KAD2_PLAF7
ID KAD2_PLAF7 Reviewed; 275 AA.
AC Q8IB06; Q14EL6;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=Adenylate kinase 2 {ECO:0000303|PubMed:18973776};
DE Short=PfAK2 {ECO:0000303|PubMed:18973776};
DE EC=2.7.4.3 {ECO:0000269|PubMed:18973776};
GN Name=AK2 {ECO:0000303|PubMed:18973776};
GN ORFNames=PF3D7_0816900 {ECO:0000312|EMBL:CAD51204.1};
OS Plasmodium falciparum (isolate 3D7).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=36329 {ECO:0000312|Proteomes:UP000001450};
RN [1] {ECO:0000312|EMBL:AAV83966.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, INTERACTION WITH NMT,
RP MYRISTOYLATION AT GLY-2, AND MUTAGENESIS OF 2-GLY--ILE-33; ASP-43; ILE-57
RP AND ASN-125.
RX PubMed=18973776; DOI=10.1016/j.molbiopara.2008.09.008;
RA Rahlfs S., Koncarevic S., Iozef R., Mailu B.M., Savvides S.N.,
RA Schirmer R.H., Becker K.;
RT "Myristoylated adenylate kinase-2 of Plasmodium falciparum forms a
RT heterodimer with myristoyltransferase.";
RL Mol. Biochem. Parasitol. 163:77-84(2009).
RN [2] {ECO:0000312|Proteomes:UP000001450}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7 {ECO:0000312|Proteomes:UP000001450};
RX PubMed=12368864; DOI=10.1038/nature01097;
RA Gardner M.J., Hall N., Fung E., White O., Berriman M., Hyman R.W.,
RA Carlton J.M., Pain A., Nelson K.E., Bowman S., Paulsen I.T., James K.D.,
RA Eisen J.A., Rutherford K.M., Salzberg S.L., Craig A., Kyes S., Chan M.-S.,
RA Nene V., Shallom S.J., Suh B., Peterson J., Angiuoli S., Pertea M.,
RA Allen J., Selengut J., Haft D., Mather M.W., Vaidya A.B., Martin D.M.A.,
RA Fairlamb A.H., Fraunholz M.J., Roos D.S., Ralph S.A., McFadden G.I.,
RA Cummings L.M., Subramanian G.M., Mungall C., Venter J.C., Carucci D.J.,
RA Hoffman S.L., Newbold C., Davis R.W., Fraser C.M., Barrell B.G.;
RT "Genome sequence of the human malaria parasite Plasmodium falciparum.";
RL Nature 419:498-511(2002).
RN [3] {ECO:0000312|Proteomes:UP000001450}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7 {ECO:0000312|Proteomes:UP000001450};
RX PubMed=12368867; DOI=10.1038/nature01095;
RA Hall N., Pain A., Berriman M., Churcher C.M., Harris B., Harris D.,
RA Mungall K.L., Bowman S., Atkin R., Baker S., Barron A., Brooks K.,
RA Buckee C.O., Burrows C., Cherevach I., Chillingworth C., Chillingworth T.,
RA Christodoulou Z., Clark L., Clark R., Corton C., Cronin A., Davies R.M.,
RA Davis P., Dear P., Dearden F., Doggett J., Feltwell T., Goble A.,
RA Goodhead I., Gwilliam R., Hamlin N., Hance Z., Harper D., Hauser H.,
RA Hornsby T., Holroyd S., Horrocks P., Humphray S., Jagels K., James K.D.,
RA Johnson D., Kerhornou A., Knights A., Konfortov B., Kyes S., Larke N.,
RA Lawson D., Lennard N., Line A., Maddison M., Mclean J., Mooney P.,
RA Moule S., Murphy L., Oliver K., Ormond D., Price C., Quail M.A.,
RA Rabbinowitsch E., Rajandream M.A., Rutter S., Rutherford K.M., Sanders M.,
RA Simmonds M., Seeger K., Sharp S., Smith R., Squares R., Squares S.,
RA Stevens K., Taylor K., Tivey A., Unwin L., Whitehead S., Woodward J.R.,
RA Sulston J.E., Craig A., Newbold C., Barrell B.G.;
RT "Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.";
RL Nature 419:527-531(2002).
