SUB2_PLAFP
ID SUB2_PLAFP Reviewed; 1337 AA.
AC Q9Y008;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=Subtilisin-like protease 2 {ECO:0000303|PubMed:10339607};
DE EC=3.4.21.62 {ECO:0000250|UniProtKB:Q8IHZ5};
DE AltName: Full=Merozoite surface sheddase {ECO:0000250|UniProtKB:O97364};
DE Short=MESH {ECO:0000250|UniProtKB:O97364};
DE AltName: Full=PfSUB2 {ECO:0000303|PubMed:10339607};
DE Flags: Precursor;
GN Name=SUB2 {ECO:0000303|PubMed:10339607};
OS Plasmodium falciparum (isolate Palo Alto / Uganda).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=57270;
RN [1] {ECO:0000312|EMBL:CAB43592.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBCELLULAR LOCATION, DEVELOPMENTAL
RP STAGE, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=10339607; DOI=10.1073/pnas.96.11.6445;
RA Barale J.C., Blisnick T., Fujioka H., Alzari P.M., Aikawa M.,
RA Braun-Breton C., Langsley G.;
RT "Plasmodium falciparum subtilisin-like protease 2, a merozoite candidate
RT for the merozoite surface protein 1-42 maturase.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:6445-6450(1999).
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. May cleave
CC TRAMP/PTTRAMP, thereby shedding TRAMP from the merozoite surface during
CC erythrocyte invasion. {ECO:0000250|UniProtKB:Q8IHZ5}.
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:0000250|UniProtKB:Q8IHZ5};
CC -!- ACTIVITY REGULATION: Activation may be calcium-dependent. Inhibited by
CC the non-covalent interaction with the cleaved propeptide.
CC {ECO:0000250|UniProtKB:Q8IHZ5}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10339607};
CC Single-pass type I membrane protein {ECO:0000305}. Cytoplasmic vesicle,
CC secretory vesicle, microneme membrane {ECO:0000269|PubMed:10339607};
CC Single-pass type I membrane protein {ECO:0000305}. Note=In mature
CC schizonts, localizes to micronemes at the merozoite apical region
CC (PubMed:10339607). Immediately after schizont rupture, secreted from
CC the micronemes to the merozoite surface where it redistributes in an
CC actin-dependent manner to accumulate at the posterior end of newly
CC released merozoites (By similarity). {ECO:0000250|UniProtKB:Q8IHZ5,
CC ECO:0000269|PubMed:10339607}.
CC -!- DEVELOPMENTAL STAGE: Expressed during the parasite blood stage,
CC specifically in schizonts and merozoites (at protein level).
CC {ECO:0000269|PubMed:10339607}.
CC -!- DOMAIN: The propeptide domain acts as an intramolecular chaperone for
CC the folding of the catalytic domain (By similarity). Also acts as an
CC inhibitor of the catalytic domain thereby regulating SUB2 activity
CC during secretion (By similarity). {ECO:0000250|UniProtKB:O97364,
CC ECO:0000250|UniProtKB:Q8IHZ5}.
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:10339607). The first maturation cleavage is autocatalytic,
CC occurs in the ER and is necessary for the subsequent SUB2 trafficking
CC to the microneme (By similarity). The second cleavage may be mediated
CC by PMX/plasmepsin X (By similarity). {ECO:0000250|UniProtKB:Q8IHZ5,
CC ECO:0000269|PubMed:10339607}.
CC -!- SIMILARITY: Belongs to the peptidase S8 family. {ECO:0000255|PROSITE-
CC ProRule:PRU01240}.
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DR EMBL; AJ132006; CAB43592.1; -; Genomic_DNA.
DR AlphaFoldDB; Q9Y008; -.
DR SMR; Q9Y008; -.
DR MEROPS; S08.013; -.
