Q9CTG6 · AT132_MOUSE
- ProteinPolyamine-transporting ATPase 13A2
- GeneAtp13a2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1169 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
Function
function
ATPase which acts as a lysosomal polyamine exporter with high affinity for spermine (By similarity).
Also stimulates cellular uptake of polyamines and protects against polyamine toxicity (By similarity).
Plays a role in intracellular cation homeostasis and the maintenance of neuronal integrity (By similarity).
Contributes to cellular zinc homeostasis (By similarity).
Confers cellular protection against Mn2+ and Zn2+ toxicity and mitochondrial stress (By similarity).
Required for proper lysosomal and mitochondrial maintenance (By similarity).
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 (By similarity).
Plays a role in lipid homeostasis (By similarity).
Also stimulates cellular uptake of polyamines and protects against polyamine toxicity (By similarity).
Plays a role in intracellular cation homeostasis and the maintenance of neuronal integrity (By similarity).
Contributes to cellular zinc homeostasis (By similarity).
Confers cellular protection against Mn2+ and Zn2+ toxicity and mitochondrial stress (By similarity).
Required for proper lysosomal and mitochondrial maintenance (By similarity).
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 (By similarity).
Plays a role in lipid homeostasis (By similarity).
Catalytic activity
- ATP + H2O + spermidine(out) = ADP + H+ + phosphate + spermidine(in)
CHEBI:30616 + CHEBI:15377 + spermidine (out)CHEBI:57834= CHEBI:456216 + CHEBI:15378 + CHEBI:43474 + spermidine (in)CHEBI:57834 - ATP + H2O + spermine(out) = ADP + H+ + phosphate + spermine(in)
Activity regulation
Accumulates in an inactive autophosphorylated state. The presence of spermine results in a dose-dependent reduction in autophosphorylation.
Features
Showing features for active site, binding site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namePolyamine-transporting ATPase 13A2
- EC number
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9CTG6
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Lysosome membrane ; Multi-pass membrane protein
Late endosome membrane ; Multi-pass membrane protein
Endosome, multivesicular body membrane ; Multi-pass membrane protein
Cytoplasmic vesicle, autophagosome membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, intramembrane, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-44 | Cytoplasmic | ||||
Sequence: MSADSSLLMGSTPPSYGTLTTGTSIDPLSSSASSVRLSGYCGSP | ||||||
Intramembrane | 45-65 | |||||
Sequence: WRAIGYHAAVWMLAGIPWLLF | ||||||
Topological domain | 66-225 | Cytoplasmic | ||||
Sequence: RWKPLWGVRLRLKPCSLAHAETLVIEIKDKEGSSRQLFTVQVQTEAVVQGSLELPPQAQAEDGRSQAAVGVTPEGTWQDTSELHRQEEAKQVLRYYVLQGQRYVWMETQQAFCQVSLLDHGRTCDDVHCSSSGLSLQDQATRKTIYGPNVISIPVKSYLQ | ||||||
Transmembrane | 226-246 | Helical | ||||
Sequence: LLADEALNPYYGFQAFSIALW | ||||||
Topological domain | 247-250 | Lumenal | ||||
Sequence: LADH | ||||||
Transmembrane | 251-271 | Helical | ||||
Sequence: YYWYALCIFLISAISICLALY | ||||||
