AP1B1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0016192 vesicle-mediated transport	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation from phylogenetic inference. AP-1 complex is well-established as mediating vesicle-mediated transport between TGN and endosomes, forming clathrin-coated carriers for cargo sorting (PMID:23415225, Buser & Spang 2023). Reason: Core function of AP-1 complex. The beta1 subunit is integral to vesicle formation at TGN and endosomes. IBA annotation is well-supported by extensive literature on AP-1 function in clathrin-mediated trafficking. Supporting Evidence: PMID:23415225 AP-1 is a clathrin adaptor complex that sorts cargo between the trans-Golgi network and endosomes. file:human/AP1B1/AP1B1-deep-research-falcon.md AP1B1 encodes beta-1 adaptin, the large beta subunit of the heterotetrameric adaptor protein complex 1 (AP-1)
GO:0005765 lysosomal membrane	IEA GO_REF:0000117	ACCEPT	Summary: ARBA machine learning annotation. AP-1 is involved in trafficking to lysosomes via transport of lysosomal hydrolase receptors (mannose-6-phosphate receptors) from TGN. Reason: AP-1 mediates transport of cargo to lysosomal compartments, and Reactome annotations support lysosomal membrane localization during vesicle uncoating. The annotation is consistent with AP-1's role in lysosome biogenesis. Supporting Evidence: PMID:23247405 Packaging of the tyrosinases into transport vesicles at early/recycling endosome-associated tubules is dependent on ubiquitous adaptor protein complex (AP)-1 and AP-3
GO:0005794 Golgi apparatus	IEA GO_REF:0000044	MODIFY	Summary: UniProt subcellular location mapping. AP-1 localizes predominantly at the trans-Golgi network (TGN), consistent with UniProt annotation and extensive structural/localization studies (PMID:15377783). Reason: While Golgi apparatus is accurate, the more specific term GO:0032588 (trans-Golgi network membrane) better reflects AP-1's primary localization site where it functions. Proposed replacements: trans-Golgi network membrane Supporting Evidence: PMID:15377783 The crystal structure of the core of the AP-1 complex, which functions in the trans-Golgi network (TGN).
GO:0006886 intracellular protein transport	IEA GO_REF:0000002	ACCEPT	Summary: InterPro domain-based annotation. AP-1 complex mediates intracellular protein transport by selecting and packaging cargo into clathrin-coated vesicles. Reason: Core function of AP-1. The complex recognizes sorting signals on cargo proteins and mediates their transport between TGN and endosomes. This is a direct consequence of AP-1's adaptor function. Supporting Evidence: UniProt:Q10567 Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes (PubMed:31630791).
GO:0012505 endomembrane system	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: ARBA machine learning annotation. AP-1 functions within the endomembrane system, specifically at TGN and endosomal membranes. Reason: While technically accurate, this term is too broad. More specific CC terms like GO:0032588 (trans-Golgi network membrane) and GO:0030121 (AP-1 adaptor complex) already capture AP-1B1's localization with greater precision.
GO:0015031 protein transport	IEA GO_REF:0000120	ACCEPT	Summary: Combined IEA annotation from InterPro and UniProt keywords. AP-1 mediates protein transport as a clathrin adaptor. Reason: Core function. While GO:0006886 (intracellular protein transport) is more specific, this broader term is also accurate and can coexist. AP-1 fundamentally functions in protein transport pathways. Supporting Evidence: UniProt:Q10567 The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. file:human/AP1B1/AP1B1-deep-research-falcon.md AP1B1 encodes beta-1 adaptin, the large beta subunit of the heterotetrameric adaptor protein complex 1 (AP-1)
GO:0016192 vesicle-mediated transport	IEA GO_REF:0000002	ACCEPT	Summary: InterPro domain-based annotation. Duplicate of IBA annotation for same term. Reason: Core function, same as IBA annotation above. The IEA annotation from InterPro domains provides independent computational support for this core function.
