ORC1_PLAF7
ID ORC1_PLAF7 Reviewed; 1189 AA.
AC Q8I615; A0A144A1W6; Q967Q7;
DT 13-OCT-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Origin recognition complex subunit 1 {ECO:0000303|PubMed:12543146};
DE Short=PfORC1 {ECO:0000303|PubMed:12543146};
DE EC=3.6.4.- {ECO:0000269|PubMed:16216221, ECO:0000269|PubMed:19633266};
GN Name=ORC1 {ECO:0000303|PubMed:12543146}; ORFNames=PF3D7_1203000, PFL0150w;
OS Plasmodium falciparum (isolate 3D7).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=36329;
RN [1] {ECO:0000312|EMBL:AAK54602.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND DEVELOPMENTAL STAGE.
RX PubMed=12543146; DOI=10.1016/s1383-5769(02)00079-x;
RA Li J.-L., Cox L.S.;
RT "Characterisation of a sexual stage-specific gene encoding ORC1 homologue
RT in the human malaria parasite Plasmodium falciparum.";
RL Parasitol. Int. 52:41-52(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7;
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]
RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=16216221; DOI=10.1016/j.bbrc.2005.09.131;
RA Mehra P., Biswas A.K., Gupta A., Gourinath S., Chitnis C.E., Dhar S.K.;
RT "Expression and characterization of human malaria parasite Plasmodium
RT falciparum origin recognition complex subunit 1.";
RL Biochem. Biophys. Res. Commun. 337:955-966(2005).
RN [4]
RP SYNTHESIS OF 131-161, AND POSSIBLE CANDIDATE MALARIA EPITOPE.
RX PubMed=17653272; DOI=10.1371/journal.pone.0000645;
RA Villard V., Agak G.W., Frank G., Jafarshad A., Servis C., Nebie I.,
RA Sirima S.B., Felger I., Arevalo-Herrera M., Herrera S., Heitz F.,
RA Baecker V., Druilhe P., Kajava A.V., Corradin G.;
RT "Rapid identification of malaria vaccine candidates based on alpha-helical
RT coiled coil protein motif.";
RL PLoS ONE 2:E645-E645(2007).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=18525026; DOI=10.1242/jcs.026427;
RA Mancio-Silva L., Rojas-Meza A.P., Vargas M., Scherf A., Hernandez-Rivas R.;
RT "Differential association of Orc1 and Sir2 proteins to telomeric domains in
RT Plasmodium falciparum.";
RL J. Cell Sci. 121:2046-2053(2008).
RN [6]
RP INTERACTION WITH PCNA1, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND
RP MOTIF.
RX PubMed=18554328; DOI=10.1111/j.1365-2958.2008.06316.x;
RA Gupta A., Mehra P., Dhar S.K.;
RT "Plasmodium falciparum origin recognition complex subunit 5: functional
RT characterization and role in DNA replication foci formation.";
RL Mol. Microbiol. 69:646-665(2008).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH PCNA1, SUBCELLULAR LOCATION,
RP DEVELOPMENTAL STAGE, DOMAIN, AND MOTIF.
RX PubMed=19633266; DOI=10.1128/ec.00170-09;
RA Gupta A., Mehra P., Deshmukh A., Dar A., Mitra P., Roy N., Dhar S.K.;
RT "Functional dissection of the catalytic carboxyl-terminal domain of origin
RT recognition complex subunit 1 (PfORC1) of the human malaria parasite
RT Plasmodium falciparum.";
RL Eukaryot. Cell 8:1341-1351(2009).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, LEUCINE HEPTAD REPEAT,
RP AND DOMAIN.
RX PubMed=22379140; DOI=10.1093/nar/gks202;
RA Deshmukh A.S., Srivastava S., Herrmann S., Gupta A., Mitra P.,
RA Gilberger T.W., Dhar S.K.;
RT "The role of N-terminus of Plasmodium falciparum ORC1 in telomeric
RT localization and var gene silencing.";
RL Nucleic Acids Res. 40:5313-5331(2012).
RN [9]
RP FUNCTION, AND DOMAIN.
