SERA6_PLAFA
ID SERA6_PLAFA Reviewed; 1041 AA.
AC Q26015;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 82.
DE RecName: Full=Serine-repeat antigen protein 6 {ECO:0000305};
DE EC=3.4.22.- {ECO:0000305|PubMed:29459732};
DE AltName: Full=Cysteine protease SERA6 {ECO:0000305};
DE AltName: Full=SERP H {ECO:0000303|PubMed:1840623};
DE Flags: Precursor;
GN Name=SERA6 {ECO:0000305};
OS Plasmodium falciparum.
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=5833 {ECO:0000312|EMBL:AAA29764.1};
RN [1] {ECO:0000312|EMBL:AAA29764.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBCELLULAR LOCATION, AND DEVELOPMENTAL
RP STAGE.
RC STRAIN=FCBR {ECO:0000312|EMBL:AAA29764.1};
RX PubMed=1840623; DOI=10.1016/0166-6851(91)90215-r;
RA Knapp B., Nau U., Hundt E., Kuepper H.A.;
RT "A new blood stage antigen of Plasmodium falciparum highly homologous to
RT the serine-stretch protein SERP.";
RL Mol. Biochem. Parasitol. 44:1-13(1991).
RN [2] {ECO:0000305}
RP FUNCTION, PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF CYS-654 AND
RP 379-ALA--GLN-380.
RX PubMed=22984267; DOI=10.1074/jbc.m112.400820;
RA Ruecker A., Shea M., Hackett F., Suarez C., Hirst E.M., Milutinovic K.,
RA Withers-Martinez C., Blackman M.J.;
RT "Proteolytic activation of the essential parasitophorous vacuole cysteine
RT protease SERA6 accompanies malaria parasite egress from its host
RT erythrocyte.";
RL J. Biol. Chem. 287:37949-37963(2012).
RN [3] {ECO:0000305}
RP FUNCTION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP CYS-654 AND 379-ALA--GLN-380.
RX PubMed=29459732; DOI=10.1038/s41564-018-0111-0;
RA Thomas J.A., Tan M.S.Y., Bisson C., Borg A., Umrekar T.R., Hackett F.,
RA Hale V.L., Vizcay-Barrena G., Fleck R.A., Snijders A.P., Saibil H.R.,
RA Blackman M.J.;
RT "A protease cascade regulates release of the human malaria parasite
RT Plasmodium falciparum from host red blood cells.";
RL Nat. Microbiol. 3:447-455(2018).
CC -!- FUNCTION: Cysteine protease which plays an essential role in merozoite
CC egress from host erythrocytes (PubMed:22984267, PubMed:29459732). May
CC cleave host SPTB/beta spectrin and ANK1/ankyrin-1 which disrupts host
CC erythrocyte actin cytoskeleton and leads to host erythrocyte cell
CC membrane rupture (PubMed:29459732). {ECO:0000269|PubMed:22984267,
CC ECO:0000269|PubMed:29459732}.
CC -!- SUBCELLULAR LOCATION: Parasitophorous vacuole lumen
CC {ECO:0000250|UniProtKB:Q9TY96}. Parasitophorous vacuole membrane
CC {ECO:0000250|UniProtKB:Q9TY96}; Peripheral membrane protein
CC {ECO:0000305}.
CC -!- DEVELOPMENTAL STAGE: Expressed during parasite asexual blood stages,
CC specifically at the schizont stage (at protein level).
CC {ECO:0000269|PubMed:29459732}.
CC -!- PTM: Just prior to merozoite egress from host erythrocytes,
CC proteolytically cleaved by SUB1 to generate the active 75kDa form.
CC {ECO:0000250|UniProtKB:Q9TY96}.
CC -!- DISRUPTION PHENOTYPE: Blood stage parasites are not viable
CC (PubMed:29459732). Initial schizont development is normal but merozoite
CC egress is abolished due to a failure to rupture the host erythrocyte
CC membrane (PubMed:29459732). Does not affect poration of the host
CC erythrocyte membrane which precedes erythrocyte membrane rupture
CC (PubMed:29459732). Cleavage of host erythrocyte SPTB/beta spectrin and
CC ANK1/ankyrin-1 is impaired (PubMed:29459732).
CC {ECO:0000269|PubMed:29459732}.
CC -!- SIMILARITY: Belongs to the peptidase C1 family. {ECO:0000255}.
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DR EMBL; M55428; AAA29764.1; -; Genomic_DNA.
DR AlphaFoldDB; Q26015; -.
DR SMR; Q26015; -.
DR MEROPS; C01.A64; -.
DR VEuPathDB; PlasmoDB:PF3D7_0207500; -.
DR VEuPathDB; PlasmoDB:Pf7G8-2_000055500; -.
DR VEuPathDB; PlasmoDB:Pf7G8_020012200; -.
DR VEuPathDB; PlasmoDB:PfCD01_020012400; -.
DR VEuPathDB; PlasmoDB:PfDd2_020010300; -.
DR VEuPathDB; PlasmoDB:PfGA01_020010500; -.
DR VEuPathDB; PlasmoDB:PfGB4_020010500; -.
DR VEuPathDB; PlasmoDB:PfGN01_020012800; -.
DR VEuPathDB; PlasmoDB:PfHB3_020012200; -.