GO:0030117 membrane coat	IEA GO_REF:0000002	MODIFY	Summary: InterPro annotation. AP-1 is part of the membrane coat that forms on clathrin-coated vesicles. Reason: While membrane coat is accurate, the more specific term GO:0030121 (AP-1 adaptor complex) better describes the actual complex that AP1B1 is part of. The beta1 subunit is a structural component of the AP-1 heterotetrameric complex. Proposed replacements: AP-1 adaptor complex Supporting Evidence: PMID:15377783 The AP-1 core comprises N-terminal fragments of the two large chains, beta1 and gamma, and the intact medium and small chains, micro1 and sigma1.
GO:0030131 clathrin adaptor complex	IEA GO_REF:0000002	MODIFY	Summary: InterPro annotation. AP1B1 is part of a clathrin adaptor complex (AP-1). Reason: Accurate but can be made more specific. The specific complex is AP-1 (GO:0030121), which is a child term of clathrin adaptor complex. Proposed replacements: AP-1 adaptor complex Supporting Evidence: PMID:23415225 AP-1 is a clathrin adaptor complex that sorts cargo between the trans-Golgi network and endosomes.
GO:0030276 clathrin binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro annotation. The AP-1 complex, including the beta1 subunit, binds clathrin to form clathrin-coated vesicles. Beta-adaptins contain clathrin-binding domains. Reason: Core molecular function. Beta-adaptins are known to directly bind clathrin through their hinge region, recruiting clathrin to form coated vesicles. This is a fundamental property of the beta1 subunit. Supporting Evidence: PMID:23247405 AP-3 and AP-1 act as clathrin-binding adaptor proteins
GO:0030665 clathrin-coated vesicle membrane	IEA GO_REF:0000044	ACCEPT	Summary: UniProt subcellular location annotation. AP-1 complex is found on clathrin-coated vesicle membranes at the TGN. Reason: Core localization. AP1B1 as part of AP-1 is a component of the coat on clathrin-coated vesicles forming at the TGN and endosomes. Supporting Evidence: UniProt:Q10567 Note=Component of the coat surrounding the cytoplasmic face of coated vesicles located at the Golgi complex.
GO:0031410 cytoplasmic vesicle	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: Combined IEA annotation. AP-1 functions on cytoplasmic vesicles. Reason: Too general. More specific terms like GO:0030665 (clathrin-coated vesicle membrane) are already annotated and provide better specificity for AP-1's localization.
GO:0005515 protein binding	IPI PMID:23415225 Structural basis for recruitment and activation of the AP-1 ...	REMOVE	Summary: Physical interaction data. PMID:23415225 describes crystal structure of AP-1 core with Arf1-GTP, showing direct binding between Arf1 and the beta1 subunit N-terminus. Reason: Generic protein binding is uninformative. The paper specifically shows Arf1 binding to beta1-adaptin. The core complex assembly and Arf1 recruitment functions are better captured by the AP-1 adaptor complex CC annotation and vesicle-mediated transport BP. Supporting Evidence: PMID:23415225 The GTP-dependent switch I and II regions of Arf1 bind to the N terminus of the beta1 subunit of one AP-1 complex
GO:0005515 protein binding	IPI PMID:24189400 Perturbation of the mutated EGFR interactome identifies vuln...	REMOVE	Summary: Physical interaction with EGFR from interactome study. High-throughput data. Reason: Generic protein binding is uninformative and this appears to be from a high-throughput interactome screen. The biological relevance of EGFR-AP1B1 interaction is unclear and not well-supported by targeted studies of AP-1 function. Supporting Evidence: PMID:24189400 Perturbation of the mutated EGFR interactome identifies vulnerabilities and resistance mechanisms.
GO:0005515 protein binding	IPI PMID:24843023 Structural basis of HIV-1 Vpu-mediated BST2 antagonism via h...	REMOVE	Summary: Physical interaction data showing HIV-1 Vpu hijacks AP-1 complex. Shows interaction between viral protein and AP-1. Reason: Generic protein binding is uninformative. While the paper shows viral hijacking of AP-1, this is not a physiological function of AP1B1 and does not inform about its normal cellular role. Supporting Evidence: PMID:24843023 Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1.
