SERA6_PLAF7
ID SERA6_PLAF7 Reviewed; 1031 AA.
AC Q9TY96;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 3.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Serine-repeat antigen protein 6 {ECO:0000305};
DE EC=3.4.22.- {ECO:0000250|UniProtKB:Q26015};
DE AltName: Full=Cysteine protease SERA6 {ECO:0000305};
DE Flags: Precursor;
GN Name=SERA6 {ECO:0000305};
GN ORFNames=PF3D7_0207500 {ECO:0000312|EMBL:CZT98088.1};
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|Proteomes:UP000001450}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7 {ECO:0000312|Proteomes:UP000001450};
RX PubMed=9804551; DOI=10.1126/science.282.5391.1126;
RA Gardner M.J., Tettelin H., Carucci D.J., Cummings L.M., Aravind L.,
RA Koonin E.V., Shallom S.J., Mason T., Yu K., Fujii C., Pederson J., Shen K.,
RA Jing J., Aston C., Lai Z., Schwartz D.C., Pertea M., Salzberg S.L.,
RA Zhou L., Sutton G.G., Clayton R., White O., Smith H.O., Fraser C.M.,
RA Adams M.D., Venter J.C., Hoffman S.L.;
RT "Chromosome 2 sequence of the human malaria parasite Plasmodium
RT falciparum.";
RL Science 282:1126-1132(1998).
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:0000305}
RP DEVELOPMENTAL STAGE, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=18083098; DOI=10.1016/j.cell.2007.10.049;
RA Yeoh S., O'Donnell R.A., Koussis K., Dluzewski A.R., Ansell K.H.,
RA Osborne S.A., Hackett F., Withers-Martinez C., Mitchell G.H.,
RA Bannister L.H., Bryans J.S., Kettleborough C.A., Blackman M.J.;
RT "Subcellular discharge of a serine protease mediates release of invasive
RT malaria parasites from host erythrocytes.";
RL Cell 131:1072-1083(2007).
RN [4] {ECO:0000305}
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND PROTEOLYTIC CLEAVAGE.
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).
CC -!- FUNCTION: Cysteine protease which plays an essential role in merozoite
CC egress from host erythrocytes. May cleave host SPTB/beta spectrin and
CC ANK1/ankyrin-1 which disrupts host erythrocyte actin cytoskeleton and
CC leads to host erythrocyte cell membrane rupture.
CC {ECO:0000250|UniProtKB:Q26015}.
CC -!- INTERACTION:
CC Q9TY96; Q8I0V0: SUB1; NbExp=2; IntAct=EBI-827996, EBI-1568896;
CC -!- SUBCELLULAR LOCATION: Parasitophorous vacuole lumen
CC {ECO:0000269|PubMed:22984267}. Parasitophorous vacuole membrane
CC {ECO:0000269|PubMed:22984267}; 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:18083098, ECO:0000269|PubMed:22984267}.
CC -!- PTM: Just prior to merozoite egress from host erythrocytes,
CC proteolytically cleaved by SUB1 to generate the active 75kDa form.
CC {ECO:0000269|PubMed:18083098, ECO:0000269|PubMed:22984267}.
CC -!- SIMILARITY: Belongs to the peptidase C1 family. {ECO:0000255}.
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DR EMBL; LN999943; CZT98088.1; -; Genomic_DNA.
DR RefSeq; XP_001349585.2; XM_001349549.2.
DR AlphaFoldDB; Q9TY96; -.
DR SMR; Q9TY96; -.
DR IntAct; Q9TY96; 3.
DR STRING; 5833.PFB0335c; -.
DR MEROPS; C01.169; -.
DR MEROPS; C01.A64; -.
DR SwissPalm; Q9TY96; -.
DR PRIDE; Q9TY96; -.
DR EnsemblProtists; CZT98088; CZT98088; PF3D7_0207500.
DR GeneID; 812667; -.
DR KEGG; pfa:PF3D7_0207500; -.
DR VEuPathDB; PlasmoDB:PF3D7_0207500; -.
DR HOGENOM; CLU_005127_0_0_1; -.
DR InParanoid; Q9TY96; -.
DR OMA; KYCNYEY; -.
DR PhylomeDB; Q9TY96; -.
DR Reactome; R-PFA-114608; Platelet degranulation.
DR Proteomes; UP000001450; Chromosome 2.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005764; C:lysosome; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0020003; C:symbiont-containing vacuole; IDA:GeneDB.
DR GO; GO:0020005; C:symbiont-containing vacuole membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0008234; F:cysteine-type peptidase activity; ISS:GeneDB.
DR GO; GO:0006508; P:proteolysis; ISS:GeneDB.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IBA:GO_Central.
DR GO; GO:0050776; P:regulation of immune response; TAS:GeneDB.
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; Reference proteome; Signal;
KW Thiol protease; Zymogen.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..1031
FT /note="Serine-repeat antigen protein 6"
FT /evidence="ECO:0000255"
FT /id="PRO_0000450442"
FT REGION 91..163
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 490..567
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 490..507
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 508..555
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 644
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10088"
FT ACT_SITE 810
FT /evidence="ECO:0000250|UniProtKB:O60911"
FT ACT_SITE 835
FT /evidence="ECO:0000250|UniProtKB:O60911"
FT SITE 95..96
FT /note="Cleavage; by SUB1"
FT /evidence="ECO:0000250|UniProtKB:Q26015"
FT SITE 370..371
FT /note="Cleavage; by SUB1"
FT /evidence="ECO:0000305|PubMed:18083098"
FT SITE 927..928
FT /note="Cleavage; by SUB1"
FT /evidence="ECO:0000305|PubMed:18083098"
FT CARBOHYD 74
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 120
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 544
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 573
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 674
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 929
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 974
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 1031 AA; 118836 MW; 6DF255195338D316 CRC64;
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 RHNPDFMYSL
YYNNYEPETS QDFESENDYD NAFVHGQSNE SDETNKEGKN VHNSVEKKIQ ILHILKHIKD
SQIKRGLVKY DNINETKDEH TCSRVNSQDA EKYEECKKFC LTKWNECKDH YSPGYCLTDL
YKGEDCNFCY V
