NT5C1A encodes cytosolic 5'-nucleotidase 1A (cN-IA; also cN-I / cN1A), a Mg2+-dependent cytosolic enzyme of the 5'-nucleotidase type 3 (haloacid dehalogenase-like phosphatase) family. It catalyzes hydrolysis of ribonucleoside and deoxyribonucleoside 5'-monophosphates to the corresponding nucleoside plus inorganic phosphate. It is AMP-preferring (AMP is the major substrate) but also hydrolyzes dCMP and IMP, and its activity is allosterically stimulated by ADP. By dephosphorylating AMP to adenosine, cN-IA is a principal intracellular source of adenosine during nucleotide (ATP) breakdown, a role that is physiologically prominent in skeletal muscle and in heart, where it can account for adenosine formation during ischemia. The protein is highly expressed in skeletal muscle and at intermediate levels in heart, brain, kidney and pancreas. cN-IA is also a well-known autoantigen: circulating anti-cN1A (anti-NT5C1A) autoantibodies are a serological marker of sporadic inclusion body myositis and related inflammatory myopathies.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0008253 5'-nucleotidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically-inferred 5'-nucleotidase activity. This is the core, experimentally established molecular function of cN-IA and is well supported by direct assays of the human enzyme. Supporting Evidence: file:human/NT5C1A/NT5C1A-uniprot.txt AMP is the major substrate but can |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically-inferred cytosolic location, consistent with the experimentally supported cytoplasmic/cytosolic localization of this soluble enzyme. Core cellular component. Supporting Evidence: file:human/NT5C1A/NT5C1A-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:7599155}. |
| GO:0046085 adenosine metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: cN-IA dephosphorylates AMP to adenosine, making it a direct participant in adenosine metabolism. Accepted as a core biological process. Supporting Evidence: PMID:34814800 preferentially converting adenosine monophosphate to adenosine. |
| GO:0000166 nucleotide binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Generic InterPro/keyword-derived nucleotide-binding term. It is not incorrect (the enzyme binds nucleotide monophosphate substrates), but it is uninformative relative to the specific catalytic activity captured by GO:0008253. Retained as non-core. |
| GO:0000287 magnesium ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: Magnesium is a genuine, experimentally demonstrated cofactor of cN-IA. This IEA is redundant with the IDA (PMID:8967393) but is a correct feature of the enzyme. Supporting Evidence: file:human/NT5C1A/NT5C1A-uniprot.txt Name=Mg(2+); Xref=ChEBI:CHEBI:18420; |
| GO:0002953 5'-deoxynucleotidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: 5'-deoxynucleotidase (dNMP hydrolase) activity, mapped from EC/Rhea. This is a real, measured activity of cN-IA (it hydrolyzes dCMP), so the electronic assignment is correct and consistent with the EXP annotation from PMID:11133996. Supporting Evidence: PMID:11133996 The recombinant cN-I showed high affinity toward dCMP and |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Cytoplasmic localization inferred electronically from InterPro/UniProt-SubCell. Correct and consistent with experimental and phylogenetic evidence; a somewhat less precise sibling of the cytosol annotation. Supporting Evidence: file:human/NT5C1A/NT5C1A-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:7599155}. |
| GO:0008253 5'-nucleotidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (EC/Rhea-mapped) assignment of the core 5'-nucleotidase activity. Correct and redundant with the direct experimental annotations. Supporting Evidence: file:human/NT5C1A/NT5C1A-uniprot.txt AMP is the major substrate but can |
| GO:0009117 nucleotide metabolic process | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Broad InterPro-derived process term. Correct but general; the specific catabolic processes (AMP catabolic process, adenosine metabolic process) are the more informative annotations. Retained as non-core. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from a proteome-scale binary interactome screen (interactor NTAQ1, Q96HA8). High-throughput Y2H with no gene-specific functional interpretation for NT5C1A and no informative molecular function. Over-annotated for core-function purposes. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from a systematic SNV-interaction perturbation screen (interactor NTAQ1, Q96HA8). Uninformative high-throughput interaction; no specific function is implied for NT5C1A. |
| 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 reference binary interactome (interactors CDC37, Q16543; and NTAQ1, Q96HA8). Systematic mapping with no functional characterization; over-annotated relative to the enzyme's core catalytic role. |
