1.A.91.1.1
The plasmodial three-component surface broad specificity anion channel complex. One component is PSAC (Clag3.2, Clag3/2, RhopH1, of 1416 aas and at least two putative TMSs, one N-terminal and one C-terminal (residues 1199 to 1223)). The latter is an amphipathic α-helix thought to form the channel in the multisubunit complex (Sharma et al. 2015). CLAG3 undergoes hetero-association, and its expression determines the channel phenotype quantitatively, leading to host erythrocyte permeability to ions and nutrients (Gupta et al. 2018). The isoforms traffic to and insert in the host membrane while remaining associated with two unrelated parasite proteins, RhopH2 (CLAG3.2 of 1414 aas (B0M163) and RhopH3 (CLAG3.3 (B0M0W2) of 897 aas and up to 4 TMSs, one N-terminal and up to three centrally located. Both the channel phenotypes and molecular changes are consistent with a multiprotein complex that forms the nutrient pore, supporting direct involvement of the CLAG3 protein in channel formation (Gupta et al. 2018). Inhibitors potentially useful theraputically at 5 μM concentrations include PRT1-20 and ISPA-28. Their use suggested that there may be two routes of nutrient entry via the PSAC (Pain et al. 2016). Reviewed by Meier et al. 2018. Malaria parasites use a soluble RhopH complex for erythrocyte invasion and an integral membrane channel form for nutrient uptake (Schureck et al. 2021). (See family description for more details.) The kinetics of CLAG3.2 insertion into the erythrocyte membrane has been studied (Shao et al. 2022). Ion channel proteins in P. falciparum have been reviewed (Desai 2024).
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| Accession Number: | O77309 |
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| Protein Name: | RhopH1(3.2) protein |
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| Length: | 1416 |
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| Molecular Weight: | 167489.00 |
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| Species: | Plasmodium falciparum (isolate 3D7) [36329] |
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| Number of TMSs: | 2 |
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| Substrate |
anion, nutrient |
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1: MVSFFKTPII IFFFLLCLNE KVLCSINENE NLGENKNENA NVNTPENLNK LLNEYDNIEQ
61: LKSMIGNDEL HKNLTILEKL ILESLEKDKL KYPLLKQGTE QLIDISKFNK KNITDADDET
121: YIIPTVQSSF HDIVKYEHLI KEQSIEIYNS DISDKIKKKI FIVRTLKTIK LMLIPLNSYK
181: QNNDLKSALE ELNNVFTNKE AQKESSPIGD HGTFFRKLLT HVRTIKENED IENKGETLIL
241: GDNKIDVMNS NDFFFTTNSN VKFMENLDDI TNQYGLGLIN HLGPHLIALG HFVVLKLALK
301: NYKNYFEAKN IKFFSWQKIL EFSMSDRFKV LDMMCNHESV YYSEKKRRKT YLKVDRSSTS
361: MECNILEYLL HYFNKYQLEI IKTTQDTDFD LHGMMEHKYI KDYFFSFMCN DPKECIIYHT
421: NQFKKEANEE NTFPEQEEPN RQISAFNLYL NYYYFMKRYS SYGTKKTLYV HLLNLTGLLN
481: HDTRAYVTSL YLPGYYNAVE MSFTDDKEFS TLFESLIQCI EKCHSDQARQ ISKDSNLLNN
541: ITKCDLCKGA FLYANMKFDE VPSMLQKFYV YLTKGLKIQK VSSLIKTLDI YQDYSNFLSH
601: DINWYTFLFL FRLTSFKEIA NKNVAEAMYL NIKDEDTFNK TIVTNYWYPS PIKKYYTLYV
661: RKHIPNNLVD ELEKLMKSGT LEKMKKSLTF LVHVNSFLQL DFFHQLNEPP LGLPRSYPLS
721: LVLEHKFKEW MDSSPAGFYF SNYQNPYIRK DLHDKVLSQK FEPPKMNQWN KVLKSLIECA
781: YDMYFEQRHV KNLYKYHNIY NINNKLMLMR DSIDLYKNNF DDVLFFADIF NMRKYMTATP
841: VYKKVKDRVY HTLHSITGNS VNFYKYGIIY GFKVNKEILK EVVDELYSIY NFNTDIFTDT
901: SFLQTVYLLF RRIEETYRTQ RRDDKISVNN VFFMNVANNY SKLNKEEREI EIHNSMASRY
961: YAKTMFAAFQ MLFSTMLSNN VDNLDKAYGL SENIQVATST SAFLTFAYVY NGSIMDSVTN
1021: SLLPPYAKKP ITQLKYGKTF VFSNYFMLAS KMYDMLNYKN LSLLCEYQAV ASANFYSAKK
1081: VGQFLGRKFL PITTYFLVMR ISWTHAFTTG QHLICAFDPK RCTPDCKNST SYKSPQSFFY
1141: GWPPSSETYL FFYFFTNLYL DAYKSFPGGF GPAIKEQTQH VQEQTYERKP SVHSFNRNFF
1201: MELVNGFMYA FCFFAISQMY AYFENINFYI TSNFRFLDRY YGVFNKYFIN YAIIKLKEIT
1261: SDLLIKYERE AYLSMKKYGY LGEVIAARLS PKDKIMNYVH ETNEDIMSNL RRYDMENAFK
1321: NKMVTYVDDF AFFDDCGKNE QFLNERCDYC PVIEEVEETQ LFTTTGDKNT NETTEIKKQT
1381: STYIDTEKMN EADSADSDDE KDFDTPDNEL MIARFH