DR VEuPathDB; PlasmoDB:PfIT_020012200; -.
DR VEuPathDB; PlasmoDB:PfKE01_020010000; -.
DR VEuPathDB; PlasmoDB:PfKH01_020012700; -.
DR VEuPathDB; PlasmoDB:PfKH02_020011500; -.
DR VEuPathDB; PlasmoDB:PfML01_020010400; -.
DR VEuPathDB; PlasmoDB:PfNF135_020013700; -.
DR VEuPathDB; PlasmoDB:PfNF166_020012600; -.
DR VEuPathDB; PlasmoDB:PfNF54_020012300; -.
DR VEuPathDB; PlasmoDB:PfSD01_020013000; -.
DR VEuPathDB; PlasmoDB:PfSN01_020010500; -.
DR VEuPathDB; PlasmoDB:PfTG01_020012500; -.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0020005; C:symbiont-containing vacuole membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR000169; Pept_cys_AS.
DR InterPro; IPR000668; Peptidase_C1A_C.
DR Pfam; PF00112; Peptidase_C1; 1.
DR SMART; SM00645; Pept_C1; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Hydrolase; Membrane; Protease; Signal; Thiol protease;
KW Zymogen.
FT SIGNAL 1..34
FT /evidence="ECO:0000305"
FT CHAIN 35..1041
FT /note="Serine-repeat antigen protein 6"
FT /evidence="ECO:0000255"
FT /id="PRO_0000450443"
FT REGION 101..173
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 500..577
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 500..517
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 518..565
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 654
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10088"
FT ACT_SITE 820
FT /evidence="ECO:0000250|UniProtKB:O60911"
FT ACT_SITE 845
FT /evidence="ECO:0000250|UniProtKB:O60911"
FT SITE 105..106
FT /note="Cleavage; by SUB1"
FT /evidence="ECO:0000269|PubMed:1840623"
FT SITE 380..381
FT /note="Cleavage; by SUB1"
FT /evidence="ECO:0000269|PubMed:1840623"
FT SITE 937..938
FT /note="Cleavage; by SUB1"
FT /evidence="ECO:0000269|PubMed:1840623"
FT CARBOHYD 84
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 130
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 459
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 554
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 583
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 684
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 984
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT MUTAGEN 379..380
FT /note="AQ->LL: No viable blood stage parasites."
FT /evidence="ECO:0000269|PubMed:22984267,
FT ECO:0000269|PubMed:29459732"
FT MUTAGEN 654
FT /note="C->A: No viable blood stage parasites."
FT /evidence="ECO:0000269|PubMed:22984267,
FT ECO:0000269|PubMed:29459732"
SQ SEQUENCE 1041 AA; 120152 MW; 18A71B1242BA1DE6 CRC64;
MIFFNFKLNR MICPIFFLYI INVLFTQYFI KCEGNKVTVI SHNNGHNDNL DVNKNGVISQ
ENVFDTSESL NLPSNKKVGS DDLNTTTISF TVPDNLENEV KVVSSSESGK GATVSHTKVT
SEGLSDTQPN VTQSVSSSTH TPGSLDSTMS TEQHSSVSQS SLPTESSSET LNKATVPEIP
IQINSGLLKN YNGVKVTGSC GSYFRVYLVP HILIYALTKY SVIQLESLFN DNARIDVEHK
GELQNKCSEG YHFKLVVYIT HNVLNLKWKT YKPNEESKSE DSDVRKYRIP KLERPFTSIQ
VYTANSKAGV IETKNYNIRT DIPDTCDAIA TDCFLNGNVN IEKCFQCTLL VQKKDKSHEC
FKYVSSEMKK KMNEIKVKAQ DDFNPNEYKL IESIDNILSK IYKKANKPFE ISKDLINLED
LDYQFKNELL EYCKLLKKVD TSGTLEEYEL GNAEDIYNNL TRLLKSHSDE NIVTLQGKLR
NTAICIKNVD EWILNKRGLT LPSESPSESS SKSDSYLNTF NDKDKNEDKD DMSKNSKEEF
KNDDKENSDD QNNNDSNKKD DENNINNGDT NYVYDFDDDD YDNNSYEKDM YESPIKENKN
GVIDLEKYGN QIKLKSPYFK NSKYCNYEYC NRWRDKTSCI SQIEVEEQGN CGLCWIFASK
LHFETIRCMR GYGHFRSSAL YVANCSKRKP IDRCEEGSNP LEFLRILDEK KFLPLESNYP
YSYTSAGNSC PKLPNSWTNL WGDTKLLFNK KVHRYIGNKG FISHETSYFK NNMDLFIDMV
KREVQNKGSV IIYIKTQDVI GYDFNGKGVH SMCGDRTPDH AANIIGYGNY INKKGEKRSY
WLIRNSWSYY WGDEGNFRVD MLGPKNCLYN FIHTVVFFKL DLGTIHVPKK KSWKKNVYFL
RHNTDFMYSL YYNNYEPETS QDFESENDYD NAFVHGQSDE SDETNKEGKN VHNSVEKKIQ
ILHILKHIKD SQIKRGLVKY DNINETKDEH TCSRVNSQDA EKYEECKKFC LTKWNECKDH
YSPGYCLTDL YKGEDCNFCY V