GO:0005515 protein binding	IPI PMID:35384245 Physical and functional interactome atlas of human receptor ...	REMOVE	Summary: Physical interactome of receptor tyrosine kinases. High-throughput study. Reason: Generic protein binding is uninformative. High-throughput interactome data without clear biological interpretation for AP-1 function. Supporting Evidence: PMID:35384245 Physical and functional interactome atlas of human receptor tyrosine kinases.
GO:0005515 protein binding	IPI PMID:9811611 A dileucine motif in HIV-1 Nef is essential for sorting into...	REMOVE	Summary: Shows HIV-1 Nef dileucine motif binds to beta-adaptin subunit of AP-1 and AP-2 for CD4 downregulation. Reason: Generic protein binding is uninformative. While it demonstrates the dileucine motif recognition by beta-adaptin, this reflects viral exploitation of AP-1, not physiological function. The cargo-binding activity of AP-1 is better captured by its role in vesicle-mediated transport. Supporting Evidence: PMID:9811611 The dileucine-motif-containing segment of Nef bound directly and specifically to the beta-adaptin subunit of the clathrin adaptor complexes AP-1 and AP-2
GO:0008021 synaptic vesicle	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl orthology transfer from mouse. AP-1 may be present on synaptic vesicles but this is not a primary site of AP-1 function. Reason: AP-1 primarily functions at TGN and endosomes. Synaptic vesicle localization may occur but is not the core function of AP-1. This likely reflects broader expression rather than specialized synaptic function.
GO:0019901 protein kinase binding	IEA GO_REF:0000107	UNDECIDED	Summary: Ensembl orthology transfer from mouse. Evidence for protein kinase binding is limited. Reason: The evidence for protein kinase binding is indirect (orthology transfer). Without primary literature support for this specific function, cannot determine if this is a core function of AP1B1.
GO:0005794 Golgi apparatus	IDA GO_REF:0000052	MODIFY	Summary: HPA immunofluorescence data showing Golgi localization. Direct experimental evidence. Reason: The IDA evidence is valuable, but more specific localization to trans-Golgi network membrane is more accurate for AP-1 function. Proposed replacements: trans-Golgi network membrane Supporting Evidence: PMID:15377783 The crystal structure of the core of the AP-1 complex, which functions in the trans-Golgi network (TGN).
GO:0005765 lysosomal membrane	NAS PMID:23247405 Cell type-specific Rab32 and Rab38 cooperate with the ubiqui...	ACCEPT	Summary: ComplexPortal annotation based on AP-1's role in lysosome-related organelle biogenesis. PMID:23247405 discusses AP-1 function in trafficking to melanosomes and LROs. Reason: AP-1 is involved in transport to lysosomal compartments. The paper demonstrates AP-1's role in LRO biogenesis, and AP-1 mediates retrograde retrieval of M6P receptors that deliver hydrolases to lysosomes. Supporting Evidence: PMID:23247405 lysosome integral membrane proteins, such as LAMPs, reach the lysosome-limiting membrane from analogous early/recycling endosome tubules in vesicles formed by the same AP and BLOC complexes
GO:0005769 early endosome	NAS PMID:23247405 Cell type-specific Rab32 and Rab38 cooperate with the ubiqui...	ACCEPT	Summary: ComplexPortal annotation. AP-1 localizes to early/recycling endosomal tubular domains. Reason: AP-1 functions at early endosomes in addition to TGN. The paper demonstrates AP-1 localization to early/recycling endosomal tubules where cargo sorting occurs. Supporting Evidence: PMID:23247405 The localization of Rab32 and Rab38 is likely to specific tubular domains of early/recycling endosomes that contain AP-1, AP-3 or BLOC-2
GO:0016192 vesicle-mediated transport	NAS PMID:23247405 Cell type-specific Rab32 and Rab38 cooperate with the ubiqui...	ACCEPT	Summary: ComplexPortal annotation from LRO biogenesis paper. Another instance of this core function annotation. Reason: Core function. Multiple lines of evidence support vesicle-mediated transport as the primary function of AP-1. Supporting Evidence: PMID:23247405 Cell type-specific Rab32 and Rab38 cooperate with the ubiquitous lysosome biogenesis machinery to synthesize specialized lysosome-related organelles.
