| IED ID | IndEnz0002009532 |
| Enzyme Type ID | protease009532 |
| Protein Name |
Reticulocyte-binding protein homolog 2b PfR2Hb PfRH2b Cleaved into: Reticulocyte-binding protein homolog 2b 85 kDa form; Reticulocyte-binding protein homolog 2b 297 kDa form |
| Gene Name | RH2b MAL13P1.176 PF3D7_1335300 |
| Organism | Plasmodium falciparum (isolate 3D7) |
| Taxonomic Lineage | cellular organisms Eukaryota Sar Alveolata Apicomplexa Aconoidasida Haemosporida (haemosporidians) Plasmodiidae Plasmodium Plasmodium (Laverania) Plasmodium falciparum Plasmodium falciparum (isolate 3D7) |
| Enzyme Sequence | MKTTLFCSISFCNIIFFFLELSHEHFVGQSSNTHGASSVTDFNFSEEKNLKSFEGKNNNNDNYASINRLYRKKPYMKRSLINLENDLFRLEPISYIQRYYKKNINRSDIFHNKKERGSKVYSNVSSFHSFIQEGKEEVEVFSIWGSNSVLDHIDVLRDNGTVVFSVQPYYLDIYTCKEAILFTTSFYKDLDKSSITKINEDIEKFNEEIIKNEEQCLVGGKTDFDNLLIVLENAEKANVRKTLFDNTFNDYKNKKSSFYNCLKNKKNDYDKKIKNIKNEITKLLKNIESTGNMCKTESYVMNNNLYLLRVNEVKSTPIDLYLNRAKELLESSSKLVNPIKMKLGDNKNMYSIGYIHDEIKDIIKRYNFHLKHIEKGKEYIKRITQANNIADKMKKDELIKKIFESSKHFASFKYSNEMISKLDSLFIKNEEILNNLFNNIFNIFKKKYETYVDMKTIESKYTTVMTLSEHLLEYAMDVLKANPQKPIDPKANLDSEVVKLQIKINEKSNELDNAISQVKTLIIIMKSFYDIIISEKASMDEMEKKELSLNNYIEKTDYILQTYNIFKSKSNIINNNSKNISSKYITIEGLKNDIDELNSLISYFKDSQETLIKDDELKKNMKTDYLNNVKYIEENVTHINEIILLKDSITQRIADIDELNSLNLININDFINEKNISQEKVSYNLNKLYKGSFEELESELSHFLDTKYLFHEKKSVNELQTILNTSNNECAKLNFMKSDNNNNNNNSNIINLLKTELSHLLSLKENIIKKLLNHIEQNIQNSSNKYTITYTDINNRMEDYKEEIESLEVYKHTIGNIQKEYILHLYENDKNALAVHNTSMQILQYKDAIQNIKNKISDDIKILKKYKEMNQDLLNYYEILDKKLKDNTYIKEMHTASLVQITQYIPYEDKTISELEQEFNNNNQKLDNILQDINAMNLNINILQTLNIGINACNTNNKNVEHLLNKKIELKNILNDQMKIIKNDDIIQDNEKENFSNVLKKEEEKLEKELDDIKFNNLKMDIHKLLNSYDHTKQNIESNLKINLDSFEKEKDSWVHFKSTIDSLYVEYNICNQKTHNTIKQQKNDIIELIYKRIKDINQEIIEKVDNYYSLSDKALTKLKSIHFNIDKEKYKNPKSQENIKLLEDRVMILEKKIKEDKDALIQIKNLSHDHFVNADNEKKKQKEKEEDDEQTHYSKKRKVMGDIYKDIKKNLDELNNKNLIDITLNEANKIESEYEKILIDDICEQITNEAKKSDTIKEKIESYKKDIDYVDVDVSKTRNDHHLNGDKIHDSFFYEDTLNYKAYFDKLKDLYENINKLTNESNGLKSDAHNNNTQVDKLKEINLQVFSNLGNIIKYVEKLENTLHELKDMYEFLETIDINKILKSIHNSMKKSEEYSNETKKIFEQSVNITNQFIEDVEILKTSINPNYESLNDDQIDDNIKSLVLKKEEISEKRKQVNKYITDIESNKEQSDLHLRYASRSIYVIDLFIKHEIINPSDGKNFDIIKVKEMINKTKQVSNEAMEYANKMDEKNKDIIKIENELYNLINNNIRSLKGVKYEKVRKQARNAIDDINNIHSNIKTILTKSKERLDEIKKQPNIKREGDVLNNDKTKIAYITIQINNGRIESNLLNILNMKHNIDTILNKAMDYMNDVSKSDQIVINIDSLNMNDIYNKDKDLLINILKEKQNMEAEYKKMNEMYNYVNETEKEIIKHKKNYEIRIMEHIKKETNEKKKKFMESNNKSLTTLMDSFRSMFYNEYINDYNINENFEKHQNILNEIYNGFNESYNIINTKMTEIINDNLDYNEIKEIKEVAQTEYDKLNKKVDELKNYLNNIKEQEGHRLIDYIKEKIFNLYIKCSEQQNIIDDSYNYITVKKQYIKTIEDVKFLLDSLNTIEEKNKSVANLEICTNKEDIKNLLKHVIKLANFSGIIVMSDTNTEITPENPLEDNDLLNLQLYFERKHEITSTLENDSDLELDHLGSNSDESIDNLKVYNDIIELHTYSTQILKYLDNIQKLKGDCNDLVKDCKELRELSTALYDLKIQITSVINRENDISNNIDIVSNKLNEIDAIQYNFEKYKEIFDNVEEYKTLDDTKNAYIVKKAEILKNVDINKTKEDLDIYFNDLDELEKSLTLSSNEMEIKTIVQNSYNSFSDINKNINDIDKEMKTLIPMLDELLNEGHNIDISLYNFIIRNIQIKIGNDIKNIREQENDTNICFEYIQNNYNFIKSDISIFNKYDDHIKVDNYISNNIDVVNKHNSLLSEHVINATNIIENIMTSIVEINEDTEMNSLEETQDKLLELYENFKKEKNIINNNYKIVHFNKLKEIENSLETYNSISTNFNKINETQNIDILKNEFNNIKTKINDKVKELVHVDSTLTLESIQTFNNLYGDLMSNIQDVYKYEDINNVELKKVKLYIENITNLLGRINTFIKELDKYQDENNGIDKYIEINKENNSYIIKLKEKANNLKENFSKLLQNIKRNETELYNINNIKDDIMNTGKSVNNIKQKFSSNLPLKEKLFQMEEMLLNINNIMNETKRISNTDAYTNITLQDIENNKNKENNNMNIETIDKLIDHIKIHNEKIQAEILIIDDAKRKVKEITDNINKAFNEITENYNNENNGVIKSAKNIVDKATYLNNELDKFLLKLNELLSHNNNDIKDLGDEKLILKEEEERKERERLEKAKQEEERKERERIEKEKQEKERLEREKQEQLKKEALKKQEQERQEQQQKEEALKRQEQERLQKEEELKRQEQERLEREKQEQLQKEEELRKKEQEKQQQRNIQELEEQKKPEIINEALVKGDKILEGSDQRNMELSKPNVSMDNTNNSPISNSEITESDDIDNSENIHTSHMSDIESTQTSHRSNTHGQQISDIVEDQITHPSNIGGEKITHNDEISITGERNNISDVNDYSESSNIFENGDSTINTSTRNTSSTHDESHISPISNAYDHVVSDNKKSMDENIKDKLKIDESITTDEQIRLDDNSNIVRIDSTDQRDASSHGSSNRDDDEISHVGSDIHMDSVDIHDSIDTDENADHRHNVNSVDSLSSSDYTDTQKDFSSIIKDGGNKEGHAENESKEYESQTEQTHEEGIMNPNKYSISEVDGIKLNEEAKHKITEKLVDIYPSTYRTLDEPMETHGPNEKFHMFGSPYVTEEDYTEKHDYDKHEDFNNERYSNHNKMDDFVYNAGGVVCCVLFFASITFFSMDRSNKDECDFDMCEEVNNNDHLSNYADKEEIIEIVFDENEEKYF |
| Enzyme Length | 3254 |
| Uniprot Accession Number | C0H5F4 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: [Reticulocyte-binding protein homolog 2b]: During the asexual blood stage, binds to a chymotrypsin sensitive, neuraminidase and trypsin resistant receptor on the surface of the host erythrocyte and thus is involved in merozoite invasion (PubMed:27438226, PubMed:12606570). The various processed forms have different binding affinities for the erythrocyte receptor; full length form binds with higher affinity followed by the 250 kDa form and finally the 300 kDa form while the 160 kDa form does not bind erythrocytes (PubMed:27438226). After merozoite attachment and reorientation, RH2b binding to its erythrocyte receptor triggers an increase in intracellular Ca(2+) within the parasite resulting in the release of microneme proteins such as EBA175 which in turn leads to the formation of the tight junction between parasite and host cell (PubMed:27438226). {ECO:0000269|PubMed:12606570, ECO:0000269|PubMed:27438226}.; FUNCTION: [Reticulocyte-binding protein homolog 2b 85 kDa form]: During the asexual blood stage, binds to a trypsin-resistant and chymotrypsin and neuraminidase sensitive receptor on the surface of the host erythrocyte and thus is involved in merozoite invasion. {ECO:0000269|PubMed:21698217}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Chain (3); Coiled coil (3); Compositional bias (6); Glycosylation (40); Modified residue (1); Motif (1); Region (6); Repeat (23); Signal peptide (1); Topological domain (2); Transmembrane (1) |
| Keywords | Cell junction;Cell membrane;Coiled coil;Cytoplasmic vesicle;Glycoprotein;Leucine-rich repeat;Membrane;Merozoite;Phosphoprotein;Receptor;Reference proteome;Repeat;Secreted;Signal;Tight junction;Transmembrane;Transmembrane helix |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:27438226}; Single-pass type I membrane protein {ECO:0000305}. Cytoplasmic vesicle, secretory vesicle, rhoptry {ECO:0000269|PubMed:12228308, ECO:0000269|PubMed:27438226}. Cell junction, tight junction {ECO:0000269|PubMed:27438226}. Secreted {ECO:0000269|PubMed:27438226}. Note=Localizes to the rhoptry neck at the apical end of the