ID FCLN_PLAF7 Reviewed; 1193 AA. AC Q76NL8; Q9U7N7; DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 23-FEB-2022, entry version 117. DE RecName: Full=Falcilysin {ECO:0000303|PubMed:10542284}; DE EC=3.4.24.- {ECO:0000269|PubMed:17074076}; GN Name=FLN {ECO:0000303|PubMed:17074076}; GN ORFNames=PF3D7_1360800 {ECO:0000312|EMBL:CAD52728.1}; OS Plasmodium falciparum (isolate 3D7). OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida; OC Plasmodiidae; Plasmodium; Plasmodium (Laverania). OX NCBI_TaxID=36329 {ECO:0000312|Proteomes:UP000001450}; RN [1] {ECO:0000312|EMBL:AAF06062.1} RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=3D7 {ECO:0000312|EMBL:AAF06062.1}; RX PubMed=10542284; DOI=10.1074/jbc.274.45.32411; RA Eggleson K.K., Duffin K.L., Goldberg D.E.; RT "Identification and characterization of falcilysin, a metallopeptidase RT involved in hemoglobin catabolism within the malaria parasite Plasmodium RT falciparum."; RL J. Biol. Chem. 274:32411-32417(1999). RN [2] {ECO:0000312|Proteomes:UP000001450} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=3D7 {ECO:0000312|Proteomes:UP000001450}; RX PubMed=12368864; DOI=10.1038/nature01097; RA Gardner M.J., Hall N., Fung E., White O., Berriman M., Hyman R.W., RA Carlton J.M., Pain A., Nelson K.E., Bowman S., Paulsen I.T., James K.D., RA Eisen J.A., Rutherford K.M., Salzberg S.L., Craig A., Kyes S., Chan M.-S., RA Nene V., Shallom S.J., Suh B., Peterson J., Angiuoli S., Pertea M., RA Allen J., Selengut J., Haft D., Mather M.W., Vaidya A.B., Martin D.M.A., RA Fairlamb A.H., Fraunholz M.J., Roos D.S., Ralph S.A., McFadden G.I., RA Cummings L.M., Subramanian G.M., Mungall C., Venter J.C., Carucci D.J., RA Hoffman S.L., Newbold C., Davis R.W., Fraser C.M., Barrell B.G.; RT "Genome sequence of the human malaria parasite Plasmodium falciparum."; RL Nature 419:498-511(2002). RN [3] {ECO:0000312|Proteomes:UP000001450} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=3D7 {ECO:0000312|Proteomes:UP000001450}; RX PubMed=12368867; DOI=10.1038/nature01095; RA Hall N., Pain A., Berriman M., Churcher C.M., Harris B., Harris D., RA Mungall K.L., Bowman S., Atkin R., Baker S., Barron A., Brooks K., RA Buckee C.O., Burrows C., Cherevach I., Chillingworth C., Chillingworth T., RA Christodoulou Z., Clark L., Clark R., Corton C., Cronin A., Davies R.M., RA Davis P., Dear P., Dearden F., Doggett J., Feltwell T., Goble A., RA Goodhead I., Gwilliam R., Hamlin N., Hance Z., Harper D., Hauser H., RA Hornsby T., Holroyd S., Horrocks P., Humphray S., Jagels K., James K.D., RA Johnson D., Kerhornou A., Knights A., Konfortov B., Kyes S., Larke N., RA Lawson D., Lennard N., Line A., Maddison M., Mclean J., Mooney P., RA Moule S., Murphy L., Oliver K., Ormond D., Price C., Quail M.A., RA Rabbinowitsch E., Rajandream M.A., Rutter S., Rutherford K.M., Sanders M., RA Simmonds M., Seeger K., Sharp S., Smith R., Squares R., Squares S., RA Stevens K., Taylor K., Tivey A., Unwin L., Whitehead S., Woodward J.R., RA Sulston J.E., Craig A., Newbold C., Barrell B.G.; RT "Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13."; RL Nature 419:527-531(2002). RN [4] {ECO:0000305} RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND DEVELOPMENTAL RP STAGE. RX PubMed=17074076; DOI=10.1111/j.1365-2958.2006.05443.x; RA Ponpuak M., Klemba M., Park M., Gluzman I.Y., Lamppa G.K., Goldberg D.E.; RT "A role for falcilysin in transit peptide degradation in the Plasmodium RT falciparum apicoplast."; RL Mol. Microbiol. 