NUBPL

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005739 mitochondrion	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Phylogenetic (IBA) localization to mitochondrion. Correct but generic relative to the experimentally supported and more specific mitochondrial matrix localization. Reason: NUBPL is experimentally localized to mitochondrion (IDA, PMID:19752196) and more specifically to the mitochondrial matrix (Reactome TAS, ARBA IEA), consistent with a matrix-soluble assembly factor. The broad IBA "mitochondrion" call is superseded by the specific matrix annotation and is not treated as a distinct core localization. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: GRANULARITY MISMATCH Supporting Evidence: file:human/NUBPL/NUBPL-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion
GO:0032981 mitochondrial respiratory chain complex I assembly	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment of the core biological process. This matches the experimentally established role of NUBPL/IND1 as an assembly factor critically required for respiratory Complex I. Reason: Independently supported by experimental IMP evidence (PMID:19752196), where huInd1 knockdown strongly decreased Complex I protein and activity. This is a core function. Supporting Evidence: PMID:19752196 huInd1, that is critically required for the assembly of complex I
GO:0016226 iron-sulfur cluster assembly	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment of iron-sulfur cluster assembly. NUBPL binds a [4Fe-4S] cluster and delivers Fe-S cofactor(s) to Complex I subunits, so it participates in the Fe-S maturation of the Complex I assembly pathway. Reason: Consistent with the family (Mrp/NBP35 Fe-S carrier proteins) and with the experimentally demonstrated Fe-S delivery role toward Complex I (PMID:19752196). This is a core function, complementary to Complex I assembly. Supporting Evidence: PMID:19752196 a possible role in the delivery of one or more Fe/S clusters to complex I subunits
GO:0051539 4 iron, 4 sulfur cluster binding	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment of [4Fe-4S] cluster binding, the core molecular function. NUBPL binds one [4Fe-4S] cluster via a conserved CXXC motif. Reason: Directly and independently supported by experimental IDA (PMID:19752196) and by the UniProt COFACTOR annotation ("Binds 1 [4Fe-4S] cluster"). This is a genuine, core MF. Supporting Evidence: file:human/NUBPL/NUBPL-uniprot.txt Note=Binds 1 [4Fe-4S] cluster.
GO:0005524 ATP binding	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro/keyword-based ATP binding. NUBPL is a Mrp/NBP35 P-loop NTPase with a Walker-A/P-loop motif and an annotated ATP-binding site (residues 75-82). Reason: The ATP-binding P-loop is a real, conserved feature of the family, but nucleotide binding is ancillary to NUBPL's defining function (Fe-S cluster binding and delivery to Complex I). No experimental characterization of ATP hydrolysis by human NUBPL is available, so it is retained as a non-core feature-based annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: GRANULARITY MISMATCH Supporting Evidence: file:human/NUBPL/NUBPL-uniprot.txt /ligand="ATP"
GO:0005739 mitochondrion	IEA GO_REF:0000044	MARK AS OVER ANNOTATED	Summary: UniProt Subcellular Location keyword mapping to mitochondrion. Correct but generic relative to the specific mitochondrial matrix localization. Reason: Duplicates the experimentally supported mitochondrion localization at a broad granularity; the matrix-specific annotation is preferred as the core localization. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: GRANULARITY MISMATCH Supporting Evidence: file:human/NUBPL/NUBPL-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion
GO:0005759 mitochondrial matrix	IEA GO_REF:0000117	ACCEPT	Summary: ARBA machine-learning assignment to mitochondrial matrix. Consistent with a matrix-soluble assembly factor that acts on the peripheral (matrix) arm of Complex I and with the Reactome TAS matrix annotations. Reason: NUBPL is a soluble mitochondrial protein imported via a cleavable transit peptide, and its Complex I substrate subunits (NDUFS1, NDUFV1) mature in the matrix. The matrix is the most specific well-supported localization. Propagation Review Root cause: NO FAILURE CORE Supporting Evidence: file:human/NUBPL/NUBPL-uniprot.txt TRANSIT 1..38
