ATP6AP2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0009897 external side of plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: The PTN001000649 ancestral assertion is consistent with experimentally established extracellular renin binding at the human plasma membrane. Reason: The PTN001000649 ancestral assertion is consistent with experimentally established extracellular renin binding at the human plasma membrane. The target itself in WITH/FROM is legitimate evidence, not circularity.
GO:0030177 positive regulation of Wnt signaling pathway	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Retain the PTN000331504 inherited Wnt assertion as a signaling context supported by human Wnt-response experiments. Reason: Retain the PTN000331504 inherited Wnt assertion as a signaling context supported by human Wnt-response experiments. The actual PAINT node placement was not reconstructed; no donor-count objection is warranted.
GO:0000421 autophagosome membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Retain the curated UniProt subcellular mapping as a contextual autophagosome-membrane localization. Reason: Retain the curated UniProt subcellular mapping as a contextual autophagosome-membrane localization. Its underlying Q9CYN9 similarity attribution is explicit; no new human autophagosome imaging claim is made.
GO:0005737 cytoplasm	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Cytoplasmic localization is correct broad cellular context. Reason: Cytoplasm includes intracellular organelles and their membranes. The ARBA assertion is compatible with ATP6AP2 localization; the core locations are the specific membranes at which its receptor and pump roles operate.
GO:0005765 lysosomal membrane	IEA GO_REF:0000120	ACCEPT	Summary: The combined Q9CYN9/ENSMUSP00000033313 and UniProt subcellular mapping is concordant with the human endolysosomal complex role. Reason: The combined Q9CYN9/ENSMUSP00000033313 and UniProt subcellular mapping is concordant with the human endolysosomal complex role. Retain the existing lysosomal-membrane assertion without claiming a new localization experiment.
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: ER-membrane localization is supported by the actual human HeLa localization work and ER-retrieval behavior, beyond the UniProt subcellular mapping. Reason: ER-membrane localization is supported by the actual human HeLa localization work and ER-retrieval behavior, beyond the UniProt subcellular mapping.
GO:0010008 endosome membrane	IEA GO_REF:0000120	ACCEPT	Summary: The mouse Atp6ap2-based and UniProt subcellular inference is consistent with an endosomal membrane component that supports endolysosomal proton-pump function. Reason: The mouse Atp6ap2-based and UniProt subcellular inference is consistent with an endosomal membrane component that supports endolysosomal proton-pump function.
GO:0016020 membrane	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: The InterPro membrane annotation is correct broad cellular context. Reason: The single-pass membrane topology supports this assertion. Specific endolysosomal and plasma-membrane locations describe the core functions more precisely.
GO:0030424 axon	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Retain axonal localization as a specialized neuronal context from the curated Q9CYN9-based UniProt annotation. Reason: Retain axonal localization as a specialized neuronal context from the curated Q9CYN9-based UniProt annotation. This consultation did not independently inspect the underlying axonal images.
GO:0030665 clathrin-coated vesicle membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Retain the clathrin-coated-vesicle membrane mapping with its explicit Q6AXS4 rat similarity provenance; it is a trafficking context, not a separate molecular activity. Reason: Retain the clathrin-coated-vesicle membrane mapping with its explicit Q6AXS4 rat similarity provenance; it is a trafficking context, not a separate molecular activity.
GO:0030672 synaptic vesicle membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Retain synaptic-vesicle membrane localization with the Q6AXS4 similarity boundary. Reason: Retain synaptic-vesicle membrane localization with the Q6AXS4 similarity boundary. Do not relabel it as a direct human synaptic-vesicle assay.
GO:0032591 dendritic spine membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: The curated dendritic-spine membrane location is a neuronal context transferred through Q9CYN9. Reason: The curated dendritic-spine membrane location is a neuronal context transferred through Q9CYN9. No independently inspected human spine imaging is claimed.
GO:0038023 signaling receptor activity	IEA GO_REF:0000002	ACCEPT	Summary: Human receptor expression and ligand-dependent ERK activation support genuine signaling receptor activity. Reason: Human receptor expression and ligand-dependent ERK activation support genuine signaling receptor activity. Supporting Evidence: PMID:12045255 Transfected cells stably expressing the receptor showed renin- and prorenin-specific binding. PMID:12045255 induced an intracellular signal with phosphorylation of serine and tyrosine residues associated to an activation of MAP kinases ERK1 and ERK2.
