P25705 · ATPA_HUMAN
- ProteinATP synthase subunit alpha, mitochondrial
- GeneATP5F1A
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids553 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Mitochondrial membrane ATP synthase (F1F0 ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F1 - containing the extramembraneous catalytic core, and F0 - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F1 is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Subunits alpha and beta form the catalytic core in F1. Rotation of the central stalk against the surrounding alpha3beta3 subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits. Subunit alpha does not bear the catalytic high-affinity ATP-binding sites (By similarity).
Binds the bacterial siderophore enterobactin and can promote mitochondrial accumulation of enterobactin-derived iron ions (PubMed:30146159).
Binds the bacterial siderophore enterobactin and can promote mitochondrial accumulation of enterobactin-derived iron ions (PubMed:30146159).
Miscellaneous
The siderophore enterobactin (Ent) produced by enteric bacteria binds Fe3+ and helps bacteria scavenge iron ions from the environment (PubMed:30146159).
As a consequence, the mammalian siderocalin LCN2 plays an important role in defense against bacterial infections by sequestering iron bound to microbial siderophores. LCN2 can also bind iron bound to endogenous or nutrient-derived iron chelators and plays an important role in cellular iron homeostasis. Enterobactin produced by non-pathogenic E.coli strains can facilitate mitochondrial iron assimilation, suggesting that iron bound to siderophores from non-pathogenic bacteria may contribute to iron absorption by the host (PubMed:30146159).
As a consequence, the mammalian siderocalin LCN2 plays an important role in defense against bacterial infections by sequestering iron bound to microbial siderophores. LCN2 can also bind iron bound to endogenous or nutrient-derived iron chelators and plays an important role in cellular iron homeostasis. Enterobactin produced by non-pathogenic E.coli strains can facilitate mitochondrial iron assimilation, suggesting that iron bound to siderophores from non-pathogenic bacteria may contribute to iron absorption by the host (PubMed:30146159).
Features
Showing features for binding site, site.
GO annotations
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameATP synthase subunit alpha, mitochondrial
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP25705
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Mitochondrion inner membrane ; Peripheral membrane protein
Cell membrane ; Peripheral membrane protein
Note: Colocalizes with HRG on the cell surface of T-cells (PubMed:19285951).
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Combined oxidative phosphorylation deficiency 22 (COXPD22)
- Note
- DescriptionA mitochondrial disorder characterized by intrauterine growth retardation, microcephaly, hypotonia, pulmonary hypertension, failure to thrive, encephalopathy, and heart failure.
- See alsoMIM:616045
Natural variants in COXPD22
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_071982 | 321 | Y>C | in COXPD22; dbSNP:rs587777788 |
Mitochondrial complex V deficiency, nuclear type 4A (MC5DN4A)
- Note
- DescriptionAn autosomal dominant mitochondrial disorder characterized by failure to thrive, feeding difficulties, hyperlactatemia, hyperammonemia, and increased serum alanine levels. Some affected individuals show spontaneous resolution of the symptoms in early childhood and have subsequent normal growth and development, whereas others show developmental delay with impaired intellectual development and movement abnormalities, including dystonia, ataxia, or spasticity.
- See alsoMIM:620358
Natural variants in MC5DN4A
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_088541 | 182 | R>Q | in MC5DN4A; uncertain significance | |
VAR_088542 | 207 | R>H | in MC5DN4A; likely pathogenic | |
VAR_088543 | 346 | S>F | in MC5DN4A; uncertain significance |
Mitochondrial complex V deficiency, nuclear type 4B (MC5DN4B)
- Note
- DescriptionAn autosomal recessive mitochondrial disorder characterized by severe neonatal encephalopathy resulting in death in the first weeks of life. Affected individuals do not show dysmorphic features or organomegaly, and manifest neurologic features such as irritability, a high-pitched cry, a horizontal and vertical nystagmus, abnormal primitive reflexes, and tonus dysregulation. Post-mortem anatomopathological examination shows extensive cerebral damage, hypoplastic lungs, and renal and skeletal lesions.
