AMA1_TOXGV
ID AMA1_TOXGV Reviewed; 569 AA.
AC B6KAM0; B9QC59; O15681; V4ZTW1;
DT 03-APR-2013, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 1.
DT 25-MAY-2022, entry version 55.
DE RecName: Full=Apical membrane antigen 1;
DE Short=TgAMA-1;
DE Short=TgAMA1;
DE Contains:
DE RecName: Full=Apical membrane antigen 1, soluble form;
DE Flags: Precursor;
GN Name=AMA1; ORFNames=TGVEG_255260;
OS Toxoplasma gondii (strain ATCC 50861 / VEG).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Conoidasida; Coccidia;
OC Eucoccidiorida; Eimeriorina; Sarcocystidae; Toxoplasma.
OX NCBI_TaxID=432359;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 50861 / VEG;
RA Lorenzi H., Inman J., Amedeo P., Brunk B., Roos D., Caler E.;
RT "Annotation of Toxoplasma gondii VEG.";
RL Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 29-569, FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=ATCC 50611 / Me49;
RX PubMed=11083833; DOI=10.1128/iai.68.12.7078-7086.2000;
RA Hehl A.B., Lekutis C., Grigg M.E., Bradley P.J., Dubremetz J.F.,
RA Ortega-Barria E., Boothroyd J.C.;
RT "Toxoplasma gondii homologue of plasmodium apical membrane antigen 1 is
RT involved in invasion of host cells.";
RL Infect. Immun. 68:7078-7086(2000).
RN [3]
RP PROTEIN SEQUENCE OF 67-72 AND 482-487, PROTEOLYTIC PROCESSING, FUNCTION,
RP AND SUBCELLULAR LOCATION.
RX PubMed=16102004; DOI=10.1111/j.1365-2958.2005.04772.x;
RA Howell S.A., Hackett F., Jongco A.M., Withers-Martinez C., Kim K.,
RA Carruthers V.B., Blackman M.J.;
RT "Distinct mechanisms govern proteolytic shedding of a key invasion protein
RT in apicomplexan pathogens.";
RL Mol. Microbiol. 57:1342-1356(2005).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11087913; DOI=10.1016/s0166-6851(00)00289-9;
RA Donahue C.G., Carruthers V.B., Gilk S.D., Ward G.E.;
RT "The Toxoplasma homolog of Plasmodium apical membrane antigen-1 (AMA-1) is
RT a microneme protein secreted in response to elevated intracellular calcium
RT levels.";
RL Mol. Biochem. Parasitol. 111:15-30(2000).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16000372; DOI=10.1091/mbc.e05-04-0281;
RA Mital J., Meissner M., Soldati D., Ward G.E.;
RT "Conditional expression of Toxoplasma gondii apical membrane antigen-1
RT (TgAMA1) demonstrates that TgAMA1 plays a critical role in host cell
RT invasion.";
RL Mol. Biol. Cell 16:4341-4349(2005).
RN [6]
RP FUNCTION, INTERACTION WITH RON2; RON4 AND RON5, AND SUBCELLULAR LOCATION.
RX PubMed=16244709; DOI=10.1371/journal.ppat.0010017;
RA Alexander D.L., Mital J., Ward G.E., Bradley P., Boothroyd J.C.;
RT "Identification of the moving junction complex of Toxoplasma gondii: a
RT collaboration between distinct secretory organelles.";
RL PLoS Pathog. 1:E17-E17(2005).
RN [7]
RP FUNCTION, IDENTIFICATION IN THE MJ COMPLEX, AND INTERACTION WITH RON2.
RX PubMed=19247437; DOI=10.1371/journal.ppat.1000309;
RA Besteiro S., Michelin A., Poncet J., Dubremetz J.F., Lebrun M.;
RT "Export of a Toxoplasma gondii rhoptry neck protein complex at the host
RT cell membrane to form the moving junction during invasion.";
RL PLoS Pathog. 5:E1000309-E1000309(2009).
RN [8]
RP FUNCTION, AND CLEAVAGE BY ROM4.