Topological domain | 272-422 | Cytoplasmic | ||||
Sequence: KTRKQSLTLRDMVKLSVRVQVCRPGGEEEWVDSSELVPGDCLVLPQEGGVMPCDAALVAGECVVNESSLTGESTPVLKTALPEGPKPYCPETHRRHTLFCGTLILQARAYVGPRVLAVVTRTGFCTAKGGLVSSILHPRPISFKFYKHSMK | ||||||
Transmembrane | 423-443 | Helical | ||||
Sequence: FVAALSVLALLGTVYSIIILY | ||||||
Topological domain | 444-458 | Lumenal | ||||
Sequence: RNRVPVREIVIRALD | ||||||
Transmembrane | 459-479 | Helical | ||||
Sequence: LVTVVVPPALPAAMTVCTLYA | ||||||
Topological domain | 480-919 | Cytoplasmic | ||||
Sequence: QSRLRTQGIFCIHPLRINLGGKLRLVCFDKTGTLTEDGLDVMGVVPLKGQVLLPLVPEPCHLPLGPLLRALATCHALSQLHDTPVGDPMDLKMVESTGWVLEEGPAAGSAPGSQVLVVMRPPPGGPRQQEEPPVPVSVLCRFPFSSALQRMDVVVTWPGATQPEAYVKGSPELVASLCSPETVPSDFSQVLQSYTAAGYRVVALAGKPLPIAPSLAAAQQLTRDTVERELSLLGLLVMRNLLKPQTAPVIQTLRKTGIRTVMVTGDNLQTAVTVARACGMVGAQEHLAVIHATHPEQGQPAALEFLPTESSAVMNGAKATGYPTVPEPQSCHLALSGSTFAVLRKHFPKLLPKVLVQATVFARMAPEQKTELVCELQRLQYCVGMCGDGANDCGALKAADVGISLSQAEASVVSPFTSSMASIECVPTVIREGRCSLDTS | ||||||
Transmembrane | 920-940 | Helical | ||||
Sequence: FSVFKYMALYSLTQFISVLIL | ||||||
Topological domain | 941-946 | Lumenal | ||||
Sequence: YTINTN | ||||||
Transmembrane | 947-967 | Helical | ||||
Sequence: LGDLQFLAIDLVITTTVAVLM | ||||||
Topological domain | 968-993 | Cytoplasmic | ||||
Sequence: SRTGPALTLVRARPPGALLSVPVLGS | ||||||
Transmembrane | 994-1014 | Helical | ||||
Sequence: LLLQVALVAGIQLGGYFLVIA | ||||||
Topological domain | 1015-1037 | Lumenal | ||||
Sequence: QPWFVPLNRTVPAPDNLPNYENT | ||||||
Transmembrane | 1038-1058 | Helical | ||||
Sequence: VVFSLSGFQYLILAAAVSKGA | ||||||
Topological domain | 1059-1069 | Cytoplasmic | ||||
Sequence: PFRQPLYTNVP | ||||||
Transmembrane | 1070-1090 | Helical | ||||
Sequence: FLVALALLGSVLVGLILVPGL | ||||||
Topological domain | 1091-1106 | Lumenal | ||||
Sequence: LQGPLGLRNIVDSSFK | ||||||
Transmembrane | 1107-1127 | Helical | ||||
Sequence: LLLLGLVAFNFVGAFMLESVL | ||||||
Topological domain | 1128-1169 | Cytoplasmic | ||||
Sequence: DQCLPACLRWLRPKRASKKQFKRLQQELAEHPWPTLPVGSVR |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
No visible phenotype at 4 months (PubMed:30538141).
At 10 months, gradual loss of body weight, increased liver size and reduced adipose tissue mass (PubMed:30538141).
These phenotypes further progress to 18 months with significantly smaller body size, hepatomegaly, increased intracellular vacuolation in liver tissues, markedly reduced adipose tissue with small adipocytes, accumulation of autophagy receptor Sqstm1/p62 and autophagy-related protein LC3 in liver, and accumulation of ubiquitinated insoluble proteins (PubMed:30538141).
At 10 months, gradual loss of body weight, increased liver size and reduced adipose tissue mass (PubMed:30538141).
These phenotypes further progress to 18 months with significantly smaller body size, hepatomegaly, increased intracellular vacuolation in liver tissues, markedly reduced adipose tissue with small adipocytes, accumulation of autophagy receptor Sqstm1/p62 and autophagy-related protein LC3 in liver, and accumulation of ubiquitinated insoluble proteins (PubMed:30538141).
