AZIN1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0009446 putrescine biosynthetic process	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Phylogenetic (IBA) propagation from the ornithine/arginine decarboxylase family. AZIN1 is a catalytically dead ODC paralog and does not itself synthesize putrescine; it promotes polyamine synthesis only indirectly by protecting active ODC1 from antizyme. This is a fold-based over-annotation of a direct biosynthetic role. Reason: AZIN1 lacks ornithine/arginine decarboxylase catalytic activity, so it cannot directly catalyze putrescine biosynthesis; the term is propagated from catalytically active family members. AZIN1's genuine BP role is regulatory (positive regulation of polyamine synthesis via antizyme sequestration), captured better by GO:0010967. Propagation Review Root cause: PROPAGATION BAD Failure modes: PSEUDO OR SUBACTIVITY LOSS FUNCTIONAL DIVERGENCE Supporting Evidence: file:human/AZIN1/AZIN1-uniprot.txt AZI is an enzymatically inactive ODC homolog that counteracts the negative effect
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: Cytoplasmic localization is consistent with AZIN1's role in polyamine metabolism, where the ODC/antizyme/antizyme-inhibitor machinery operates. Supported phylogenetically (IBA) and by the biology of the pathway.
GO:0004586 ornithine decarboxylase activity	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Over-annotation. The defining feature of AZIN1 is that it is a catalytically INACTIVE ODC homolog: it retains the ODC fold but does not decarboxylate ornithine. This ODC-activity term is propagated by phylogeny from the catalytically active ODC family and must not be assigned to AZIN1 as a function. Reason: AZIN1 lacks ornithine decarboxylase catalytic activity; assigning GO:0004586 contradicts its well-established status as an enzymatically inactive ODC paralog / antizyme inhibitor. Propagation Review Root cause: PROPAGATION BAD Failure modes: PSEUDO OR SUBACTIVITY LOSS FUNCTIONAL DIVERGENCE Supporting Evidence: file:human/AZIN1/AZIN1-uniprot.txt AZI is an enzymatically inactive ODC homolog that counteracts the negative effect
GO:0042177 negative regulation of protein catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: AZIN1 inhibits antizyme-dependent (proteasomal) degradation of ODC1 by sequestering antizymes, so negative regulation of protein catabolic process is a correct core BP role. Supported phylogenetically and by experimental IDA (see PMID:17900240 annotation below). Supporting Evidence: file:human/AZIN1/AZIN1-uniprot.txt Inhibits antizyme-dependent ODC degradation and releases ODC monomers
GO:0042978 ornithine decarboxylase activator activity	IBA GO_REF:0000033	ACCEPT	Summary: Core molecular function. GO:0042978 is defined as "Binds to and increases ornithine decarboxylase activity", which precisely captures AZIN1's mechanism: it binds ODC antizymes, sequestering them and releasing active ODC1, thereby increasing ODC activity without any catalytic activity of its own. Well supported by phylogeny and experiment. Supporting Evidence: file:human/AZIN1/AZIN1-uniprot.txt Antizyme inhibitor (AZI) protein that positively regulates
GO:1902269 positive regulation of polyamine transmembrane transport	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Polyamine uptake stimulation via antizyme counteraction is best characterized for the paralog AZIN2 (PMID:18508777). By phylogeny AZIN1 may share this activity, but for human AZIN1 it is a peripheral, less-established role rather than a core function. Retain as non-core. Reason: AZIN1's dominant and well-documented role is ODC activation and stabilization; the effect on polyamine transmembrane transport is derived largely from AZIN2 studies and is secondary.
GO:0003824 catalytic activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: InterPro2GO (IEA) propagation of generic catalytic activity from the decarboxylase-family domain signatures (IPR000183/IPR009006/IPR022644). AZIN1 is a catalytically dead ODC paralog with no known enzymatic activity, so this is an over-annotation from fold homology. Reason: AZIN1 has lost catalytic activity; the InterPro domains that trigger this mapping are shared with active decarboxylases but AZIN1 does not catalyze a reaction. Supporting Evidence: file:human/AZIN1/AZIN1-uniprot.txt AZI is an enzymatically inactive ODC homolog that counteracts the negative effect
