PLIGA_CRODU
ID PLIGA_CRODU Reviewed; 200 AA.
AC Q90358;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 63.
DE RecName: Full=Phospholipase A2 inhibitor CNF {ECO:0000305};
DE AltName: Full=Crotalus neutralizing factor {ECO:0000303|PubMed:33387548};
DE Short=CNF {ECO:0000303|PubMed:33387548};
DE AltName: Full=Crotoxin inhibitor from Crotulus serum {ECO:0000303|PubMed:7851385};
DE Short=CICS {ECO:0000303|PubMed:7851385};
DE AltName: Full=Snake blood gamma-PLI {ECO:0000303|PubMed:24820993};
DE Short=Sb-gamma-PLI {ECO:0000303|PubMed:24820993};
DE Short=gamma-PLI {ECO:0000303|PubMed:33387548};
DE Flags: Precursor;
OS Crotalus durissus terrificus (South American rattlesnake).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Crotalus.
OX NCBI_TaxID=8732;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBUNIT.
RC TISSUE=Liver;
RX PubMed=8195214; DOI=10.1016/s0021-9258(17)40730-7;
RA Fortes-Dias C.L., Lin Y., Ewell J., Diniz C.R., Liu T.-Y.;
RT "A phospholipase A2 inhibitor from the plasma of the South American
RT rattlesnake (Crotalus durissus terrificus): protein structure, genomic
RT structure and mechanism of action.";
RL J. Biol. Chem. 269:15646-15651(1994).
RN [2]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Plasma;
RX PubMed=1949070; DOI=10.1016/0041-0101(91)90082-3;
RA Fortes-Dias C.L., Fonseca B.C., Kochva E., Diniz C.R.;
RT "Purification and properties of an antivenom factor from the plasma of the
RT South American rattlesnake (Crotalus durissus terrificus).";
RL Toxicon 29:997-1008(1991).
RN [3]
RP PROTEIN SEQUENCE OF 20-49, FUNCTION, AND PROBABLE PARTIAL GLYCOSYLATION.
RC TISSUE=Serum;
RX PubMed=7851385; DOI=10.1111/j.1432-1033.1995.tb20355.x;
RA Perales J., Villela C., Domont G.B., Choumet V., Saliou B., Moussatche H.,
RA Bon C., Faure G.;
RT "Molecular structure and mechanism of action of the crotoxin inhibitor from
RT Crotalus durissus terrificus serum.";
RL Eur. J. Biochem. 227:19-26(1995).
RN [4]
RP PROTEIN SEQUENCE OF 20-39, SUBUNIT, MASS SPECTROMETRY, 3D-STRUCTURE
RP MODELING, AND GLYCOSYLATION.
RC TISSUE=Plasma;
RX PubMed=24820993; DOI=10.1016/j.bbapap.2014.05.001;
RA Fortes-Dias C.L., Ortolani P.L., Fernandes C.A., Lobo K.R.,
RA Amaral de Melo L., Borges M.H., Pazin W.M., de Oliveira Neto O.,
RA Fernandez R.M., Fontes M.R.;
RT "Insights on the structure of native CNF, an endogenous phospholipase A2
RT inhibitor from Crotalus durissus terrificus, the South American
RT rattlesnake.";
RL Biochim. Biophys. Acta 1844:1569-1579(2014).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CBD.
RX PubMed=10903514; DOI=10.1046/j.1432-1327.2000.01532.x;
RA Faure G., Villela C., Perales J., Bon C.;
RT "Interaction of the neurotoxic and nontoxic secretory phospholipases A2
RT with the crotoxin inhibitor from Crotalus serum.";
RL Eur. J. Biochem. 267:4799-4808(2000).
RN [6]
RP FUNCTION.
RC TISSUE=Plasma;
RX PubMed=32183984; DOI=10.1016/j.imbio.2020.151932;
RA Macedo Tavares M.N., Reis V.P., Alves Rego C.M., Paloschi M.V.,
RA Santana H.M., Ferreira E Ferreira A.A., Souza Silva M.D., Setubal S.S.,
RA Fortes-Dias C.L., Zuliani J.P.;
RT "Crotalus neutralising factor and its role in human leukocyte modulation.";
RL Immunobiology 225:151932-151932(2020).
RN [7]
RP FUNCTION.
RC TISSUE=Plasma;
RX PubMed=33387548; DOI=10.1016/j.toxicon.2020.12.016;
RA Pinto E.K.R., Souza N.M.V., Maciel F.V., de Abreu T.A.G., Reis H.F.F.,
RA Ortolani P.L., Fortes-Dias C.L., Cavalcante W.L.G.;
RT "Crotalus neutralizing factor (CNF) inhibits the toxic effects of Crotoxin
RT at mouse neuromuscular preparations.";
RL Toxicon 191:48-53(2021).
