| IED ID | IndEnz0002014381 |
| Enzyme Type ID | protease014381 |
| Protein Name |
Polyamine-transporting ATPase 13A2 EC 7.6.2.- |
| Gene Name | ATP13A2 PARK9 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MSADSSPLVGSTPTGYGTLTIGTSIDPLSSSVSSVRLSGYCGSPWRVIGYHVVVWMMAGIPLLLFRWKPLWGVRLRLRPCNLAHAETLVIEIRDKEDSSWQLFTVQVQTEAIGEGSLEPSPQSQAEDGRSQAAVGAVPEGAWKDTAQLHKSEEAVSVGQKRVLRYYLFQGQRYIWIETQQAFYQVSLLDHGRSCDDVHRSRHGLSLQDQMVRKAIYGPNVISIPVKSYPQLLVDEALNPYYGFQAFSIALWLADHYYWYALCIFLISSISICLSLYKTRKQSQTLRDMVKLSMRVCVCRPGGEEEWVDSSELVPGDCLVLPQEGGLMPCDAALVAGECMVNESSLTGESIPVLKTALPEGLGPYCAETHRRHTLFCGTLILQARAYVGPHVLAVVTRTGFCTAKGGLVSSILHPRPINFKFYKHSMKFVAALSVLALLGTIYSIFILYRNRVPLNEIVIRALDLVTVVVPPALPAAMTVCTLYAQSRLRRQGIFCIHPLRINLGGKLQLVCFDKTGTLTEDGLDVMGVVPLKGQAFLPLVPEPRRLPVGPLLRALATCHALSRLQDTPVGDPMDLKMVESTGWVLEEEPAADSAFGTQVLAVMRPPLWEPQLQAMEEPPVPVSVLHRFPFSSALQRMSVVVAWPGATQPEAYVKGSPELVAGLCNPETVPTDFAQMLQSYTAAGYRVVALASKPLPTVPSLEAAQQLTRDTVEGDLSLLGLLVMRNLLKPQTTPVIQALRRTRIRAVMVTGDNLQTAVTVARGCGMVAPQEHLIIVHATHPERGQPASLEFLPMESPTAVNGVKDPDQAASYTVEPDPRSRHLALSGPTFGIIVKHFPKLLPKVLVQGTVFARMAPEQKTELVCELQKLQYCVGMCGDGANDCGALKAADVGISLSQAEASVVSPFTSSMASIECVPMVIREGRCSLDTSFSVFKYMALYSLTQFISVLILYTINTNLGDLQFLAIDLVITTTVAVLMSRTGPALVLGRVRPPGALLSVPVLSSLLLQMVLVTGVQLGGYFLTLAQPWFVPLNRTVAAPDNLPNYENTVVFSLSSFQYLILAAAVSKGAPFRRPLYTNVPFLVALALLSSVLVGLVLVPGLLQGPLALRNITDTGFKLLLLGLVTLNFVGAFMLESVLDQCLPACLRRLRPKRASKKRFKQLERELAEQPWPPLPAGPLR |
| Enzyme Length | 1180 |
| Uniprot Accession Number | Q9NQ11 |
| Absorption | |
| Active Site | ACT_SITE 513; /note=4-aspartylphosphate intermediate; /evidence=ECO:0000269|PubMed:26134396 |
| Activity Regulation | ACTIVITY REGULATION: Accumulates in an inactive autophosphorylated state (PubMed:26134396). The presence of spermine results in a dose-dependent reduction in autophosphorylation (PubMed:31996848). {ECO:0000269|PubMed:26134396, ECO:0000269|PubMed:31996848}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=ATP + H2O + spermidine(out) = ADP + H(+) + phosphate + spermidine(in); Xref=Rhea:RHEA:29999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57834, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:31996848}; CATALYTIC ACTIVITY: Reaction=ATP + H2O + spermine(out) = ADP + H(+) + phosphate + spermine(in); Xref=Rhea:RHEA:63368, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:45725, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:31996848}; |
| DNA Binding | |
| EC Number | 7.6.2.- |
| Enzyme Function | FUNCTION: ATPase which acts as a lysosomal polyamine exporter with high affinity for spermine (PubMed:31996848). Also stimulates cellular uptake of polyamines and protects against polyamine toxicity (PubMed:31996848). Plays a role in intracellular cation homeostasis and the maintenance of neuronal integrity (PubMed:22186024). Contributes to cellular zinc homeostasis (PubMed:24603074). Confers cellular protection against Mn(2+) and Zn(2+) toxicity and mitochondrial stress (PubMed:26134396). Required for proper lysosomal and mitochondrial maintenance (PubMed:22296644, PubMed:28137957). Regulates the autophagy-lysosome pathway through the control of SYT11 expression at both transcriptional and post-translational levels (PubMed:27278822). Facilitates recruitment of deacetylase HDAC6 to lysosomes to deacetylate CTTN, leading to actin polymerization, promotion of autophagosome-lysosome fusion and completion of autophagy (PubMed:30538141). Promotes secretion of exosomes as well as secretion of SCNA via exosomes (PubMed:25392495, PubMed:24603074). Plays a role in lipid homeostasis (PubMed:31132336). {ECO:0000269|PubMed:22186024, ECO:0000269|PubMed:22296644, ECO:0000269|PubMed:24603074, ECO:0000269|PubMed:25392495, ECO:0000269|PubMed:26134396, ECO:0000269|PubMed:27278822, ECO:0000269|PubMed:28137957, ECO:0000269|PubMed:30538141, ECO:0000269|PubMed:31132336, ECO:0000269|PubMed:31996848}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Alternative sequence (3); Chain (1); Frameshift (1); Glycosylation (2); Intramembrane (1); Metal binding (2); Modified residue (1); Mutagenesis (10); Natural variant (19); Sequence conflict (3); Topological domain (12); Transmembrane (10) |
| Keywords | ATP-binding;Alternative splicing;Cytoplasmic vesicle;Disease variant;Endosome;Glycoprotein;Hereditary spastic paraplegia;Lipid-binding;Lysosome;Magnesium;Membrane;Metal-binding;Neurodegeneration;Neuronal ceroid lipofuscinosis;Nucleotide-binding;Parkinsonism;Phosphoprotein;Reference proteome;Translocase;Transmembrane;Transmembrane helix;Transport |
| Interact With | Q2M2I8; O60238; O14976; Q9UBN7; P11142; Q9BT88; O95070 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:21542062, ECO:0000269|PubMed:22186024, ECO:0000269|PubMed:22768177, ECO:0000269|PubMed:24603074, ECO:0000269|PubMed:26134396, ECO:0000269|PubMed:28137957}; Multi-pass membrane protein {ECO:0000255}. Late endosome membrane {ECO:0000269|PubMed:24603074, ECO:0000269|PubMed:25392495, ECO:0000269|PubMed:26134396}; Multi-pass membrane protein {ECO:0000255}. Endosome, multivesicular body membrane {ECO:0000269|PubMed:24603074, ECO:0000269|PubMed:25392495}; Multi-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle, autophagosome membrane {ECO:0000269|PubMed:24603074}; Multi-pass membrane protein {ECO:0000255}. |
| Modified Residue | MOD_RES 151; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163 |
| Post Translational Modification | PTM: Autophosphorylated (PubMed:26134396, PubMed:28137957). Accumulates in an inactive autophosphorylated state and autophosphorylation is stimulated by phosphatidic acid and phosphatidylinositol 3,5-bisphosphate but not by Mn(2+) or Zn(2+) (PubMed:26134396). The presence of spermine results in a dose-dependent reduction in autophosphorylation (PubMed:31996848). {ECO:0000269|PubMed:26134396, ECO:0000269|PubMed:31996848, ECO:0000305|PubMed:28137957}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 18785233; 19097176; 19224617; 19705361; 19806583; 20036179; 20137506; 20189936; 20227461; 20310007; 20483373; 20669327; 20816920; 20842691; 20976737; 21060012; 21362476; 21665991; 21696388; 21714071; 21724849; 21900206; 22104014; 22117566; 22285144; 22288903; 22442086; 22457822; 22490479; 22645275; 22647602; 22743658; 22847264; 23121889; 23196729; 23499937; 23522931; 24252509; 24334770; 24399444; 24949580; 25197640; 25374329; 25855184; 25912790; 26000924; 26818499; 26965689; 27282395; 27399248; 28302480; 28334751; 29442384; 30232368; 30992063; 31393918; 31944623; 32019516; 32032734; 33091395; 33229544; 33335927; 33799982; 34695705; 34715013; 34715014; 34798056; |
| Motif | |
| Gene Encoded By | |
| Mass | 128,794 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=76 uM for spermine {ECO:0000269|PubMed:31996848}; Vmax=159 nmol/min/mg enzyme {ECO:0000269|PubMed:31996848}; |
| Metal Binding | METAL 878; /note=Magnesium; /evidence=ECO:0000250; METAL 882; /note=Magnesium; /evidence=ECO:0000250 |
| Rhea ID | RHEA:29999; RHEA:63368 |
| Cross Reference Brenda |