RN [4] {ECO:0000305}
RP SUBCELLULAR LOCATION, MYRISTOYLATION AT GLY-2, PALMITOYLATION, AND
RP MUTAGENESIS OF GLY-2; CYS-4 AND 21-LYS--LYS-30.
RX PubMed=25909331; DOI=10.1371/journal.pone.0125191;
RA Thavayogarajah T., Gangopadhyay P., Rahlfs S., Becker K., Lingelbach K.,
RA Przyborski J.M., Holder A.A.;
RT "Alternative Protein Secretion in the Malaria Parasite Plasmodium
RT falciparum.";
RL PLoS ONE 10:e0125191-e0125191(2015).
CC -!- FUNCTION: Catalyzes the reversible transfer of the terminal phosphate
CC group between ATP and AMP (PubMed:18973776). Has very low activity with
CC CTP, GTP, ITP and UTP and no activity with GMP, UMP or IMP in vitro
CC (PubMed:18973776). {ECO:0000269|PubMed:18973776}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=AMP + ATP = 2 ADP; Xref=Rhea:RHEA:12973, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:456215, ChEBI:CHEBI:456216; EC=2.7.4.3;
CC Evidence={ECO:0000269|PubMed:18973776};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=290 uM for AMP (at 25 degrees Celsius and pH 7.6)
CC {ECO:0000269|PubMed:18973776};
CC KM=75 uM for ATP (at 25 degrees Celsius and pH 7.6)
CC {ECO:0000269|PubMed:18973776};
CC Vmax=10 umol/min/mg enzyme (at 25 degrees Celsius and pH 7.6)
CC {ECO:0000269|PubMed:18973776};
CC Note=kcat is 5.4 sec(-1) (at 25 degrees Celsius and pH 7.6).
CC {ECO:0000269|PubMed:18973776};
CC pH dependence:
CC Optimum pH is 8. {ECO:0000269|PubMed:18973776};
CC -!- SUBUNIT: Monomer (PubMed:18973776). Oligomer (PubMed:18973776).
CC Heterodimer composed of NMT and AK2; AK2 myristoylation stabilizes the
CC complex (PubMed:18973776). {ECO:0000269|PubMed:18973776}.
CC -!- SUBCELLULAR LOCATION: Parasitophorous vacuole membrane
CC {ECO:0000269|PubMed:25909331}; Lipid-anchor
CC {ECO:0000269|PubMed:25909331}. Note=Localizes to the vacuolar side of
CC the parasitophorous vacuole. {ECO:0000269|PubMed:25909331}.
CC -!- PTM: Myristoylation is required for cell membrane localization.
CC {ECO:0000269|PubMed:25909331}.
CC -!- PTM: May be palmitoylated at Cys-4 which stabilizes cell membrane
CC localization of the myristoylated protein.
CC {ECO:0000269|PubMed:25909331}.
CC -!- SIMILARITY: Belongs to the adenylate kinase family.
CC {ECO:0000255|RuleBase:RU003330}.
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DR EMBL; AY667503; AAV83966.1; -; mRNA.
DR EMBL; AL844507; CAD51204.1; -; Genomic_DNA.
DR RefSeq; XP_001349355.1; XM_001349319.1.
DR AlphaFoldDB; Q8IB06; -.
DR SMR; Q8IB06; -.
DR IntAct; Q8IB06; 2.
DR MINT; Q8IB06; -.
DR STRING; 5833.PF08_0062; -.
DR PRIDE; Q8IB06; -.
DR EnsemblProtists; CAD51204; CAD51204; PF3D7_0816900.
DR GeneID; 2655261; -.
DR KEGG; pfa:PF3D7_0816900; -.
DR VEuPathDB; PlasmoDB:PF3D7_0816900; -.
DR VEuPathDB; PlasmoDB:Pf7G8-2_000232200; -.
DR VEuPathDB; PlasmoDB:Pf7G8_080022000; -.
DR VEuPathDB; PlasmoDB:PfCD01_080022500; -.
DR VEuPathDB; PlasmoDB:PfDd2_080022100; -.
DR VEuPathDB; PlasmoDB:PfGA01_080020600; -.
DR VEuPathDB; PlasmoDB:PfGB4_080021700; -.
DR VEuPathDB; PlasmoDB:PfGN01_080022600; -.