GO:0098588 bounding membrane of organelle	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: An organelle-bounding membrane is a correct broad cellular location. Reason: ATP6AP2 is associated with endomembranes. The lysosomal and endosomal membrane terms specify the pump core; this broader location is retained as context.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	UNDECIDED	Summary: GOA identifies eleven HuRI interaction partners; their individual assay records remain unresolved. Reason: The deterministic WITH/FROM entries identify O00526, O95183, P21854, P42857, P53801, Q01453, Q16617, Q5BJF2, Q969S6, Q96IW7 and Q9NPL8. These identifiers establish the curated pairs, but do not establish the construct-level evidence or a specific molecular function for ATP6AP2. The individual pair assays remain unverified, so the assertion remains UNDECIDED.
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	UNDECIDED	Summary: GOA identifies O00526 as the interaction partner in the 2025 multimodal map. Reason: The WITH/FROM entry resolves the partner accession; uncertainty concerns the individual ATP6AP2-O00526 assay and its functional interpretation. The study abstract alone does not settle those points, so the source assertion remains UNDECIDED.
GO:0021626 central nervous system maturation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: The mouse Q9CYN9/ENSMUSP00000033313 transfer is consistent with the original mouse developmental and human patient-neuron evidence. Reason: The mouse Q9CYN9/ENSMUSP00000033313 transfer is consistent with the original mouse developmental and human patient-neuron evidence. CNS maturation is a developmental consequence, not a separate molecular core.
GO:0030177 positive regulation of Wnt signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Retain the mouse orthology-based Wnt process in light of direct human ATP6AP2-dependent Wnt responses. Reason: Retain the mouse orthology-based Wnt process in light of direct human ATP6AP2-dependent Wnt responses. This is not a PAINT annotation and should not be described as one.
GO:0097401 synaptic vesicle lumen acidification	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: The donor is mouse Atp6ap2 Q9CYN9/ENSMUSP00000033313; the official MGI record independently shows synaptic-vesicle acidification experimental annotations under J:326652. Reason: The donor is mouse Atp6ap2 Q9CYN9/ENSMUSP00000033313; the official MGI record independently shows synaptic-vesicle acidification experimental annotations under J:326652. Retain this specialized conserved pump context, without claiming that donor paper's full assays were read.
GO:0005765 lysosomal membrane	EXP PMID:29127204 Mutations in the X-linked ATP6AP2 cause a glycosylation diso...	ACCEPT	Summary: Retain the experimental lysosomal-membrane assertion in the original disease/assembly study, consistent with the established endolysosomal component. Reason: Retain the experimental lysosomal-membrane assertion in the original disease/assembly study, consistent with the established endolysosomal component. Selected original localization and functional sections were read, not every panel.
GO:0010008 endosome membrane	ISS GO_REF:0000024	ACCEPT	Summary: Retain the Q9CYN9-based ISS endosome-membrane assertion. Reason: Retain the Q9CYN9-based ISS endosome-membrane assertion. The donor identity is mouse Atp6ap2 and the location agrees with the broader human endolysosomal evidence.
GO:0000139 Golgi membrane	NAS PMID:32001091 Structure and Roles of V-type ATPases.	KEEP AS NON CORE	Summary: Golgi-membrane location is corroborated by the actual HeLa localization and ER-retrieval experiments in 29127204. Reason: Golgi-membrane location is corroborated by the actual HeLa localization and ER-retrieval experiments in 29127204. This supports localization, without implying a specifically measured Golgi acidification function.
GO:0005765 lysosomal membrane	NAS PMID:32001091 Structure and Roles of V-type ATPases.	ACCEPT	Summary: Retain the review-derived lysosomal-membrane annotation with independent original-paper corroboration of the pump component and its lysosomal role. Reason: Retain the review-derived lysosomal-membrane annotation with independent original-paper corroboration of the pump component and its lysosomal role.
GO:0005886 plasma membrane	NAS PMID:32001091 Structure and Roles of V-type ATPases.	ACCEPT	Summary: Plasma-membrane localization is a functional location of the renin/prorenin receptor, supported directly by the human expression and binding work. Reason: Plasma-membrane localization is a functional location of the renin/prorenin receptor, supported directly by the human expression and binding work.