GO:0032588 trans-Golgi network membrane	NAS PMID:15377783 Crystal structure of the clathrin adaptor protein 1 core.	ACCEPT	Summary: ComplexPortal annotation based on AP-1 crystal structure paper showing TGN localization. Reason: Core localization. The trans-Golgi network membrane is the primary site of AP-1 function where it assembles clathrin-coated vesicles. Supporting Evidence: PMID:15377783 The crystal structure of the core of the AP-1 complex, which functions in the trans-Golgi network (TGN).
GO:0060155 platelet dense granule organization	NAS PMID:23247405 Cell type-specific Rab32 and Rab38 cooperate with the ubiqui...	KEEP AS NON CORE	Summary: ComplexPortal annotation. AP-1 is involved in biogenesis of platelet dense granules, which are lysosome-related organelles. Reason: This is a specialized function in platelet cells where AP-1 contributes to LRO biogenesis. Not a core function but valid for specialized cell types. Supporting Evidence: PMID:23247405 Hermansky-Pudlak Syndrome (HPS) patients and the corresponding animal models have abnormal melanosomes, platelet dense granules and lamellar bodies
GO:1903232 melanosome assembly	NAS PMID:23247405 Cell type-specific Rab32 and Rab38 cooperate with the ubiqui...	KEEP AS NON CORE	Summary: ComplexPortal annotation. AP-1 participates in melanosome biogenesis by trafficking tyrosinase and related enzymes. Reason: Specialized function in melanocytes. AP-1 contributes to melanosome biogenesis but this is a cell type-specific function, not the core function of the complex. Supporting Evidence: PMID:23247405 Packaging of the tyrosinases into transport vesicles at early/recycling endosome-associated tubules is dependent on ubiquitous adaptor protein complex (AP)-1 and AP-3
GO:0016192 vesicle-mediated transport	NAS PMID:27057418 Role of the epithelial cell-specific clathrin adaptor comple...	ACCEPT	Summary: ComplexPortal annotation from AP-1B review in epithelial polarity. Reason: Core function, supported by multiple references. Supporting Evidence: PMID:27057418 eCollection 2015 Apr-Jun.
GO:0032588 trans-Golgi network membrane	NAS PMID:27057418 Role of the epithelial cell-specific clathrin adaptor comple...	ACCEPT	Summary: ComplexPortal annotation from epithelial polarity review. Reason: Core localization. Consistent with other annotations and the deep research showing AP-1 functions at TGN. Supporting Evidence: PMID:27057418 Sorting takes place at one of 2 major sorting stations in the cells, the trans-Golgi network (TGN) and recycling endosomes (REs).
GO:0110010 basolateral protein secretion	NAS PMID:27057418 Role of the epithelial cell-specific clathrin adaptor comple...	KEEP AS NON CORE	Summary: ComplexPortal annotation. AP-1B (containing mu1B) mediates basolateral sorting in polarized epithelial cells. Reason: This is a specialized function of the AP-1B complex variant (with mu1B subunit) in polarized epithelial cells. While beta1 (AP1B1) is shared between AP-1A and AP-1B, basolateral sorting is not the universal function of AP-1. Supporting Evidence: PMID:27057418 AP-1B facilitates basolateral sorting from REs.
GO:0019901 protein kinase binding	ISS GO_REF:0000024	UNDECIDED	Summary: Manual transfer from mouse ortholog. Evidence for protein kinase binding. Reason: Same as the IEA annotation for this term - without primary literature demonstrating AP1B1 protein kinase binding, cannot confirm this function.