RX PubMed=24018145; DOI=10.1016/j.molbiopara.2013.08.004;
RA Varunan S.M., Tripathi J., Bhattacharyya S., Suhane T., Bhattacharyya M.K.;
RT "Plasmodium falciparum origin recognition complex subunit 1 (PfOrc1)
RT functionally complements Deltasir3 mutant of Saccharomyces cerevisiae.";
RL Mol. Biochem. Parasitol. 191:28-35(2013).
RN [10]
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, DOMAIN, AND PHOSPHORYLATION AT
RP THR-2 AND SER-20.
RX PubMed=26094711; DOI=10.1111/mmi.13099;
RA Deshmukh A.S., Agarwal M., Mehra P., Gupta A., Gupta N., Doerig C.D.,
RA Dhar S.K.;
RT "Regulation of Plasmodium falciparum Origin Recognition Complex subunit 1
RT (PfORC1) function through phosphorylation mediated by CDK-like kinase
RT PK5.";
RL Mol. Microbiol. 98:17-33(2015).
CC -!- FUNCTION: Component of the origin recognition complex (ORC) that binds
CC origins of replication and thus may regulate the initiation of DNA
CC replication (Probable). DNA-binding may not be ATP-dependent
CC (PubMed:19633266). In a SIR2A/Sir2-dependent manner, binds to and
CC silences telomers and subtelomeric repeat regions (TAREs)
CC (PubMed:18525026, PubMed:22379140, PubMed:24018145). In a SIR2A/Sir2-
CC dependent manner, binds to promoters of var genes localized next to
CC TAREs resulting in their silencing (PubMed:22379140).
CC {ECO:0000269|PubMed:18525026, ECO:0000269|PubMed:19633266,
CC ECO:0000269|PubMed:22379140, ECO:0000269|PubMed:24018145,
CC ECO:0000305|PubMed:19633266}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:16216221, ECO:0000269|PubMed:19633266};
CC -!- SUBUNIT: Component of the origin recognition complex (ORC) (By
CC similarity). Interacts (via PIP-box) with PCNA1; the interaction occurs
CC during DNA replication in trophozoites (PubMed:18554328,
CC PubMed:19633266). {ECO:0000250|UniProtKB:P54784,
CC ECO:0000269|PubMed:18554328, ECO:0000269|PubMed:19633266}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16216221,
CC ECO:0000269|PubMed:18525026, ECO:0000269|PubMed:18554328,
CC ECO:0000269|PubMed:19633266, ECO:0000269|PubMed:22379140}. Chromosome,
CC telomere {ECO:0000269|PubMed:18525026, ECO:0000269|PubMed:22379140}.
CC Nucleus, nucleolus {ECO:0000269|PubMed:18525026}. Note=At the late ring
CC stage/early trophozoites, co-localizes with SIR2A/Sir2 to telomeres and
CC subtelomeric regions (TAREs) in the nuclear periphery (PubMed:18525026,
CC PubMed:22379140, PubMed:26094711). Also, partially localizes to the
CC nucleolus (PubMed:18525026). In trophozoites and early schizonts
CC localizes throughout the nucleus (PubMed:18525026, PubMed:26094711).
CC During early-to mid replicating trophozoite stages, colocalizes with
CC PCNA1 and ORC1 to distinct nuclear foci which probably are DNA
CC replication origin sites (PubMed:18554328, PubMed:19633266). In
CC schizonts, relocalizes to the nuclear periphery and cytoplasm
CC (PubMed:18525026, PubMed:26094711). In late schizonts, expression
CC decreases probably due to proteosome-mediated degradation
CC (PubMed:18554328, PubMed:26094711). {ECO:0000269|PubMed:18525026,
CC ECO:0000269|PubMed:18554328, ECO:0000269|PubMed:19633266,
CC ECO:0000269|PubMed:22379140, ECO:0000269|PubMed:26094711}.
CC -!- DEVELOPMENTAL STAGE: Expressed during the asexual blood stage,
CC specifically during the late trophozoite and early schizont stages (at
CC protein level) (PubMed:16216221, PubMed:18525026, PubMed:18554328,
CC PubMed:19633266, PubMed:22379140, PubMed:26094711). Some expression has
CC been found also at the ring stage (at protein level) (PubMed:18525026,
CC PubMed:18554328, PubMed:22379140, PubMed:26094711). Highly expressed
CC during the sexual blood stage (PubMed:12543146).
