ATP5MD

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0045259 proton-transporting ATP synthase complex	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) inference that ATP5MD is part of the proton-transporting ATP synthase complex. This is the well-established core cellular-component assignment for this protein: it is subunit k of the membrane F(o) sector of mitochondrial ATP synthase (Complex V). Reason: Correct and core. UniProt describes the protein as "Subunit k, of the mitochondrial membrane ATP synthase complex" and a component of the F(o) domain; the IBA assignment matches the experimental and orthology evidence. Supporting Evidence: file:human/ATP5MD/ATP5MD-uniprot.txt Subunit k, of the mitochondrial membrane ATP synthase complex PMID:29917077 a novel CV subunit disease gene, USMG5
GO:0031966 mitochondrial membrane	IEA GO_REF:0000044	ACCEPT	Summary: Electronic annotation (from the UniProt Subcellular Location keyword mapping) placing ATP5MD in the mitochondrial membrane. This is correct but less specific than the mitochondrial inner membrane, where the F(o) sector actually resides. Reason: Consistent with the curated UniProt subcellular location ("Mitochondrion membrane"; single-pass membrane protein). It is a valid, if broad, location; the more specific GO:0005743 (mitochondrial inner membrane) captures the exact compartment and is retained as core. Supporting Evidence: file:human/ATP5MD/ATP5MD-uniprot.txt Mitochondrion membrane
GO:0005739 mitochondrion	IEA GO_REF:0000107	ACCEPT	Summary: Electronic annotation (Ensembl Compara transfer from mouse ortholog) placing ATP5MD in the mitochondrion. Correct but the least specific of the location terms for this protein. Reason: Uncontroversial; ATP5MD is a mitochondrial protein. Retained as accurate but general; the inner-membrane term is the informative core location. Supporting Evidence: file:human/ATP5MD/ATP5MD-uniprot.txt Subunit k, of the mitochondrial membrane ATP synthase complex
GO:0005743 mitochondrial inner membrane	NAS PMID:26297831 Assembly of human mitochondrial ATP synthase through two sep...	ACCEPT	Summary: ComplexPortal-curated (NAS) annotation locating ATP5MD in the mitochondrial inner membrane, the compartment that houses the membrane F(o) sector of ATP synthase. This is the most specific and informative location for this subunit. Reason: Correct and core. As a single-pass membrane subunit of the F(o) sector, ATP5MD resides in the inner mitochondrial membrane where oxidative phosphorylation occurs. The cited assembly study establishes the inner-membrane ATP synthase context. Supporting Evidence: PMID:29917077 OXPHOS occurs at the inner mitochondrial membrane through the integrated PMID:26297831 Mitochondrial ATP synthase is a motor enzyme in which a central shaft rotates
GO:0015986 proton motive force-driven ATP synthesis	NAS PMID:26297831 Assembly of human mitochondrial ATP synthase through two sep...	ACCEPT	Summary: ComplexPortal-curated (NAS) annotation that ATP5MD is involved in proton motive force-driven ATP synthesis. As a subunit of the F(o) proton-channel sector, ATP5MD contributes to the complex that synthesizes ATP using the transmembrane proton gradient. Reason: Correct core biological process for a Complex V subunit. Knockdown/loss of DAPIT reduces mitochondrial ATP synthesis, linking this subunit to the ATP-synthesis process. The more specific mitochondrial term (GO:0042776) is used in core_functions. Supporting Evidence: PMID:21345788 DAPIT-knockdown cells show smaller mitochondrial ATP synthesis activity PMID:29917077 reduced both CV dimer expression and ATP synthesis rate
GO:0045259 proton-transporting ATP synthase complex	NAS PMID:26297831 Assembly of human mitochondrial ATP synthase through two sep...	ACCEPT	Summary: ComplexPortal-curated (NAS) statement of complex membership, duplicating the IBA/ISS/IMP assignments to the proton-transporting ATP synthase complex. Correct and core. Reason: ATP5MD is a bona fide subunit (subunit k) of the F(o) sector of mitochondrial ATP synthase. Duplicate complex-membership annotations with different evidence are acceptable and mutually reinforcing. Supporting Evidence: file:human/ATP5MD/ATP5MD-uniprot.txt a membrane F(0) domain - the membrane proton channel (subunits c, a, 8, e, f, g, k and j)
