SUB2_PLAFA
ID SUB2_PLAFA Reviewed; 1342 AA.
AC O97364;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 25-MAY-2022, entry version 98.
DE RecName: Full=Subtilisin-like protease 2 {ECO:0000305};
DE EC=3.4.21.62 {ECO:0000305|PubMed:16322767};
DE AltName: Full=Merozoite surface sheddase {ECO:0000303|PubMed:16322767};
DE Short=MESH {ECO:0000303|PubMed:16322767};
DE AltName: Full=PfSUB2 {ECO:0000303|PubMed:10551362};
DE Flags: Precursor;
GN Name=SUB2 {ECO:0000303|PubMed:10551362};
OS Plasmodium falciparum.
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=5833 {ECO:0000312|EMBL:CAB37326.1};
RN [1] {ECO:0000312|EMBL:CAB37326.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBCELLULAR LOCATION, DEVELOPMENTAL
RP STAGE, AND PROTEOLYTIC CLEAVAGE.
RC STRAIN=T9/96 {ECO:0000312|EMBL:CAB37326.1};
RX PubMed=10551362; DOI=10.1016/s0166-6851(99)00122-x;
RA Hackett F., Sajid M., Martinez-Withers C., Blackman M.J.;
RT "PfSUB-2: a second subtilisin-like protein in Plasmodium falciparum
RT merozoites.";
RL Mol. Biochem. Parasitol. 103:183-195(1999).
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP DOMAIN, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=16322767; DOI=10.1371/journal.ppat.0010029;
RA Harris P.K., Yeoh S., Dluzewski A.R., O'Donnell R.A., Withers-Martinez C.,
RA Hackett F., Bannister L.H., Mitchell G.H., Blackman M.J.;
RT "Molecular identification of a malaria merozoite surface sheddase.";
RL PLoS Pathog. 1:241-251(2005).
RN [3] {ECO:0007744|PDB:2LU1}
RP STRUCTURE BY NMR OF 530-676.
RX PubMed=23011838; DOI=10.1002/prot.24187;
RA He Y., Chen Y., Oganesyan N., Ruan B., O'Brochta D., Bryan P.N., Orban J.;
RT "Solution NMR structure of a sheddase inhibitor prodomain from the malarial
RT parasite Plasmodium falciparum.";
RL Proteins 80:2810-2817(2012).
CC -!- FUNCTION: Serine protease which plays an essential role in the shedding
CC of AMA1, MSP1 and MSP7 from the surface of the invading merozoite; this
CC step is essential for productive invasion and the release of the
CC adhesion between the erythrocyte and the merozoite (PubMed:16322767).
CC May cleave TRAMP/PTTRAMP, thereby shedding TRAMP from the merozoite
CC surface during erythrocyte invasion (By similarity).
CC {ECO:0000250|UniProtKB:Q8IHZ5, ECO:0000269|PubMed:16322767}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of proteins with broad specificity for peptide
CC bonds, and a preference for a large uncharged residue in P1.
CC Hydrolyzes peptide amides.; EC=3.4.21.62;
CC Evidence={ECO:0000305|PubMed:16322767};
CC -!- ACTIVITY REGULATION: Activation may be calcium-dependent
CC (PubMed:16322767). Inhibited by the non-covalent interaction with the
CC cleaved propeptide (PubMed:16322767). {ECO:0000269|PubMed:16322767}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10551362,
CC ECO:0000269|PubMed:16322767}; Single-pass type I membrane protein
CC {ECO:0000305}. Cytoplasmic vesicle, secretory vesicle, microneme
CC membrane {ECO:0000269|PubMed:16322767}; Single-pass type I membrane
CC protein {ECO:0000305}. Note=In mature schizonts, localizes to
CC micronemes at the merozoite apical region (PubMed:10551362,
CC PubMed:16322767). Immediately after schizont rupture, secreted from the
CC micronemes to the merozoite surface where it redistributes in an actin-
CC dependent manner to accumulate at the posterior end of newly released
CC merozoites (PubMed:16322767). {ECO:0000269|PubMed:10551362,
CC ECO:0000269|PubMed:16322767}.
CC -!- DEVELOPMENTAL STAGE: Expressed during the parasite blood stage,
CC specifically in schizonts and merozoites (at protein level).
CC {ECO:0000269|PubMed:10551362}.
CC -!- DOMAIN: The propeptide domain acts as an intramolecular chaperone for
CC the folding of the catalytic domain (PubMed:16322767). Also acts as an
CC inhibitor of the catalytic domain thereby regulating SUB2 activity
CC during secretion (PubMed:16322767). {ECO:0000269|PubMed:16322767}.