GO:0007035 vacuolar acidification	NAS PMID:32001091 Structure and Roles of V-type ATPases.	ACCEPT	Summary: The broad vacuolar-acidification assertion is compatible with this component's contribution to endolysosomal proton pumping. Reason: Acidification is central to ATP6AP2 contribution to the V-ATPase pump. The core synthesis records the supported lysosomal and endosomal instances without repeating their broader process ancestor. This existing NAS assertion remains valid and core.
GO:0007042 lysosomal lumen acidification	NAS PMID:32001091 Structure and Roles of V-type ATPases.	ACCEPT	Summary: The review-derived lysosomal-acidification claim has direct ATP6AP2-targeted depletion/rescue and pH corroboration in human cells. Reason: The review-derived lysosomal-acidification claim has direct ATP6AP2-targeted depletion/rescue and pH corroboration in human cells. Attribute proton translocation to the assembled pump. Supporting Evidence: PMID:30985297 severe deficiency in lysosomal acidification and protein degradation leading to neuronal cell death. These deficiencies could be rescued by expression of full-length ATP6AP2.
GO:0007042 lysosomal lumen acidification	NAS PMID:33065002 Structures of a Complete Human V-ATPase Reveal Mechanisms of...	ACCEPT	Summary: The structural complex membership supports a contribution to lysosomal acidification, corroborated by target-specific perturbation. Reason: The structural complex membership supports a contribution to lysosomal acidification, corroborated by target-specific perturbation. The structural study alone is not an ATP6AP2 catalytic assay. Supporting Evidence: PMID:30985297 severe deficiency in lysosomal acidification and protein degradation leading to neuronal cell death. These deficiencies could be rescued by expression of full-length ATP6AP2.
GO:0010008 endosome membrane	NAS PMID:32001091 Structure and Roles of V-type ATPases.	ACCEPT	Summary: Retain the review-derived endosome-membrane annotation, consistent with the curated localization and human endosomal/lysosomal fraction studies. Reason: Retain the review-derived endosome-membrane annotation, consistent with the curated localization and human endosomal/lysosomal fraction studies.
GO:0016020 membrane	IDA PMID:33065002 Structures of a Complete Human V-ATPase Reveal Mechanisms of...	KEEP AS NON CORE	Summary: The structural study supports ATP6AP2 membrane association. Reason: The membrane-complex structure supports this location. The generic membrane term is retained as context, while the specific membranes and V-ATPase complex describe the core role.
GO:0033176 proton-transporting V-type ATPase complex	NAS PMID:33065002 Structures of a Complete Human V-ATPase Reveal Mechanisms of...	ACCEPT	Summary: Retain V-type ATPase complex membership from the human structural study. Reason: Retain V-type ATPase complex membership from the human structural study. ATP6AP2 is an accessory structural component; this does not make it an independently catalytic ATPase.
GO:0048388 endosomal lumen acidification	NAS PMID:32001091 Structure and Roles of V-type ATPases.	ACCEPT	Summary: Retain endosomal lumen acidification as a contribution of the endomembrane V-ATPase component, with human vesicular-pH and endosomal-functional corroboration. Reason: Retain endosomal lumen acidification as a contribution of the endomembrane V-ATPase component, with human vesicular-pH and endosomal-functional corroboration. Supporting Evidence: PMID:30985297 severe deficiency in lysosomal acidification and protein degradation leading to neuronal cell death. These deficiencies could be rescued by expression of full-length ATP6AP2.
GO:0051452 intracellular pH reduction	NAS PMID:32001091 Structure and Roles of V-type ATPases.	ACCEPT	Summary: Intracellular pH reduction is a correct broad description of the pump-supported process. Reason: Reduction of compartmental pH is the central outcome of the ATP6AP2-supported proton pump. The core synthesis gives the supported lysosomal and endosomal instances; a broader existing annotation need not become peripheral merely because that synthesis is concise.
GO:0061795 Golgi lumen acidification	NAS PMID:32001091 Structure and Roles of V-type ATPases.	UNDECIDED	Summary: The cited review cache is abstract-only and does not establish ATP6AP2-specific Golgi lumen acidification. Reason: The cited review cache is abstract-only and does not establish ATP6AP2-specific Golgi lumen acidification. Golgi localization alone does not resolve this compartment-specific functional claim; retain uncertainty rather than reject it.
GO:1902600 proton transmembrane transport	NAS PMID:33065002 Structures of a Complete Human V-ATPase Reveal Mechanisms of...	ACCEPT	Summary: ATP6AP2 contributes structural support to the proton-transporting V-type complex, so this process annotation is defensible. Reason: ATP6AP2 is a structural accessory component of the proton-transporting V-type complex. Its contribution to proton transport is core, without implying that isolated ATP6AP2 hydrolyzes ATP or forms an independent pump.