- See alsoMIM:615228
Natural variants in MC5DN4B
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_069769 | 329 | R>C | in MC5DN4B; dbSNP:rs587776960 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_048369 | 32 | in dbSNP:rs2228437 | |||
Sequence: A → S | ||||||
Natural variant | VAR_088541 | 182 | in MC5DN4A; uncertain significance | |||
Sequence: R → Q | ||||||
Natural variant | VAR_088542 | 207 | in MC5DN4A; likely pathogenic | |||
Sequence: R → H | ||||||
Natural variant | VAR_071982 | 321 | in COXPD22; dbSNP:rs587777788 | |||
Sequence: Y → C | ||||||
Natural variant | VAR_069769 | 329 | in MC5DN4B; dbSNP:rs587776960 | |||
Sequence: R → C | ||||||
Natural variant | VAR_088543 | 346 | in MC5DN4A; uncertain significance | |||
Sequence: S → F |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 551 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for transit peptide, chain, modified residue (large scale data), modified residue, glycosylation.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Transit peptide | 1-43 | UniProt | Mitochondrion | ||||
Sequence: MLSVRVAAAVVRALPRRAGLVSRNALGSSFIAARNFHASNTHL | |||||||
Chain | PRO_0000002424 | 44-553 | UniProt | ATP synthase subunit alpha, mitochondrial | |||
Sequence: QKTGTAEMSSILEERILGADTSVDLEETGRVLSIGDGIARVHGLRNVQAEEMVEFSSGLKGMSLNLEPDNVGVVVFGNDKLIKEGDIVKRTGAIVDVPVGEELLGRVVDALGNAIDGKGPIGSKTRRRVGLKAPGIIPRISVREPMQTGIKAVDSLVPIGRGQRELIIGDRQTGKTSIAIDTIINQKRFNDGSDEKKKLYCIYVAIGQKRSTVAQLVKRLTDADAMKYTIVVSATASDAAPLQYLAPYSGCSMGEYFRDNGKHALIIYDDLSKQAVAYRQMSLLLRRPPGREAYPGDVFYLHSRLLERAAKMNDAFGGGSLTALPVIETQAGDVSAYIPTNVISITDGQIFLETELFYKGIRPAINVGLSVSRVGSAAQTRAMKQVAGTMKLELAQYREVAAFAQFGSDLDAATQQLLSRGVRLTELLKQGQYSPMAIEEQVAVIYAGVRGYLDKLEPSKITKFENAFLSHVVSQHQALLGTIRADGKISEQSDAKLKEIVTNFLAGFEA | |||||||
Modified residue (large scale data) | 48 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 52 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 53 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 53 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 64 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 65 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 65 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 76 | UniProt | Phosphoserine; alternate | ||||
Sequence: S | |||||||
Glycosylation | 76 | UniProt | O-linked (GlcNAc) serine; alternate | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 76 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 106 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 123 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 126 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 132 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 134 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 134 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 161 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 161 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 166 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 166 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 167 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 167 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 184 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 184 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 198 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 204 | UniProt | Omega-N-methylarginine | ||||
Sequence: R | |||||||
Modified residue | 230 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 230 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 236 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 239 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 239 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 240 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 254 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 261 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 261 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 305 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 305 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 315 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 337 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 413 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 419 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 427 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 427 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 434 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 451 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 462 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 498 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 498 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 506 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 506 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 513 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 517 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 525 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 531 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 531 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 539 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 539 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 541 | UniProt | N6-acetyllysine | ||||
Sequence: K |
Post-translational modification
The N-terminus is blocked.
Acetylated on lysine residues. BLOC1S1 is required for acetylation.
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
Tissue specificity
Fetal lung, heart, liver, gut and kidney. Expressed at higher levels in the fetal brain, retina and spinal cord.