CC -!- DOMAIN: The transmembrane domain is required for SUB2 progression
CC through the secretory pathway. {ECO:0000250|UniProtKB:Q8IHZ5}.
CC -!- DOMAIN: The cytoplasmic domain is required for the correct
CC redistribution at the merozoite surface and posterior capping but is
CC dispensable for its progression through the secretory pathway.
CC {ECO:0000250|UniProtKB:Q8IHZ5}.
CC -!- PTM: Proteolytically cleaved at the N-terminus to generate a 74kDa
CC intermediate which is further processed into a 72kDa form
CC (PubMed:10551362, PubMed:16322767). The first maturation cleavage is
CC autocatalytic, occurs in the ER and is necessary for the subsequent
CC SUB2 trafficking to the microneme (By similarity). The second cleavage
CC may be mediated by PMX/plasmepsin X (By similarity).
CC {ECO:0000250|UniProtKB:Q8IHZ5, ECO:0000269|PubMed:10551362,
CC ECO:0000269|PubMed:16322767}.
CC -!- SIMILARITY: Belongs to the peptidase S8 family. {ECO:0000255|PROSITE-
CC ProRule:PRU01240}.
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DR EMBL; AJ132422; CAB37326.1; -; Genomic_DNA.
DR PDB; 2LU1; NMR; -; A=530-676.
DR PDBsum; 2LU1; -.
DR AlphaFoldDB; O97364; -.
DR SMR; O97364; -.
DR MEROPS; S08.013; -.
DR VEuPathDB; PlasmoDB:PF3D7_1136900; -.
DR VEuPathDB; PlasmoDB:Pf7G8-2_000359700; -.
DR VEuPathDB; PlasmoDB:Pf7G8_110040700; -.
DR VEuPathDB; PlasmoDB:PfCD01_110042300; -.
DR VEuPathDB; PlasmoDB:PfDd2_110040100; -.
DR VEuPathDB; PlasmoDB:PfGA01_110041100; -.
DR VEuPathDB; PlasmoDB:PfGB4_110043400; -.
DR VEuPathDB; PlasmoDB:PfGN01_110041400; -.
DR VEuPathDB; PlasmoDB:PfHB3_110040300; -.
DR VEuPathDB; PlasmoDB:PfIT_110041400; -.
DR VEuPathDB; PlasmoDB:PfKE01_110041400; -.
DR VEuPathDB; PlasmoDB:PfKH01_110041200; -.
DR VEuPathDB; PlasmoDB:PfKH02_110042100; -.
DR VEuPathDB; PlasmoDB:PfML01_110041700; -.
DR VEuPathDB; PlasmoDB:PfNF135_110040000; -.
DR VEuPathDB; PlasmoDB:PfNF166_110040200; -.
DR VEuPathDB; PlasmoDB:PfNF54_110041100; -.
DR VEuPathDB; PlasmoDB:PfSD01_110039500; -.
DR VEuPathDB; PlasmoDB:PfSN01_110040000; -.
DR VEuPathDB; PlasmoDB:PfTG01_110041300; -.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0033163; C:microneme membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IMP:UniProtKB.
DR Gene3D; 3.40.50.200; -; 1.
DR InterPro; IPR000209; Peptidase_S8/S53_dom.
DR InterPro; IPR036852; Peptidase_S8/S53_dom_sf.
DR InterPro; IPR022398; Peptidase_S8_His-AS.
DR InterPro; IPR023828; Peptidase_S8_Ser-AS.
DR InterPro; IPR015500; Peptidase_S8_subtilisin-rel.
DR InterPro; IPR040935; Pro_sub2.
DR Pfam; PF00082; Peptidase_S8; 1.
DR Pfam; PF18513; Pro_sub2; 1.
DR PRINTS; PR00723; SUBTILISIN.
DR SUPFAM; SSF52743; SSF52743; 1.
DR PROSITE; PS51892; SUBTILASE; 1.
DR PROSITE; PS00137; SUBTILASE_HIS; 1.