GO:0000139 Golgi membrane	TAS Reactome:R-HSA-421831	MODIFY	Summary: Reactome annotation for trans-Golgi network coat assembly pathway. Reason: Golgi membrane is accurate but less specific than trans-Golgi network membrane. The Reactome pathway specifically involves TGN. Proposed replacements: trans-Golgi network membrane
GO:0000139 Golgi membrane	TAS Reactome:R-HSA-421833	MODIFY	Summary: Reactome annotation for VAMP and AP-1 binding with cargo capture. Reason: Same as above - TGN membrane is more specific. Proposed replacements: trans-Golgi network membrane
GO:0000139 Golgi membrane	TAS Reactome:R-HSA-421835	MODIFY	Summary: Reactome annotation for TGN vesicle scission. Reason: TGN membrane is more specific. Proposed replacements: trans-Golgi network membrane
GO:0000139 Golgi membrane	TAS Reactome:R-HSA-432706	MODIFY	Summary: Reactome annotation for lysosome vesicle destined coat assembly. Reason: TGN membrane is more specific. Proposed replacements: trans-Golgi network membrane
GO:0000139 Golgi membrane	TAS Reactome:R-HSA-432707	MODIFY	Summary: Reactome annotation for lysosomal vesicle scission. Reason: TGN membrane is more specific. Proposed replacements: trans-Golgi network membrane
GO:0000139 Golgi membrane	TAS Reactome:R-HSA-432712	MODIFY	Summary: Reactome annotation for VAMP and AP-1 binding on lysosome destined membrane. Reason: TGN membrane is more specific. Proposed replacements: trans-Golgi network membrane
GO:0005765 lysosomal membrane	TAS Reactome:R-HSA-432688	ACCEPT	Summary: Reactome annotation for TGN-derived lysosomal vesicle uncoating, indicating AP-1 reaches lysosomal membrane during vesicle delivery. Reason: AP-1 coated vesicles deliver cargo to lysosomes, and during vesicle uncoating the complex transiently associates with lysosomal membrane before recycling.
GO:0005765 lysosomal membrane	TAS Reactome:R-HSA-432707	ACCEPT	Summary: Reactome annotation for lysosomal vesicle scission. Reason: Same as above - valid localization during AP-1-mediated transport to lysosomes.
GO:0005829 cytosol	TAS Reactome:R-HSA-182263	ACCEPT	Summary: Reactome annotation. AP-1 complex cycles between cytosol and membranes. Reason: AP-1 is recruited from cytosol to membranes in an Arf1-GTP dependent manner. Cytosolic localization is valid as part of the AP-1 cycle. Supporting Evidence: PMID:23415225 AP-1 recruitment to these compartments requires Arf1-GTP.
GO:0005829 cytosol	TAS Reactome:R-HSA-182279	ACCEPT	Summary: Reactome annotation for MHC I:Nef:AP-1:PACS-1 complex formation. Reason: Valid - AP-1 cycles through cytosol.
GO:0005829 cytosol	TAS Reactome:R-HSA-182286	ACCEPT	Summary: Reactome annotation for transport of MHC I:Nef:AP-1:PACS-1 complex. Reason: Valid - AP-1 cycles through cytosol.
GO:0005829 cytosol	TAS Reactome:R-HSA-2130619	ACCEPT	Summary: Reactome annotation for TGN-lysosomal vesicle coat assembly. Reason: Valid - AP-1 is recruited from cytosol during coat assembly.
GO:0005829 cytosol	TAS Reactome:R-HSA-2213236	ACCEPT	Summary: Reactome annotation for vesicle uncoating and release of complex. Reason: Valid - AP-1 returns to cytosol after vesicle uncoating.
GO:0005829 cytosol	TAS Reactome:R-HSA-421833	ACCEPT	Summary: Reactome annotation. Reason: Valid - part of AP-1 cycling.
GO:0005829 cytosol	TAS Reactome:R-HSA-421836	ACCEPT	Summary: Reactome annotation for TGN vesicle uncoating. Reason: Valid - AP-1 returns to cytosol after uncoating.
GO:0005829 cytosol	TAS Reactome:R-HSA-432688	ACCEPT	Summary: Reactome annotation for lysosomal vesicle uncoating. Reason: Valid - AP-1 returns to cytosol.
GO:0005829 cytosol	TAS Reactome:R-HSA-432712	ACCEPT	Summary: Reactome annotation. Reason: Valid - part of AP-1 cycling.