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 85 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000046424 | 1-1169 | Polyamine-transporting ATPase 13A2 | |||
Sequence: MSADSSLLMGSTPPSYGTLTTGTSIDPLSSSASSVRLSGYCGSPWRAIGYHAAVWMLAGIPWLLFRWKPLWGVRLRLKPCSLAHAETLVIEIKDKEGSSRQLFTVQVQTEAVVQGSLELPPQAQAEDGRSQAAVGVTPEGTWQDTSELHRQEEAKQVLRYYVLQGQRYVWMETQQAFCQVSLLDHGRTCDDVHCSSSGLSLQDQATRKTIYGPNVISIPVKSYLQLLADEALNPYYGFQAFSIALWLADHYYWYALCIFLISAISICLALYKTRKQSLTLRDMVKLSVRVQVCRPGGEEEWVDSSELVPGDCLVLPQEGGVMPCDAALVAGECVVNESSLTGESTPVLKTALPEGPKPYCPETHRRHTLFCGTLILQARAYVGPRVLAVVTRTGFCTAKGGLVSSILHPRPISFKFYKHSMKFVAALSVLALLGTVYSIIILYRNRVPVREIVIRALDLVTVVVPPALPAAMTVCTLYAQSRLRTQGIFCIHPLRINLGGKLRLVCFDKTGTLTEDGLDVMGVVPLKGQVLLPLVPEPCHLPLGPLLRALATCHALSQLHDTPVGDPMDLKMVESTGWVLEEGPAAGSAPGSQVLVVMRPPPGGPRQQEEPPVPVSVLCRFPFSSALQRMDVVVTWPGATQPEAYVKGSPELVASLCSPETVPSDFSQVLQSYTAAGYRVVALAGKPLPIAPSLAAAQQLTRDTVERELSLLGLLVMRNLLKPQTAPVIQTLRKTGIRTVMVTGDNLQTAVTVARACGMVGAQEHLAVIHATHPEQGQPAALEFLPTESSAVMNGAKATGYPTVPEPQSCHLALSGSTFAVLRKHFPKLLPKVLVQATVFARMAPEQKTELVCELQRLQYCVGMCGDGANDCGALKAADVGISLSQAEASVVSPFTSSMASIECVPTVIREGRCSLDTSFSVFKYMALYSLTQFISVLILYTINTNLGDLQFLAIDLVITTTVAVLMSRTGPALTLVRARPPGALLSVPVLGSLLLQVALVAGIQLGGYFLVIAQPWFVPLNRTVPAPDNLPNYENTVVFSLSGFQYLILAAAVSKGAPFRQPLYTNVPFLVALALLGSVLVGLILVPGLLQGPLGLRNIVDSSFKLLLLGLVAFNFVGAFMLESVLDQCLPACLRWLRPKRASKKQFKRLQQELAEHPWPTLPVGSVR | ||||||
Glycosylation | 1022 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
Autophosphorylated. Accumulates in an inactive autophosphorylated state and autophosphorylation is stimulated by phosphatidic acid and phosphatidylinositol 3,5-bisphosphate but not by Mn2+ or Zn2+. The presence of spermine results in a dose-dependent reduction in autophosphorylation.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
Interacts with MYCBP2; the interaction inhibits the ubiquitination of TSC2 by MYCBP2 (By similarity).
Interacts with HDAC6; the interaction results in recruitment of HDAC6 to lysosomes to promote CTTN deacetylation (By similarity).
Interacts with HDAC6; the interaction results in recruitment of HDAC6 to lysosomes to promote CTTN deacetylation (By similarity).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Domain
The N-terminal region is required for targeting to late endosomes/lysosomes. It does not traverse the membrane but contains a membrane-embedded intramembrane domain and interacts with the lipids phosphatidic acid (PA) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2). PA and PI(3,5)P2 are required for the protective effect against mitochondrial stress.
Sequence similarities
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type V subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,169
- Mass (Da)126,443
- Last updated2011-07-27 v3
- Checksum35458FE5B45FEFBE
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 112 | in Ref. 2; AAH42661 | ||||
Sequence: V → L | ||||||
Sequence conflict | 186 | in Ref. 2; AAH42661 | ||||
Sequence: G → S | ||||||
Sequence conflict | 440 | in Ref. 2; AAH42661 | ||||
Sequence: I → V | ||||||
Sequence conflict | 485 | in Ref. 2; AAH42661 | ||||
Sequence: T → A | ||||||
Sequence conflict | 539 | in Ref. 2; AAH42661 | ||||
Sequence: C → R | ||||||
Sequence conflict | 695 | in Ref. 2; AAH42661 | ||||
Sequence: A → E | ||||||
Sequence conflict | 809 | in Ref. 2; AAH42661 | ||||
Sequence: S → F | ||||||
Sequence conflict | 943 | in Ref. 3; BAB22896 | ||||
Sequence: I → V |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AL645625 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC042661 EMBL· GenBank· DDBJ | AAH42661.1 EMBL· GenBank· DDBJ | mRNA | ||
AK003623 EMBL· GenBank· DDBJ | BAB22896.1 EMBL· GenBank· DDBJ | mRNA |