GO:0005634 nucleus	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Nuclear localization is asserted by automated IEA methods and mirrors the mouse-ortholog (O35484)-derived ISS annotation and the UniProt SUBCELLULAR LOCATION statement. Plausible but based on similarity/electronic inference rather than direct human evidence; retain as non-core. Reason: Nuclear localization for human AZIN1 rests on cross-species similarity and automated pipelines, not direct experimental data; AZIN1's characterized action is cytoplasmic.
GO:0006596 polyamine biosynthetic process	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: InterPro2GO (IEA) propagation from IPR002433 (ornithine decarboxylase signature). AZIN1 does not directly biosynthesize polyamines; it promotes polyamine synthesis only indirectly by stabilizing active ODC1. The direct biosynthetic term is a fold-based over-annotation. Reason: As a catalytically inactive paralog, AZIN1 has no direct role in polyamine biosynthesis; its contribution is regulatory and indirect (better captured by GO:0010967 regulation of polyamine biosynthetic process). Supporting Evidence: file:human/AZIN1/AZIN1-uniprot.txt AZI is an enzymatically inactive ODC homolog that counteracts the negative effect
GO:0042978 ornithine decarboxylase activator activity	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO (IEA) assignment of ODC activator activity from the AZIN1-specific signature IPR031178 ("Azin1"). This correctly captures AZIN1's core molecular function (binds antizyme, increases ODC activity) and agrees with the experimental IDA and phylogenetic annotations. Supporting Evidence: file:human/AZIN1/AZIN1-uniprot.txt Antizyme inhibitor (AZI) protein that positively regulates
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" IPI from a large-scale interactome map (Rolland et al.), with the interactor recorded as OAZ3 (Q9UMX2). The binding partner is biologically meaningful (antizyme binding underlies AZIN1's function), but the bare GO:0005515 term is uninformative and the interaction is from high-throughput data not discussed in the text. Reason: "Protein binding" conveys no specific function; AZIN1's antizyme-binding role is captured informatively by GO:0042978. Per policy, over-annotated rather than removed.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" IPI from the BioPlex protein-community interactome (Huttlin et al.), interactor OAZ3 (Q9UMX2). Corroborates antizyme binding but the term is uninformative. Reason: Non-specific binding term from high-throughput AP-MS data; AZIN1's functional binding (antizyme) is better represented by GO:0042978.
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" IPI from a variant-interactome study (Fragoza et al.), interactor OAZ3 (Q9UMX2). Again supports antizyme binding but the GO:0005515 term is uninformative. Reason: Non-specific binding term; the meaningful antizyme-binding function is captured by GO:0042978.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" IPI from the HuRI reference binary interactome (Luck et al.). This dataset records AZIN1 interactions with BMAL1 (O00327-8) and OAZ3 (Q9UMX2-2). The OAZ3 interaction supports antizyme binding; BMAL1 is a two-hybrid hit of unclear physiological significance. The bare term is uninformative. Reason: "Protein binding" is non-specific; the biologically meaningful antizyme interaction is captured by GO:0042978, and the BMAL1 hit is unvalidated high-throughput data.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" IPI from BioPlex 3.0 (Huttlin et al.), interactor OAZ3 (Q9UMX2). Consistent with antizyme binding but uninformative as a bare term. Reason: Non-specific binding term from high-throughput data; antizyme-binding function is captured by GO:0042978.
GO:1902269 positive regulation of polyamine transmembrane transport	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Automated Ensembl-Compara transfer (IEA) from the mouse ortholog (O35484) of the polyamine-uptake role. As with the IDA/IBA versions, this is best characterized for AZIN2 and is a peripheral role for human AZIN1; retain as non-core. Reason: Electronic orthology transfer of a secondary, largely AZIN2-derived phenotype; not a core AZIN1 function.
GO:0005634 nucleus	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sequence-similarity (ISS) transfer of nuclear localization from the mouse ortholog O35484, matching the UniProt SUBCELLULAR LOCATION "Nucleus {ECO:0000250\|UniProtKB:O35484}". Plausible by similarity; not a core, directly-demonstrated human localization. Reason: Nuclear localization is inferred from the mouse ortholog by similarity, not shown directly for human AZIN1; the characterized site of action is cytoplasmic. Supporting Evidence: file:human/AZIN1/AZIN1-uniprot.txt Nucleus {ECO:0000250\|UniProtKB:O35484}