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; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
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 Autocatalytic cleavage; Cell membrane; Cytoplasmic vesicle; Glycoprotein;
KW Hydrolase; Membrane; Protease; Serine protease; Signal; Transmembrane;
KW Transmembrane helix; Zymogen.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..682
FT /note="Inhibition peptide"
FT /evidence="ECO:0000250|UniProtKB:O97364"
FT /id="PRO_0000450753"
FT CHAIN 683..1337
FT /note="Subtilisin-like protease 2"
FT /evidence="ECO:0000250|UniProtKB:O97364"
FT /id="PRO_5004337835"
FT TOPO_DOM 683..1132
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1133..1153
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1154..1337
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 722..1015
FT /note="Peptidase S8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT REGION 85..105
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 135..163
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 407..470
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 495..526
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 143..163
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 418..470
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 495..514
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 750
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 793
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 956
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT CARBOHYD 157
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 335
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 445
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 449
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 488
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 546
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 570
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 637
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 724
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 816
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 852
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 888
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 946
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1005
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 1337 AA; 154394 MW; 42B900BE2E8FC1A4 CRC64;
MLNIIYVVSL ILIKFIFYKE CNNNNNNYLS NIELYNYKLR KRNRILNNNI NDRKSFLSDL
EQNYKPLFDI YELSANFEKR RKELEKKTKG EENEIEKKKE NDLEKKKEND LEKEYNDVIN
LLELSLSSEY KELNADVSNN DNSGHEENNK HKLNKKNSSN YKNDKSLDEL IKGAILKLKQ
NPNIKNKNML DYDKIFKIIK EKLINKNLAS NKIRGGDNEK LKEEKKQSDI STNVEVKKDI
INDQLNKGIP TKKENKDDMI NKESNKEDIT NEGKSNSLNN LNTLNNDGNI ITKVYDHYTI
VTNSNDILND ISIDASDISK NSIGGINIPF NENDNSSFTH QRYIVLSNNG EKKYKIVLMT
KNPKFMDMDG IYDEEEKKES LIELNQKVNK EENTNLYDGT GTLYYGKKSK KEKENTQQKG
GNNPNVDINI LNNNNNNNNN NNNNNNSNNN SNSMNDEEIN YNNNNNNKES PSMFRRFINF
LSFSGNENET EDTLIYHNKN DNSYKNKKEG TGKNNDNNDP NNNNNKKILL NVDKLVDQYL
LNLKNNHTSK QELILVLKGE LDLHSKNMKN VTNNAKKNLE KYFKEHFKEF DKISYDISTP
INFLCIFIPT VFDMNNMDLL KQALLILHSD LHEYVENWSF SSTYHTYEAD YIKEQDSVYD
RSPKKKYIKA SKKLYNNKYS FLNKFLNIEP LILFAKKLNS KRSNIEKEIL NFLPKELRDY
STWNLSIIRV FNAWFLAGYG NKNVKVCVVD SGADINRVDL NGNLYIPEYN EKYEMTQDFY
NFMVKKSYRC LGHGSHVTGI IGGVANDLGV VGVAPNITLI SLRFIDGKKY GGSFHAIKAL
NVCILNKAPI INASWGSSHF DVNLHLTVER LKYTLNGKGS VLIAASGNKS NDNDISPLYP
ATFTFPHVYS VASISRNFEI SPFSNYGYKS VHILAPGHHI YSTIPNNSYK IFTGTSMAAP
HVCGVSALVY SVCYNQGFIP QAEEVLDILT RTSIKIISTK KRTINDSLVN AEGAVLTTLL
GGLWMQMDCY FVKFNLEKGK KKHIPVVFSA YKKGVYETDI VIAIIPIDGK SKIYGEIHIP
IKIVTDVNIP NFQESPRRGK NYTIDSNEAQ HDEVLSYICE NALYNLYEYD SHYLLASVIL
FFLALLSIFV GMIYMKSRKH SDKKCSKNLI KSNYIPEMDD GMEETQQLQQ ERRQYFRELF
GENLEKNYDQ HFVQDFGQDF RQDFKLGSTP DLKQYSDIDL QNKIQQPERK TVKIIINNFE
DRKKETIRRL LKGLNYDGEN AKKHDFTNES ISNSRKNFKF SNNTEMKKNT IKSEDVKIAS
DDNVNKAMNQ LDDMFMK