GO:0000220 vacuolar proton-transporting V-type ATPase, V0 domain	ISS GO_REF:0000024	ACCEPT	Summary: The ISS donor P81134 is bovine ATP6AP2, independently verified in UniProt. Reason: The ISS donor P81134 is bovine ATP6AP2, independently verified in UniProt. Human structural complex evidence corroborates the V0-domain association; no species conflation is needed.
GO:0016471 vacuolar proton-transporting V-type ATPase complex	IMP PMID:30985297 ATP6AP2 variant impairs CNS development and neuronal surviva...	ACCEPT	Summary: Human depletion/rescue and membrane-fraction V1B2:V0a1 measurements support participation in the assembled vacuolar V-ATPase complex. Reason: Human depletion/rescue and membrane-fraction V1B2:V0a1 measurements support participation in the assembled vacuolar V-ATPase complex. This is complex support, not isolated enzyme activity. Supporting Evidence: PMID:30985297 severe deficiency in lysosomal acidification and protein degradation leading to neuronal cell death. These deficiencies could be rescued by expression of full-length ATP6AP2.
GO:0005765 lysosomal membrane	ISS GO_REF:0000024	ACCEPT	Summary: Retain the mouse Q9CYN9-based lysosomal-membrane ISS with concordant human structural/functional context. Reason: Retain the mouse Q9CYN9-based lysosomal-membrane ISS with concordant human structural/functional context.
GO:0021626 central nervous system maturation	IMP PMID:30985297 ATP6AP2 variant impairs CNS development and neuronal surviva...	KEEP AS NON CORE	Summary: The study includes human patient-derived neurons and conditional mouse-brain deletion, supporting a CNS-developmental phenotype with explicit model boundaries. Reason: The study includes human patient-derived neurons and conditional mouse-brain deletion, supporting a CNS-developmental phenotype with explicit model boundaries.
GO:0005515 protein binding	IPI PMID:30374053 TMEM9 promotes intestinal tumorigenesis through vacuolar-ATP...	KEEP AS NON CORE	Summary: The original TMEM9 paper includes ATP6AP2 interactions and ATP6AP2-dependent cellular Wnt effects. Reason: The original TMEM9 paper includes ATP6AP2 interactions and ATP6AP2-dependent cellular Wnt effects. Its ATPase assay uses ATP6AP2-associated complexes while varying TMEM9; it does not justify replacing this binding assertion with standalone ATPase regulation or a new assembly process.
GO:0090263 positive regulation of canonical Wnt signaling pathway	IMP PMID:30374053 TMEM9 promotes intestinal tumorigenesis through vacuolar-ATP...	KEEP AS NON CORE	Summary: Actual human-cell ATP6AP2 depletion reduces the TMEM9-dependent Wnt response. Reason: Actual human-cell ATP6AP2 depletion reduces the TMEM9-dependent Wnt response. Retain this specific signaling context rather than dismiss the source because its title foregrounds TMEM9.
GO:0007042 lysosomal lumen acidification	IMP PMID:32276428 Interaction between PHB2 and Enterovirus A71 VP1 Induces Aut...	ACCEPT	Summary: The PHB2-titled paper actually assays ATP6AP2 depletion in human RD cells and measures calibrated lysosomal pH. Reason: The PHB2-titled paper actually assays ATP6AP2 depletion in human RD cells and measures calibrated lysosomal pH. It supports acidification; the paper's background assembly statement in Results 3.4 is not a new assembly experiment. Supporting Evidence: PMID:32276428 To evaluate the effect of ATP6AP2 knockdown on lysosomal pH, we employed an acidophilic fluorescent probe to measure the lysosomal pH, which increased significantly
GO:0005515 protein binding	IPI PMID:29127204 Mutations in the X-linked ATP6AP2 cause a glycosylation diso...	KEEP AS NON CORE	Summary: The original study shows ATP6AP2 in complexes with assembly-associated partners, including endogenous ATP6AP1 co-immunoprecipitation. Reason: The original study shows ATP6AP2 in complexes with assembly-associated partners, including endogenous ATP6AP1 co-immunoprecipitation. Preserve this interaction evidence without converting it into a different MF or BP merely to avoid a generic term. Supporting Evidence: PMID:29127204 For the top candidates ATP6AP1 and VMA21, the interaction was confirmed by coimmunoprecipitation (coIP) of overexpressed tagged proteins in HEK293T cells
GO:0005764 lysosome	IDA PMID:29127204 Mutations in the X-linked ATP6AP2 cause a glycosylation diso...	ACCEPT	Summary: Retain lysosomal localization with the experimental annotation and concordant original target/complex studies; no claim that all localization figures were inspected. Reason: Retain lysosomal localization with the experimental annotation and concordant original target/complex studies; no claim that all localization figures were inspected.