GO:0016226 iron-sulfur cluster assembly	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based iron-sulfur cluster assembly, redundant with the IBA assignment of the same term. Core biological process for this Fe-S carrier protein. Reason: Same conclusion as the IBA annotation of GO:0016226; supported by the [4Fe-4S] binding and delivery role toward Complex I. Propagation Review Root cause: NO FAILURE CORE Supporting Evidence: PMID:19752196 a possible role in the delivery of one or more Fe/S clusters to complex I subunits
GO:0032981 mitochondrial respiratory chain complex I assembly	IEA GO_REF:0000117	ACCEPT	Summary: ARBA machine-learning assignment of Complex I assembly, redundant with the IBA and IMP annotations of the same term. Core biological process. Reason: Same core conclusion as the experimental IMP (PMID:19752196) and IBA annotations. Propagation Review Root cause: NO FAILURE CORE Supporting Evidence: PMID:19752196 huInd1, that is critically required for the assembly of complex I
GO:0051536 iron-sulfur cluster binding	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: InterPro-based generic iron-sulfur cluster binding. This is the parent of the specific [4Fe-4S] cluster binding (GO:0051539) that is experimentally supported. Reason: NUBPL binds specifically a [4Fe-4S] cluster (UniProt COFACTOR; IDA PMID:19752196), which is captured by the more precise GO:0051539. The broad parent term is uninformative and redundant relative to the specific child. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: GRANULARITY MISMATCH Supporting Evidence: file:human/NUBPL/NUBPL-uniprot.txt Note=Binds 1 [4Fe-4S] cluster.
GO:0140663 ATP-dependent FeS chaperone activity	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based ATP-dependent FeS chaperone activity, defined as "binding to and delivering metal ions to a target protein, driven by ATP hydrolysis." This is the most specific molecular-function term for NUBPL's role as an Fe-S carrier that delivers its [4Fe-4S] cluster to Complex I subunits. Reason: Matches the experimentally supported function: NUBPL binds a [4Fe-4S] cluster and delivers Fe-S cofactor(s) to Complex I subunits (PMID:19752196), and belongs to the ATP-binding Mrp/NBP35 carrier family. This captures the carrier/delivery molecular activity better than bare Fe-S binding and is retained as core. Propagation Review Root cause: NO FAILURE CORE Supporting Evidence: PMID:19752196 a possible role in the delivery of one or more Fe/S clusters to complex I subunits
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" from the HuRI binary (Y2H) interactome, capturing NUBPL interactions with NUBP2 (Q9Y5Y2) and a KDM8/JMJD5 isoform (Q8N371-3). Uninformative as a molecular function. Reason: GO:0005515 conveys no specific function. The high-throughput binary interactions do not establish a defined mitochondrial molecular activity for NUBPL; per policy an experimental IPI is retained but flagged as over-annotated rather than removed. Supporting Evidence: file:human/NUBPL/NUBPL-uniprot.txt Q8TB37; Q9Y5Y2: NUBP2; NbExp=6
GO:0005739 mitochondrion	IDA GO_REF:0000052	ACCEPT	Summary: Immunofluorescence-based (HPA, IDA) localization to mitochondrion. Directly supports mitochondrial localization of NUBPL. Reason: Experimental (IDA) mitochondrial localization consistent with the UniProt subcellular location and the more specific matrix annotations. Retained; the matrix term is the finer-grained core localization. Supporting Evidence: file:human/NUBPL/NUBPL-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	KEEP AS NON CORE	Summary: High-throughput (HTP) mitochondrial-proteome localization to mitochondrion from a quantitative high-confidence human mitochondrial proteome study. Reason: Corroborating high-throughput evidence for mitochondrial localization; consistent with the IDA annotations but non-core relative to the specific matrix localization. Supporting Evidence: file:human/NUBPL/NUBPL-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-5690023	ACCEPT	Summary: Reactome TAS placing NUBPL in the mitochondrial matrix, in the reaction where NUBPL binds the [4Fe-4S] cluster. Consistent with a matrix-soluble assembly factor. Reason: Mitochondrial matrix is the specific, well-supported localization for this soluble assembly factor whose Complex I substrate subunits mature in the matrix. Supporting Evidence: file:human/NUBPL/NUBPL-uniprot.txt TRANSIT 1..38
