ID   SORI_BLABR              Reviewed;          54 AA.
AC   P0C2P6;
DT   03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT   03-APR-2007, sequence version 1.
DT   25-MAY-2022, entry version 25.
DE   RecName: Full=Soricidin {ECO:0000303|Ref.1};
DE   AltName: Full=Ps peptide {ECO:0000303|Ref.1};
OS   Blarina brevicauda (Northern short-tailed shrew).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Eulipotyphla; Soricidae; Soricinae; Blarina.
OX   NCBI_TaxID=9387;
RN   [1]
RP   PROTEIN SEQUENCE, MASS SPECTROMETRY, FUNCTION, AND SUBCELLULAR LOCATION.
RC   TISSUE=Saliva;
RA   Stewart J.M., Steeves B.J., Vernes K.;
RT   "Shrew paralytic peptide for use in neuromuscular therapy.";
RL   Patent number WO2004046178, 03-JUN-2004.
RN   [2]
RP   FUNCTION.
RC   TISSUE=Saliva;
RA   Stewart J.M., Steeves B.J., Vernes K.;
RT   "Paralytic peptide for use in neuromuscular therapy.";
RL   Patent number US7119168, 10-OCT-2006.
RN   [3]
RP   FUNCTION OF SHORTER PEPTIDES (SOR-C13 AND SOR-C27).
RX   PubMed=23554944; DOI=10.1371/journal.pone.0058866;
RA   Bowen C.V., DeBay D., Ewart H.S., Gallant P., Gormley S., Ilenchuk T.T.,
RA   Iqbal U., Lutes T., Martina M., Mealing G., Merkley N., Sperker S.,
RA   Moreno M.J., Rice C., Syvitski R.T., Stewart J.M.;
RT   "In vivo detection of human TRPV6-rich tumors with anti-cancer peptides
RT   derived from soricidin.";
RL   PLoS ONE 8:E58866-E58866(2013).
RN   [4]
RP   PHARMACEUTICAL.
RX   PubMed=28150073; DOI=10.1007/s10637-017-0438-z;
RA   Fu S., Hirte H., Welch S., Ilenchuk T.T., Lutes T., Rice C., Fields N.,
RA   Nemet A., Dugourd D., Piha-Paul S., Subbiah V., Liu L., Gong J., Hong D.,
RA   Stewart J.M.;
RT   "First-in-human phase I study of SOR-C13, a TRPV6 calcium channel
RT   inhibitor, in patients with advanced solid tumors.";
RL   Invest. New Drugs 35:324-333(2017).
CC   -!- FUNCTION: Inhibits the transient receptor potential cation channel
CC       subfamily V member 6 (TRPV6) (Ref.2). Paralytic toxin (Ref.1). This
CC       peptide immobilizes a mealworm for 7 days (Ref.1). {ECO:0000269|Ref.1,
CC       ECO:0000269|Ref.2}.
CC   -!- SUBUNIT: Member of a multiprotein complex. {ECO:0000305|Ref.1,
CC       ECO:0000305|Ref.2}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|Ref.1}.
CC   -!- TISSUE SPECIFICITY: Salivary gland. {ECO:0000305|Ref.1}.
CC   -!- MASS SPECTROMETRY: Mass=5805.8; Method=MALDI;
CC       Evidence={ECO:0000269|Ref.1};
CC   -!- PHARMACEUTICAL: Is under phase I clinical trial by Soricimed under the
CC       name SOR-C13. This shorter analog (AA 42-54) of soricidin is tested for
CC       the treatment of advanced solid tumors of epithelial origin which are
CC       refractory to all standard-of-care treatments.
CC       {ECO:0000269|PubMed:28150073}.
CC   -!- MISCELLANEOUS: Two synthetic peptides SOR-C13 (AA 42-54) and SOR-C27
CC       (AA 28-54) inhibit calcium influx in TRPV6 over-expressing cells
CC       (IC(50)=14 and IC(50)=65 nM, respectively).
CC       {ECO:0000269|PubMed:23554944}.
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DR   AlphaFoldDB; P0C2P6; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005246; F:calcium channel regulator activity; IEA:UniProtKB-KW.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   GO; GO:0007218; P:neuropeptide signaling pathway; IEA:InterPro.
DR   InterPro; IPR006024; Opioid_neupept.
DR   Pfam; PF01160; Opiods_neuropep; 1.
PE   1: Evidence at protein level;
KW   Calcium channel impairing toxin; Direct protein sequencing; Disulfide bond;
KW   Ion channel impairing toxin; Neurotoxin; Pharmaceutical; Secreted; Toxin.
FT   CHAIN           1..54
FT                   /note="Soricidin"
FT                   /evidence="ECO:0000269|Ref.1"
FT                   /id="PRO_0000283772"
FT   DISULFID        2..23
FT                   /evidence="ECO:0000250|UniProtKB:P01210"
FT   DISULFID        6..27
FT                   /evidence="ECO:0000250|UniProtKB:P01210"
FT   DISULFID        9..41
FT                   /evidence="ECO:0000250|UniProtKB:P01210"
SQ   SEQUENCE   54 AA;  5813 MW;  1D7F7D00021CEBC5 CRC64;
     DCSQDCAACS ILARPAELNT ETCILECEGK LSSNDTEGGL CKEFLHPSKV DLPR