Gene expression databases
Organism-specific databases
Interaction
Subunit
F-type ATPases have 2 components, CF1 - the catalytic core - and CF0 - the membrane proton channel. CF1 has five subunits: alpha3, beta3, gamma1, delta1, epsilon1. CF0 has three main subunits: a, b and c (By similarity).
Interacts with ATPAF2 (PubMed:11410595).
Interacts with HRG; the interaction occurs on the surface of T-cells and alters the cell morphology when associated with concanavalin (in vitro) (PubMed:19285951).
Interacts with PLG (angiostatin peptide); the interaction inhibits most of the angiogenic properties of angiostatin (PubMed:10077593).
Component of an ATP synthase complex composed of ATP5PB, ATP5MC1, ATP5F1E, ATP5PD, ATP5ME, ATP5PF, ATP5MF, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C, ATP5PO, ATP5MG, ATP5MK and ATP5MJ (By similarity).
Interacts with BLOC1S1 (PubMed:22309213).
Interacts with BCL2L1 isoform BCL-X(L); the interaction mediates the association of BCL2L1 isoform BCL-X(L) with the mitochondrial membrane F1F0 ATP synthase and enhances neurons metabolic efficiency (By similarity).
Interacts with CLN5 and PPT1 (By similarity).
Interacts with S100A1; this interaction increases F1-ATPase activity (By similarity).
Interacts with ABCB7; this interaction allows the regulation of cellular iron homeostasis and cellular reactive oxygen species (ROS) levels in cardiomyocytes (By similarity).
Interacts with ATPAF2 (PubMed:11410595).
Interacts with HRG; the interaction occurs on the surface of T-cells and alters the cell morphology when associated with concanavalin (in vitro) (PubMed:19285951).
Interacts with PLG (angiostatin peptide); the interaction inhibits most of the angiogenic properties of angiostatin (PubMed:10077593).
Component of an ATP synthase complex composed of ATP5PB, ATP5MC1, ATP5F1E, ATP5PD, ATP5ME, ATP5PF, ATP5MF, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C, ATP5PO, ATP5MG, ATP5MK and ATP5MJ (By similarity).
Interacts with BLOC1S1 (PubMed:22309213).
Interacts with BCL2L1 isoform BCL-X(L); the interaction mediates the association of BCL2L1 isoform BCL-X(L) with the mitochondrial membrane F1F0 ATP synthase and enhances neurons metabolic efficiency (By similarity).
Interacts with CLN5 and PPT1 (By similarity).
Interacts with S100A1; this interaction increases F1-ATPase activity (By similarity).
Interacts with ABCB7; this interaction allows the regulation of cellular iron homeostasis and cellular reactive oxygen species (ROS) levels in cardiomyocytes (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P25705 | ATP5F1B P06576 | 7 | EBI-351437, EBI-356231 | |
BINARY | P25705 | ATP5PB P24539 | 10 | EBI-351437, EBI-1044810 | |
BINARY | P25705 | ATP5PF P18859 | 6 | EBI-351437, EBI-2606700 | |
BINARY | P25705 | ATP5PO P48047 | 5 | EBI-351437, EBI-355815 | |
BINARY | P25705 | ATPAF2 Q8N5M1 | 4 | EBI-351437, EBI-1166928 | |
BINARY | P25705 | BLOC1S1 P78537 | 2 | EBI-351437, EBI-348630 | |
BINARY | P25705 | HTT P42858 | 3 | EBI-351437, EBI-466029 | |
BINARY | P25705 | SIRT3 Q9NTG7 | 2 | EBI-351437, EBI-724621 | |
BINARY | P25705 | YWHAZ P63104 | 3 | EBI-351437, EBI-347088 |
Protein-protein interaction databases
Miscellaneous
Structure
Sequence & Isoforms
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 3 isoforms produced by Alternative splicing.