63:314-334(2007). RN [5] {ECO:0007744|PDB:3S5H, ECO:0007744|PDB:3S5I, ECO:0007744|PDB:3S5K, ECO:0007744|PDB:3S5M} RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) IN COMPLEX WITH ZINC. RA Morgunova E., Ponpuak M., Istvan E., Popov A., Goldberg D., Eneqvist T.; RT "Crystal structures of falcilysin, a M16 metalloprotease from the malaria RT parasite Plasmodium falciparum."; RL Submitted (MAY-2011) to the PDB data bank. CC -!- FUNCTION: In the food vacuole, acts downstream of proteases plasmepsins CC PMI and PMII and falcipains during the catabolism of host hemoglobin by CC cleaving peptide fragments of alpha and beta hemoglobin subunits CC generated by PMI and PMII and falcipains (PubMed:17074076). In the CC apicoplast, degrades apicoplast transit peptides after their cleavage CC (PubMed:17074076). Prefers bulky hydrophobic amino acids in the P1' CC position at both acidic and neutral pH (By similarity). At P2', prefers CC hydrophobic residues at acidic pH; at neutral pH, these same residues CC are abundant but prefers Arg (By similarity). At P3', prefers CC hydrophobic residues, especially Met, at both pH conditions. At P4' and CC P5', prefers acidic residues at acidic pH, however, at neutral pH, the CC enzyme is less selective at these positions (By similarity). The CC optimal site cleavage at acidic pH is YNEHS-|-FFMEE and, at neutral pH, CC MKRHS-|-FRMRG (By similarity). {ECO:0000250|UniProtKB:A0A0L7KF24, CC ECO:0000269|PubMed:17074076}. CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000250|UniProtKB:A0A0L7KF24}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|Ref.5}; CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:A0A0L7KF24}. CC -!- SUBCELLULAR LOCATION: Vacuole membrane {ECO:0000269|PubMed:17074076}; CC Peripheral membrane protein {ECO:0000250|UniProtKB:A0A0L7KF24}. CC Plastid, apicoplast {ECO:0000269|PubMed:17074076}. Vesicle CC {ECO:0000250|UniProtKB:A0A0L7KF24}. Note=Localizes to the food (or CC digestive) vacuole, an acidic vacuole where host hemoglobin is digested CC (PubMed:17074076). During the trophozoite and early to mid-schizont CC stages, localizes to the apicoplast (PubMed:17074076). CC {ECO:0000269|PubMed:17074076}. CC -!- DEVELOPMENTAL STAGE: Expressed during the asexual blood stage; CC expression begins at the late ring, early trophozoite stage, increases CC in the mid-trophozoite stage, and persists throughout the schizont CC stage (at protein level). {ECO:0000269|PubMed:17074076}. CC -!- PTM: Does not require processing for targeting to the food vacuole or CC maturation. {ECO:0000250|UniProtKB:A0A0L7KF24}. CC -!