GO:0005789 endoplasmic reticulum membrane	IDA PMID:29127204 Mutations in the X-linked ATP6AP2 cause a glycosylation diso...	ACCEPT	Summary: Actual ER localization, retrieval-motif effects, and the type-I membrane topology support this original ER-membrane assertion. Reason: Actual ER localization, retrieval-motif effects, and the type-I membrane topology support this original ER-membrane assertion.
GO:0016471 vacuolar proton-transporting V-type ATPase complex	IMP PMID:29127204 Mutations in the X-linked ATP6AP2 cause a glycosylation diso...	ACCEPT	Summary: The selected original partner/assembly studies support vacuolar V-ATPase complex association. Reason: The selected original partner/assembly studies support vacuolar V-ATPase complex association. Preserve the existing experimental assertion without promoting association into autonomous ATPase activity.
GO:0070821 tertiary granule membrane	TAS Reactome:R-HSA-6798747	KEEP AS NON CORE	Summary: The official human Reactome ATP6AP2 entity R-HSA-6799717 is explicitly located in tertiary-granule membrane and belongs to the event's protein set. Reason: The official human Reactome ATP6AP2 entity R-HSA-6799717 is explicitly located in tertiary-granule membrane and belongs to the event's protein set. Retain contextual localization; underlying proteomic spectra were not inspected.
GO:0101003 ficolin-1-rich granule membrane	TAS Reactome:R-HSA-6800426	KEEP AS NON CORE	Summary: Official human ATP6AP2 entity R-HSA-6800921 explicitly belongs to the ficolin-rich granule membrane set. Reason: Official human ATP6AP2 entity R-HSA-6800921 explicitly belongs to the ficolin-rich granule membrane set. This resolves the target membership that the generic cached event summary alone lacked.
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	KEEP AS NON CORE	Summary: Detected in an extracellular-vesicle proteome. The protein is plausible EV content, but this is not where it functions. Reason: Prorenin receptor / V-ATPase accessory protein, with UniProt lysosome-membrane and cell-surface locations. Transmembrane/lipid-anchored protein of the plasma membrane or endosomal system (UniProt); such proteins are expected EV contents (MISEV2018 (PMID:30637094) category 1). True, but not its core location. (Manual re-review for OMICS_EVIDENCE, 2026-10-10; previous action: UNDECIDED.)
GO:0005515 protein binding	IPI PMID:20093472 Requirement of prorenin receptor and vacuolar H+-ATPase-medi...	KEEP AS NON CORE	Summary: The original Science Fig3 describes endogenous human HEK293T PRR associations with LRP6 and V-ATPase components, plus tagged controls. Reason: The original Science Fig3 describes endogenous human HEK293T PRR associations with LRP6 and V-ATPase components, plus tagged controls. These are real source-specific interactions; they do not alone establish the legacy regulator/assembly replacements.
GO:0021903 rostrocaudal neural tube patterning	IMP PMID:20093472 Requirement of prorenin receptor and vacuolar H+-ATPase-medi...	KEEP AS NON CORE	Summary: Retain the existing developmental annotation with an explicit Xenopus assay boundary: morpholino phenotypes and neural-patterning experiments are complemented by human PRR mRNA rescue, not direct human embryonic patterning assays. Reason: Retain the existing developmental annotation with an explicit Xenopus assay boundary: morpholino phenotypes and neural-patterning experiments are complemented by human PRR mRNA rescue, not direct human embryonic patterning assays.
GO:0030177 positive regulation of Wnt signaling pathway	IMP PMID:20093472 Requirement of prorenin receptor and vacuolar H+-ATPase-medi...	KEEP AS NON CORE	Summary: Human cell Wnt-response depletion and original receptor/complex experiments support Wnt regulation. Reason: Human cell Wnt-response depletion and original receptor/complex experiments support Wnt regulation. Keep the signaling context without inventing a separate Wnt-ligand receptor activity.