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-6788523	ACCEPT	Summary: Reactome TAS matrix localization from the reaction "NUBPL transfers 4Fe-4S to Complex I subunits." Duplicate of the same matrix localization. Reason: Same well-supported matrix localization; consistent with NUBPL's Fe-S delivery role. Supporting Evidence: file:human/NUBPL/NUBPL-uniprot.txt TRANSIT 1..38
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-6788556	ACCEPT	Summary: Reactome TAS matrix localization from the reaction "NUBPL transfers 4Fe-4S to NDUFV1, V2." Duplicate of the same matrix localization. Reason: Same well-supported matrix localization; consistent with NUBPL's Fe-S delivery role. Supporting Evidence: file:human/NUBPL/NUBPL-uniprot.txt TRANSIT 1..38
GO:0005739 mitochondrion	IDA PMID:19752196 Human ind1, an iron-sulfur cluster assembly factor for respi...	ACCEPT	Summary: Experimental (IDA) mitochondrial localization from the primary characterization of huInd1 (Sheftel et al. 2009), which established the subcellular location of NUBPL. Reason: This is the source experimental IDA underlying the UniProt "Mitochondrion" subcellular location (ECO:0000269\|PubMed:19752196). Core mitochondrial localization. Supporting Evidence: file:human/NUBPL/NUBPL-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269\|PubMed:19752196}
GO:0007005 mitochondrion organization	IMP PMID:19752196 Human ind1, an iron-sulfur cluster assembly factor for respi...	KEEP AS NON CORE	Summary: IMP annotation based on the altered mitochondrial morphology observed upon huInd1 knockdown. This is a downstream, pleiotropic consequence of loss of Complex I rather than a direct core function of NUBPL. Reason: NUBPL's direct role is Fe-S cluster binding and delivery for Complex I assembly; the "alteration of mitochondrial morphology" reported on knockdown is a secondary effect of respiratory-chain dysfunction, so this BP is retained as non-core rather than a defining function. Supporting Evidence: PMID:19752196 remodeling of respiratory supercomplexes, and alteration of mitochondrial morphology
GO:0032981 mitochondrial respiratory chain complex I assembly	IMP PMID:19752196 Human ind1, an iron-sulfur cluster assembly factor for respi...	ACCEPT	Summary: Experimental (IMP) evidence that NUBPL/huInd1 is required for Complex I assembly: RNAi knockdown caused strong decreases in Complex I protein and activity. This is a core biological process. Reason: This IMP is the primary experimental basis for NUBPL's function as a Complex I assembly factor and underlies the disease association (MC1DN21). Supporting Evidence: PMID:19752196 Knockdown of huInd1 in HeLa cells by RNA interference technology led to strong decreases in complex I protein and activity levels
GO:0051539 4 iron, 4 sulfur cluster binding	IDA PMID:19752196 Human ind1, an iron-sulfur cluster assembly factor for respi...	ACCEPT	Summary: Experimental (IDA) evidence that NUBPL/huInd1 binds an Fe-S cluster via a conserved CXXC motif. This is the core molecular function, matching the UniProt COFACTOR annotation of one [4Fe-4S] cluster. Reason: Directly demonstrated cofactor binding; the CXXC-motif cysteines (Cys-244/Cys-247) are required for Complex I assembly, tying the [4Fe-4S] binding to function. Supporting Evidence: PMID:19752196 huInd1 can bind an Fe/S cluster via a conserved CXXC motif in a labile fashion

Gene Description

Existing Annotations Review

Core Functions

Binds a single [4Fe-4S] cluster via a conserved CXXC motif and acts as an ATP-binding Mrp/NBP35-family Fe-S carrier that delivers Fe-S cofactor(s) to respiratory Complex I subunits during their maturation in the mitochondrial matrix.

Binds a [4Fe-4S] iron-sulfur cluster, the cofactor that NUBPL carries and transfers; the cluster is coordinated by a conserved CXXC motif (Cys-244/Cys-247) required for Complex I assembly.

References

📚 Additional Documentation

Notes

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