RX PubMed=20421941; DOI=10.1371/journal.ppat.1000858;
RA Buguliskis J.S., Brossier F., Shuman J., Sibley L.D.;
RT "Rhomboid 4 (ROM4) affects the processing of surface adhesins and
RT facilitates host cell invasion by Toxoplasma gondii.";
RL PLoS Pathog. 6:E1000858-E1000858(2010).
RN [9]
RP INTERACTION WITH RON2.
RX PubMed=21347354; DOI=10.1371/journal.ppat.1001282;
RA Tyler J.S., Boothroyd J.C.;
RT "The C-terminus of Toxoplasma RON2 provides the crucial link between AMA1
RT and the host-associated invasion complex.";
RL PLoS Pathog. 7:E1001282-E1001282(2011).
RN [10]
RP FUNCTION, AND MUTAGENESIS OF 547-PHE-TRP-548 AND 568-ASP-TYR-569.
RX PubMed=21205639; DOI=10.1126/science.1199284;
RA Santos J.M., Ferguson D.J., Blackman M.J., Soldati-Favre D.;
RT "Intramembrane cleavage of AMA1 triggers Toxoplasma to switch from an
RT invasive to a replicative mode.";
RL Science 331:473-477(2011).
RN [11]
RP MUTAGENESIS OF LEU-51.
RX PubMed=21438967; DOI=10.1111/j.1600-0854.2011.01192.x;
RA Gaji R.Y., Flammer H.P., Carruthers V.B.;
RT "Forward targeting of Toxoplasma gondii proproteins to the micronemes
RT involves conserved aliphatic amino acids.";
RL Traffic 12:840-853(2011).
RN [12]
RP FUNCTION, AND MUTAGENESIS OF 487-ALA-GLY-488; LEU-489 AND 492-GLY-GLY-493.
RX PubMed=22523242; DOI=10.1073/pnas.1114661109;
RA Parussini F., Tang Q., Moin S.M., Mital J., Urban S., Ward G.E.;
RT "Intramembrane proteolysis of Toxoplasma apical membrane antigen 1
RT facilitates host-cell invasion but is dispensable for replication.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:7463-7468(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 64-519, DISULFIDE BONDS, AND
RP GLYCOSYLATION AT ASN-86.
RX PubMed=20304917; DOI=10.1074/jbc.m109.092619;
RA Crawford J., Tonkin M.L., Grujic O., Boulanger M.J.;
RT "Structural characterization of apical membrane antigen 1 (AMA1) from
RT Toxoplasma gondii.";
RL J. Biol. Chem. 285:15644-15652(2010).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 64-484 IN COMPLEX WITH RON2,
RP DISULFIDE BONDS, AND MUTAGENESIS OF TYR-213.
RX PubMed=21778402; DOI=10.1126/science.1204988;
RA Tonkin M.L., Roques M., Lamarque M.H., Pugniere M., Douguet D.,
RA Crawford J., Lebrun M., Boulanger M.J.;
RT "Host cell invasion by apicomplexan parasites: insights from the co-
RT structure of AMA1 with a RON2 peptide.";
RL Science 333:463-467(2011).
CC -!- FUNCTION: Essential microneme protein that plays an important role in
CC host cell invasion. Part of the moving junction (MJ) complex, a
CC ringlike structure formed between the plasma membranes of the apical
CC tip of the parasite and the target host cell. During invasion, the MJ
CC migrates from the anterior to the posterior of the parasite, leading to
CC internalization of the parasite into a parasitophorous vacuole (PV).
CC {ECO:0000269|PubMed:11083833, ECO:0000269|PubMed:11087913,
CC ECO:0000269|PubMed:16000372, ECO:0000269|PubMed:16102004,
CC ECO:0000269|PubMed:16244709, ECO:0000269|PubMed:19247437,
CC ECO:0000269|PubMed:20421941, ECO:0000269|PubMed:21205639,
CC ECO:0000269|PubMed:22523242}.
