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 22-FEB-2023, entry version 65. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U08289; AAA19162.1; -; mRNA. DR PIR; A54020; A54020. DR AlphaFoldDB; Q90358; -. DR iPTMnet; 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; CD59; 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 PANTHER; PTHR20914:SF9; COILED, ISOFORM A; 1. DR PANTHER; PTHR20914; LY6/PLAUR DOMAIN-CONTAINING PROTEIN 8; 1. DR Pfam; PF02988; PLA2_inh; 1. DR PIRSF; PIRSF002023; PLA2_inhib_alpha/gamma; 1. DR SMART; SM00134; LU; 1. DR SUPFAM; SSF57302; Snake toxin-like; 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 //