About Gene List

PF3D7_1133400 (AMA1)

Genome location: Pf3D7_11_v3:1,292,966..1,296,696(+)

Genome classification: Core

Function and Localization

Product Description: apical membrane antigen 1

SignalP Peptide: MRKLYCVLLLSAFEFTYMINFGRG

# Transmembrane Domains: 1

EC Numbers: None

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0020007 apical complex
Component GO:0020009 microneme
Component GO:0005886 plasma membrane
Function GO:0046812 host cell surface binding
Function GO:0005515 protein binding
Process GO:0044409 entry into host

Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):

Stage LR class MCA mean MCA prop. zeros
Sporozoite expressed N/A N/A
Ring expressed 0.39 0.87
Trophozoite expressed 0.10 0.94
Schizont expressed 0.55 0.81
Gametocyte not expressed 0.05 0.97

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1133400

Resistome Missense Mutations: None

Resistome Compounds with Missense Mutations: None

Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Non - Mutable in CDS

MIS: 0.776 | MFS: -2.387 | #Insertions: 0

PlasmoGEM Phenotype: N/A

RMgmDB ABS Phenotype: Not different from wild type (Pb ortholog: PBANKA_0915000)

Modification: Mutated | RMgm-5150

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q7KQK5

"Best" AlphaFill ligand hit: MTN (s-[(1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1h-pyrrol-3-yl)methyl] methanesulfonothioate, Local RMSD=1.51) with 6N87 (Global RMSD=4.61)

No associated EC numbers

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_130922

No human ortholog(s)

Genetic Variation

MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 5 4 7 18
disruptive 93 30 7 48
missense 93 27 7 39

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 7 10 19 19
disruptive 103 46 18 86
missense 99 40 17 59

PlasmoDB Total SNPs: 162

Non-coding: 64 | Synonymous: 9 | Nonsynonymous: 89 | Stop Codon: 0

Protein Information

Protein Length: 622 | Molecular Weight (kDa): 72.042

UniProt ID(s): A0A193PBX3, A0A193PCS2, A0A193PCS6, B2LUX3, B2LV51, M1V1F7, M1VGJ3, Q7KQK5, Q94661, Q967K1, Q967K2

PDB ID(s): 1YXE, 1Z40, 2Q8A, 2Q8B, 2Z8V, 2Z8W, 3SRI, 3SRJ, 3ZWZ, 4R19, 4R1B, 4R1C, 8G6B, 8GID, 8GIE, 8GIF

Isoelectric Point: 5.23

Protein Domain Annotations:

Source Family ID Description
InterPro IPR003298 Apical membrane antigen 1
InterPro IPR024056 Apical membrane antigen 1 domain superfamily
PFam PF02430 Apical membrane antigen 1
Superfamily SSF82910 Apical membrane antigen 1 domain superfamily