GO:0048069 eye pigmentation	IMP PMID:20093472 Requirement of prorenin receptor and vacuolar H+-ATPase-medi...	KEEP AS NON CORE	Summary: The Xenopus eye-pigmentation phenotype is rescued by human PRR mRNA in the original study. Reason: The Xenopus eye-pigmentation phenotype is rescued by human PRR mRNA in the original study. Retain the conserved contextual phenotype with this species boundary.
GO:0060323 head morphogenesis	IMP PMID:20093472 Requirement of prorenin receptor and vacuolar H+-ATPase-medi...	KEEP AS NON CORE	Summary: The original Xenopus small-head phenotype and human PRR rescue support a contextual developmental annotation; they are not evidence of a distinct human morphogen activity. Reason: The original Xenopus small-head phenotype and human PRR rescue support a contextual developmental annotation; they are not evidence of a distinct human morphogen activity.
GO:0070062 extracellular exosome	HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid...	KEEP AS NON CORE	Summary: Detected in an extracellular-vesicle proteome. The protein is plausible EV content, but this is not where it functions. Reason: Prorenin receptor / V-ATPase accessory protein, with UniProt lysosome-membrane and cell-surface locations. Transmembrane/lipid-anchored protein of the plasma membrane or endosomal system (UniProt); such proteins are expected EV contents (MISEV2018 (PMID:30637094) category 1). True, but not its core location. (Manual re-review for OMICS_EVIDENCE, 2026-10-10; previous action: UNDECIDED.)
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	KEEP AS NON CORE	Summary: The original NIH/NHLBI study inventory explicitly lists human ATP6AP2, NP_005756, one peptide, reference 2 linked to 19056867. Reason: The original NIH/NHLBI study inventory explicitly lists human ATP6AP2, NP_005756, one peptide, reference 2 linked to 19056867. Retain contextual exosome occurrence, not vesicular activity or topology.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-2022403	ACCEPT	Summary: The original Reactome renin-receptor complex is at the plasma membrane, consistent with the directly demonstrated human receptor function. Reason: The original Reactome renin-receptor complex is at the plasma membrane, consistent with the directly demonstrated human receptor function.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-2065357	ACCEPT	Summary: The prorenin-receptor Reactome event uses plasma-membrane ATP6AP2. Reason: The prorenin-receptor Reactome event uses plasma-membrane ATP6AP2. The receptor supports renin activity; ATP6AP2 is not the protease.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6798747	ACCEPT	Summary: Official R-HSA-2022356 links ATP6AP2 at the plasma membrane to the tertiary-granule exocytosis output set. Reason: Official R-HSA-2022356 links ATP6AP2 at the plasma membrane to the tertiary-granule exocytosis output set. The same established plasma-membrane location is retained as core, while the evidence here concerns trafficking rather than a receptor-activity assay.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6800426	ACCEPT	Summary: Official R-HSA-2022356 links the same human ATP6AP2 plasma-membrane entity to the ficolin-rich exocytosis output set. Reason: Official R-HSA-2022356 links the same human ATP6AP2 plasma-membrane entity to the ficolin-rich exocytosis output set. The same established plasma-membrane location is retained as core. This source concerns trafficking and does not establish a receptor-activity assay or an exocytosis catalyst role.
GO:0032914 positive regulation of transforming growth factor beta1 production	IDA PMID:16374430 Renin increases mesangial cell transforming growth factor-be...	KEEP AS NON CORE	Summary: The complete abstract describes renin-driven TGF-beta1 production in human and rat mesangial cells, with receptor-siRNA evidence specifically in rat cells. Reason: The complete abstract describes renin-driven TGF-beta1 production in human and rat mesangial cells, with receptor-siRNA evidence specifically in rat cells. Retain the existing context with that boundary, not a universal human downstream function.
GO:0002003 angiotensin maturation	IDA PMID:15746149 A unique exonic splice enhancer mutation in a family with X-...	ACCEPT	Summary: The source abstract reports retained renin-binding and catalytic-efficiency enhancement by the human splice-altered receptor, with reduced signaling. Reason: The human splice-altered receptor retains renin binding and catalytic enhancement in the source abstract. This supports participation as a renin-associated cofactor, independently corroborated by PMID:12045255; ATP6AP2 is not assigned protease activity. Full Methods of PMID:15746149 were not independently inspected. Supporting Evidence: PMID:15746149 Functional analysis demonstrated that the mutated receptor could bind renin and increase renin catalytic activity, similar to the wild-type receptor, but resulted in a modest and reproducible impairment of ERK1/2 activation.