| GO:0046085 adenosine metabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: Adenosine metabolic process transferred electronically from a rat ortholog via Ensembl Compara. Consistent with the enzyme's role in generating adenosine from AMP; correct core process. Supporting Evidence: PMID:34814800 preferentially converting adenosine monophosphate to adenosine. |
| GO:0002953 5'-deoxynucleotidase activity | EXP PMID:11133996 Human cytosolic 5'-nucleotidase I: characterization and role... | ACCEPT | Summary: Direct experimental (recombinant enzyme) demonstration of dNMP/dCMP hydrolysis. cN-IA showed high affinity toward dCMP, confirming genuine 5'-deoxynucleotidase activity. Supporting Evidence: PMID:11133996 The recombinant cN-I showed high affinity toward dCMP and |
| GO:0008253 5'-nucleotidase activity | EXP PMID:7599155 Kinetics of adenylate metabolism in human and rat myocardium... | ACCEPT | Summary: Experimental assay of AMP- and IMP-specific 5'-nucleotidase activity in human (and rat) myocardium. Directly supports the core 5'-nucleotidase molecular function. Supporting Evidence: PMID:7599155 AMP- and IMP-specific 5'-nucleotidases, adenosine |
| GO:0000287 magnesium ion binding | IDA PMID:8967393 Soluble forms of 5'-nucleotidase in rat and human heart. | ACCEPT | Summary: Mg2+ dependence of the human heart cytosolic 5'-nucleotidase was determined experimentally; Mg2+ is the required cofactor. Accepted. Supporting Evidence: file:human/NT5C1A/NT5C1A-uniprot.txt Name=Mg(2+); Xref=ChEBI:CHEBI:18420; |
| GO:0005737 cytoplasm | TAS PMID:599155 Regulation of the fatty acid composition of alkyl ether phos... | UNDECIDED | Summary: The cited PMID:599155 is a 1977 J Biochem paper on Ehrlich-ascites acyltransferases (Waku & Nakazawa), unrelated to NT5C1A. This is a transcription error for PMID:7599155 (Tavenier 1995, "Kinetics of adenylate metabolism in human and rat myocardium"), which UniProt cites for the cytoplasmic location call (ECO:0000305|PubMed:7599155). The cytoplasmic localization itself is correct, but the identifier is wrong, so this annotation instance cannot be verified as cited. See the correctly-attributed cytosol/cytoplasm annotations. |
| GO:0008253 5'-nucleotidase activity | IDA PMID:34814800 The decreased serum activity of cytosolic 5'-nucleotidase IA... | ACCEPT | Summary: Direct measurement of serum cN-IA 5'-nucleotidase activity (AMP -> adenosine). Supports the core molecular function. Supporting Evidence: PMID:34814800 preferentially converting adenosine monophosphate to adenosine. |
| GO:0008253 5'-nucleotidase activity | IDA PMID:599155 Regulation of the fatty acid composition of alkyl ether phos... | UNDECIDED | Summary: Cited PMID:599155 is an unrelated 1977 acyltransferase paper; this is a transcription error for PMID:7599155 (Tavenier 1995), which measured AMP-/IMP-specific 5'-nucleotidase activity in human myocardium. The 5'-nucleotidase activity is correct and is captured by the correctly-cited PMID:7599155 annotation, but this instance's identifier cannot be verified as cited. |
| GO:0008253 5'-nucleotidase activity | IDA PMID:8967393 Soluble forms of 5'-nucleotidase in rat and human heart. | ACCEPT | Summary: Direct assay of cytosolic 5'-nucleotidase activity in human left ventricle (AMP-preferring N-I isozyme). Core molecular function. Supporting Evidence: PMID:8967393 the AMP-preferring one (N-I, 107 +/- 61 mU/g, |
| GO:0005829 cytosol | IDA PMID:11133996 Human cytosolic 5'-nucleotidase I: characterization and role... | ACCEPT | Summary: Cytosolic localization of the cloned human cN-I (a soluble cytosolic enzyme). Core cellular component. Supporting Evidence: file:human/NT5C1A/NT5C1A-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:7599155}. |
| GO:0006196 AMP catabolic process | IDA PMID:11133996 Human cytosolic 5'-nucleotidase I: characterization and role... | ACCEPT | Summary: cN-I dephosphorylates AMP to adenosine, the committed step of AMP catabolism. Core biological process. (The involved_in duplicate is the preferred qualifier; this acts_upstream_of_or_within instance is accepted as the same underlying claim.) Supporting Evidence: PMID:34814800 preferentially converting adenosine monophosphate to adenosine. |
| GO:0006204 IMP catabolic process | IDA PMID:11133996 Human cytosolic 5'-nucleotidase I: characterization and role... | KEEP AS NON CORE | Summary: cN-I hydrolyzes IMP (EC 3.1.3.99), placing it in IMP catabolism. Supported by the recombinant-enzyme kinetics (IMP is a demonstrated, lower-affinity substrate). Genuine but secondary relative to AMP catabolism. Supporting Evidence: file:human/NT5C1A/NT5C1A-uniprot.txt Reaction=IMP + H2O = inosine + phosphate; Xref=Rhea:RHEA:27718, |
| GO:0008253 5'-nucleotidase activity | IDA PMID:11133996 Human cytosolic 5'-nucleotidase I: characterization and role... | ACCEPT | Summary: Direct characterization of the cloned recombinant human cN-I 5'-nucleotidase. Core molecular function. Supporting Evidence: PMID:11133996 lower affinity toward AMP and IMP. ADP was necessary for maximal catalytic |