CC -!- SUBUNIT: Component of the moving junction (MJ) complex, composed of
CC AMA1, a transmembrane protein on the parasite surface, and a complex of
CC the rhoptry neck proteins RON2, RON4, RON5 and RON8 localized to the
CC cytoplasmic face of the host plasma membrane. Interacts (via
CC ectodomain) with RON2 (via C-terminus); RON2 serves as the receptor for
CC AMA1 on the host plasma membrane. AMA1 and the RON proteins are
CC initially in distinct compartments within the parasite, namely the
CC micronemes and the rhoptries, and interaction happens only upon
CC initiation of invasion when the micronemes and rhoptries discharge.
CC {ECO:0000269|PubMed:16244709, ECO:0000269|PubMed:19247437,
CC ECO:0000269|PubMed:21347354, ECO:0000269|PubMed:21778402}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}. Secreted {ECO:0000269|PubMed:11083833,
CC ECO:0000269|PubMed:11087913, ECO:0000269|PubMed:16102004,
CC ECO:0000269|PubMed:16244709}. Note=Initially localizes to micronemes,
CC specialized secretory organelles of apicomplexan parasites important
CC for host cell invasion. Relocalizes to the surface membrane upon host
CC invasion by tachyzoites. Found predominantly on the apical end of the
CC parasite surface. A cleavage product of the large ectodomain is
CC released into the medium by extracellular parasites.
CC -!- PTM: Proteolytically cleaved during invasion within its transmembrane
CC domain, releasing a soluble form from the tachyzoite surface. The
CC cytosolic tail generated by ROM4 cleavage during invasion may trigger
CC parasite replication within the parasitophorous vacuole.
CC {ECO:0000269|PubMed:16102004, ECO:0000269|PubMed:20421941}.
CC -!- DISRUPTION PHENOTYPE: Severely compromises the parasite in its ability
CC to invade host cells. Inhibits secretion of the rhoptries, organelles
CC whose discharge is coupled to active host cell penetration.
CC {ECO:0000269|PubMed:16000372}.
CC -!- SIMILARITY: Belongs to the apicomplexan parasites AMA1 family.
CC {ECO:0000305}.
CC -!- CAUTION: PubMed:21205639 reported that AMA1 may also be involved in a
CC signaling pathway leading to replication. However, PubMed:22523242
CC refutes this model. {ECO:0000305}.
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DR EMBL; AAYL02000028; ESS35482.1; -; Genomic_DNA.
DR EMBL; AF010264; AAB65410.1; -; mRNA.
DR PDB; 2X2Z; X-ray; 2.00 A; A/B/D/E=64-519.
DR PDB; 2Y8R; X-ray; 2.45 A; A/B/D/E=64-484.
DR PDB; 2Y8S; X-ray; 2.55 A; A/D=64-484.
DR PDB; 2Y8T; X-ray; 1.95 A; A/D=64-484.
DR PDBsum; 2X2Z; -.
DR PDBsum; 2Y8R; -.
DR PDBsum; 2Y8S; -.
DR PDBsum; 2Y8T; -.
DR AlphaFoldDB; B6KAM0; -.
DR SMR; B6KAM0; -.
DR STRING; 5811.TGME49_055260; -.
DR iPTMnet; B6KAM0; -.
DR SwissPalm; B6KAM0; -.
DR EnsemblProtists; ESS35482; ESS35482; TGVEG_255260.
DR EnsemblProtists; TGME49_255260-t26_1; TGME49_255260-t26_1; TGME49_255260.
DR VEuPathDB; ToxoDB:TGVEG_255260; -.
DR eggNOG; ENOG502QYHF; Eukaryota.
DR InParanoid; B6KAM0; -.
DR OMA; LMGERYC; -.
DR EvolutionaryTrace; B6KAM0; -.
DR Proteomes; UP000002226; Partially assembled WGS sequence.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR InterPro; IPR003298; Apmem_Ag1.
DR Pfam; PF02430; AMA-1; 1.
DR PRINTS; PR01361; MEROZOITESA.
