FCLN_PLAFX
ID FCLN_PLAFX Reviewed; 1193 AA.
AC A0A0L7KF24;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 11-NOV-2015, sequence version 1.
DT 03-AUG-2022, entry version 23.
DE RecName: Full=Falcilysin {ECO:0000303|PubMed:10542284};
DE EC=3.4.24.- {ECO:0000269|PubMed:10542284, ECO:0000269|PubMed:12876284};
GN Name=FLN {ECO:0000303|PubMed:12798513};
GN ORFNames=PFHG_03273 {ECO:0000312|EMBL:KOB61499.1};
OS Plasmodium falciparum (isolate HB3).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=137071 {ECO:0000312|Proteomes:UP000054289};
RN [1] {ECO:0000312|Proteomes:UP000054289}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=HB3 {ECO:0000312|Proteomes:UP000054289};
RG The Broad Institute Genome Sequencing Platform;
RA Volkman S.K., Neafsey D.E., Dash A.P., Chitnis C.E., Hartl D.L.,
RA Young S.K., Zeng Q., Koehrsen M., Alvarado L., Berlin A., Borenstein D.,
RA Chapman S.B., Chen Z., Engels R., Freedman E., Gellesch M., Goldberg J.,
RA Griggs A., Gujja S., Heilman E.R., Heiman D.I., Howarth C., Jen D.,
RA Larson L., Mehta T., Neiman D., Park D., Pearson M., Roberts A., Saif S.,
RA Shea T., Shenoy N., Sisk P., Stolte C., Sykes S., Walk T., White J.,
RA Yandava C., Haas B., Henn M.R., Nusbaum C., Birren B.;
RT "Annotation of Plasmodium falciparum HB3.";
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000305}
RP PROTEIN SEQUENCE OF 56-64; 76-83; 549-555; 619-626; 685-693; 897-907;
RP 971-984 AND 1189-1193, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBUNIT, AND
RP SUBCELLULAR LOCATION.
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 [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, DEVELOPMENTAL STAGE, AND LACK OF PROTEOLYTIC CLEAVAGE.
RX PubMed=12876284; DOI=10.1074/jbc.m306842200;
RA Murata C.E., Goldberg D.E.;
RT "Plasmodium falciparum falcilysin: a metalloprotease with dual
RT specificity.";
RL J. Biol. Chem. 278:38022-38028(2003).
RN [4] {ECO:0000305}
RP DEVELOPMENTAL STAGE, AND LACK OF PROTEOLYTIC CLEAVAGE.
RX PubMed=12798513; DOI=10.1016/s0166-6851(03)00098-7;
RA Murata C.E., Goldberg D.E.;
RT "Plasmodium falciparum falcilysin: an unprocessed food vacuole enzyme.";
RL Mol. Biochem. Parasitol. 129:123-126(2003).
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:10542284,
CC PubMed:12876284). In the apicoplast, degrades apicoplast transit
CC peptides after their cleavage (By similarity). Prefers bulky
CC hydrophobic amino acids in the P1' position at both acidic and neutral
CC pH (PubMed:12876284). At P2', prefers hydrophobic residues at acidic
CC pH; at neutral pH, these same residues are abundant but prefers Arg
CC (PubMed:12876284). At P3', prefers hydrophobic residues, especially
CC Met, at both pH conditions. At P4' and P5', prefers acidic residues at
CC acidic pH, however, at neutral pH, the enzyme is less selective at
CC these positions (PubMed:12876284). The optimal site cleavage at acidic
CC pH is YNEHS-|-FFMEE and, at neutral pH, MKRHS-|-FRMRG
CC (PubMed:12876284). {ECO:0000250|UniProtKB:Q76NL8,
CC ECO:0000269|PubMed:10542284, ECO:0000269|PubMed:12876284}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:10542284};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q76NL8};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 5 (food vacuole) (PubMed:12876284). Optimum pH is 7
CC (PubMed:12876284). {ECO:0000269|PubMed:12876284};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:10542284}.
CC -!- SUBCELLULAR LOCATION: Vacuole membrane {ECO:0000269|PubMed:10542284};
CC Peripheral membrane protein {ECO:0000269|PubMed:12876284}. Plastid,
CC apicoplast {ECO:0000250|UniProtKB:Q76NL8}. Vesicle
CC {ECO:0000269|PubMed:12876284}. Note=Localizes to the food (or
CC digestive) vacuole, an acidic vacuole where host hemoglobin is digested
CC (PubMed:10542284, PubMed:12876284). During the trophozoite and early to
CC mid-schizont stages, localizes to the apicoplast (By similarity).
CC {ECO:0000250|UniProtKB:Q76NL8, ECO:0000269|PubMed:10542284,
CC ECO:0000269|PubMed:12876284}.
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:12798513,
CC ECO:0000269|PubMed:12876284}.
CC -!- PTM: Does not require processing for targeting to the food vacuole or
CC maturation. {ECO:0000269|PubMed:12798513, ECO:0000269|PubMed:12876284}.
CC -!- MISCELLANEOUS: Met-54 may be used as the initiation methionine.
CC {ECO:0000303|PubMed:12798513}.
CC -!- SIMILARITY: Belongs to the peptidase M16 family. {ECO:0000305}.
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DR EMBL; CH672006; KOB61499.1; -; Genomic_DNA.
DR EnsemblProtists; KOB61499; KOB61499; PFHG_03273.
DR VEuPathDB; PlasmoDB:PfHB3_130067200; -.
DR Proteomes; UP000054289; Unassembled WGS sequence.
DR GO; GO:0020011; C:apicoplast; IEA:UniProtKB-SubCell.
DR GO; GO:0020020; C:food vacuole; IDA:UniProtKB.
DR GO; GO:0005774; C:vacuolar membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:UniProtKB.
DR GO; GO:0044002; P:acquisition of nutrients from host; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
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 Apicoplast; Coiled coil; Direct protein sequencing; Hydrolase; Membrane;
KW Metal-binding; Metalloprotease; Plastid; Protease; Reference proteome;
KW Vacuole; Zinc.
FT CHAIN 1..1193
FT /note="Falcilysin"
FT /id="PRO_0000454645"
FT REGION 376..404
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 583..619
FT /evidence="ECO:0000255"
FT ACT_SITE 132
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10096"
FT BINDING 129
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q76NL8"
FT BINDING 133
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q76NL8"
FT BINDING 243
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q76NL8"
SQ SEQUENCE 1193 AA; 138896 MW; 6F029100C417AD9C CRC64;
MNLTKLMKVF 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 KIKIFDKVHY
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