Associated Publications

PMID Title Authors DOI/Link
2701947 Integral membrane protein located in the apical complex of Plasmodium falciparum. Peterson MG, Marshall VM, ..., Kemp DJ 10.1128/mcb.9.7.3151-3154.1989
12228305 Independent translocation of two micronemal proteins in developing Plasmodiumfalciparum merozoites. Healer J, Crawford S, ..., Cowman AF 10.1128/IAI.70.10.5751-5758.2002
12368864 Genome sequence of the human malaria parasite Plasmodium falciparum. Gardner MJ, Hall N, ..., Barrell B 10.1038/nature01097
14676185 A role for apical membrane antigen 1 during invasion of hepatocytes by Plasmodiumfalciparum sporozoites. Silvie O, Franetich JF, ..., Mazier D 10.1074/jbc.M311331200
15805191 Domain III of Plasmodium falciparum apical membrane antigen 1 binds to theerythrocyte membrane protein Kx. Kato K, Mayer DC, ..., Miller LH 10.1073/pnas.0501594102
16129835 Structure of AMA1 from Plasmodium falciparum reveals a clustering ofpolymorphisms that surround a conserved hydrophobic pocket. Bai T, Becker M, ..., Batchelor AH https://pubmed.ncbi.nlm.nih.gov/16129835/
16835460 Plasmodium falciparum AMA1 binds a rhoptry neck protein homologous to TgRON4, acomponent of the moving junction in Toxoplasma gondii. Alexander DL, Arastu-Kapur S, Dubremetz JF, Boothroyd JC 10.1128/EC.00040-06
18343371 Plasmodium falciparum: genetic polymorphism in apical membrane antigen-1 genefrom Indian isolates. Rajesh V, Singamsetti VK, ..., Das A 10.1016/j.exppara.2008.01.019
18952195 Rhoptry neck protein RON2 forms a complex with microneme protein AMA1 inPlasmodium falciparum merozoites. Cao J, Kaneko O, ..., Torii M 10.1016/j.parint.2008.09.005
19283086 Functional analysis of the leading malaria vaccine candidate AMA-1 reveals anessential role for the cytoplasmic domain in the invasion process. Treeck M, Zacherl S, ..., Gilberger TW 10.1371/journal.ppat.1000322
19357945 Polymorphism at the apical membrane antigen 1 gene (AMA1) of the malaria parasitePlasmodium falciparum in a Vietnamese population. Quang ND, Hoa PT, ..., Matsuoka H 10.1007/s10528-009-9236-4
19502690 Genetic polymorphism in msp-2, ama-1 and csp genes in Plasmodium falciparum fieldisolates from north and north-western India. Farooq U, Malla N, Dubey ML https://pubmed.ncbi.nlm.nih.gov/19502690/
20236549 Solution structure of a Plasmodium falciparum AMA-1/MSP 1 chimeric proteinvaccine candidate (PfCP-2.9) for malaria. Peng H, Hu Y, ..., Pan W 10.1186/1475-2875-9-76
20532217 Protein kinase a dependent phosphorylation of apical membrane antigen 1 plays animportant role in erythrocyte invasion by the malaria parasite. Leykauf K, Treeck M, ..., Crabb BS 10.1371/journal.ppat.1000941
21082025 Generation of humoral immune responses to multi-allele PfAMA1 vaccines; effect ofadjuvant and number of component alleles on the breadth of response. Kusi KA, Faber BW, ..., Remarque EJ 10.1371/journal.pone.0015391
21292899 Genetic diversity of polymorphic vaccine candidate antigens (apical membraneantigen-1, merozoite surface protein-3, and erythrocyte binding antigen-175) inPlasmodium falciparum isolates from western and central Africa. Soulama I, Bigoga JD, ..., Sirima SB 10.4269/ajtmh.2011.10-0365
22033736 The cysteine-rich regions of Plasmodium falciparum RON2 bind with hosterythrocyte and AMA1 during merozoite invasion. Hossain ME, Dhawan S, Mohmmed A 10.1007/s00436-011-2690-z
22194692 Juxtamembrane shedding of Plasmodium falciparum AMA1 is sequence independent andessential, and helps evade invasion-inhibitory antibodies. 10.1371/journal.ppat.1002448
22306282 Genetic diversity and natural selection at the domain I of apical membraneantigen-1 (AMA-1) of Plasmodium falciparum in isolates from Iran. Mardani A, Keshavarz H, ..., Khorramizadeh MR 10.1016/j.exppara.2012.01.006
