RH5IP_PLAF7
ID RH5IP_PLAF7 Reviewed; 1086 AA.
AC O97302;
DT 13-NOV-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Rh5-interacting protein {ECO:0000303|PubMed:21909261};
DE Short=PfRipr {ECO:0000303|PubMed:21909261};
DE Flags: Precursor;
GN Name=RIPR; Synonyms=PFC1045C {ECO:0000303|PubMed:21909261};
GN ORFNames=PF3D7_0323400 {ECO:0000312|EMBL:CAB39049.1};
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=10448855; DOI=10.1038/22964;
RA Bowman S., Lawson D., Basham D., Brown D., Chillingworth T., Churcher C.M.,
RA Craig A., Davies R.M., Devlin K., Feltwell T., Gentles S., Gwilliam R.,
RA Hamlin N., Harris D., Holroyd S., Hornsby T., Horrocks P., Jagels K.,
RA Jassal B., Kyes S., McLean J., Moule S., Mungall K.L., Murphy L.,
RA Oliver K., Quail M.A., Rajandream M.A., Rutter S., Skelton J., Squares R.,
RA Squares S., Sulston J.E., Whitehead S., Woodward J.R., Newbold C.,
RA Barrell B.G.;
RT "The complete nucleotide sequence of chromosome 3 of Plasmodium
RT falciparum.";
RL Nature 400:532-538(1999).
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:0000312|Proteomes:UP000001450}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7 {ECO:0000312|Proteomes:UP000001450};
RX PubMed=12368867; DOI=10.1038/nature01095;
RA Hall N., Pain A., Berriman M., Churcher C.M., Harris B., Harris D.,
RA Mungall K.L., Bowman S., Atkin R., Baker S., Barron A., Brooks K.,
RA Buckee C.O., Burrows C., Cherevach I., Chillingworth C., Chillingworth T.,
RA Christodoulou Z., Clark L., Clark R., Corton C., Cronin A., Davies R.M.,
RA Davis P., Dear P., Dearden F., Doggett J., Feltwell T., Goble A.,
RA Goodhead I., Gwilliam R., Hamlin N., Hance Z., Harper D., Hauser H.,
RA Hornsby T., Holroyd S., Horrocks P., Humphray S., Jagels K., James K.D.,
RA Johnson D., Kerhornou A., Knights A., Konfortov B., Kyes S., Larke N.,
RA Lawson D., Lennard N., Line A., Maddison M., Mclean J., Mooney P.,
RA Moule S., Murphy L., Oliver K., Ormond D., Price C., Quail M.A.,
RA Rabbinowitsch E., Rajandream M.A., Rutter S., Rutherford K.M., Sanders M.,
RA Simmonds M., Seeger K., Sharp S., Smith R., Squares R., Squares S.,
RA Stevens K., Taylor K., Tivey A., Unwin L., Whitehead S., Woodward J.R.,
RA Sulston J.E., Craig A., Newbold C., Barrell B.G.;
RT "Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.";
RL Nature 419:527-531(2002).
RN [4] {ECO:0000305}
RP FUNCTION, IDENTIFICATION IN COMPLEX WITH RH5, SUBCELLULAR LOCATION,
RP DEVELOPMENTAL STAGE, IDENTIFICATION BY MASS SPECTROMETRY, DISULFIDE BONDS,
RP AND PROTEOLYTIC CLEAVAGE.
RX PubMed=21909261; DOI=10.1371/journal.ppat.1002199;
RA Chen L., Lopaticki S., Riglar D.T., Dekiwadia C., Uboldi A.D., Tham W.H.,
RA O'Neill M.T., Richard D., Baum J., Ralph S.A., Cowman A.F.;
RT "An EGF-like protein forms a complex with PfRh5 and is required for
RT invasion of human erythrocytes by Plasmodium falciparum.";
RL PLoS Pathog. 7:E1002199-E1002199(2011).
RN [5] {ECO:0000305}
RP FUNCTION, IDENTIFICATION IN THE PFRH5 ADHESION COMPLEX, SUBCELLULAR
RP LOCATION, DEVELOPMENTAL STAGE, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP BIOTECHNOLOGY.