DR SMART; SM00815; AMA-1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Membrane; Reference proteome; Secreted; Signal; Tachyzoite;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..48
FT /evidence="ECO:0000255"
FT PROPEP 49..66
FT /note="Removed in mature form; required for microneme
FT targeting of the proprotein"
FT /evidence="ECO:0000269|PubMed:16102004"
FT /id="PRO_0000421959"
FT CHAIN 67..569
FT /note="Apical membrane antigen 1"
FT /id="PRO_0000421960"
FT CHAIN 67..487
FT /note="Apical membrane antigen 1, soluble form"
FT /id="PRO_0000421961"
FT TOPO_DOM 49..483
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 484..504
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 505..569
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 67..287
FT /note="DI"
FT REGION 288..415
FT /note="DII"
FT REGION 416..487
FT /note="DIII"
FT REGION 518..548
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 518..540
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 487..488
FT /note="Cleavage; by rhomboid protease ROM4"
FT CARBOHYD 86
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:20304917"
FT DISULFID 117..286
FT DISULFID 194..226
FT DISULFID 242..255
FT DISULFID 304..393
FT DISULFID 324..384
FT DISULFID 435..459
FT DISULFID 447..471
FT DISULFID 452..479
FT MUTAGEN 51
FT /note="L->K: Mislocalizes to the endosomal system."
FT /evidence="ECO:0000269|PubMed:21438967"
FT MUTAGEN 213
FT /note="Y->A: Abolishes interaction with RON2."
FT /evidence="ECO:0000269|PubMed:21778402"
FT MUTAGEN 487..488
FT /note="AG->FF: Reduces cleavage 30-fold. Uncleavable; when
FT associated with 492-FF-493."
FT /evidence="ECO:0000269|PubMed:22523242"
FT MUTAGEN 489
FT /note="L->G: Enhances cleavage 13-fold."
FT /evidence="ECO:0000269|PubMed:22523242"
FT MUTAGEN 492..493
FT /note="GG->FF: Minor effect on proteolysis. Uncleavable;
FT when associated with 487-FF-488."
FT /evidence="ECO:0000269|PubMed:22523242"
FT MUTAGEN 547..548
FT /note="FW->AA: Does not impair function."
FT /evidence="ECO:0000269|PubMed:21205639"
FT MUTAGEN 568..569
FT /note="DY->AA: Does not impair function."
FT /evidence="ECO:0000269|PubMed:21205639"
FT CONFLICT 35..36
FT /note="AS -> QV (in Ref. 2; AAB65410)"
FT /evidence="ECO:0000305"
FT CONFLICT 132
FT /note="P -> L (in Ref. 2; AAB65410)"
FT /evidence="ECO:0000305"
FT HELIX 71..73
FT /evidence="ECO:0007829|PDB:2Y8T"
FT HELIX 76..83
FT /evidence="ECO:0007829|PDB:2Y8T"
FT TURN 87..91
FT /evidence="ECO:0007829|PDB:2Y8T"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:2Y8T"
FT STRAND 101..105
FT /evidence="ECO:0007829|PDB:2Y8T"
FT STRAND 108..112
FT /evidence="ECO:0007829|PDB:2Y8T"
FT STRAND 119..121
FT /evidence="ECO:0007829|PDB:2Y8R"
FT STRAND 123..126