merozoite (PubMed:27438226, PubMed:12228308). During merozoite invasion, mainly localizes to the tight junction formed between the parasite and the host erythrocyte membranes and then moves with the tight junction to the posterior end as the parasite enters the erythrocyte (PubMed:27438226). Also, the different processed forms are released from the membrane following proteolytic cleavage (PubMed:27438226). The remaining 7 kDa processed transmembrane fragment is incorporated into the newly formed ring stage (PubMed:21698217). {ECO:0000269|PubMed:12228308, ECO:0000269|PubMed:21698217, ECO:0000269|PubMed:27438226}.; SUBCELLULAR LOCATION: [Reticulocyte-binding protein homolog 2b 85 kDa form]: Secreted {ECO:0000269|PubMed:21698217}. Cell membrane {ECO:0000269|PubMed:21698217}; Peripheral membrane protein {ECO:0000269|PubMed:21698217}; Extracellular side {ECO:0000269|PubMed:21698217}. Note=In mature schizont, co-localizes to the apical end of the schizont and the merozoite with reticulocyte-binding protein homolog 2b 297 kDa form. During merozoite invasion, shed from the cell surface. {ECO:0000269|PubMed:21698217}.; SUBCELLULAR LOCATION: [Reticulocyte-binding protein homolog 2b 297 kDa form]: Secreted {ECO:0000269|PubMed:21698217}. Cell membrane {ECO:0000269|PubMed:21698217}; Single-pass type I membrane protein {ECO:0000305}. Note=In mature schizont, co-localizes to the apical end of the schizont and the merozoite with reticulocyte-binding protein homolog 2b 85 kDa form. During merozoite invasion, shed from the cell surface. {ECO:0000269|PubMed:21698217}. |
| Modified Residue | MOD_RES 3233; /note=Phosphoserine; by CK2; /evidence=ECO:0000269|PubMed:23544851 |
| Post Translational Modification | PTM: Proteolytically processed into multiple fragments following schizont rupture (PubMed:27438226, PubMed:12228308, PubMed:21698217). In the mature schizont stage prior to merozoite release, full length RH2b is processed post-Golgi into C-terminal 297 kDa and N-terminal 85 kDa forms (PubMed:21698217, PubMed:27438226). Alternatively, full length RH2b can also be processed into C-terminal 250 kDa and N-terminal 130 kDa forms (PubMed:27438226). During merozoite invasion of host erythrocytes, further processing occurs generating a 160 kDa form (PubMed:27438226). At the same time, the C-terminal transmembrane region is cleaved, probably by a rhomboid protease, to shed all the different processed protein forms from the membrane leaving a transmembrane 7 kDa form on the merozoite surface (PubMed:27438226, PubMed:21698217). {ECO:0000269|PubMed:12228308, ECO:0000269|PubMed:21698217, ECO:0000269|PubMed:27438226}.; PTM: Phosphorylated at Ser-3233 by CK2alpha in schizonts. {ECO:0000269|PubMed:23544851}. |
| Signal Peptide | SIGNAL 1..24; /evidence=ECO:0000255 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | MOTIF 3253..3254; /note=Mediates the interaction with FBPA; /evidence=ECO:0000269|PubMed:22991428 |
| Gene Encoded By | |
| Mass | 382,883 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |