APOL1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005254 chloride channel activity	IDA PMID:16020735 Apolipoprotein L-I promotes trypanosome lysis by forming por...	UNDECIDED	Summary: Historical anion selectivity requires comparison with later full-length channel measurements. Reason: The cited abstract explicitly reports anion channels in lipid bilayers and chloride entry into trypanosome lysosomes. Later full-length APOL1 work (PMID:25730870) reports cation selectivity under pH-dependent conditions. Original construct details and experimental conditions must be compared before choosing a replacement or rejecting the historical measurement; the 2005 cache is abstract-only. Supporting Evidence: PMID:16020735 In lipid bilayer membranes, apolipoprotein L-I formed anion channels.
GO:0005515 protein binding	IPI PMID:12621437 Apolipoprotein L-I is the trypanosome lytic factor of human ...	KEEP AS NON CORE	Summary: Trypanosome SRA directly recognizes human APOL1. Reason: The original abstract directly reports contact between the SRA amino-terminal helix and the APOL1 carboxy-terminal helix. This antagonist association is experimentally supported, but it does not establish a more specific APOL1 molecular activity. Retain the positive interaction outside the core synthesis; lack of functional specificity is not evidence that the interaction is unlikely correct. Supporting Evidence: PMID:12621437 This domain interacts strongly with a carboxy-terminal alpha-helix of the human-specific serum protein apolipoprotein L-I (apoL-I).
GO:0005515 protein binding	IPI PMID:22582013 Secreted kinase phosphorylates extracellular proteins that r...	UNDECIDED	Summary: The exact APOL1–FAM20C interaction evidence remains uninspected. Reason: UniProt records APOL1 phosphorylation by FAM20C with later PMID:26091039 and lists two IntAct interaction experiments, providing independent curated corroboration of a relationship. The original PMID:22582013 main text was inspected, but its APOL1-specific interaction or supplementary experiment remains unadjudicated. Targeted reading of the later kinase study did not expose its APOL1-specific record either. These limits concern the exact original IPI evidence, not a claim that the interaction is false. The later PTM citation and experiment count are not substituted for inspection of the original pair record.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	UNDECIDED	Summary: The APOL1–CDC23 screen pair requires its original interaction record. Reason: The proteome-scale study is available, but its APOL1/CDC23 pair-level evidence was not exposed in the inspected article body. The UniProt interaction trace does not replace the actual pair record; no interaction error or functional mechanism is inferred.
GO:0005576 extracellular region	IDA PMID:17192540 Human Trypanosoma evansi infection linked to a lack of apoli...	ACCEPT	Summary: Circulating APOL1 supplies extracellular trypanolytic activity. Reason: The human APOL1-deficiency study locates the loss and recombinant restoration of trypanolytic activity in patient serum. This directly supports the extracellular defense pool rather than merely a predicted signal peptide. Supporting Evidence: PMID:17192540 Trypanolytic activity was restored by the addition of recombinant APOL1.
GO:0005576 extracellular region	IEA GO_REF:0000120	ACCEPT	Summary: Electronic extracellular localization agrees with the human serum pool. Reason: The combined InterPro and UniProt subcellular mapping is independently corroborated by APOL1 isolation from human plasma lipoproteins and the patient-serum rescue experiment. The assertion is not extrapolated to every alternative product. Supporting Evidence: PMID:9325276 apolipoprotein L was identified and partially sequenced from immunoisolated high density lipoprotein (Lp(A-I)).
GO:0005576 extracellular region	TAS Reactome:R-HSA-2168889	ACCEPT	Summary: The Reactome TLF-1 complex contains extracellular APOL1. Reason: The exact event summary places APOL1 with APOA1 and HDL3 in the human-serum TLF-1 complex. HPR performs the hemoglobin binding in this event; APOL1 membership supports its location without assigning that binding activity to APOL1. Supporting Evidence: Reactome:R-HSA-2168889 a complex known as trypanosome lytic factor-1 (TLF-1) that contains APOL1, APOA1, and HDL3.
GO:0005788 endoplasmic reticulum lumen	TAS Reactome:R-HSA-8952289	UNDECIDED	Summary: The APOL1-specific ER-lumen entity is not exposed in this event summary. Reason: The normal Reactome cache describes FAM20C phosphorylation of secreted proteins but does not expose APOL1 or its compartmented substrate entity. Secretory passage is plausible; the precise ER-lumen assignment from this source remains unverified. It is not rejected simply because the event also has an extracellular kinase description.
GO:0006869 lipid transport	IEA GO_REF:0000002	UNDECIDED	Summary: The inferred lipid-transport role remains unresolved at the target and mapping levels. Reason: GO:0006869 concerns directed lipid movement, including movement through a transporter or pore. UniProt proposes lipid exchange and reverse cholesterol transport for APOL1 with qualified wording. The inspected APOL1 assays establish membrane association, ion conductance and lipoprotein membership, but do not resolve whether APOL1 additionally moves lipid cargo. A lipid-moving function is therefore possible rather than disproved. The target-specific rationale underlying the InterPro mapping remains unadjudicated; its origin is not inferred from the family name alone. Retain UNDECIDED for this genuinely unclear process assertion. Propagation Review Root cause: UNRESOLVED Sources checked: InterPro:IPR008405 · IPR008405 UNRESOLVED Actual IPR008405 source retained. The current primary entry/rationale was not retrieved; the inspected target literature does not settle a lipid-moving role. No family-name or propagation-error mechanism is asserted.
GO:0008289 lipid binding	IBA GO_REF:0000033	ACCEPT	Summary: The inherited lipid-binding function agrees with APOL1 membrane interaction. Reason: PAINT assigns this function through PTN001422588. APOL1 itself is a legitimate descendant evidence source, not circular support. Its membrane-addressing region and lipid-bilayer channel experiments independently corroborate lipid interaction; exact IBD placement was not reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001422588 · PTN001422588 UNRESOLVED Actual seeded ancestral source retained. Target-specific membrane evidence corroborates the inherited assertion, but the exact IBD topology and ancestral experimental placement were not reconstructed. Supporting Evidence: PMID:16020735 flanked by a membrane-addressing domain. PMID:16020735 In lipid bilayer membranes, apolipoprotein L-I formed anion channels.
GO:0008289 lipid binding	IDA PMID:16020735 Apolipoprotein L-I promotes trypanosome lysis by forming por...	ACCEPT	Summary: APOL1 lipid interaction underlies membrane insertion and pore formation. Reason: The cited study describes a membrane-addressing domain and channel formation in lipid bilayers. These findings support interaction with membrane lipid even while ion selectivity awaits construct-specific resolution. The abstract does not settle an individual phospholipid preference. Supporting Evidence: PMID:16020735 flanked by a membrane-addressing domain. PMID:16020735 In lipid bilayer membranes, apolipoprotein L-I formed anion channels.
GO:0008289 lipid binding	IEA GO_REF:0000002	ACCEPT	Summary: The family lipid-binding mapping is consistent with direct membrane experiments. Reason: APOL1 has direct experimental membrane-addressing and bilayer activity, independently supporting the InterPro lipid-binding mapping. No lipid-transport or lipid-metabolic process is inferred from that molecular interaction. Supporting Evidence: PMID:16020735 flanked by a membrane-addressing domain. PMID:16020735 In lipid bilayer membranes, apolipoprotein L-I formed anion channels.
GO:0016020 membrane	IBA GO_REF:0000033	ACCEPT	Summary: Membrane association is an independently supported APOL1 property. Reason: The inherited membrane assertion agrees with APOL1 membrane targeting and bilayer activity in its own literature. The Q96LR9 descendant and ancestral PTN are preserved; donor count does not evaluate IBD validity, and the detailed tree was not reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001422588 · PTN001422588 UNRESOLVED Actual seeded ancestral source retained. Target-specific membrane evidence corroborates the inherited assertion, but the exact IBD topology and ancestral experimental placement were not reconstructed. Supporting Evidence: PMID:16020735 apolipoprotein L-I was targeted to the lysosomal membrane
GO:0016020 membrane	IC PMID:16020735 Apolipoprotein L-I promotes trypanosome lysis by forming por...	ACCEPT	Summary: The cited channel experiment independently establishes membrane association. Reason: The IC originally derives from chloride-channel activity, whose exact ion specificity remains unresolved here. Nonetheless the same source explicitly reports APOL1 lysosomal membrane targeting and reconstituted bilayer channels, independently supporting the broader membrane location. This is a parasite membrane context, not a claim of human lysosomal residency. Supporting Evidence: PMID:16020735 apolipoprotein L-I was targeted to the lysosomal membrane
GO:0034361 very-low-density lipoprotein particle	IDA PMID:17154273 Proteomic analysis of human very low-density lipoprotein by ...	KEEP AS NON CORE	Summary: APOL1 was experimentally detected among human VLDL proteins. Reason: The source explicitly identifies seven apoL-I proteomic forms in human VLDL. Keep the particle membership as a secondary circulating context; those forms are not automatically the three sequence products in UniProt, and membership does not establish lipid transport. Supporting Evidence: PMID:17154273 we also identified seven isoforms of apoL-I
GO:0034364 high-density lipoprotein particle	IDA PMID:9325276 Apolipoprotein L, a new human high density lipoprotein apoli...	ACCEPT	Summary: Human plasma HDL contains APOL1. Reason: The original study identifies and partially sequences apoL from immunoisolated human HDL and purifies apoL-containing particles from plasma. HDL association is a central extracellular delivery context for the trypanolytic protein; it does not imply APOL1 performs all HDL metabolic functions. Supporting Evidence: PMID:9325276 apolipoprotein L was identified and partially sequenced from immunoisolated high density lipoprotein (Lp(A-I)).
GO:0042157 lipoprotein metabolic process	IEA GO_REF:0000002	UNDECIDED	Summary: The specific lipoprotein-metabolism inference remains unresolved. Reason: The current GO definition places this term under protein metabolic process and concerns reactions or pathways involving proteins with a covalently attached lipid group. APOL1 association with HDL or VLDL does not by itself identify such a metabolic contribution. Conversely, the inspected sources do not establish that APOL1 lacks one. The target-level biological role and the original IPR008405 mapping rationale remain unadjudicated, so retain UNDECIDED without asserting a demonstrably wrong electronic inference. Propagation Review Root cause: UNRESOLVED Sources checked: InterPro:IPR008405 · IPR008405 UNRESOLVED Actual IPR008405 source retained. A target-specific contribution to the defined metabolic process and the original mapping rationale remain unresolved; particle membership is neither sufficient confirmation nor disproof.
GO:0045087 innate immune response	IDA PMID:17192540 Human Trypanosoma evansi infection linked to a lack of apoli...	ACCEPT	Summary: APOL1 is an active effector of innate defense against trypanosomes. Reason: Human loss of APOL1 eliminates serum trypanolysis, and recombinant APOL1 restores it. Together with APOL1 membrane pore activity, this supports an effector that does the defensive work, not merely a permissive upstream requirement. Supporting Evidence: PMID:17192540 Trypanolytic activity was restored by the addition of recombinant APOL1.
GO:0072562 blood microparticle	HDA PMID:22516433 Proteomic analysis of microvesicles from plasma of healthy d...	UNDECIDED	Summary: The exact APOL1 plasma-microvesicle detection needs the original protein table. Reason: The abstract reports 161 microvesicle-associated proteins but does not identify the APOL1 entry, peptides or enrichment result. Without that source-local record the compartment assignment cannot be assessed. No contamination or misidentification is alleged.
GO:0140367 antibacterial innate immune response	IDA PMID:12621437 Apolipoprotein L-I is the trypanosome lytic factor of human ...	MODIFY	Summary: The measured defense is against protozoan trypanosomes. Reason: The paper explicitly studies Trypanosoma brucei and rescue of serum trypanolysis. GO:0140367 denotes antibacterial defense, whereas GO:0042832 captures protection against protozoa. Refine this specific assertion to the organism actually assayed; this does not claim APOL1 can never influence bacterial defense. The independently supported existing innate immune response annotation is retained; this taxon-specific refinement does not discard that broader immune context. Proposed replacements: defense response to protozoan Supporting Evidence: PMID:12621437 Addition of native or recombinant apoL-I either to apoL-I-depleted NHS or to fetal calf serum induced lysis of NHS-sensitive, but not NHS-resistant, trypanosomes.
GO:0140367 antibacterial innate immune response	IDA PMID:17192540 Human Trypanosoma evansi infection linked to a lack of apoli...	MODIFY	Summary: The human APOL1-deficiency phenotype concerns Trypanosoma evansi. Reason: The cited patient study links deficient serum killing and recombinant rescue to T. evansi, a protozoan. Replace the antibacterial term with GO:0042832 defense response to protozoan while retaining the original evidence and citation; no universal negative about other pathogens is inferred. The independently supported existing innate immune response annotation is retained; this taxon-specific refinement does not discard that broader immune context. Proposed replacements: defense response to protozoan Supporting Evidence: PMID:17192540 The lack of APOL1 explained the patient's infection with T. evansi.
GO:1902476 chloride transmembrane transport	IDA PMID:16020735 Apolipoprotein L-I promotes trypanosome lysis by forming por...	UNDECIDED	Summary: Historical chloride flux awaits condition-specific channel reconciliation. Reason: The 2005 abstract explicitly reports lysosomal chloride influx, while the later full-length work reports cation conductance. Both construct and pH conditions may matter. The abstract-only original record cannot settle their relationship, so no unsupported replacement or contradiction is asserted. Supporting Evidence: PMID:16020735 continuous influx of chloride
GO:0005261 monoatomic cation channel activity	IDA PMID:25730870 Human trypanolytic factor APOL1 forms pH-gated cation-select...	NEW	Summary: Mature human APOL1 forms pH-dependent cation channels. Reason: Purified mature O14791 protein produces cation-selective bilayer currents; the assay tests APOL1 itself. This MF is absent from the seed and is not an ancestor or descendant of its chloride-channel term. It does not adjudicate the distinct historical chloride measurements. Targeted source Methods and current term definition are documented in notes. Supporting Evidence: PMID:25730870 full-length recombinant APOL1 induce ideally cation-selective macroscopic conductances

Gene Description

Existing Annotations Review

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