ATAD3B is a primate-specific AAA+ ATPase-family mitochondrial membrane protein, a paralog of ATAD3A, expressed mainly in pluripotent stem cells and re-expressed in cancers. It hetero-oligomerizes with ATAD3A, which places its C-terminus in the intermembrane space, and it limits ATAD3A's association with mtDNA nucleoids, favouring a fragmented mitochondrial network. When oxidative stress damages or depletes mtDNA, the hetero-oligomer dissociates and the ATAD3B C-terminus is exposed on the outer membrane. There its LC3-interacting region recruits LC3 and triggers PINK1-independent mitophagy that clears damaged mtDNA.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding (IEA, InterPro AAA domain). ATAD3B has the AAA+ Walker A nucleotide-binding motif; UniProt's binding site 352-359 is a sequence prediction (ECO:0000255). Accepted. Reason: [file:human/ATAD3B/ATAD3B-uniprot.txt "FT BINDING 352..359"] [file:human/ATAD3B/ATAD3B-uniprot.txt "CC -!- SIMILARITY: Belongs to the AAA ATPase family."] Supporting Evidence: file:human/ATAD3B/ATAD3B-uniprot.txt FT BINDING 352..359 file:human/ATAD3B/ATAD3B-uniprot.txt CC -!- SIMILARITY: Belongs to the AAA ATPase family. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: Mitochondrion (HTP). ATAD3B localizes to mitochondria in several independent studies. The HTP row comes from the MitoCoP high-confidence mitochondrial proteome, whose per-protein data are in supplementary tables; the cached main text does not name ATAD3B. Core location. Reason: [PMID:16909202 "Both isoforms are early targets of c-myc and are located in mitochondria."] [PMID:33665835 "Under normal conditions, ATAD3B hetero-oligomerizes with ATAD3A, thus promoting the targeting of the C-terminal region of ATAD3B to the mitochondrial intermembrane space."] Supporting Evidence: PMID:16909202 Both isoforms are early targets of c-myc and are located in mitochondria. PMID:33665835 Under normal conditions, ATAD3B hetero-oligomerizes with ATAD3A, thus promoting the targeting of the C-terminal region of ATAD3B to the mitochondrial intermembrane space. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrion (IBA). ATAD3B localizes to mitochondria in several independent studies. Core location. Reason: [PMID:16909202 "Both isoforms are early targets of c-myc and are located in mitochondria."] [PMID:33665835 "Under normal conditions, ATAD3B hetero-oligomerizes with ATAD3A, thus promoting the targeting of the C-terminal region of ATAD3B to the mitochondrial intermembrane space."] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000554019 SUPPORTS TRANSFER ATAD3 family node; human ATAD3B (Q5T9A4) is itself among the experimentally annotated members. Supporting Evidence: PMID:16909202 Both isoforms are early targets of c-myc and are located in mitochondria. PMID:33665835 Under normal conditions, ATAD3B hetero-oligomerizes with ATAD3A, thus promoting the targeting of the C-terminal region of ATAD3B to the mitochondrial intermembrane space. |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | ACCEPT | Summary: Mitochondrion (IDA). ATAD3B localizes to mitochondria in several independent studies. Core location. Reason: [PMID:16909202 "Both isoforms are early targets of c-myc and are located in mitochondria."] [PMID:33665835 "Under normal conditions, ATAD3B hetero-oligomerizes with ATAD3A, thus promoting the targeting of the C-terminal region of ATAD3B to the mitochondrial intermembrane space."] Supporting Evidence: PMID:16909202 Both isoforms are early targets of c-myc and are located in mitochondria. PMID:33665835 Under normal conditions, ATAD3B hetero-oligomerizes with ATAD3A, thus promoting the targeting of the C-terminal region of ATAD3B to the mitochondrial intermembrane space. |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Mitochondrial inner membrane (IEA, UniProt subcellular location). UniProt records ATAD3B as a peripheral inner-membrane protein. Through hetero-oligomerization with ATAD3A, its C-terminus faces the intermembrane space, and under oxidative stress it becomes exposed at the outer