GO:0005739 mitochondrion	IDA GO_REF:0000052	ACCEPT	Summary: Human Protein Atlas immunofluorescence (IDA) localizing ATP5MD to the mitochondrion. Directly consistent with all other evidence for this protein. Reason: Experimental localization consistent with a mitochondrial ATP synthase subunit. Correct but general; the inner-membrane term is the informative core location. Supporting Evidence: file:human/ATP5MD/ATP5MD-uniprot.txt Subunit k, of the mitochondrial membrane ATP synthase complex
GO:0031966 mitochondrial membrane	EXP PMID:21345788 Knockdown of DAPIT (diabetes-associated protein in insulin-s...	ACCEPT	Summary: Experimental (EXP) annotation of mitochondrial membrane localization from the DAPIT knockdown study, which characterized DAPIT as associated with mitochondrial ATP synthase in the mitochondrial membrane. Reason: Supported by experimental characterization of DAPIT as a mitochondrial ATP synthase-associated membrane protein. Correct; the inner-membrane term is the more specific location retained as core. Supporting Evidence: PMID:21345788 the suppressed expression of DAPIT in DAPIT-knockdown HeLa cells causes
GO:0031966 mitochondrial membrane	EXP PMID:29917077 USMG5 Ashkenazi Jewish founder mutation impairs mitochondria...	ACCEPT	Summary: Experimental (EXP) annotation of mitochondrial membrane localization from the USMG5 disease study, which analyzed the protein in the context of inner-membrane Complex V. Reason: Consistent with the protein's role as a membrane subunit of Complex V embedded in the inner mitochondrial membrane. Correct; general term retained alongside the specific inner-membrane assignment. Supporting Evidence: PMID:29917077 OXPHOS occurs at the inner mitochondrial membrane through the integrated
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: High-throughput (HTP) proteomic identification of ATP5MD in the high-confidence human mitochondrial proteome. Corroborates mitochondrial localization. Reason: Consistent, high-throughput support for mitochondrial localization. Correct but general; retained as corroborating evidence for the mitochondrial location. Supporting Evidence: PMID:34800366 high-confidence human mitochondrial proteome
GO:0045259 proton-transporting ATP synthase complex	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity (ISS) transfer, from the bovine ortholog (UniProtKB:Q3ZBI7), of membership in the proton-transporting ATP synthase complex. Duplicate of the core complex-membership assignment. Reason: The bovine ortholog is a validated ATP synthase subunit k; ISS transfer to the human protein is well justified and matches the experimental IMP/NAS evidence. Supporting Evidence: file:human/ATP5MD/ATP5MD-uniprot.txt Subunit k, of the mitochondrial membrane ATP synthase complex
GO:0045259 proton-transporting ATP synthase complex	IMP PMID:29917077 USMG5 Ashkenazi Jewish founder mutation impairs mitochondria...	ACCEPT	Summary: IMP annotation of complex membership from the USMG5 disease study: a founder splice mutation abolished the protein and selectively reduced Complex V dimer expression and ATP synthesis, with wild-type cDNA rescue restoring both, directly demonstrating that the protein is a functional subunit of Complex V. Reason: Strong experimental evidence (mutation plus rescue) that ATP5MD/USMG5 is a subunit of the proton-transporting ATP synthase complex required for its dimeric assembly. Core annotation. Supporting Evidence: PMID:29917077 reduced both CV dimer expression and ATP synthesis rate PMID:29917077 Rescue with wild-type USMG5 cDNA in proband fibroblasts restored USMG5 protein, increased CV
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-164832	ACCEPT	Summary: Reactome traceable-author-statement (TAS) inner-membrane localization associated with the "ATPase synthesizes ATP" reaction of the F1Fo ATP synthase. Reason: Reactome places ATP synthase and its subunits in the mitochondrial inner membrane, consistent with all other evidence. Correct core location. Supporting Evidence: PMID:29917077 OXPHOS occurs at the inner mitochondrial membrane through the integrated
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-164834	ACCEPT	Summary: Reactome TAS inner-membrane localization associated with the "Enzyme-bound ATP is released" reaction of the F1Fo ATP synthase. Reason: Correct inner-membrane location for an ATP synthase subunit; consistent with the curated UniProt and experimental evidence. Supporting Evidence: PMID:29917077 OXPHOS occurs at the inner mitochondrial membrane through the integrated