RX PubMed=25583518; DOI=10.1073/pnas.1415466112;
RA Reddy K.S., Amlabu E., Pandey A.K., Mitra P., Chauhan V.S., Gaur D.;
RT "Multiprotein complex between the GPI-anchored CyRPA with PfRH5 and PfRipr
RT is crucial for Plasmodium falciparum erythrocyte invasion.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:1179-1184(2015).
RN [6] {ECO:0000305}
RP FUNCTION, IDENTIFICATION IN THE PFRH5 ADHESION COMPLEX, SUBCELLULAR
RP LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=27374406; DOI=10.1016/j.chom.2016.06.004;
RA Volz J.C., Yap A., Sisquella X., Thompson J.K., Lim N.T., Whitehead L.W.,
RA Chen L., Lampe M., Tham W.H., Wilson D., Nebl T., Marapana D., Triglia T.,
RA Wong W., Rogers K.L., Cowman A.F.;
RT "Essential Role of the PfRh5/PfRipr/CyRPA Complex during Plasmodium
RT falciparum Invasion of Erythrocytes.";
RL Cell Host Microbe 20:60-71(2016).
RN [7] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND BIOTECHNOLOGY.
RX PubMed=27692771; DOI=10.1016/j.vaccine.2016.09.028;
RA Ntege E.H., Arisue N., Ito D., Hasegawa T., Palacpac N.M.Q., Egwang T.G.,
RA Horii T., Takashima E., Tsuboi T.;
RT "Identification of Plasmodium falciparum reticulocyte binding protein
RT homologue 5-interacting protein, PfRipr, as a highly conserved blood-stage
RT malaria vaccine candidate.";
RL Vaccine 34:5612-5622(2016).
RN [8] {ECO:0000305}
RP IDENTIFICATION IN THE PFRH5 ADHESION COMPLEX.
RX PubMed=28186186; DOI=10.1038/ncomms14333;
RA Galaway F., Drought L.G., Fala M., Cross N., Kemp A.C., Rayner J.C.,
RA Wright G.J.;
RT "P113 is a merozoite surface protein that binds the N terminus of
RT Plasmodium falciparum RH5.";
RL Nat. Commun. 8:14333-14333(2017).
RN [9] {ECO:0000305}
RP IDENTIFICATION IN THE PFRH5 ADHESION COMPLEX.
RX PubMed=30542156; DOI=10.1038/s41586-018-0779-6;
RA Wong W., Huang R., Menant S., Hong C., Sandow J.J., Birkinshaw R.W.,
RA Healer J., Hodder A.N., Kanjee U., Tonkin C.J., Heckmann D., Soroka V.,
RA Sogaard T.M.M., Jorgensen T., Duraisingh M.T., Czabotar P.E.,
RA de Jongh W.A., Tham W.H., Webb A.I., Yu Z., Cowman A.F.;
RT "Structure of Plasmodium falciparum Rh5-CyRPA-Ripr invasion complex.";
RL Nature 565:118-121(2019).
CC -!- FUNCTION: Essential for the invasion of host erythrocytes by blood
CC stage merozoites (PubMed:21909261, PubMed:25583518, PubMed:27374406,
CC PubMed:27692771). As part of the PfRH5 adhesion complex, facilitates
CC the interaction of RH5 and human BSG required for the Ca(2+) release
CC into the erythrocyte (PubMed:27374406). {ECO:0000269|PubMed:21909261,
CC ECO:0000269|PubMed:25583518, ECO:0000269|PubMed:27374406,
CC ECO:0000269|PubMed:27692771}.
CC -!- SUBUNIT: Component of the PfRH5 adhesion complex composed of 1 copy of
CC CyRPA, RH5 and RIPR; the complex is formed during merozoite invasion of
CC host erythrocytes specifically at the interface between the parasite
CC and host membranes (PubMed:21909261, PubMed:25583518, PubMed:27374406,
CC PubMed:28186186, PubMed:30542156). Within the complex, interacts with
CC CyRPA (PubMed:28186186, PubMed:30542156). CyRPA recruitment of RIPR to
CC RH5-P113-BSG leads to the formation of the PfRH5 adhesion complex which
CC probably in turn releases RH5 from P113 while maintaining the
CC interaction of the PfRH5 adhesion complex with BSG (PubMed:28186186).
