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   22-FEB-2023, entry version 26.
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   BIOTECHNOLOGY (ANALOGS 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 (ANALOG SOR-C13).
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).
RN   [5]
RP   ERRATUM OF PUBMED:28150073.
RX   PubMed=28389981; DOI=10.1007/s10637-017-0455-y;
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.;
RL   Invest. New Drugs 35:397-397(2017).
RN   [6]
RP   BIOTECHNOLOGY (ANALOGS SOR-C13 AND SOR-C27).
RX   PubMed=30210643; DOI=10.7150/jca.20639;
RA   Xue H., Wang Y., MacCormack T.J., Lutes T., Rice C., Davey M., Dugourd D.,
RA   Ilenchuk T.T., Stewart J.M.;
RT   "Inhibition of transient receptor potential vanilloid 6 channel, elevated
RT   in human ovarian cancers, reduces tumour growth in a xenograft model.";
RL   J. Cancer 9:3196-3207(2018).
CC   -!- FUNCTION: Paralytic toxin that immobilizes a mealworm for 7 days
CC       (Ref.1). Inhibits the transient receptor potential cation channel
CC       subfamily V member 6 (TRPV6) (Ref.2). {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   -!- BIOTECHNOLOGY: The two short analogs SOR-C13 (AA 42-54) and SOR-C27 (AA
CC       28-54) bind to and inhibit calcium influx through TRPV6 expressed in
CC       HEK-293 cells (EC(50)=14 nM and 65 nM respectively). Since TRPV6
CC       channels are overexpressed in a number of cancers (including breast,
CC       prostate, ovarian), these analogs have potential application as
CC       diagnostic and therapeutic tools to detect or treat TRPV6-rich tumors.
CC       It is noteworthy that these peptides delivered a conjugated fluorescent
CC       label to TRPV6-rich xenografts of human ovarian cancer (SK-OV-3) and
CC       prostate cancer (DU-145) and negatively affected a number of
CC       epithelial-type cancer cell lines including SK-OV-3 in preliminary in
CC       vivo and in vitro studies. Additionally, a negative contrast MRI agent
CC       to which SOR-C27 was chemically attached targeted SK-OV-3 xenografts
CC       allowing detection and accurate determination of tumor volume
CC       (PubMed:23554944). Furthermore, daily injection into SK-OV-3 xenografts
CC       mice with SOR-C13 or SOR-C27 over 12 days inhibits tumor growth by more
CC       that 50% at the highest dose compared to non-treated controls
CC       (PubMed:28150073). {ECO:0000269|PubMed:23554944,
CC       ECO:0000269|PubMed:28150073}.
CC   -!- PHARMACEUTICAL: The shorter analog SOC-C13 is under phase I clinical
CC       trial by Soricimed. This short analog (AA 42-54) of soricidin is tested
CC       for the treatment of advanced solid tumors of epithelial origin which
CC       are refractory to all standard-of-care treatments.
CC       {ECO:0000269|PubMed:28150073}.
CC   -!- SIMILARITY: Belongs to the opioid neuropeptide precursor family.
CC       {ECO:0000305}.
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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
//