no activity of
CC stimulation of insulin release (PubMed:31639404).
CC {ECO:0000269|PubMed:31639404}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:28951157}.
CC -!- TISSUE SPECIFICITY: Expressed by the skin glands.
CC {ECO:0000305|PubMed:31639404}.
CC -!- MASS SPECTROMETRY: [Rhinophrynin-33]: Mass=3727.4; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:28951157};
CC -!- MASS SPECTROMETRY: [Rhinophrynin-27]: Mass=3027.2; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:28951157};
CC -!- PHARMACEUTICAL: May represent a template for the development of an
CC agent for use in anti-inflammatory and type 2 diabetes therapies.
CC {ECO:0000305|PubMed:31639404}.
CC -!- MISCELLANEOUS: RP-33 is present in skin secretions in higher
CC concentration than RP-27 (PubMed:28951157). RP-33 may be a precursor of
CC RP-27 that is activated in the skin in response to an appropriate
CC stimulus (Probable). {ECO:0000269|PubMed:28951157,
CC ECO:0000305|PubMed:31639404}.
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DR AlphaFoldDB; P0DTU2; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0006952; P:defense response; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW Amphibian defense peptide; Direct protein sequencing; Pharmaceutical;
KW Secreted.
FT CHAIN 1..33
FT /note="Rhinophrynin-33"
FT /evidence="ECO:0000269|PubMed:28951157"
FT /id="PRO_0000450016"
FT PEPTIDE 1..27
FT /note="Rhinophrynin-27"
FT /evidence="ECO:0000269|PubMed:28951157"
FT /id="PRO_0000450017"
FT MUTAGEN 1
FT /note="E->R: In [E1R]RP-27; decrease in stimulation of
FT insulin release and loss of cytokine production effect on
FT mouse peritoneal cells. In [E1R,E6R]RP-27; loss of
FT stimulation of insulin release, loss of TNF-alpha
FT production effect on mouse peritoneal cells, and no change
FT on IL-10 and IL-1beta production effect. In
FT [E1R,E6R,E13R]RP-27; loss of stimulation of insulin
FT release, increase of IL-10 and TNF-alpha production effect
FT on mouse peritoneal cells, and no change on IL-1beta
FT production effect."
FT /evidence="ECO:0000269|PubMed:31639404"
FT MUTAGEN 6
FT /note="E->R: In [E1R,E6R]RP-27; loss of stimulation of
FT insulin release, loss of TNF-alpha production effect on
FT mouse peritoneal cells, and no change on IL-10 and IL-1beta
FT production effect. In [E1R,E6R,E13R]RP-27; loss of
FT stimulation of insulin release, increase of IL-10 and TNF-
FT alpha production effect on mouse peritoneal cells, and no
FT change on IL-1beta production effect."
FT /evidence="ECO:0000269|PubMed:31639404"
FT MUTAGEN 8
FT /note="A->W: In [A8W]RP-27; loss of stimulation of insulin
FT release, increase of TNF-alpha and IL-1beta production
FT effect on mouse peritoneal cells, and decrease of IL-10
FT production effect. In [A8W,A17W]RP-27; important decrease
FT of stimulation of insulin release, increase of TNF-alpha
FT and IL-1beta production effect on mouse peritoneal cells,
FT and non-significant decrease of IL-10 production effect. In
FT [A8W,A17W,A23W]RP-27; important decrease of stimulation of
FT insulin release, increase of TNF-alpha and IL-1beta
FT production effect on mouse peritoneal cells, and no change
FT of IL-10 production effect."
FT /evidence="ECO:0000269|PubMed:31639404"
FT MUTAGEN 13
FT /note="E->R: In [E1R,E6R,E13R]RP-27; loss of stimulation of
FT insulin release and increase of IL-10 and TNF-alpha
FT production effect on mouse peritoneal cells, and no change
FT on IL-1beta production effect."
FT /evidence="ECO:0000269|PubMed:31639404"
FT MUTAGEN 17
FT /note="A->W: In [A8W,A17W]RP-27; important decrease of
FT stimulation of insulin release, increase of TNF-alpha and
FT IL-1beta production effect on mouse peritoneal cells, and
FT non-significant decrease of IL-10 production effect. In
FT [A8W,A17W,A23W]RP-27; important decrease of stimulation of
FT insulin release, increase of TNF-alpha and IL-1beta
FT production effect on mouse peritoneal cells, and no change
FT of IL-10 production effect."
FT /evidence="ECO:0000269|PubMed:31639404"
FT MUTAGEN 23
FT /note="A->W: In [A8W,A17W,A23W]RP-27; important decrease of
FT stimulation of insulin release, increase of TNF-alpha and
FT IL-1beta production effect on mouse peritoneal cells, and
FT no change of IL-10 production effect."
FT /evidence="ECO:0000269|PubMed:31639404"
SQ SEQUENCE 33 AA; 3729 MW; 7A94BC8CC0D30D55 CRC64;
ELRLPEIARP VPEVLPARLP LPALPRNKMA KNQ