CC {ECO:0000269|PubMed:21909261, ECO:0000269|PubMed:25583518,
CC ECO:0000269|PubMed:27374406, ECO:0000269|PubMed:28186186,
CC ECO:0000269|PubMed:30542156}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:21909261,
CC ECO:0000269|PubMed:25583518}. Cytoplasmic vesicle, secretory vesicle,
CC microneme lumen {ECO:0000269|PubMed:21909261,
CC ECO:0000269|PubMed:25583518, ECO:0000269|PubMed:27374406,
CC ECO:0000269|PubMed:27692771}. Cell membrane
CC {ECO:0000269|PubMed:21909261, ECO:0000269|PubMed:25583518,
CC ECO:0000269|PubMed:27374406}; Peripheral membrane protein
CC {ECO:0000269|PubMed:21909261, ECO:0000269|PubMed:25583518,
CC ECO:0000269|PubMed:27374406}; Extracellular side
CC {ECO:0000269|PubMed:21909261, ECO:0000269|PubMed:25583518,
CC ECO:0000269|PubMed:27374406}. Host cell membrane
CC {ECO:0000269|PubMed:30542156}. Note=In late schizonts, colocalizes with
CC CyRPA in the microneme lumen (PubMed:21909261, PubMed:25583518,
CC PubMed:27374406, PubMed:27692771). During merozoite invasion of host
CC erythrocytes, secreted at the merozoite apical surface where it
CC colocalizes with CyPRA and RH5 at the interface between the merozoite
CC and the erythrocyte (PubMed:27374406, PubMed:21909261,
CC PubMed:25583518). {ECO:0000269|PubMed:21909261,
CC ECO:0000269|PubMed:25583518, ECO:0000269|PubMed:27374406,
CC ECO:0000269|PubMed:27692771}.
CC -!- DEVELOPMENTAL STAGE: Expressed in late throphozoide to schizonts and in
CC merozoites (at protein level). {ECO:0000269|PubMed:21909261,
CC ECO:0000269|PubMed:25583518, ECO:0000269|PubMed:27374406,
CC ECO:0000269|PubMed:27692771}.
CC -!- PTM: Proteolytically cleaved into two chains of 125kDa and 65kDa which
CC remain associated. The cleavage occurs at the schizont stage prior to
CC the release of merozoites. {ECO:0000269|PubMed:21909261}.
CC -!- PTM: Contains disulfide bonds. {ECO:0000269|PubMed:21909261}.
CC -!- DISRUPTION PHENOTYPE: Conditional knockdown causes loss of cell growth
CC and severely impairs merozoite invasion of erythrocytes. Attachment to
CC and deformation of erythrocyte membrane is normal, however the
CC subsequent step, which triggers an increase in Ca(2+) from the attached
CC merozoite into the erythrocyte, is impaired.
CC {ECO:0000269|PubMed:27374406}.
CC -!- BIOTECHNOLOGY: Potential candidate for the development of parasite
CC blood stage vaccines. In vitro and in vivo, induces neutralizing
CC antibodies capable of inhibiting merozoite invasion of host
CC erythrocytes. {ECO:0000269|PubMed:25583518,
CC ECO:0000269|PubMed:27692771}.
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DR EMBL; AL844502; CAB39049.1; -; Genomic_DNA.
DR RefSeq; XP_001351305.1; XM_001351269.1.
DR AlphaFoldDB; O97302; -.
DR IntAct; O97302; 3.
DR STRING; 5833.PFC1045c; -.
DR PRIDE; O97302; -.
DR EnsemblProtists; CAB39049; CAB39049; PF3D7_0323400.
DR GeneID; 814549; -.
DR KEGG; pfa:PF3D7_0323400; -.
DR VEuPathDB; PlasmoDB:PF3D7_0323400; -.
DR HOGENOM; CLU_285371_0_0_1; -.
DR InParanoid; O97302; -.
DR OMA; DSCGPKG; -.
DR PhylomeDB; O97302; -.
DR Proteomes; UP000001450; Chromosome 3.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0033644; C:host cell membrane; IDA:UniProtKB.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043655; C:host extracellular space; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:GeneDB.
DR GO; GO:0020009; C:microneme; IDA:UniProtKB.
DR GO; GO:0034494; C:microneme lumen; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0044409; P:entry into host; IDA:UniProtKB.