FT /evidence="ECO:0007829|PDB:2Y8T"
FT HELIX 145..151
FT /evidence="ECO:0007829|PDB:2Y8T"
FT STRAND 170..175
FT /evidence="ECO:0007829|PDB:2Y8T"
FT HELIX 176..180
FT /evidence="ECO:0007829|PDB:2Y8T"
FT HELIX 190..199
FT /evidence="ECO:0007829|PDB:2Y8T"
FT STRAND 201..204
FT /evidence="ECO:0007829|PDB:2Y8T"
FT STRAND 206..208
FT /evidence="ECO:0007829|PDB:2X2Z"
FT STRAND 210..214
FT /evidence="ECO:0007829|PDB:2X2Z"
FT STRAND 217..220
FT /evidence="ECO:0007829|PDB:2Y8T"
FT TURN 221..224
FT /evidence="ECO:0007829|PDB:2Y8T"
FT STRAND 225..230
FT /evidence="ECO:0007829|PDB:2Y8T"
FT TURN 239..241
FT /evidence="ECO:0007829|PDB:2Y8T"
FT STRAND 242..244
FT /evidence="ECO:0007829|PDB:2Y8T"
FT STRAND 247..250
FT /evidence="ECO:0007829|PDB:2Y8S"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:2Y8T"
FT STRAND 256..259
FT /evidence="ECO:0007829|PDB:2Y8T"
FT STRAND 262..264
FT /evidence="ECO:0007829|PDB:2Y8T"
FT STRAND 268..271
FT /evidence="ECO:0007829|PDB:2Y8T"
FT HELIX 273..276
FT /evidence="ECO:0007829|PDB:2Y8T"
FT TURN 279..281
FT /evidence="ECO:0007829|PDB:2Y8T"
FT HELIX 282..285
FT /evidence="ECO:0007829|PDB:2Y8T"
FT STRAND 291..300
FT /evidence="ECO:0007829|PDB:2Y8T"
FT STRAND 303..306
FT /evidence="ECO:0007829|PDB:2Y8T"
FT HELIX 307..309
FT /evidence="ECO:0007829|PDB:2Y8T"
FT STRAND 314..317
FT /evidence="ECO:0007829|PDB:2Y8T"
FT HELIX 321..330
FT /evidence="ECO:0007829|PDB:2Y8T"
FT STRAND 346..349
FT /evidence="ECO:0007829|PDB:2X2Z"
FT TURN 353..357
FT /evidence="ECO:0007829|PDB:2Y8T"
FT STRAND 371..376
FT /evidence="ECO:0007829|PDB:2Y8T"
FT STRAND 382..389
FT /evidence="ECO:0007829|PDB:2Y8T"
FT STRAND 392..407
FT /evidence="ECO:0007829|PDB:2Y8T"
FT HELIX 415..417
FT /evidence="ECO:0007829|PDB:2Y8T"
FT HELIX 429..432
FT /evidence="ECO:0007829|PDB:2Y8T"
FT HELIX 437..439
FT /evidence="ECO:0007829|PDB:2Y8T"
FT TURN 449..452
FT /evidence="ECO:0007829|PDB:2Y8T"
FT STRAND 453..460
FT /evidence="ECO:0007829|PDB:2Y8T"
FT STRAND 463..470
FT /evidence="ECO:0007829|PDB:2Y8T"
FT HELIX 473..478
FT /evidence="ECO:0007829|PDB:2Y8T"
SQ SEQUENCE 569 AA; 63021 MW; 44EDB7C933D75193 CRC64;
MICSIMGGLR SLRAARPYSH QSNTETKHMG LVGVASLLVL VADCTIFASG LSSSTRSRES
QTLSASTSGN PFQANVEMKT FMERFNLTHH HQSGIYVDLG QDKEVDGTLY REPAGLCPIW
GKHIELQQPD RPPYRNNFLE DVPTEKEYKQ SGNPLPGGFN LNFVTPSGQR ISPFPMELLE
KNSNIKASTD LGRCAEFAFK TVAMDKNNKA TKYRYPFVYD SKKRLCHILY VSMQLMEGKK
YCSVKGEPPD LTWYCFKPRK SVTENHHLIY GSAYVGENPD AFISKCPNQA LRGYRFGVWK
KGRCLDYTEL TDTVIERVES KAQCWVKTFE NDGVASDQPH TYPLTSQASW NDWWPLHQSD
QPHSGGVGRN YGFYYVDTTG EGKCALSDQV PDCLVSDSAA VSYTAAGSLS EETPNFIIPS
NPSVTPPTPE TALQCTADKF PDSFGACDVQ ACKRQKTSCV GGQIQSTSVD CTADEQNECG
SNTALIAGLA VGGVLLLALL GGGCYFAKRL DRNKGVQAAH HEHEFQSDRG ARKKRPSDLM
QEAEPSFWDE AEENIEQDGE THVMVEGDY
