ID   VKTHC_DENAN             Reviewed;          60 AA.
AC   P81658;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   30-MAY-2000, sequence version 1.
DT   25-MAY-2022, entry version 100.
DE   RecName: Full=Kunitz-type serine protease inhibitor homolog calcicludine;
DE            Short=CAC;
DE   AltName: Full=L-type calcium channel blocker;
OS   Dendroaspis angusticeps (Eastern green mamba) (Naja angusticeps).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Elapidae; Elapinae; Dendroaspis.
OX   NCBI_TaxID=8618;
RN   [1]
RP   PROTEIN SEQUENCE.
RC   TISSUE=Venom;
RX   PubMed=8302860; DOI=10.1073/pnas.91.3.878;
RA   Schweitz H., Heurteaux C., Bois P., Moinier D., Romey G., Lazdunski M.;
RT   "Calcicludine, a venom peptide of the Kunitz-type protease inhibitor
RT   family, is a potent blocker of high-threshold Ca2+ channels with a high
RT   affinity for L-type channels in cerebellar granule neurons.";
RL   Proc. Natl. Acad. Sci. U.S.A. 91:878-882(1994).
RN   [2]
RP   STRUCTURE BY NMR.
RX   PubMed=10081964;
RX   DOI=10.1002/(sici)1097-0134(19990301)34:4<520::aid-prot11>3.0.co;2-n;
RA   Gilquin B., Lecoq A., Desne F., Guenneugues M., Zinn-Justin S., Menez A.;
RT   "Conformational and functional variability supported by the BPTI fold:
RT   solution structure of the Ca2+ channel blocker calcicludine.";
RL   Proteins 34:520-532(1999).
CC   -!- FUNCTION: Potent blocker of high-voltage-activated calcium ion channels
CC       in the nanomolar range, particularly the L-type channels in cerebellar
CC       granule cells. The sensitivity of L-, N- and P-type channels to CAC is
CC       tissue and species-dependent. Blocks the L-type current of cardiac
CC       cells, depressing cardiac contractility.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC   -!- SIMILARITY: Belongs to the venom Kunitz-type family. {ECO:0000305}.
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DR   PIR; A36989; A36989.
DR   PDB; 1BF0; NMR; -; A=1-60.
DR   PDB; 5YV7; X-ray; 2.40 A; A=1-60.
DR   PDB; 6KZF; X-ray; 2.52 A; A=1-60.
DR   PDBsum; 1BF0; -.
DR   PDBsum; 5YV7; -.
DR   PDBsum; 6KZF; -.
DR   AlphaFoldDB; P81658; -.
DR   SMR; P81658; -.
DR   MEROPS; I02.056; -.
DR   PRIDE; P81658; -.
DR   EvolutionaryTrace; P81658; -.
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:0004867; F:serine-type endopeptidase inhibitor activity; IEA:InterPro.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   CDD; cd00109; KU; 1.
DR   Gene3D; 4.10.410.10; -; 1.
DR   InterPro; IPR002223; Kunitz_BPTI.
DR   InterPro; IPR036880; Kunitz_BPTI_sf.
DR   InterPro; IPR020901; Prtase_inh_Kunz-CS.
DR   Pfam; PF00014; Kunitz_BPTI; 1.
DR   PRINTS; PR00759; BASICPTASE.
DR   SMART; SM00131; KU; 1.
DR   SUPFAM; SSF57362; SSF57362; 1.
DR   PROSITE; PS00280; BPTI_KUNITZ_1; 1.
DR   PROSITE; PS50279; BPTI_KUNITZ_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Calcium channel impairing toxin; Cardiotoxin;
KW   Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW   Neurotoxin; Secreted; Toxin.
FT   CHAIN           1..60
FT                   /note="Kunitz-type serine protease inhibitor homolog
FT                   calcicludine"
FT                   /id="PRO_0000155447"
FT   DOMAIN          7..57
FT                   /note="BPTI/Kunitz inhibitor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT   DISULFID        7..57
FT   DISULFID        16..40
FT   DISULFID        32..53
FT   HELIX           5..8
FT                   /evidence="ECO:0007829|PDB:5YV7"
FT   STRAND          15..17
FT                   /evidence="ECO:0007829|PDB:5YV7"
FT   STRAND          20..26
FT                   /evidence="ECO:0007829|PDB:5YV7"
FT   TURN            27..30
FT                   /evidence="ECO:0007829|PDB:5YV7"
FT   STRAND          31..37
FT                   /evidence="ECO:0007829|PDB:5YV7"
FT   STRAND          39..41
FT                   /evidence="ECO:0007829|PDB:5YV7"
FT   STRAND          47..49
FT                   /evidence="ECO:0007829|PDB:5YV7"
FT   HELIX           50..58
FT                   /evidence="ECO:0007829|PDB:5YV7"
SQ   SEQUENCE   60 AA;  6986 MW;  3339405B78A7BA18 CRC64;
     WQPPWYCKEP VRIGSCKKQF SSFYFKWTAK KCLPFLFSGC GGNANRFQTI GECRKKCLGK