CC -!- FUNCTION: Inhibits the PLA2 activity of crotoxin (CTX) by replacing the
CC acid subunit (CA) in the CTX complex (PubMed:8195214, PubMed:1949070,
CC PubMed:7851385, PubMed:10903514). Displays a pro-inflammatory action
CC through activation of important main signaling pathways for human
CC leukocytes, in vitro (PubMed:32183984). Abolishes both the muscle-
CC paralyzing and muscle-damaging activities of CTX in mice phrenic nerve-
CC diaphragm muscle preparations (PubMed:33387548).
CC {ECO:0000269|PubMed:10903514, ECO:0000269|PubMed:1949070,
CC ECO:0000269|PubMed:32183984, ECO:0000269|PubMed:33387548,
CC ECO:0000269|PubMed:7851385, ECO:0000269|PubMed:8195214}.
CC -!- SUBUNIT: Occurs as a mixture of oligomers (PubMed:24820993). Tetrameric
CC arrangement appears to be the predominant quaternary structure
CC (PubMed:24820993). Interacts with phospholipase A2 crotoxin basic
CC subunit CBd; the interaction leads to dissociation of the CA-CB
CC heterodimer and to inhibition of PLA2 activity of the CB subunit
CC (PubMed:10903514). {ECO:0000269|PubMed:10903514,
CC ECO:0000269|PubMed:24820993}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10903514,
CC ECO:0000269|PubMed:1949070}. Note=Secreted in blood plasma.
CC {ECO:0000269|PubMed:1949070}.
CC -!- TISSUE SPECIFICITY: Expressed by the liver.
CC {ECO:0000305|PubMed:8195214}.
CC -!- PTM: The carbohydrate moiety increases the inhibition capacity of CNF,
CC but is not essential for activity and for oligomerization.
CC {ECO:0000269|PubMed:24820993}.
CC -!- MASS SPECTROMETRY: Mass=22201; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:24820993};
CC -!- SIMILARITY: Belongs to the CNF-like-inhibitor family. {ECO:0000305}.
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DR EMBL; U08289; AAA19162.1; -; mRNA.
DR PIR; A54020; A54020.
DR AlphaFoldDB; Q90358; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0019834; F:phospholipase A2 inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0032429; P:regulation of phospholipase A2 activity; IEA:InterPro.
DR Gene3D; 2.10.60.10; -; 1.
DR InterPro; IPR016054; LY6_UPA_recep-like.
DR InterPro; IPR016338; PLipase_A2-inh_a/b-type.
DR InterPro; IPR004126; PLipase_A2_inh.
DR InterPro; IPR045860; Snake_toxin-like_sf.
DR Pfam; PF02988; PLA2_inh; 1.
DR PIRSF; PIRSF002023; PLA2_inhib_alpha/gamma; 1.
DR SMART; SM00134; LU; 1.
DR SUPFAM; SSF57302; SSF57302; 2.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Phospholipase A2 inhibitor; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..200
FT /note="Phospholipase A2 inhibitor CNF"
FT /evidence="ECO:0000305|PubMed:1949070"
FT /id="PRO_0000022999"
FT CARBOHYD 176
FT /note="N-linked (GlcNAc...) asparagine; partial"
FT /evidence="ECO:0000305|PubMed:7851385"
FT DISULFID 22..46
FT /evidence="ECO:0000250|UniProtKB:Q7LZI1"
FT DISULFID 25..32
FT /evidence="ECO:0000250|UniProtKB:Q7LZI1"
FT DISULFID 39..67
FT /evidence="ECO:0000250|UniProtKB:Q7LZI1"
FT DISULFID 73..94
FT /evidence="ECO:0000250|UniProtKB:Q7LZI1"
FT DISULFID 95..100
FT /evidence="ECO:0000250|UniProtKB:Q7LZI1"
FT DISULFID 118..143
FT /evidence="ECO:0000250|UniProtKB:Q7LZI1"
FT DISULFID 136..165
FT /evidence="ECO:0000250|UniProtKB:Q7LZI1"
FT DISULFID 169..191
FT /evidence="ECO:0000250|UniProtKB:Q7LZI1"
SQ SEQUENCE 200 AA; 22267 MW; AE848DD6EDD9BBFF CRC64;
MKYLHTICLL FIFVARGNSR SCDFCHNIGK DCDGYEEECS SPEDVCGKVL LEISSASLSV
RTVHKNCFSS SICKLGQFDV NIGHHSYIRG RINCCEKELC EDQPFPGLPL SKPNGYYCPG
AIGLFTKDST EYEAICKGTE TKCINIVGHR YEQFPGDISY NLKGCVSSCP LLSLSNATFE
QNRNYLEKVE CKDAIRLASL
