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Protein

Apical membrane antigen 1

Gene

AMA1

Organism
Toxoplasma gondii (strain ATCC 50861 / VEG)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Essential microneme protein that plays an important role in host cell invasion. Part of the moving junction (MJ) complex, a ringlike structure formed between the plasma membranes of the apical tip of the parasite and the target host cell. During invasion, the MJ migrates from the anterior to the posterior of the parasite, leading to internalization of the parasite into a parasitophorous vacuole (PV).9 Publications

GO - Biological processi

Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
Apical membrane antigen 1
Short name:
TgAMA-1
Short name:
TgAMA1
Cleaved into the following chain:
Gene namesi
Name:AMA1
ORF Names:TGVEG_255260
OrganismiToxoplasma gondii (strain ATCC 50861 / VEG)
Taxonomic identifieri432359 [NCBI]
Taxonomic lineageiEukaryotaAlveolataApicomplexaConoidasidaCoccidiaEucoccidioridaEimeriorinaSarcocystidaeToxoplasma
Proteomesi
  • UP000002226 Componenti: Partially assembled WGS sequence

Organism-specific databases

EuPathDBiToxoDB:TGME49_255260.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini49 – 483435ExtracellularSequence analysisAdd
BLAST
Transmembranei484 – 50421HelicalSequence analysisAdd
BLAST
Topological domaini505 – 56965CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Disruption phenotypei

Severely compromises the parasite in its ability to invade host cells. Inhibits secretion of the rhoptries, organelles whose discharge is coupled to active host cell penetration.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi51 – 511L → K: Mislocalizes to the endosomal system. 1 Publication
Mutagenesisi213 – 2131Y → A: Abolishes interaction with RON2. 1 Publication
Mutagenesisi487 – 4882AG → FF: Reduces cleavage 30-fold. Uncleavable; when associated with 492-FF-493. 1 Publication
Mutagenesisi489 – 4891L → G: Enhances cleavage 13-fold. 1 Publication
Mutagenesisi492 – 4932GG → FF: Minor effect on proteolysis. Uncleavable; when associated with 487-FF-488. 1 Publication
Mutagenesisi547 – 5482FW → AA: Does not impair function. 1 Publication
Mutagenesisi568 – 5692DY → AA: Does not impair function. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 4848Sequence analysisAdd
BLAST
Propeptidei49 – 6618Removed in mature form; required for microneme targeting of the proprotein1 PublicationPRO_0000421959Add
BLAST
Chaini67 – 569503Apical membrane antigen 1PRO_0000421960Add
BLAST
Chaini67 – 487421Apical membrane antigen 1, soluble formPRO_0000421961Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi86 – 861N-linked (GlcNAc...)1 Publication
Disulfide bondi117 ↔ 286
Disulfide bondi194 ↔ 226
Disulfide bondi242 ↔ 255
Disulfide bondi304 ↔ 393
Disulfide bondi324 ↔ 384
Disulfide bondi435 ↔ 459
Disulfide bondi447 ↔ 471
Disulfide bondi452 ↔ 479

Post-translational modificationi

Proteolytically cleaved during invasion within its transmembrane domain, releasing a soluble form from the tachyzoite surface. The cytosolic tail generated by ROM4 cleavage during invasion may trigger parasite replication within the parasitophorous vacuole.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei487 – 4882Cleavage; by rhomboid protease ROM4

Keywords - PTMi

Disulfide bond, Glycoprotein

PTM databases

SwissPalmiB6KAM0.

Expressioni

Keywords - Developmental stagei

Tachyzoite

Interactioni

Subunit structurei

Component of the moving junction (MJ) complex, composed of AMA1, a transmembrane protein on the parasite surface, and a complex of the rhoptry neck proteins RON2, RON4, RON5 and RON8 localized to the cytoplasmic face of the host plasma membrane. Interacts (via ectodomain) with RON2 (via C-terminus); RON2 serves as the receptor for AMA1 on the host plasma membrane. AMA1 and the RON proteins are initially in distinct compartments within the parasite, namely the micronemes and the rhoptries, and interaction happens only upon initiation of invasion when the micronemes and rhoptries discharge.4 Publications

Protein-protein interaction databases

STRINGi5811.TGME49_055260.