GO:0005829 cytosol	TAS Reactome:R-HSA-8951498	ACCEPT	Summary: Reactome annotation for dissociation of Arf1:GDP, AP-1 clathrin coated complex. Reason: Valid - AP-1 returns to cytosol upon coat disassembly.
GO:0030659 cytoplasmic vesicle membrane	TAS Reactome:R-HSA-421835	ACCEPT	Summary: Reactome annotation for TGN vesicle scission, indicating AP-1 on nascent vesicle. Reason: Valid - AP-1 is present on budding and nascent vesicle membranes before uncoating.
GO:0030659 cytoplasmic vesicle membrane	TAS Reactome:R-HSA-421836	ACCEPT	Summary: Reactome annotation for TGN vesicle uncoating. Reason: Valid - AP-1 coats vesicle membranes.
GO:0032588 trans-Golgi network membrane	TAS Reactome:R-HSA-2130641	ACCEPT	Summary: Reactome annotation for TGN-lysosome vesicle translocation. Reason: Core localization. TGN membrane is the primary site of AP-1 function.
GO:0032588 trans-Golgi network membrane	TAS Reactome:R-HSA-2213236	ACCEPT	Summary: Reactome annotation. Reason: Core localization.
GO:0032588 trans-Golgi network membrane	TAS Reactome:R-HSA-5333658	ACCEPT	Summary: Reactome annotation for clathrin:AP1:CLVS binding PI(3,5)P2. Reason: Core localization.
GO:0032588 trans-Golgi network membrane	TAS Reactome:R-HSA-8951498	ACCEPT	Summary: Reactome annotation for dissociation of Arf1:GDP, AP-1 complex. Reason: Core localization.
GO:0005515 protein binding	IPI PMID:9733768 Identification and characterization of novel clathrin adapto...	REMOVE	Summary: UniProt annotation. Paper identifies gamma2-adaptin and shows it does NOT interact with beta1-adaptin, unlike gamma1-adaptin which does interact with beta1. Reason: Generic protein binding is uninformative. The paper actually shows that gamma2 does NOT bind beta1, while gamma1 does. This normal complex assembly is better captured by the GO:0030121 (AP-1 adaptor complex) annotation which implies subunit interactions. Supporting Evidence: PMID:9733768 gamma2-adaptin is capable of interacting not only with the sigma1 chain... but also with a novel sigma1-like protein... and that, unlike gamma1-adaptin, it is unable to interact with beta1-adaptin
GO:0030121 AP-1 adaptor complex	IDA PMID:15377783 Crystal structure of the clathrin adaptor protein 1 core.	NEW	Summary: Crystal structure of AP-1 core shows beta1 as integral subunit of the heterotetrameric AP-1 complex. This is the most specific cellular component annotation for AP1B1. Reason: This is the most appropriate CC term for AP1B1. The beta1 subunit is a core component of the AP-1 adaptor complex, and the crystal structure definitively establishes this. UniProt DR line also references ComplexPortal entries for AP-1. Supporting Evidence: PMID:15377783 The AP-1 core comprises N-terminal fragments of the two large chains, beta1 and gamma, and the intact medium and small chains, micro1 and sigma1. UniProt:Q10567 Adaptor protein complex 1 (AP-1) is a heterotetramer composed of two large adaptins (gamma-type subunit AP1G1 and beta-type subunit AP1B1), a medium adaptin (mu-type subunit AP1M1 or AP1M2) and a small adaptin (sigma-type subunit AP1S1 or AP1S2 or AP1S3).
GO:0005543 phospholipid binding	NAS	NEW	Summary: Added to align core_functions with existing annotations. Reason: Core function term not present in existing_annotations. Supporting Evidence: file:human/AP1B1/AP1B1-deep-research-cyberian.md Current evidence supports a model in which AP-1 functions primarily in retrograde trafficking, retrieving proteins from post-Golgi compartments back to the TGN. file:human/AP1B1/AP1B1-deep-research-cyberian.md MPR46 fails to recycle from endosomes back to the TGN, providing direct evidence that AP-1 is required for retrograde receptor transport PMID:23415225 The GTP-dependent switch I and II regions of Arf1 bind to the N terminus of the beta1 subunit of one AP-1 complex

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