DR PROSITE; PS00138; SUBTILASE_SER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Autocatalytic cleavage; Cell membrane; Cytoplasmic vesicle;
KW Glycoprotein; Hydrolase; Membrane; Protease; Serine protease; Signal;
KW Transmembrane; Transmembrane helix; Zymogen.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..687
FT /note="Inhibition peptide"
FT /evidence="ECO:0000305|PubMed:16322767"
FT /id="PRO_0000450751"
FT CHAIN 688..1342
FT /note="Subtilisin-like protease 2"
FT /evidence="ECO:0000305|PubMed:16322767"
FT /id="PRO_5005692366"
FT TOPO_DOM 688..1137
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1138..1158
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1159..1342
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 727..1020
FT /note="Peptidase S8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT REGION 85..111
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 143..171
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 415..474
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 500..531
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 151..171
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 426..474
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 500..519
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 755
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 798
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 961
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT CARBOHYD 165
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 343
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 451
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 455
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 493
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 551
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 642
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 729
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 821
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 857
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 893
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 951
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1010
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1106
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT STRAND 554..560
FT /evidence="ECO:0007829|PDB:2LU1"
FT HELIX 571..590
FT /evidence="ECO:0007829|PDB:2LU1"
FT STRAND 591..593
FT /evidence="ECO:0007829|PDB:2LU1"
FT STRAND 599..603
FT /evidence="ECO:0007829|PDB:2LU1"
FT TURN 604..607
FT /evidence="ECO:0007829|PDB:2LU1"
FT STRAND 608..615
FT /evidence="ECO:0007829|PDB:2LU1"
FT HELIX 625..637
FT /evidence="ECO:0007829|PDB:2LU1"
SQ SEQUENCE 1342 AA; 154932 MW; BEADADDF25CDAC96 CRC64;
MLNIIYVVSL ILIKFIFYKE CNNNNNYYLS NIELYNYKLR KRNRILNNNI NDRKSFLSDL
EQNYKPLFDI YELSANFEKR RKELEKKTKG EENEIEKKKE NDLEEKKENE IEKKKENDLE
KEYNDVINLL ELSLSSEYKE LNADVSNNDN SGHEENNKHK LNKKNSSNYK NDKSLDELIK
GAILKLKQNP NIKNKNMLDY DKIFKIIKEK LINKNLASNK IKGGDNEKLK EEKKQSDIST
NVEVKKDIIN DQLNKGIPTK IENKDDMINK ESNKEDITNE GKSNSLNNLN TLNNDGNIIT
KVYDHYTIVT NSNDILNDIS IDASDISKNS IGGINIPFNE NDNSSFTHQR YIVLSNNGEK
KYKIVLMTKN PKFMDMDGIY DEEEKKESLI ELNQKVNKEE NTNLYDGTGT LYYGKKSKKE
KENTQQKGGN NPNVDINILN NNNNNNNNNN NNSNNNSNSM NDEEINYNNN NNKESPSMFR
RFINFLSFSG NENETEDTLI YHNKNDNSYK NKKEGTGKNN DNNDPNNNNN KKILLNVDKL
VDQYLLNLKN NHTSKQELIL VLKGELDLHS KNMKNVINNA KKNLEKYFKE HFKEFDKISY
DISTPINFLC IFIPTLFDMN NMDLLKQALL ILHNDLHEYV ENWSFSSTYH TYEADYIKEQ
DSVYDRSPKK KYIKASKKLY NNKYSFLNKF LNIEPLILFA KKLNSKRSNI EKEILNFLPK
ELRDYSTWNL SIIRVFNAWF LAGYGNKNVK VCVVDSGADI KHVDLNGNLY IPEYNEKYEM
TQDFYNFMVK NPTDASGHGT HVTGIIGGVA NDLGVVGVAP NITLISLRFI DGKKYGGSFH
AIKALNVCIL NKAPIINASW GSSHFDVNLH LAVERLKYTL NGKGSVLIAA SGNKSNDNDI
SPLYPATFTF PHVYSVASIS RNFEISPFSN YGHKSVHILA PGHHIYSTIP NNSYKIFTGT
SMAAPHVCGV SALVYSVCYN QGFIPQAEEV LDILTRTSIK IISTKKRTIN DSLVNAEGAV
LTTLLGGLWM QMDCYFVKFN LEKGKKKHIP VVFSAYKKGV YETDIVIAII PIDGKSKIYG
EIHIPIKIVT DVNIPNFQES PRRGKNYTID SNEAQHDEVL SYICENALYN LYEYDSHYLL
ASVILFFLAL LSIFVGMIYM KSRKHSDKKC SKNLMKSNYI PEMDDGMEET QQLQQERRQY
FRELFGENLE KNYDQHFVQD FGQDFRQDFK LGSTPDLKQY SDIDLQNKIQ QPERKTVKII
INNFEDRKKE TKRRLLKGLN YDGENAKKHD FTNESISNSR KNFKFSNNTE MKKNTIKSED
VKIASDDNVN KAMNQLDDMF MK