DR VEuPathDB; PlasmoDB:PfHB3_080022400; -.
DR VEuPathDB; PlasmoDB:PfIT_080021900; -.
DR VEuPathDB; PlasmoDB:PfKE01_080022500; -.
DR VEuPathDB; PlasmoDB:PfKH01_080022000; -.
DR VEuPathDB; PlasmoDB:PfKH02_080022500; -.
DR VEuPathDB; PlasmoDB:PfML01_080022500; -.
DR VEuPathDB; PlasmoDB:PfNF135_000023500; -.
DR VEuPathDB; PlasmoDB:PfNF166_080020700; -.
DR VEuPathDB; PlasmoDB:PfNF54_080020700; -.
DR VEuPathDB; PlasmoDB:PfSD01_080022300; -.
DR VEuPathDB; PlasmoDB:PfSN01_080021500; -.
DR VEuPathDB; PlasmoDB:PfTG01_080022800; -.
DR HOGENOM; CLU_032354_6_1_1; -.
DR InParanoid; Q8IB06; -.
DR OMA; NGFPRTY; -.
DR PhylomeDB; Q8IB06; -.
DR BRENDA; 2.7.4.3; 4889.
DR Reactome; R-PFA-499943; Interconversion of nucleotide di- and triphosphates.
DR Proteomes; UP000001450; Chromosome 8.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0020005; C:symbiont-containing vacuole membrane; IDA:GeneDB.
DR GO; GO:0004017; F:adenylate kinase activity; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR CDD; cd01428; ADK; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR000850; Adenylat/UMP-CMP_kin.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR23359; PTHR23359; 2.
DR PRINTS; PR00094; ADENYLTKNASE.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Kinase; Lipoprotein; Membrane; Myristate; Nucleotide-binding;
KW Palmitate; Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000305"
FT CHAIN 2..275
FT /note="Adenylate kinase 2"
FT /id="PRO_0000455420"
FT REGION 21..30
FT /note="Required for cell membrane translocation but
FT dispensable for cell membrane localization"
FT /evidence="ECO:0000269|PubMed:25909331"
FT REGION 59..97
FT /note="NMP"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT REGION 165..214
FT /note="LID"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT BINDING 39..44
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT BINDING 95..97
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT BINDING 126..129
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT BINDING 133
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT BINDING 164
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT BINDING 220
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT BINDING 231
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:18973776,
FT ECO:0000305|PubMed:25909331"
FT MUTAGEN 2..33
FT /note="Missing: No effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:18973776"
FT MUTAGEN 2
FT /note="G->A: Mislocalizes to the cytoplasm. Mislocalizes to
FT the cytoplasm; when associated with A-4."
FT /evidence="ECO:0000269|PubMed:25909331"
FT MUTAGEN 4
FT /note="C->A: Partial mislocalization to the cytoplasm with
FT some localization to the cell membrane. Mislocalizes to the
FT cytoplasm; when associated with A-2."
FT /evidence="ECO:0000269|PubMed:25909331"
FT MUTAGEN 21..30
FT /note="Missing: Remains associated with the cytoplasmic
FT side of the cell membrane with no translocation across the
FT cell membrane."
FT /evidence="ECO:0000269|PubMed:25909331"
FT MUTAGEN 43
FT /note="D->G: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:18973776"
FT MUTAGEN 57
FT /note="I->H: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:18973776"
FT MUTAGEN 125
FT /note="N->D: 36% decrease in catalytic activity."
FT /evidence="ECO:0000269|PubMed:18973776"
SQ SEQUENCE 275 AA; 32497 MW; 11ED64BEAE90774A CRC64;
MGSCYSRKNK VSTISLDEEE KKKEKKKKKK IYILNGASGS GKDTQCRLLE KKYNYKIICI
SKLLKEYKEE YNKENVLNEE ENYFDEIEKC MIDGSLVNDQ IVIEIFHKQL NKYINDDKYN
GIIINGFPRN YEQALLIIQN NISITKFINI QVGKDTLWTR INNRIIDPIT NISYNENIIQ
IIKKKREGQE LSDKEQKQLI IDNHLYNNLS NDILERLTKR KDDEEQVFNK RFQLYIESEQ
KINSLFKNIC KNVDGEKSIN DIFDQICSII DDNPN