22737069 Structural and functional insights into the malaria parasite moving junctioncomplex. Vulliez-Le Normand B, Tonkin ML, ..., Lebrun M 10.1371/journal.ppat.1002755
23227229 Defining the antigenic diversity of Plasmodium falciparum apical membrane antigen1 and the requirements for a multi-allele vaccine against malaria. Drew DR, Hodder AN, ..., Beeson JG 10.1371/journal.pone.0051023
23557839 Population genetics, sequence diversity and selection in the gene encoding thePlasmodium falciparum apical membrane antigen 1 in clinical isolates from thesouth-east of Iran. Mehrizi AA, Sepehri M, ..., Zakeri S 10.1016/j.meegid.2013.03.042
23747831 Natural selection and population genetic structure of domain-I of Plasmodiumfalciparum apical membrane antigen-1 in India. Basu M, Maji AK, Mitra M, Sengupta S 10.1016/j.meegid.2013.05.015
23910910 Role of calcineurin and actin dynamics in regulated secretion of micronemeproteins in Plasmodium falciparum merozoites during erythrocyte invasion. Singh S, More KR, Chitnis CE 10.1111/cmi.12177
24108241 Apical membrane antigen 1 mediates apicomplexan parasite attachment but isdispensable for host cell invasion. Bargieri DY, Andenmatten N, ..., Menard R 10.1038/ncomms3552
24303947 Analysis of human B-cell responses following ChAd63-MVA MSP1 and AMA1immunization and controlled malaria infection. Elias SC, Choudhary P, ..., Draper SJ 10.1111/imm.12226
24321092 Seasonal changes in the antibody responses against Plasmodium falciparummerozoite surface antigens in areas of differing malaria endemicity in Indonesia. Supargiyono S, Bretscher MT, ..., Drakeley CJ 10.1186/1475-2875-12-444
24571085 Conditional expression of apical membrane antigen 1 in Plasmodium falciparumshows it is required for erythrocyte invasion by merozoites. Yap A, Azevedo MF, ..., Cowman AF 10.1111/cmi.12287
24958881 Immunization with a functional protein complex required for erythrocyte invasionprotects against lethal malaria. Srinivasan P, Ekanem E, ..., Miller LH 10.1073/pnas.1409928111
25343578 Molecular insights into the interaction between Plasmodium falciparum apicalmembrane antigen 1 and an invasion-inhibitory peptide. Wang G, MacRaild CA, ..., Scanlon MJ 10.1371/journal.pone.0109674
25360546 Structure and dynamics of apical membrane antigen 1 from Plasmodium falciparumFVO. Lim SS, Yang W, ..., McGowan S 10.1021/bi5012089
25604491 alpha-Thalassaemia trait is associated with antibody prevalence against malariaantigens AMA-1 and MSP-1. Daou M, Kituma E, ..., Doumbo O 10.1093/tropej/fmu077
25881166 Low levels of polymorphisms and no evidence for diversifying selection on thePlasmodium knowlesi Apical Membrane Antigen 1 gene. Faber BW, Abdul Kadir K, ..., Singh B 10.1371/journal.pone.0124400
26537493 A WD40-repeat protein unique to malaria parasites associates with adhesionprotein complexes and is crucial for blood stage progeny. von Bohl A, Kuehn A, ..., Pradel G 10.1186/s12936-015-0967-x
26731670 Stability of the Plasmodium falciparum AMA1-RON2 Complex Is Governed by theDomain II (DII) Loop. Delgadillo RF, Parker ML, ..., Douguet D 10.1371/journal.pone.0144764
26901523 Polymorphisms in B Cell Co-Stimulatory Genes Are Associated with IgG AntibodyResponses against Blood-Stage Proteins of Plasmodium vivax. Cassiano GC, Furini AA, ..., Machado RL 10.1371/journal.pone.0149581
28371168 A MA1 and M AEBL are important for Plasmodium falciparum sporozoite infection ofthe liver Yang ASP, Lopaticki S, ..., Boddey JA 10.1111/cmi.12745
33430886 Isolation and light chain shuffling of a Plasmodium falciparum AMA1-specifichuman monoclonal antibody with growth inhibitory activity. Seidel-Greven M, Addai-Mensah O, ..., Fendel R 10.1186/s12936-020-03548-3