Structurei

Secondary structure

1
569
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi71 – 733Combined sources
Helixi76 – 838Combined sources
Turni87 – 915Combined sources
Beta strandi95 – 973Combined sources
Beta strandi101 – 1055Combined sources
Beta strandi108 – 1125Combined sources
Beta strandi119 – 1213Combined sources
Beta strandi123 – 1264Combined sources
Helixi145 – 1517Combined sources
Beta strandi170 – 1756Combined sources
Helixi176 – 1805Combined sources
Helixi190 – 19910Combined sources
Beta strandi201 – 2044Combined sources
Beta strandi206 – 2083Combined sources
Beta strandi210 – 2145Combined sources
Beta strandi217 – 2204Combined sources
Turni221 – 2244Combined sources
Beta strandi225 – 2306Combined sources
Turni239 – 2413Combined sources
Beta strandi242 – 2443Combined sources
Beta strandi247 – 2504Combined sources
Beta strandi252 – 2543Combined sources
Beta strandi256 – 2594Combined sources
Beta strandi262 – 2643Combined sources
Beta strandi268 – 2714Combined sources
Helixi273 – 2764Combined sources
Turni279 – 2813Combined sources
Helixi282 – 2854Combined sources
Beta strandi291 – 30010Combined sources
Beta strandi303 – 3064Combined sources
Helixi307 – 3093Combined sources
Beta strandi314 – 3174Combined sources
Helixi321 – 33010Combined sources
Beta strandi346 – 3494Combined sources
Turni353 – 3575Combined sources
Beta strandi371 – 3766Combined sources
Beta strandi382 – 3898Combined sources
Beta strandi392 – 40716Combined sources
Helixi415 – 4173Combined sources
Helixi429 – 4324Combined sources
Helixi437 – 4393Combined sources
Turni449 – 4524Combined sources
Beta strandi453 – 4608Combined sources
Beta strandi463 – 4708Combined sources
Helixi473 – 4786Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2X2ZX-ray2.00A/B/D/E64-519[»]
2Y8RX-ray2.45A/B/D/E64-484[»]
2Y8SX-ray2.55A/D64-484[»]
2Y8TX-ray1.95A/D64-484[»]
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiB6KAM0.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni67 – 287221DIAdd
BLAST
Regioni288 – 415128DIIAdd
BLAST
Regioni416 – 48772DIIIAdd
BLAST

Sequence similaritiesi

Belongs to the apicomplexan parasites AMA1 family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

InParanoidiB6KAM0.

Family and domain databases

InterProiIPR003298. Apmem_Ag1.
[Graphical view]
PfamiPF02430. AMA-1. 1 hit.
[Graphical view]
PRINTSiPR01361. MEROZOITESA.
SMARTiSM00815. AMA-1. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

B6KAM0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MICSIMGGLR SLRAARPYSH QSNTETKHMG LVGVASLLVL VADCTIFASG
60 70 80 90 100
LSSSTRSRES QTLSASTSGN PFQANVEMKT FMERFNLTHH HQSGIYVDLG
110 120 130 140 150
QDKEVDGTLY REPAGLCPIW GKHIELQQPD RPPYRNNFLE DVPTEKEYKQ
160 170 180 190 200
SGNPLPGGFN LNFVTPSGQR ISPFPMELLE KNSNIKASTD LGRCAEFAFK
210 220 230 240 250
TVAMDKNNKA TKYRYPFVYD SKKRLCHILY VSMQLMEGKK YCSVKGEPPD
260 270 280 290 300
LTWYCFKPRK SVTENHHLIY GSAYVGENPD AFISKCPNQA LRGYRFGVWK
310 320 330 340 350
KGRCLDYTEL TDTVIERVES KAQCWVKTFE NDGVASDQPH TYPLTSQASW
360 370 380 390 400
NDWWPLHQSD QPHSGGVGRN YGFYYVDTTG EGKCALSDQV PDCLVSDSAA
410 420 430 440 450
VSYTAAGSLS EETPNFIIPS NPSVTPPTPE TALQCTADKF PDSFGACDVQ
460 470 480 490 500
ACKRQKTSCV GGQIQSTSVD CTADEQNECG SNTALIAGLA VGGVLLLALL
510 520 530 540 550
GGGCYFAKRL DRNKGVQAAH HEHEFQSDRG ARKKRPSDLM QEAEPSFWDE
560
AEENIEQDGE THVMVEGDY
Length:569
Mass (Da):63,021
Last modified:December 16, 2008 - v1
Checksum:i44EDB7C933D75193
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti35 – 362AS → QV in AAB65410 (PubMed:11083833).Curated
Sequence conflicti132 – 1321P → L in AAB65410 (PubMed:11083833).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AAYL02000028 Genomic DNA. Translation: ESS35482.1.
AF010264 mRNA. Translation: AAB65410.1.

Genome annotation databases

EnsemblProtistsiESS35482; ESS35482; TGVEG_255260.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AAYL02000028 Genomic DNA. Translation: ESS35482.1.
AF010264 mRNA. Translation: AAB65410.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2X2ZX-ray2.00A/B/D/E64-519[»]
2Y8RX-ray2.45A/B/D/E64-484[»]
2Y8SX-ray2.55A/D64-484[»]
2Y8TX-ray1.95A/D64-484[»]
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi5811.TGME49_055260.

PTM databases

SwissPalmiB6KAM0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblProtistsiESS35482; ESS35482; TGVEG_255260.

Organism-specific databases

EuPathDBiToxoDB:TGME49_255260.

Phylogenomic databases

InParanoidiB6KAM0.

Miscellaneous databases

EvolutionaryTraceiB6KAM0.