CC {ECO:0000269|PubMed:12543146, ECO:0000269|PubMed:16216221,
CC ECO:0000269|PubMed:18525026, ECO:0000269|PubMed:18554328,
CC ECO:0000269|PubMed:19633266, ECO:0000269|PubMed:22379140,
CC ECO:0000269|PubMed:26094711}.
CC -!- DOMAIN: The N-terminal domain binds telomeric DNA and is required for
CC the silencing of telomers and var genes. {ECO:0000269|PubMed:22379140,
CC ECO:0000269|PubMed:24018145, ECO:0000269|PubMed:26094711}.
CC -!- DOMAIN: The C-terminal domain binds ATP and is required for the binding
CC to DNA replication origin sites. {ECO:0000269|PubMed:19633266,
CC ECO:0000269|PubMed:24018145}.
CC -!- DOMAIN: Leucine heptad repeats are essential for the binding to
CC telomeric DNA. {ECO:0000269|PubMed:22379140}.
CC -!- PTM: In schizonts, may be phosphorylated by PK5; phosphorylation leads
CC to ORC1 dissociation from the telomeres and var gene promoters,
CC translocation to the cytoplasm, where it is degraded by the proteasome.
CC {ECO:0000269|PubMed:26094711}.
CC -!- BIOTECHNOLOGY: Possible candidate for an effective malaria vaccine as
CC determined by epitope response in sera. {ECO:0000269|PubMed:17653272}.
CC -!- SIMILARITY: Belongs to the ORC1 family. {ECO:0000255}.
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DR EMBL; AF373219; AAK54602.1; -; Genomic_DNA.
DR EMBL; LN999947; CZT99194.1; -; Genomic_DNA.
DR RefSeq; XP_001350439.1; XM_001350403.1.
DR AlphaFoldDB; Q8I615; -.
DR SMR; Q8I615; -.
DR STRING; 5833.PFL0150w; -.
DR PRIDE; Q8I615; -.
DR EnsemblProtists; CZT99194; CZT99194; PF3D7_1203000.
DR GeneID; 811083; -.
DR KEGG; pfa:PF3D7_1203000; -.
DR VEuPathDB; PlasmoDB:PF3D7_1203000; -.
DR HOGENOM; CLU_276761_0_0_1; -.
DR InParanoid; Q8I615; -.
DR OMA; KDKFLCT; -.
DR PhylomeDB; Q8I615; -.
DR Reactome; R-PFA-68616; Assembly of the ORC complex at the origin of replication.
DR Reactome; R-PFA-68949; Orc1 removal from chromatin.
DR Proteomes; UP000001450; Chromosome 12.
DR GO; GO:0000781; C:chromosome, telomeric region; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:GeneDB.
DR GO; GO:0005664; C:nuclear origin of replication recognition complex; IDA:GeneDB.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:UniProtKB.
DR GO; GO:0003688; F:DNA replication origin binding; IDA:GeneDB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006270; P:DNA replication initiation; IBA:GO_Central.
DR GO; GO:0033314; P:mitotic DNA replication checkpoint signaling; IBA:GO_Central.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR041083; AAA_lid_10.
DR InterPro; IPR003959; ATPase_AAA_core.
DR InterPro; IPR020793; ORC1.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR10763:SF23; PTHR10763:SF23; 1.
DR Pfam; PF00004; AAA; 1.
DR Pfam; PF17872; AAA_lid_10; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Chromosome; DNA replication; DNA-binding; Hydrolase;
KW Magnesium; Merozoite; Metal-binding; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Telomere.