34946853 Genetic Polymorphism and Natural Selection of Apical Membrane Antigen-1 in Plasmodium falciparum Isolates from Vietnam Kang JM, Le HG, ..., Na BK 10.3390/genes12121903
35193607 Genetic diversity of Plasmodium falciparum AMA-1 antigen from the NortheastIndian state of Tripura and comparison with global sequences: implications forvaccine development. Nirmolia T, Ahmed MA, ..., Patgiri SJ 10.1186/s12936-022-04081-1
37829607 IgM antibody responses against Plasmodium antigens in neotropical primates in theBrazilian Atlantic Forest de Assis GMP, de Alvarenga DAM, ..., Alves de Brito CF 10.3389/fcimb.2023.1169552
37924072 Establishment and application of an iELISA detection method for measuring apicalmembrane antigen 1 (AMA1) antibodies of Toxoplasma gondii in cats Gao Y, Shen Y, ..., Lu S 10.1186/s12917-023-03775-1
38365484 A Diversity Covering (DiCo) Plasmodium vivax apical membrane antigen-1 vaccineadjuvanted with RFASE/RSL10 yields high levels of growth-inhibitory antibodies Faber BW, Yeoh LM, ..., Kocken CHM 10.1016/j.vaccine.2024.02.029
37769577 Invasion-inhibitory peptides chosen by natural selection analysis as anantimalarial strategy Rodriguez-Obediente K, Yepes-Perez Y, ..., Patarroyo MA 10.1016/j.molimm.2023.09.013
37660103 Structure-based design of a strain transcending AMA1-RON2L malaria vaccine Patel PN, Dickey TH, ..., Tolia NH 10.1038/s41467-023-40878-7
38392804 Meiotic Cytokinesis in Saccharomyces cerevisiae: Spores That Just Need Closure Durant M, Mucelli X, Huang LS 10.3390/jof10020132
37519774 Screening of apical membrane antigen-1 (AMA1), dense granule protein-7 (GRA7) andrhoptry protein-16 (ROP16) antigens for a potential vaccine candidate againstToxoplasma gondii for chickens Madlala T, Adeleke VT, ..., Adeleke MA 10.1016/j.jvacx.2023.100347
37735574 Structure guided mimicry of an essential P. falciparum receptor-ligand complexenhances cross neutralizing antibodies Yanik S, Venkatesh V, ..., Srinivasan P 10.1038/s41467-023-41636-5
37662206 Analytic optimization of Plasmodium falciparum marker gene haplotype recoveryfrom amplicon deep sequencing of complex mixtures Lapp Z, Freedman E, ..., Taylor SM 10.1101/2023.08.17.23294237
37693871 Analytical approaches for antimalarial antibody responses to confirm historicaland recent malaria transmission: an example from the Philippines Macalinao MLM, Fornace KM, ..., Drakeley CJ 10.1016/j.lanwpc.2023.100792
37925116 Genetic diversity and natural selection of apical membrane antigen-1 (ama-1) inCameroonian Plasmodium falciparum isolates Hawadak J, Kojom Foko LP, ..., Singh V 10.1016/j.gene.2023.147956
38087335 Amplicon deep sequencing of five highly polymorphic markers of Plasmodiumfalciparum reveals high parasite genetic diversity and moderate populationstructure in Ethiopia Reda AG, Huwe T, ..., Mamo H 10.1186/s12936-023-04814-w
37691957 Dynamics of IgG antibody response against Plasmodium antigens among Nigerianinfants and young children Leonard CM, Uhomoibhi P, ..., Rogier E 10.3389/fimmu.2023.1208822
38254075 Geospatial analysis of Plasmodium falciparum serological indicators: schoolversus community sampling in a low-transmission malaria setting Jaramillo-Underwood A, Herman C, ..., Rogier E 10.1186/s12916-023-03145-6
37988347 Protein kinase PfPK2 mediated signalling is critical for host erythrocyteinvasion by malaria parasite Rawat RS, Gupta A, ..., Sharma P 10.1371/journal.ppat.1011770
38370683 Potent AMA1-specific human monoclonal antibody against P. vivax Pre-erythrocyticand Blood Stages Winnicki AC, Dietrich MH, ..., King CL 10.1101/2024.02.07.579302