CLCPP_TITSE
ID CLCPP_TITSE Reviewed; 68 AA.
AC P0DM29; A0A386IQ04;
DT 13-FEB-2019, integrated into UniProtKB/Swiss-Prot.
DT 13-FEB-2019, sequence version 1.
DT 03-AUG-2022, entry version 8.
DE RecName: Full=Intracellular calcium channel modulator CCP-Ts {ECO:0000303|PubMed:30282983};
DE AltName: Full=CaTx {ECO:0000303|PubMed:33181162};
DE AltName: Full=Calcium channel toxin Ts32 {ECO:0000303|PubMed:33181162};
DE AltName: Full=Cell penetrating peptides-Ts {ECO:0000303|PubMed:30282983};
DE Short=CPP {ECO:0000303|PubMed:30282983};
DE Short=CPP-Ts {ECO:0000303|PubMed:30282983};
DE AltName: Full=Tityustoxin-32 {ECO:0000305};
DE Flags: Precursor;
OS Tityus serrulatus (Brazilian scorpion).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Tityus.
OX NCBI_TaxID=6887;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SYNTHESIS OF 24-68, FUNCTION, TISSUE
RP SPECIFICITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 24-LEU--LEU-36 AND
RP 63-LYS--PRO-68.
RC TISSUE=Venom gland;
RX PubMed=30282983; DOI=10.1038/s41598-018-33133-3;
RA Oliveira-Mendes B.B.R., Horta C.C.R., do Carmo A.O., Biscoto G.L.,
RA Sales-Medina D.F., Leal H.G., Brandao-Dias P.F.P., Miranda S.E.M.,
RA Aguiar C.J., Cardoso V.N., de Barros A.L.B., Chavez-Olortegui C.,
RA Leite M.F., Kalapothakis E.;
RT "CPP-Ts: a new intracellular calcium channel modulator and a promising tool
RT for drug delivery in cancer cells.";
RL Sci. Rep. 8:14739-14739(2018).
RN [2] {ECO:0000312|EMBL:QPD99059.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Telson;
RX PubMed=33181162; DOI=10.1016/j.toxicon.2020.11.001;
RA Kalapothakis Y., Miranda K., Pereira A.H., Witt A.S.A., Marani C.,
RA Martins A.P., Leal H.G., Campos-Junior E., Pimenta A.M.C., Borges A.,
RA Chavez-Olortegui C., Kalapothakis E.;
RT "Novel components of Tityus serrulatus venom: a transcriptomic approach.";
RL Toxicon 189:91-104(2021).
CC -!- FUNCTION: Cell penetrating peptide (CPP) that increases intracellular
CC calcium release through the activation of nuclear inositol 1,4,5-
CC trisphosphate receptors (ITPR) of cardiomyocytes, thereby causing an
CC increase in the contraction frequency of these cells (PubMed:30282983).
CC In vivo, this toxin is not lethal to mice, hovewer anti-CPP serum
CC reduces venom lethality, suggesting that this toxin is lethal when it
CC acts in synergy with other venom components (PubMed:30282983).
CC {ECO:0000269|PubMed:30282983}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:30282983}. Nucleus
CC {ECO:0000269|PubMed:30282983}. Note=Secreted in the venom and directed
CC to the intranuclear region of cardiomyocytes (PubMed:30282983).
CC {ECO:0000269|PubMed:30282983}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland. In intravenously
CC injected mice, the labeled toxin has preference for heart, liver and
CC lungs. {ECO:0000269|PubMed:30282983}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000250|UniProtKB:P59868}.
CC -!- BIOTECHNOLOGY: The peptide(14-39) may have biotechnological
CC applications as a drug delivery system targeting cancer cells, since it
CC lacks pharmacological activity of the wild-type toxin and has selective
CC internalization properties in specific cell lines. It is directed to
CC the nucleus of six neoplastic cell lines (SK-MEL-188, HEP G2, Caco-2,
CC MDA-MB-231, A549 and DU 145), as well as in rat cardiomyocytes, and rat
CC heptocytes. However, it is unable to cross the cell membrane of six
CC normal immortalized cell lines (HUV-EC-C, HFF-1, MCR-5, HEK-293, BHK-21
CC and MDCK). {ECO:0000269|PubMed:30282983}.
CC -!- SIMILARITY: Belongs to the scorpion calcin-like family. {ECO:0000305}.
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DR EMBL; MH061344; AYD60134.1; -; mRNA.
DR EMBL; MT450723; QPD99059.1; -; mRNA.
DR AlphaFoldDB; P0DM29; -.
DR SMR; P0DM29; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; 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.
PE 1: Evidence at protein level;
KW Calcium channel impairing toxin; Cardiotoxin; Disulfide bond;
KW Ion channel impairing toxin; Knottin; Nucleus; Secreted; Signal; Toxin.
FT SIGNAL 1..23
FT /evidence="ECO:0000305|PubMed:30282983"
FT CHAIN 24..68
FT /note="Intracellular calcium channel modulator CCP-Ts"
FT /evidence="ECO:0000305|PubMed:30282983"
FT /id="PRO_0000446290"
FT DISULFID 33..47
FT /evidence="ECO:0000250|UniProtKB:P59868"
FT DISULFID 40..53
FT /evidence="ECO:0000250|UniProtKB:P59868"
FT DISULFID 46..62
FT /evidence="ECO:0000250|UniProtKB:P59868"
FT MUTAGEN 24..36
FT /note="Missing: Peptide(14-39); No change in nuclear
FT localization but complete loss of pharmacological activity
FT (calcium transient and contraction frequency), shows
FT selective internalization properties in specific cell
FT lines."
FT /evidence="ECO:0000269|PubMed:30282983"
FT MUTAGEN 63..68
FT /note="Missing: Peptide(14-39); No change in nuclear
FT localization but complete loss of pharmacological activity
FT (calcium transient and contraction frequency), shows
FT selective internalization properties in specific cell
FT lines."
FT /evidence="ECO:0000269|PubMed:30282983"
SQ SEQUENCE 68 AA; 7298 MW; 10F9DA56BE8FC5E7 CRC64;
MNPKLLIVIG LLLATGVCSF AKALDEESLR KECNHLNEPC DSDGDCCTSS EQCISTGSKY
FCKGKQGP