- SIMILARITY: Belongs to the peptidase M16 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; AF123458; AAF06062.1; -; Genomic_DNA. DR EMBL; AL844509; CAD52728.1; -; Genomic_DNA. DR RefSeq; XP_001350319.1; XM_001350283.1. DR PDB; 3S5H; X-ray; 1.60 A; A=1-1193. DR PDB; 3S5I; X-ray; 1.74 A; A=1-1193. DR PDB; 3S5K; X-ray; 3.20 A; A=1-1193. DR PDB; 3S5M; X-ray; 1.55 A; A=1-1193. DR PDBsum; 3S5H; -. DR PDBsum; 3S5I; -. DR PDBsum; 3S5K; -. DR PDBsum; 3S5M; -. DR SMR; Q76NL8; -. DR IntAct; Q76NL8; 4. DR STRING; 5833.PF13_0322; -. DR BindingDB; Q76NL8; -. DR ChEMBL; CHEMBL4295876; -. DR MEROPS; M16.011; -. DR SwissPalm; Q76NL8; -. DR PRIDE; Q76NL8; -. DR EnsemblProtists; CAD52728; CAD52728; PF3D7_1360800. DR GeneID; 814283; -. DR KEGG; pfa:PF3D7_1360800; -. DR VEuPathDB; PlasmoDB:PF3D7_1360800; -. DR HOGENOM; CLU_009165_1_0_1; -. DR InParanoid; Q76NL8; -. DR OMA; MTYPDKT; -. DR PhylomeDB; Q76NL8; -. DR Proteomes; UP000001450; Chromosome 13. DR GO; GO:0020011; C:apicoplast; IDA:GeneDB. DR GO; GO:0020020; C:food vacuole; IDA:GeneDB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:UniProtKB. DR GO; GO:0042540; P:hemoglobin catabolic process; IDA:GeneDB. DR GO; GO:0016485; P:protein processing; IBA:GO_Central. DR InterPro; IPR011249; Metalloenz_LuxS/M16. DR InterPro; IPR011765; Pept_M16_N. DR InterPro; IPR007863; Peptidase_M16_C. DR InterPro; IPR013578; Peptidase_M16C_assoc. DR Pfam; PF08367; M16C_assoc; 2. DR Pfam; PF00675; Peptidase_M16; 1. DR Pfam; PF05193; Peptidase_M16_C; 1. DR SMART; SM01264; M16C_associated; 1. DR SUPFAM; SSF63411; SSF63411; 4. PE 1: Evidence at protein level; KW 3D-structure; Apicoplast; Coiled coil; Hydrolase; Membrane; Metal-binding; KW Metalloprotease; Plastid; Protease; Reference proteome; Vacuole; Zinc. FT CHAIN 1..1193 FT /note="Falcilysin" FT /id="PRO_0000454646" FT COILED 583..619 FT /evidence="ECO:0000255" FT ACT_SITE 132 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10096" FT METAL 129 FT /note="Zinc; via tele nitrogen" FT /evidence="ECO:0000269|Ref.5, ECO:0007744|PDB:3S5K, FT ECO:0007744|PDB:3S5M" FT METAL 133 FT /note="Zinc; via tele nitrogen" FT /evidence="ECO:0000269|Ref.5, ECO:0007744|PDB:3S5K, FT ECO:0007744|PDB:3S5M" FT METAL 243 FT /note="Zinc" FT /evidence="ECO:0000269|Ref.5, ECO:0007744|PDB:3S5K, FT ECO:0007744|PDB:3S5M" SQ SEQUENCE 1193 AA; 138863 MW; DBA1FC548ED5056A CRC64; MNLTKLMKVI GYINIITNCV QSFTNRADKK RYNVFAKSFI NTINTNLYTF KAVMSKTPEW IHEKSPKHNS YDIIEKRYNE EFKMTYTVYQ HKKAKTQVIS LGTNDPLDVE QAFAFYVKTL THSGKGIPHI LEHSVLSGSK NYNYKNSIGL LEKGTLHTHL NAYTFNDRTV YMAGSMNNKD FFNIMGVYMD SVFQPNVLEN KYIFETEGWT YEVEKLKEDE KGKAEIPQMK DYKVSFNGIV YNEMKGALSS PLEDLYHEEM KYMFPDNVHS NNSGGDPKEI TNLTYEEFKE FYYKNYNPKK VKVFFFSKNN PTELLNFVDQ YLGQLDYSKY RDDAVESVEY QTYKKGPFYI KKKYGDHSEE KENLVSVAWL LNPKVDKTNN HNNNHSNNQS SENNGYSNGS HSSDLSLENP TDYFVLLIIN NLLIHTPESV LYKALTDCGL GNNVIDRGLN DSLVQYIFSI GLKGIKRNNE KIKNFDKVHY EVEDVIMNAL KKVVKEGFNK SAVEASINNI EFILKEANLK TSKSIDFVFE MTSKLNYNRD PLLIFEFEKY LNIVKNKIKN EPMYLEKFVE KHFINNAHRS VILLEGDENY AQEQENLEKQ ELKKRIENFN EQEKEQVIKN FEELSKYKNA EESPEHLNKF PIISISDLNK KTLEVPVNVY FTNINENNNI METYNKLKTN EHMLKDNMDV FLKKYVLKND KHNTNNNNNN NNNMDYSFTE TKYEGNVPIL VYEMPTTGIV YLQFVFSLDH LTVDELAYLN LFKTLILENK TNKRSSEDFV ILREKNIGSM SANVALYSKD DHLNVTDKYN AQALFNLEMH VLSHKCNDAL NIALEAVKES DFSNKKKVID ILKRKINGMK TTFSEKGYAI LMKYVKAHLN SKHYAHNIIY GYENYLKLQE QLELAENDFK TLENILVRIR NKIFNKKNLM VSVTSDYGAL KHLFVNSNES LKNLVSYFEE NDKYINDMQN KVNDPTVMGW NEEIKSKKLF DEEKVKKEFF VLPTFVNSVS MSGILFKPGE YLDPSFTVIV AALKNSYLWD TVRGLNGAYG VFADIEYDGS VVFLSARDPN LEKTLATFRE SAKGLRKMAD TMTENDLLRY IINTIGTIDK PRRGIELSKL SFLRLISNES EQDRVEFRKR IMNTKKEDFY KFADLLESKV NEFEKNIVII TTKEKANEYI ANVDGEFKKV LIE //