3SA1_NAJSU
ID 3SA1_NAJSU Reviewed; 81 AA.
AC A0A7T7DMY7;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 02-JUN-2021, sequence version 1.
DT 03-AUG-2022, entry version 4.
DE RecName: Full=Cytotoxin 1 {ECO:0000303|PubMed:33263003};
DE Short=CX1 {ECO:0000305};
DE AltName: Full=Cardiotoxin-1 {ECO:0000305};
DE Short=CTX-1 {ECO:0000305};
DE Short=CTX1 {ECO:0000305};
DE Flags: Precursor;
OS Naja sumatrana (Equatorial spitting cobra) (Naja tripudians var.
OS sumatrana).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Elapinae; Naja.
OX NCBI_TaxID=1108807;
RN [1] {ECO:0000312|EMBL:QQL13717.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland {ECO:0000312|EMBL:QQL13717.1};
RX PubMed=30754700; DOI=10.3390/toxins11020104;
RA Chong H.P., Tan K.Y., Tan N.H., Tan C.H.;
RT "Exploring the Diversity and Novelty of Toxin Genes in Naja sumatrana, the
RT Equatorial Spitting Cobra from Malaysia through De Novo Venom-Gland
RT Transcriptomics.";
RL Toxins 11:0-0(2019).
RN [2] {ECO:0000305}
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND PHARMACEUTICAL.
RX PubMed=33263003; DOI=10.3389/fmolb.2020.583587;
RA Chong H.P., Tan K.Y., Tan C.H.;
RT "Cytotoxicity of Snake Venoms and Cytotoxins From Two Southeast Asian
RT Cobras (Naja sumatrana, Naja kaouthia): Exploration of Anticancer
RT Potential, Selectivity, and Cell Death Mechanism.";
RL Front. Mol. Biosci. 7:583587-583587(2020).
CC -!- FUNCTION: Shows cytolytic activity on many different cells by forming
CC pores in lipid membranes (By similarity). Exhibits concentration-
CC dependent growth inhibitory effects in the lung cell lines A549
CC (IC(50)= 0.88) and NL20 (IC(50)= 1.91), in the prostate cell lines PC-3
CC (IC(50)= 3.13 ug/ml) and RWPE-1 (IC(50)=0.35 ug/ml), and in the breast
CC cell lines MCF-7 (IC(50)= 9.10 ug/ml) and 184B5 (IC(50)=6.21 ug/ml),
CC with high selectivity for the lung cancer cell line A549 (selectivity
CC index=2.17) (PubMed:33263003). Induces primarily necrosis in the A549
CC lung cancer cell line, and mainly caspase-independent late apoptosis in
CC the breast cancer cells line MCF-7 and in the prostate cancer cell line
CC PC-3 (PubMed:33263003). {ECO:0000250|UniProtKB:P01470,
CC ECO:0000269|PubMed:33263003}.
CC -!- SUBUNIT: Monomer in solution; homodimer and oligomer in the presence of
CC negatively charged lipids forming a pore with a size ranging between 20
CC and 30 Angstroms. {ECO:0000250|UniProtKB:P60301}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:33263003}. Target
CC cell membrane {ECO:0000250|UniProtKB:P60301}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:33263003}.
CC -!- PHARMACEUTICAL: Exhibits anticancer properties by inhibiting growth in
CC the A549 lung cancer cell line with high selectivity by inducing
CC necrosis, but not in prostate (PC-3) and breast (MCF-7) cancer cell
CC lines. {ECO:0000269|PubMed:33263003}.
CC -!- MISCELLANEOUS: Is classified as a P-type cytotoxin, since a proline
CC residue stands at position 51 (Pro-31 in standard classification).
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the snake three-finger toxin family. Short-chain
CC subfamily. Type IA cytotoxin sub-subfamily. {ECO:0000305}.
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DR EMBL; MT977669; QQL13717.1; -; mRNA.
DR SMR; A0A7T7DMY7; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0019835; P:cytolysis; IEA:UniProtKB-KW.
DR CDD; cd00206; snake_toxin; 1.
DR Gene3D; 2.10.60.10; -; 1.
DR InterPro; IPR003572; Cytotoxin_Cobra.
DR InterPro; IPR003571; Snake_3FTx.
DR InterPro; IPR045860; Snake_toxin-like_sf.
DR InterPro; IPR018354; Snake_toxin_con_site.
DR PRINTS; PR00282; CYTOTOXIN.
DR SUPFAM; SSF57302; SSF57302; 1.
PE 1: Evidence at protein level;
KW Cytolysis; Disulfide bond; Membrane; Pharmaceutical; Secreted; Signal;
KW Target cell membrane; Target membrane; Toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..81
FT /note="Cytotoxin 1"
FT /id="PRO_0000454225"
FT DISULFID 24..42
FT /evidence="ECO:0000250|UniProtKB:P60301"
FT DISULFID 35..59
FT /evidence="ECO:0000250|UniProtKB:P60301"
FT DISULFID 63..74
FT /evidence="ECO:0000250|UniProtKB:P60301"
FT DISULFID 75..80
FT /evidence="ECO:0000250|UniProtKB:P60301"
SQ SEQUENCE 81 AA; 9054 MW; 70FE0A9142F24C95 CRC64;
MKTLLLTLVV VTIVCLDLGY TLKCNKLVPL FYKTCPAGKN LCYKMYMVAT PKVPVKRGCI
DVCPKSSLLV KYVCCNTDRC N