membrane. Accepted for the basal state. Reason: [file:human/ATAD3B/ATAD3B-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane"] [PMID:33665835 "Under normal conditions, ATAD3B hetero-oligomerizes with ATAD3A, thus promoting the targeting of the C-terminal region of ATAD3B to the mitochondrial intermembrane space."] Supporting Evidence: file:human/ATAD3B/ATAD3B-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane PMID:33665835 Under normal conditions, ATAD3B hetero-oligomerizes with ATAD3A, thus promoting the targeting of the C-terminal region of ATAD3B to the mitochondrial intermembrane space. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6798743 | MARK AS OVER ANNOTATED | Summary: Plasma membrane (TAS, Reactome R-HSA-6798743). This Reactome neutrophil-degranulation event lists granule-membrane proteins identified by proteomics of neutrophil granule fractions. ATAD3B is a mitochondrial inner-membrane protein; mitochondrial carry-over into granule fractions, and peptide sharing with the near-identical ATAD3A, are the likely explanations. ATAD3A itself carries none of these Reactome rows. Over-annotation. Reason: [file:human/ATAD3B/ATAD3B-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane"] [PMID:33665835 "Under normal conditions, ATAD3B hetero-oligomerizes with ATAD3A, thus promoting the targeting of the C-terminal region of ATAD3B to the mitochondrial intermembrane space."] Supporting Evidence: file:human/ATAD3B/ATAD3B-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane PMID:33665835 Under normal conditions, ATAD3B hetero-oligomerizes with ATAD3A, thus promoting the targeting of the C-terminal region of ATAD3B to the mitochondrial intermembrane space. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6800426 | MARK AS OVER ANNOTATED | Summary: Plasma membrane (TAS, Reactome R-HSA-6800426). This Reactome neutrophil-degranulation event lists granule-membrane proteins identified by proteomics of neutrophil granule fractions. ATAD3B is a mitochondrial inner-membrane protein; mitochondrial carry-over into granule fractions, and peptide sharing with the near-identical ATAD3A, are the likely explanations. ATAD3A itself carries none of these Reactome rows. Over-annotation. Reason: [file:human/ATAD3B/ATAD3B-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane"] [PMID:33665835 "Under normal conditions, ATAD3B hetero-oligomerizes with ATAD3A, thus promoting the targeting of the C-terminal region of ATAD3B to the mitochondrial intermembrane space."] Supporting Evidence: file:human/ATAD3B/ATAD3B-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane PMID:33665835 Under normal conditions, ATAD3B hetero-oligomerizes with ATAD3A, thus promoting the targeting of the C-terminal region of ATAD3B to the mitochondrial intermembrane space. |
| GO:0007005 mitochondrion organization | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Mitochondrion organization (IBA). ATAD3B hetero-oligomerizes with ATAD3A, restrains ATAD3A's interaction with nucleoids, and contributes to mitochondrial fragmentation. It therefore affects mitochondrial organization, mainly as a dominant-negative modulator of ATAD3A. Kept as non-core; its best-supported direct role is as a mitophagy receptor. Reason: [PMID:22664726 "Using loss- and gain-of-function approaches, we show that ATAD3B associates with the ubiquitous ATAD3A species, negatively regulates the interaction of ATAD3A with matrix nucleoid complexes and contributes to a mitochondria fragmentation phenotype."] [PMID:33665835 "Under normal conditions, ATAD3B hetero-oligomerizes with ATAD3A, thus promoting the targeting of the C-terminal region of ATAD3B to the mitochondrial intermembrane space."] Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000554019 SUPPORTS TRANSFER ATAD3 family node seeded by ATAD3A and invertebrate orthologs; ATAD3B is a primate-specific paralog that modulates ATAD3A. Supporting Evidence: PMID:22664726 Using loss- and gain-of-function approaches, we show that ATAD3B associates with the ubiquitous ATAD3A species, negatively regulates the interaction of ATAD3A with matrix nucleoid complexes and contributes to a mitochondria fragmentation phenotype. PMID:33665835 Under normal conditions, ATAD3B hetero-oligomerizes with ATAD3A, thus promoting the targeting of the C-terminal region of ATAD3B to the mitochondrial intermembrane space. |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: ATP hydrolysis activity (IEA, InterPro AAA domain). ATAD3B has an AAA+ domain with the Walker A motif, but none of the cited sources reports an ATPase assay of ATAD3B. Its characterized roles (ATAD3A modulation, LC3 binding) do not depend on a demonstrated catalytic step. Plausible but undemonstrated; kept as non-core. Reason: [file:human/ATAD3B/ATAD3B-uniprot.txt "FT BINDING 352..359"] [file:human/ATAD3B/ATAD3B-uniprot.txt "CC -!- SIMILARITY: Belongs to the AAA ATPase family."] Supporting Evidence: file:human/ATAD3B/ATAD3B-uniprot.txt FT BINDING 352..359 file:human/ATAD3B/ATAD3B-uniprot.txt CC -!- SIMILARITY: Belongs to the AAA ATPase family. |
| GO:0030667 secretory granule membrane | TAS Reactome:R-HSA-6798743 | MARK AS OVER ANNOTATED | Summary: Secretory granule membrane (TAS, Reactome R-HSA-6798743). This Reactome neutrophil-degranulation event lists granule-membrane proteins identified by proteomics of neutrophil granule fractions. ATAD3B is a mitochondrial inner-membrane protein; mitochondrial carry-over into granule fractions, and peptide sharing with the near-identical ATAD3A, are the likely explanations. ATAD3A itself carries none of these Reactome rows. Over-annotation. Reason: [file:human/ATAD3B/ATAD3B-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane"] [PMID:33665835 "Under normal conditions, ATAD3B hetero-oligomerizes with ATAD3A, thus promoting the targeting of the C-terminal region of ATAD3B to the mitochondrial intermembrane space."] Supporting Evidence: file:human/ATAD3B/ATAD3B-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane PMID:33665835 Under normal conditions, ATAD3B hetero-oligomerizes with ATAD3A, thus promoting the targeting of the C-terminal region of ATAD3B to the mitochondrial intermembrane space. |
| GO:0101003 ficolin-1-rich granule membrane | TAS Reactome:R-HSA-6800426 | MARK AS OVER ANNOTATED | Summary: Ficolin-1-rich granule membrane (TAS, Reactome R-HSA-6800426). This Reactome neutrophil-degranulation event lists granule-membrane proteins identified by proteomics of neutrophil granule fractions. ATAD3B is a mitochondrial inner-membrane protein; mitochondrial carry-over into granule fractions, and peptide sharing with the near-identical ATAD3A, are the likely explanations. ATAD3A itself carries none of these Reactome rows. Over-annotation. Reason: [file:human/ATAD3B/ATAD3B-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane"] [PMID:33665835 "Under normal conditions, ATAD3B hetero-oligomerizes with ATAD3A, thus promoting the targeting of the C-terminal region of ATAD3B to the mitochondrial intermembrane space."] Supporting Evidence: file:human/ATAD3B/ATAD3B-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane PMID:33665835 Under normal conditions, ATAD3B hetero-oligomerizes with ATAD3A, thus promoting the targeting of the C-terminal region of ATAD3B to the mitochondrial intermembrane space. |
| GO:0140580 mitochondrion autophagosome adaptor activity | IDA PMID:33665835 ATAD3B is a mitophagy receptor mediating clearance of oxidat... | NEW | Summary: Mitochondrion autophagosome adaptor activity (NEW, IDA). ATAD3B has an LC3-interacting region that binds LC3. Under oxidative stress its C-terminus is exposed at the outer membrane and recruits LC3 to start mitophagy. Comparator: the mitophagy receptor BNIP3 carries this term by IDA. Abstract-only source. Reason: [PMID:33665835 "Here, we identified a novel mitophagy receptor, ATAD3B, which is specifically expressed in primates."] [PMID:33665835 "ATAD3B contains a LIR motif that binds to LC3 and promotes oxidative stress-induced mitophagy in a PINK1-independent manner, thus promoting the clearance of damaged mtDNA induced by oxidative