DR InterPro; IPR000742; EGF-like_dom.
DR SMART; SM00181; EGF; 9.
DR PROSITE; PS01186; EGF_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasmic vesicle; Disulfide bond; Glycoprotein;
KW Host cell membrane; Host membrane; Membrane; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..1086
FT /note="Rh5-interacting protein"
FT /evidence="ECO:0000255"
FT /id="PRO_5004160700"
FT DOMAIN 287..321
FT /note="EGF-like 1"
FT /evidence="ECO:0000255"
FT DOMAIN 325..362
FT /note="EGF-like 2"
FT /evidence="ECO:0000255"
FT DOMAIN 636..675
FT /note="EGF-like 3"
FT /evidence="ECO:0000255"
FT DOMAIN 679..715
FT /note="EGF-like 4"
FT /evidence="ECO:0000255"
FT DOMAIN 719..753
FT /note="EGF-like 5"
FT /evidence="ECO:0000255"
FT DOMAIN 818..854
FT /note="EGF-like 6"
FT /evidence="ECO:0000255"
FT DOMAIN 858..897
FT /note="EGF-like 7"
FT /evidence="ECO:0000255"
FT DOMAIN 901..938
FT /note="EGF-like 8"
FT /evidence="ECO:0000255"
FT DOMAIN 942..979
FT /note="EGF-like 9"
FT /evidence="ECO:0000255"
FT CARBOHYD 103
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 144
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 228
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 303
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 334
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 480
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 498
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 506
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 526
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 646
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 964
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1021
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 1086 AA; 125893 MW; BE10FC0AB5BF9194 CRC64;
MFRIFFTLLI IILIKKTSAI DLIEGIFYEK NEIDKLTFSL DHRVRDNLKT DLILNNNGEN
DYAYLNKYVY TILNRDSTEK IKTFFSHNKD MKSCDYFISK EYNSSDKTNQ ICYKKTFCGV
VIPNSEEIKT NKITNDKLYC AHFNSTHIII YYISQPLLLE PHVVYEETFF EKGKNDQINC
QGMYISLRSV HVHTHNAILQ QETLTYIKNL CDGKNNCKFD FDSIKYENKS LTHYLFFINI
QYQCISPLNL QENEMCDVYN DDTHKATCKY GFNKIELLKN VCEENYRCTQ DICSVNQFCD
GENETCTCKT SLLPSAKNNC EYNDLCTVLN CPENSTCEQI GNGKKAECKC ENGKYYHNNK
CYTKNDLELA IKIEPHKKEK FYKNNLYQGK ALKPEYIFMQ CENGFSIEVI NAYVSCYRVS
FNLNKLKYVT ESLKKMCDGK TKCAYGNTID PIDDLNHHNI CNNFNTIFKY DYLCVFNNQN
ITSDKNSHLH SNIPSLYNSS ILPDINKSKF HLISRNSRTN QYPHNNISML EIQNEISSHN
SNQFSTDPHT NSNNINNMNI KKVEIFRSRF SSKLQCQGGK INIDKAILKG GEGCNDLLLT
NSLKSYCNDL SECDIGLIYH FDTYCINDQY LFVSYSCSNL CNKCHNNSTC YGNRFNYDCF
CDNPYISKYG NKLCERPNDC ESVLCSQNQV CQILPNDKLI CQCEEGYKNV KGKCVPDNKC
DLSCPSNKVC VIENGKQTCK CSERFVLENG VCICANDYKM EDGINCIAKN KCKRKEYENI
CTNPNEMCAY NEETDIVKCE CKEHYYRSSR GECILNDYCK DINCKENEEC SIVNFKPECV
CKENLKKNNK GECIYENSCL INEGNCPKDS KCIYREYKPH ECVCNKQGHV AVNGKCVLED
KCVHNKKCSE NSICVNVMNK EPICVCTYNY YKKDGVCLIQ NPCLKDNGGC SRNSECTFKY
SKINCTCKEN YKNKDDSCVP NTNEYDESFT FQYNDDASII LGACGMIEFS YIYNQIIWKI
NNSKESYVFY YDYPTAGNIE VQIKNEIFHT IIYLKKKIGN SVIYDDFQVD HQTCIYENVF
YYSNQN