GO:0009897 external side of plasma membrane	IDA PMID:15746149 A unique exonic splice enhancer mutation in a family with X-...	ACCEPT	Summary: Retain the external plasma-membrane receptor location, corroborated by direct human expression/binding studies; full target Methods of 15746149 were not independently read. Reason: Retain the external plasma-membrane receptor location, corroborated by direct human expression/binding studies; full target Methods of 15746149 were not independently read.
GO:0043408 regulation of MAPK cascade	IDA PMID:15746149 A unique exonic splice enhancer mutation in a family with X-...	ACCEPT	Summary: The human splice-variant source distinguishes impaired ERK signaling from preserved renin activation. Reason: The human splice-variant source distinguishes impaired ERK signaling from preserved renin activation. This supports a genuine signaling function in addition to the pump-associated function. Supporting Evidence: PMID:15746149 Functional analysis demonstrated that the mutated receptor could bind renin and increase renin catalytic activity, similar to the wild-type receptor, but resulted in a modest and reproducible impairment of ERK1/2 activation.
GO:0002003 angiotensin maturation	IDA PMID:12045255 Pivotal role of the renin/prorenin receptor in angiotensin I...	ACCEPT	Summary: The receptor-bound renin experiments directly support cofactor participation in Ang I generation: ATP6AP2 binds the enzyme and improves apparent catalytic efficiency. Reason: Receptor-associated renin produces Ang I with increased apparent catalytic efficiency in the normalized membrane experiments. This is a measured cofactor contribution to angiotensin maturation; REN performs the cleavage. Neither ATP6AP2 proteolysis nor an increased renin turnover number is asserted. Supporting Evidence: PMID:12045255 The binding of renin induced a fourfold increase of the catalytic efficiency of angiotensinogen conversion to angiotensin I
GO:0005515 protein binding	IPI PMID:12045255 Pivotal role of the renin/prorenin receptor in angiotensin I...	MODIFY	Summary: Human ligand-binding and ERK responses support transmembrane signaling receptor activity. Reason: Extracellular renin/prorenin binding to the single-pass receptor is coupled to intracellular ERK activation under angiotensin-pathway blockade. This specific receptor function refines the generic binding assertion. The existing GO:0038023 IEA assertion remains compatible with its more specific child. Proposed replacements: transmembrane signaling receptor activity Supporting Evidence: PMID:12045255 Transfected cells stably expressing the receptor showed renin- and prorenin-specific binding. PMID:12045255 induced an intracellular signal with phosphorylation of serine and tyrosine residues associated to an activation of MAP kinases ERK1 and ERK2.
GO:0009897 external side of plasma membrane	IDA PMID:12045255 Pivotal role of the renin/prorenin receptor in angiotensin I...	ACCEPT	Summary: Human receptor-transfected mesangial cells show surface-associated binding and receptor localization, supporting the external plasma-membrane assertion. Reason: Human receptor-transfected mesangial cells show surface-associated binding and receptor localization, supporting the external plasma-membrane assertion.
GO:0043408 regulation of MAPK cascade	IDA PMID:12045255 Pivotal role of the renin/prorenin receptor in angiotensin I...	ACCEPT	Summary: Renin triggers receptor-dependent ERK signaling in the original human cells under angiotensin-pathway blockade. Reason: Renin triggers receptor-dependent ERK signaling in the original human cells under angiotensin-pathway blockade. Retain MAPK regulation as the signaling core's process, without calling ATP6AP2 a kinase. Supporting Evidence: PMID:12045255 Transfected cells stably expressing the receptor showed renin- and prorenin-specific binding. PMID:12045255 induced an intracellular signal with phosphorylation of serine and tyrosine residues associated to an activation of MAP kinases ERK1 and ERK2.

Gene Description

Existing Annotations Review

Core Functions

Contributes to ATP-driven proton pumping as a membrane-associated accessory component of V-ATPase, supporting endosomal and lysosomal acidification.

Binds extracellular renin and prorenin as a transmembrane receptor, mediating receptor-dependent ERK signaling and supporting angiotensin maturation by increasing receptor-associated renin catalytic efficiency. Renin performs angiotensinogen cleavage.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

📚 Additional Documentation

Notes

Pn Notes

📄 View Raw YAML