Family and domain databases

InterProiIPR003298. Apmem_Ag1.
[Graphical view]
PfamiPF02430. AMA-1. 1 hit.
[Graphical view]
PRINTSiPR01361. MEROZOITESA.
SMARTiSM00815. AMA-1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Annotation of Toxoplasma gondii VEG."
    Lorenzi H., Inman J., Amedeo P., Brunk B., Roos D., Caler E.
    Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: ATCC 50861 / VEG.
  2. "Toxoplasma gondii homologue of plasmodium apical membrane antigen 1 is involved in invasion of host cells."
    Hehl A.B., Lekutis C., Grigg M.E., Bradley P.J., Dubremetz J.F., Ortega-Barria E., Boothroyd J.C.
    Infect. Immun. 68:7078-7086(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 29-569, FUNCTION, SUBCELLULAR LOCATION.
    Strain: ATCC 50611 / Me49.
  3. "Distinct mechanisms govern proteolytic shedding of a key invasion protein in apicomplexan pathogens."
    Howell S.A., Hackett F., Jongco A.M., Withers-Martinez C., Kim K., Carruthers V.B., Blackman M.J.
    Mol. Microbiol. 57:1342-1356(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 67-72 AND 482-487, PROTEOLYTIC PROCESSING, FUNCTION, SUBCELLULAR LOCATION.
  4. "The Toxoplasma homolog of Plasmodium apical membrane antigen-1 (AMA-1) is a microneme protein secreted in response to elevated intracellular calcium levels."
    Donahue C.G., Carruthers V.B., Gilk S.D., Ward G.E.
    Mol. Biochem. Parasitol. 111:15-30(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  5. "Conditional expression of Toxoplasma gondii apical membrane antigen-1 (TgAMA1) demonstrates that TgAMA1 plays a critical role in host cell invasion."
    Mital J., Meissner M., Soldati D., Ward G.E.
    Mol. Biol. Cell 16:4341-4349(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  6. "Identification of the moving junction complex of Toxoplasma gondii: a collaboration between distinct secretory organelles."
    Alexander D.L., Mital J., Ward G.E., Bradley P., Boothroyd J.C.
    PLoS Pathog. 1:E17-E17(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH RON2; RON4 AND RON5, SUBCELLULAR LOCATION.
  7. "Export of a Toxoplasma gondii rhoptry neck protein complex at the host cell membrane to form the moving junction during invasion."
    Besteiro S., Michelin A., Poncet J., Dubremetz J.F., Lebrun M.
    PLoS Pathog. 5:E1000309-E1000309(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, IDENTIFICATION IN THE MJ COMPLEX, INTERACTION WITH RON2.
  8. "Rhomboid 4 (ROM4) affects the processing of surface adhesins and facilitates host cell invasion by Toxoplasma gondii."
    Buguliskis J.S., Brossier F., Shuman J., Sibley L.D.
    PLoS Pathog. 6:E1000858-E1000858(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CLEAVAGE BY ROM4.
  9. "The C-terminus of Toxoplasma RON2 provides the crucial link between AMA1 and the host-associated invasion complex."
    Tyler J.S., Boothroyd J.C.
    PLoS Pathog. 7:E1001282-E1001282(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RON2.
  10. "Intramembrane cleavage of AMA1 triggers Toxoplasma to switch from an invasive to a replicative mode."
    Santos J.M., Ferguson D.J., Blackman M.J., Soldati-Favre D.
    Science 331:473-477(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF 547-PHE-TRP-548 AND 568-ASP-TYR-569.
  11. "Forward targeting of Toxoplasma gondii proproteins to the micronemes involves conserved aliphatic amino acids."
    Gaji R.Y., Flammer H.P., Carruthers V.B.
    Traffic 12:840-853(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF LEU-51.
  12. "Intramembrane proteolysis of Toxoplasma apical membrane antigen 1 facilitates host-cell invasion but is dispensable for replication."
    Parussini F., Tang Q., Moin S.M., Mital J., Urban S., Ward G.E.
    Proc. Natl. Acad. Sci. U.S.A. 109:7463-7468(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF 487-ALA-GLY-488; LEU-489 AND 492-GLY-GLY-493.
  13. "Structural characterization of apical membrane antigen 1 (AMA1) from Toxoplasma gondii."
    Crawford J., Tonkin M.L., Grujic O., Boulanger M.J.
    J. Biol. Chem. 285:15644-15652(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 64-519, DISULFIDE BONDS, GLYCOSYLATION AT ASN-86.
  14. "Host cell invasion by apicomplexan parasites: insights from the co-structure of AMA1 with a RON2 peptide."
    Tonkin M.L., Roques M., Lamarque M.H., Pugniere M., Douguet D., Crawford J., Lebrun M., Boulanger M.J.
    Science 333:463-467(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 64-484 IN COMPLEX WITH RON2, DISULFIDE BONDS, MUTAGENESIS OF TYR-213.

Entry informationi

Entry nameiAMA1_TOXGV
AccessioniPrimary (citable) accession number: B6KAM0
Secondary accession number(s): B9QC59, O15681, V4ZTW1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 3, 2013
Last sequence update: December 16, 2008
Last modified: April 13, 2016
This is version 39 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)

Miscellaneousi

Caution

PubMed:21205639 reported that AMA1 may also be involved in a signaling pathway leading to replication. However, PubMed:22523242 refutes this model.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.