stress."] [PMID:33665835 "Oxidative stress-induced mtDNA damage or mtDNA depletion reduces ATAD3B-ATAD3A hetero-oligomerization and leads to exposure of the ATAD3B C-terminus at the mitochondrial outer membrane and subsequent recruitment of LC3 for initiating mitophagy."] Supporting Evidence: PMID:33665835 Here, we identified a novel mitophagy receptor, ATAD3B, which is specifically expressed in primates. PMID:33665835 ATAD3B contains a LIR motif that binds to LC3 and promotes oxidative stress-induced mitophagy in a PINK1-independent manner, thus promoting the clearance of damaged mtDNA induced by oxidative stress. PMID:33665835 Oxidative stress-induced mtDNA damage or mtDNA depletion reduces ATAD3B-ATAD3A hetero-oligomerization and leads to exposure of the ATAD3B C-terminus at the mitochondrial outer membrane and subsequent recruitment of LC3 for initiating mitophagy. |
| GO:0000423 mitophagy | IMP PMID:33665835 ATAD3B is a mitophagy receptor mediating clearance of oxidat... | NEW | Summary: Mitophagy (NEW, IMP). As an LC3-binding receptor, ATAD3B mediates oxidative-stress-induced, PINK1-independent mitophagy that clears damaged mtDNA, and re-expressing it clears m.3243A>G mtDNA in MELAS cells. The receptor does part of the work by tethering the mitochondrion to LC3. Comparators BNIP3 (IMP) and FUNDC1 (IGI) carry this term. Reason: [PMID:33665835 "ATAD3B contains a LIR motif that binds to LC3 and promotes oxidative stress-induced mitophagy in a PINK1-independent manner, thus promoting the clearance of damaged mtDNA induced by oxidative stress."] [PMID:33665835 "Furthermore, ATAD3B is little expressed in m.3243A > G mutated cells and MELAS patient fibroblasts showing endogenous oxidative stress, and ATAD3B re-expression promotes the clearance of m.3243A > G mutated mtDNA."] Supporting Evidence: PMID:33665835 ATAD3B contains a LIR motif that binds to LC3 and promotes oxidative stress-induced mitophagy in a PINK1-independent manner, thus promoting the clearance of damaged mtDNA induced by oxidative stress. PMID:33665835 Furthermore, ATAD3B is little expressed in m.3243A > G mutated cells and MELAS patient fibroblasts showing endogenous oxidative stress, and ATAD3B re-expression promotes the clearance of m.3243A > G mutated mtDNA. |
| GO:0005741 mitochondrial outer membrane | IDA PMID:33665835 ATAD3B is a mitophagy receptor mediating clearance of oxidat... | NEW | Summary: Mitochondrial outer membrane (NEW, IDA). When oxidative stress damages or depletes mtDNA, the ATAD3B-ATAD3A hetero-oligomer dissociates and the ATAD3B C-terminus becomes exposed at the outer membrane, where it recruits cytosolic LC3. This is the location of its mitophagy-receptor activity. The LIR mitophagy receptor BNIP3L carries this location (IMP). Abstract-only source. Reason: [PMID:33665835 "Oxidative stress-induced mtDNA damage or mtDNA depletion reduces ATAD3B-ATAD3A hetero-oligomerization and leads to exposure of the ATAD3B C-terminus at the mitochondrial outer membrane and subsequent recruitment of LC3 for initiating mitophagy."] [PMID:33665835 "ATAD3B contains a LIR motif that binds to LC3 and promotes oxidative stress-induced mitophagy in a PINK1-independent manner, thus promoting the clearance of damaged mtDNA induced by oxidative stress."] Supporting Evidence: PMID:33665835 Oxidative stress-induced mtDNA damage or mtDNA depletion reduces ATAD3B-ATAD3A hetero-oligomerization and leads to exposure of the ATAD3B C-terminus at the mitochondrial outer membrane and subsequent recruitment of LC3 for initiating mitophagy. PMID:33665835 ATAD3B contains a LIR motif that binds to LC3 and promotes oxidative stress-induced mitophagy in a PINK1-independent manner, thus promoting the clearance of damaged mtDNA induced by oxidative stress. |
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Experiment: Purify ATAD3B and ATAD3A/ATAD3B hetero-oligomers to measure ATPase activity with Walker A/B mutants, and test those mutants for LC3 recruitment and mtDNA clearance under oxidative stress.
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