GO:0005634 nucleus	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Duplicate ISS nucleus annotation (older date) from the same mouse ortholog (O35484) similarity transfer. Same assessment as the other ISS nucleus annotation: plausible by similarity, non-core. Reason: Redundant ISS nuclear-localization transfer from the mouse ortholog; retained as non-core. Supporting Evidence: file:human/AZIN1/AZIN1-uniprot.txt Nucleus {ECO:0000250\|UniProtKB:O35484}
GO:1902269 positive regulation of polyamine transmembrane transport	IDA PMID:18508777 Antizyme inhibitor 2 (AZIN2/ODCp) stimulates polyamine uptak...	KEEP AS NON CORE	Summary: Experimental IDA. The cited paper (López-Contreras et al. 2008) is about the paralog AZIN2/ODCp: it shows AZIN2 transfection markedly stimulates polyamine uptake and counteracts antizymes. The abstract is unambiguously about AZIN2, not AZIN1 (cache is abstract-only, full_text_available: false). The polyamine-uptake role is therefore primarily an AZIN2 finding; for AZIN1 it is at best a peripheral, non-core role. Per policy, an experimental annotation is not removed; retained as non-core with the citation flagged. Reason: The supporting reference characterizes AZIN2, not AZIN1; polyamine transport stimulation is not a core, AZIN1-specific function. Kept (not removed) as it is an experimental annotation. Supporting Evidence: PMID:18508777 Transfection of COS7 cells with mouse or human AZIN2, a novel member of the antizyme inhibitor family, recently characterized by our group, markedly stimulated polyamine uptake
GO:0042177 negative regulation of protein catabolic process	IDA PMID:17900240 Human ornithine decarboxylase paralogue (ODCp) is an antizym...	ACCEPT	Summary: Experimental IDA for inhibition of antizyme-dependent ODC degradation. The cached abstract (Kanerva et al. 2008) foregrounds the paralog ODCp/AZIN2 ("ODCp inhibits AZ1 function ... and ODC degradation"), and the cache is abstract-only. The function - blocking antizyme-mediated ODC proteolysis - is nonetheless a bona fide core role of AZIN1 (UniProt cites this same paper for AZIN1's FUNCTION), so the annotation is biologically correct. Accept, with a note that the primary experimental subject in the abstract is AZIN2. Supporting Evidence: file:human/AZIN1/AZIN1-uniprot.txt Inhibits antizyme-dependent ODC degradation and releases ODC monomers
GO:0042978 ornithine decarboxylase activator activity	IDA PMID:17900240 Human ornithine decarboxylase paralogue (ODCp) is an antizym...	ACCEPT	Summary: Experimental IDA for the core molecular function - counteracting antizyme to increase ODC activity (GO:0042978, "Binds to and increases ornithine decarboxylase activity"). The cached abstract characterizes ODCp/AZIN2 as an antizyme inhibitor that rescues ODC activity; UniProt cites this same reference for AZIN1's antizyme-inhibitor FUNCTION. The activity is the defining, correct core function of AZIN1. Accept. Supporting Evidence: file:human/AZIN1/AZIN1-uniprot.txt Antizyme inhibitor (AZI) protein that positively regulates PMID:17900240 ODCp inhibits AZ1 function as efficiently as AZI both in vitro and in vivo
GO:0010967 regulation of polyamine biosynthetic process	IC file:human/AZIN1/AZIN1-uniprot.txt	NEW	Summary: Proposed new (regulatory) BP annotation. By sequestering antizymes and stabilizing active ODC1, AZIN1 positively regulates polyamine biosynthesis. This is AZIN1's genuine, indirect role in polyamine synthesis, replacing the fold-propagated direct biosynthetic terms (GO:0009446, GO:0006596) that were marked over-annotated. Supporting Evidence: file:human/AZIN1/AZIN1-uniprot.txt restoring polyamine production
GO:0010509 intracellular polyamine homeostasis	IC file:human/AZIN1/AZIN1-uniprot.txt	NEW	Summary: Proposed new higher-level BP annotation. AZIN1 participates in maintaining intracellular polyamine homeostasis by counteracting antizyme-mediated down-regulation of ODC, the rate-limiting enzyme of polyamine biosynthesis. Supporting Evidence: file:human/AZIN1/AZIN1-uniprot.txt positively regulates ornithine decarboxylase (ODC) activity and polyamine uptake

Gene Description

Existing Annotations Review

Core Functions

References

📚 Additional Documentation

Notes

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