P25705-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length553
- Mass (Da)59,751
- Last updated1992-05-01 v1
- ChecksumAA47BBB8EDA77EAC
P25705-2
- Name2
- Differences from canonical
- 1-50: Missing
P25705-3
- Name3
- Differences from canonical
- 140-161: Missing
Computationally mapped potential isoform sequences
There are 10 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0A0MTS3 | A0A0A0MTS3_HUMAN | ATP5F1A | 90 | ||
K7EK77 | K7EK77_HUMAN | ATP5F1A | 207 | ||
K7EJP1 | K7EJP1_HUMAN | ATP5F1A | 144 | ||
K7EM08 | K7EM08_HUMAN | ATP5F1A | 58 | ||
K7EKV9 | K7EKV9_HUMAN | ATP5F1A | 44 | ||
K7ENJ4 | K7ENJ4_HUMAN | ATP5F1A | 199 | ||
K7EQU6 | K7EQU6_HUMAN | ATP5F1A | 78 | ||
K7EQH4 | K7EQH4_HUMAN | ATP5F1A | 111 | ||
K7ERX7 | K7ERX7_HUMAN | ATP5F1A | 205 | ||
K7ESA0 | K7ESA0_HUMAN | ATP5F1A | 77 |
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_045129 | 1-50 | in isoform 2 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_054688 | 140-161 | in isoform 3 | |||
Sequence: Missing | ||||||
Sequence conflict | 162 | in Ref. 5; BAG63618 | ||||
Sequence: G → V | ||||||
Sequence conflict | 183 | in Ref. 5; BAG63618 | ||||
Sequence: I → T | ||||||
Sequence conflict | 329 | in Ref. 5; AAH39135 | ||||
Sequence: R → L | ||||||
Sequence conflict | 356 | in Ref. 5; BAG63618 | ||||
Sequence: N → D | ||||||
Sequence conflict | 510 | in Ref. 5; AAH11384 | ||||
Sequence: A → D | ||||||
Sequence conflict | 529 | in Ref. 5; AAH11384 | ||||
Sequence: D → E |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X59066 EMBL· GenBank· DDBJ | CAA41789.1 EMBL· GenBank· DDBJ | mRNA | ||
X65460 EMBL· GenBank· DDBJ | CAA46452.1 EMBL· GenBank· DDBJ | mRNA | ||
D14710 EMBL· GenBank· DDBJ | BAA03531.1 EMBL· GenBank· DDBJ | mRNA | ||
D28126 EMBL· GenBank· DDBJ | BAA05672.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BT007209 EMBL· GenBank· DDBJ | AAP35873.1 EMBL· GenBank· DDBJ | mRNA | ||
AK092735 EMBL· GenBank· DDBJ | BAG52604.1 EMBL· GenBank· DDBJ | mRNA | ||
AK289457 EMBL· GenBank· DDBJ | BAF82146.1 EMBL· GenBank· DDBJ | mRNA | ||
AK302272 EMBL· GenBank· DDBJ | BAG63618.1 EMBL· GenBank· DDBJ | mRNA | ||
AC012569 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC003119 EMBL· GenBank· DDBJ | AAH03119.1 EMBL· GenBank· DDBJ | mRNA | ||
BC007299 EMBL· GenBank· DDBJ | AAH07299.1 EMBL· GenBank· DDBJ | mRNA | ||
BC008028 EMBL· GenBank· DDBJ | AAH08028.2 EMBL· GenBank· DDBJ | mRNA | ||
BC011384 EMBL· GenBank· DDBJ | AAH11384.1 EMBL· GenBank· DDBJ | mRNA | ||
BC016046 EMBL· GenBank· DDBJ | AAH16046.1 EMBL· GenBank· DDBJ | mRNA | ||
BC019310 EMBL· GenBank· DDBJ | AAH19310.1 EMBL· GenBank· DDBJ | mRNA | ||
BC039135 EMBL· GenBank· DDBJ | AAH39135.2 EMBL· GenBank· DDBJ | mRNA | ||
BC064562 EMBL· GenBank· DDBJ | AAH64562.1 EMBL· GenBank· DDBJ | mRNA | ||
BC067385 EMBL· GenBank· DDBJ | AAH67385.1 EMBL· GenBank· DDBJ | mRNA |