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-164840	ACCEPT	Summary: Reactome TAS inner-membrane localization associated with the "ADP and Pi bind to ATPase" reaction of the F1Fo ATP synthase. Reason: Correct inner-membrane location for an ATP synthase subunit; duplicate Reactome reaction-level annotation, consistent with core biology. Supporting Evidence: PMID:29917077 OXPHOS occurs at the inner mitochondrial membrane through the integrated
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-8949580	ACCEPT	Summary: Reactome TAS inner-membrane localization associated with the "F1Fo ATP synthase dimerizes" reaction — directly relevant given ATP5MD's role in Complex V dimerization. Reason: Correct inner-membrane location; especially apt because this subunit is required for the dimerization event this Reactome reaction represents. Supporting Evidence: file:human/ATP5MD/ATP5MD-uniprot.txt Required for dimerization of the ATP synthase complex and as such regulates ATP synthesis in the mitochondria
GO:0005739 mitochondrion	IMP PMID:29917077 USMG5 Ashkenazi Jewish founder mutation impairs mitochondria...	ACCEPT	Summary: IMP annotation of mitochondrial localization from the USMG5 disease study. Correct but the least specific of the location terms. Reason: Consistent with experimental characterization of the protein as a mitochondrial Complex V subunit; general location retained alongside the specific inner-membrane term. Supporting Evidence: PMID:29917077 a novel CV subunit disease gene, USMG5
GO:0005198 structural molecule activity	IBA GO_REF:0000033	NEW	Summary: Proposed subunit-specific molecular function. ATP5MD is a small non-catalytic membrane subunit that acts as a structural constituent of the F(o) sector of ATP synthase; it does not independently catalyze ATP synthesis but is required for complex stability and dimerization. Reason: GOA carries the complex-membership CC and the ATP-synthesis BP but no molecular function for this subunit. The appropriate subunit-level MF is structural molecule activity, reflecting its role as a structural/accessory component whose loss destabilizes Complex V (the complex-level rotary activity is captured in core_functions via contributes_to GO:0046933). Supporting Evidence: file:human/ATP5MD/ATP5MD-uniprot.txt Required for dimerization of the ATP synthase complex and as such regulates ATP synthesis in the mitochondria PMID:21345788 a critical role of DAPIT in
GO:0042776 proton motive force-driven mitochondrial ATP synthesis	NAS PMID:29917077 USMG5 Ashkenazi Jewish founder mutation impairs mitochondria...	NEW	Summary: More specific (mitochondrial) counterpart of the GOA-carried GO:0015986. ATP5MD is part of the mitochondrial ATP synthase that produces ATP from the proton motive force across the inner membrane, and its loss reduces the mitochondrial ATP synthesis rate. Reason: Refines the existing GO:0015986 (proton motive force-driven ATP synthesis) to the mitochondrial-specific term, better fitting a mitochondrial inner-membrane Complex V subunit. Supported experimentally by reduced ATP synthesis on DAPIT/USMG5 loss. Supporting Evidence: PMID:29917077 reduced both CV dimer expression and ATP synthesis rate PMID:21345788 DAPIT-knockdown cells show smaller mitochondrial ATP synthesis activity
GO:0033615 mitochondrial proton-transporting ATP synthase complex assembly	IMP PMID:29917077 USMG5 Ashkenazi Jewish founder mutation impairs mitochondria...	NEW	Summary: Proposed process annotation capturing ATP5MD's role in the assembly/oligomerization of mitochondrial ATP synthase. Loss of ATP5MD reduces Complex V dimer formation and the overall ATP synthase population, and wild-type rescue restores dimerization. Reason: Well supported by both DAPIT knockdown (loss of ATP synthase population) and the USMG5 disease study (selective loss of the dimeric complex with rescue), which together establish a role in ATP synthase complex assembly/dimerization not otherwise captured by the GOA terms. Supporting Evidence: PMID:29917077 reduced both CV dimer expression and ATP synthesis rate file:human/ATP5MD/ATP5MD-uniprot.txt Required for dimerization of the ATP synthase complex and as such regulates ATP synthesis in the mitochondria

Gene Description

Existing Annotations Review

Core Functions

References

📚 Additional Documentation

Notes

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