| GO:0046055 dGMP catabolic process | IDA PMID:11133996 Human cytosolic 5'-nucleotidase I: characterization and role... | KEEP AS NON CORE | Summary: cN-I can hydrolyze deoxyribonucleoside monophosphates; dGMP catabolism is a consequence of its broad 5'-deoxynucleotidase activity. Genuine but a minor, non-core facet of the enzyme's activity spectrum. Supporting Evidence: PMID:11133996 The recombinant cN-I showed high affinity toward dCMP and |
| GO:0046059 dAMP catabolic process | IDA PMID:11133996 Human cytosolic 5'-nucleotidase I: characterization and role... | KEEP AS NON CORE | Summary: dAMP catabolism follows from cN-I 5'-deoxynucleotidase activity on deoxyribonucleoside monophosphates. Genuine but a minor, non-core facet. Supporting Evidence: PMID:11133996 The recombinant cN-I showed high affinity toward dCMP and |
| GO:0000255 allantoin metabolic process | IDA PMID:11133996 Human cytosolic 5'-nucleotidase I: characterization and role... | MARK AS OVER ANNOTATED | Summary: Allantoin metabolic process is not a valid human process context: humans (like other primates) lack functional urate oxidase and do not produce allantoin from purine catabolism. This term appears to be an over-propagation from rodent/PANTHER context; the underlying reference (Hunsucker 2001) characterizes a 5'-nucleotidase and does not establish allantoin metabolism. Over-annotated; retained (experimental IDA, not removed) but flagged as biologically inapplicable in human. |
| GO:0005829 cytosol | IDA PMID:11133996 Human cytosolic 5'-nucleotidase I: characterization and role... | ACCEPT | Summary: The enzyme is active in the cytosol. Core cellular component (is_active_in is the appropriate qualifier for a soluble catalytic enzyme). Supporting Evidence: file:human/NT5C1A/NT5C1A-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:7599155}. |
| GO:0006196 AMP catabolic process | IDA PMID:11133996 Human cytosolic 5'-nucleotidase I: characterization and role... | ACCEPT | Summary: AMP catabolic process with the preferred involved_in qualifier. This is the core catabolic role of cN-IA (AMP -> adenosine + Pi). Supporting Evidence: PMID:34814800 preferentially converting adenosine monophosphate to adenosine. |
| GO:0006204 IMP catabolic process | IDA PMID:11133996 Human cytosolic 5'-nucleotidase I: characterization and role... | KEEP AS NON CORE | Summary: IMP catabolic process (involved_in). Supported by demonstrated IMP-hydrolysis activity (EC 3.1.3.99); a genuine but secondary role relative to AMP catabolism. Supporting Evidence: file:human/NT5C1A/NT5C1A-uniprot.txt Reaction=IMP + H2O = inosine + phosphate; Xref=Rhea:RHEA:27718, |
| GO:0046055 dGMP catabolic process | IDA PMID:11133996 Human cytosolic 5'-nucleotidase I: characterization and role... | KEEP AS NON CORE | Summary: dGMP catabolic process (involved_in duplicate). Consequence of broad 5'-deoxynucleotidase activity; minor, non-core. Supporting Evidence: PMID:11133996 The recombinant cN-I showed high affinity toward dCMP and |
| GO:0046059 dAMP catabolic process | IDA PMID:11133996 Human cytosolic 5'-nucleotidase I: characterization and role... | KEEP AS NON CORE | Summary: dAMP catabolic process (involved_in duplicate). Consequence of broad 5'-deoxynucleotidase activity; minor, non-core. Supporting Evidence: PMID:11133996 The recombinant cN-I showed high affinity toward dCMP and |
| GO:0005829 cytosol | TAS Reactome:R-HSA-109380 | ACCEPT | Summary: Reactome reaction (pyrimidine/dCMP dephosphorylation by NT5C1A) localizes the enzyme to the cytosol. Consistent with all other localization evidence. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-109387 | ACCEPT | Summary: Reactome reaction ((deoxy)purine nucleoside monophosphate dephosphorylation by NT5C1A) in the cytosol. Consistent with the established cytosolic localization. |
| GO:0005829 cytosol | NAS PMID:11133996 Human cytosolic 5'-nucleotidase I: characterization and role... | ACCEPT | Summary: Author statement of cytosolic localization for the cloned human cN-I. Correct core cellular component (NAS-level support, corroborated by IDA/TAS/IBA). Supporting Evidence: file:human/NT5C1A/NT5C1A-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:7599155}. |
| GO:0008253 5'-nucleotidase activity | NAS PMID:11133996 Human cytosolic 5'-nucleotidase I: characterization and role... | ACCEPT | Summary: Author statement of 5'-nucleotidase activity for the cloned human cN-I; the core molecular function, also directly demonstrated experimentally. Supporting Evidence: file:human/NT5C1A/NT5C1A-uniprot.txt AMP is the major substrate but can |
| GO:0009116 nucleoside metabolic process | NAS PMID:11133996 Human cytosolic 5'-nucleotidase I: characterization and role... | KEEP AS NON CORE | Summary: Broad "nucleoside metabolic process" author statement. Correct but general; the specific AMP/adenosine catabolic annotations are more informative. Retained as non-core. |
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