FT CHAIN 1..1189
FT /note="Origin recognition complex subunit 1"
FT /id="PRO_0000386592"
FT REPEAT 137..143
FT /note="Leucine heptad repeat 1"
FT /evidence="ECO:0000305|PubMed:22379140"
FT REPEAT 144..150
FT /note="Leucine heptad repeat 2"
FT /evidence="ECO:0000305|PubMed:22379140"
FT REPEAT 151..157
FT /note="Leucine heptad repeat 3"
FT /evidence="ECO:0000305|PubMed:22379140"
FT REPEAT 158..164
FT /note="Leucine heptad repeat 4"
FT /evidence="ECO:0000305|PubMed:22379140"
FT REGION 1..53
FT /note="Required for peripherial nuclear localization"
FT /evidence="ECO:0000269|PubMed:22379140"
FT REGION 239..421
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 679..749
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 913..922
FT /note="PIP-box"
FT /evidence="ECO:0000305|PubMed:18554328,
FT ECO:0000305|PubMed:19633266"
FT COMPBIAS 250..302
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 303..335
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 336..352
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 353..410
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 693..708
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 734..748
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 780
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q13415"
FT BINDING 815..823
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q13415"
FT BINDING 903
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q13415"
FT BINDING 904
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q13415"
FT BINDING 904
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q13415"
FT BINDING 937
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q13415"
FT BINDING 1003
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q13415"
FT MOD_RES 2
FT /note="Phosphothreonine"
FT /evidence="ECO:0000305|PubMed:26094711"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:26094711"
SQ SEQUENCE 1189 AA; 138738 MW; 327FF926AFFDF030 CRC64;
MTPKKKIFQN FQANDNEILS PTKKGIKLNV SKLNILNFEN TIITKEKTNY EYKASLNKEI
DEVLNNNNII NTHNNKKNNL NLYDYNNIKN STHEFYIDLN EQNKQTIKYN DNKFTPINKK
EKYNLDETSS SSISSSLTNI SSSLTNISSS LTNISSSLSN SLDEKKKKKK IKKNNSTIIN
ILNNNNNNSN IHHNNKHNIY NKYNISKKPQ NKEIHTLPSN HQIKKKSNNT YNTCQQKMKK
NISKKNTHSI KNNQNDKNKE KNKEKDKNIK KDRDKDIQTK RTSHQSQDQN NHFERRILRS
YTRNNDNVKN NLKNNINNNN TLKRSSQSVR IDSDLSSAHQ NKRIKYDEKN IIHRNNNNNN
NNNNKTTSNN HNKNNKINNN NPSENYKKQT DTKHTNNTQN NKYNKTKTTN TFKHPSKDHT
DVNTKTFKSR YINTYTMEEV QKSIKSNTIK LVQENSCEYQ DGIIYESIQI NDEEYSIGED
VLIFYTPNNN TYNAKSDDKK NQNNNNIKEN IYLLKKGKIS SFYKSTNSKV IEVEICFYYD
ESDEQRIREL EKKQTSRRCK EDFNIYLDDD TKYYNLLGNI HFTILDANYI YKKIYVYNEI
ETFEEDTHAR KGKNKFLCTH FIKDKEDRLC FIPNEDHWDN LVLGSSDLYY YFANEKKLNK
NKSLKLIIEK LKINDKINDT QANQKKNNKK EYMNKAQTTT NVKANTHTKT LNDHNKSKTT
KNKESSSTSF LQDVKKKSDP HNNDFQSSLK EDQENYYINL LKNIKDPTDK AIRMMQLDVV
PKYLPCREKE IKEVHGFLES GIKQSGSNQI LYISGMPGTG KTATVYSVIQ LLQIKSRKKL
LPSFNVFEIN GMNVVHPNAA YQVFYKQLFN KKPPNALNSF KIIDRLFNKS QKDNRDVSIL
IIDEIDYLIT KTQKVLFTLF DWPTKINSKL ILIAISNTMD LPDRLIPRCR SRLAFGRLVF
SPYKGDEIEK IIKERLENCK EIIDHTAIQL CARKVANVSG DIRKALQICR KAFENKRGHK
IVPRDITEAT NQLFDSPLTN AINYLPWAFK IFLTCLIIEL RIINEFVIPY KKVVNRYKIL
IETSGKYIGM CSDNELFKIM LDKLVKMGIL LIRPYIPLEN ISKNKSKEAL LGFNESSKKG
NNQKITRAQV SPDIDKESGD MGIELNVETQ LIITALMKDP DCSKKLNFY
