GNPNAT1 (also known as GNA1) is the human glucosamine 6-phosphate N-acetyltransferase (EC 2.3.1.4), a GNAT-family (GCN5-related N-acetyltransferase) enzyme that catalyzes the acetyl-CoA-dependent transfer of an acetyl group to D-glucosamine 6-phosphate, producing N-acetyl-D-glucosamine 6-phosphate (GlcNAc-6-P) and CoA. This is the second committed step of the hexosamine biosynthetic pathway, feeding into UDP-N-acetyl-alpha-D-glucosamine (UDP-GlcNAc) biosynthesis, the activated sugar donor used for N- and O-linked glycosylation and O-GlcNAcylation. The active enzyme is a homodimer with a GNAT fold. It functions in the cytosol, where the hexosamine pathway operates, and is also reported as a peripheral membrane protein of the Golgi apparatus and endosome membranes. Loss-of-function variants cause rhizomelic dysplasia, Ain-Naz type (RHZDAN), an autosomal recessive skeletal dysplasia, consistent with a UDP-GlcNAc/glycosylation deficiency.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004343 glucosamine 6-phosphate N-acetyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred core molecular function, matching the experimentally established EC 2.3.1.4 activity. This is the correct, specific molecular function for GNPNAT1/GNA1 and is well supported across orthologs and by direct human enzyme assays. Supporting Evidence: file:human/GNPNAT1/GNPNAT1-uniprot.txt RecName: Full=Glucosamine 6-phosphate N-acetyltransferase; |
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic annotation from UniProt SubCell mapping. UniProt records GNPNAT1 as a Golgi apparatus membrane peripheral membrane protein, so this is not wrong, but the hexosamine pathway is cytosolic and the catalytic reaction is placed in the cytosol (Reactome). This is a peripheral membrane association rather than the core catalytic compartment, so keep as non-core. Supporting Evidence: file:human/GNPNAT1/GNPNAT1-uniprot.txt SUBCELLULAR LOCATION: Golgi apparatus membrane; Peripheral membrane |
| GO:0004343 glucosamine 6-phosphate N-acetyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation derived from the RHEA:10292 / EC 2.3.1.4 mapping, which correctly captures the core molecular function. Redundant with the experimental and IBA annotations to the same term but accurate. Supporting Evidence: file:human/GNPNAT1/GNPNAT1-uniprot.txt EC=2.3.1.4 |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA machine-learning electronic annotation. Cytoplasm is correct but is the general parent of cytosol, which is the specific compartment where the hexosamine pathway operates (captured by the more specific GO:0005829 cytosol annotation). Keep as non-core given the more precise cytosol term is present. Supporting Evidence: Reactome:R-HSA-449734 Cytosolic GNPNAT1 catalyzes the reaction of glucosamine 6-phosphate and acetyl-CoA to form N-acetyl-glucosamine 6-phosphate (GlcNAc6P) and CoA-SH. |
| GO:0010008 endosome membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic annotation from UniProt SubCell mapping. In UniProt the endosome membrane location is annotated by similarity (ECO:0000250) rather than by direct human evidence, and is a peripheral membrane association, not the cytosolic catalytic compartment. Keep as non-core. Supporting Evidence: file:human/GNPNAT1/GNPNAT1-uniprot.txt Endosome membrane {ECO:0000250}; Peripheral membrane |
| GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro-to-GO electronic annotation based on the general GNAT domain (IPR000182). This is a correct but overly general parent term; the specific and experimentally supported molecular function is glucosamine 6-phosphate N-acetyltransferase activity (GO:0004343). Mark as over-annotated in favor of the specific term. Supporting Evidence: file:human/GNPNAT1/GNPNAT1-uniprot.txt DOMAIN 39..184 |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: Bare protein binding from a proteome-scale interactome study (WITH/FROM FABP1, P07148). Uninformative as a molecular function per curation guidelines. Retained as an experimental IPI annotation but marked as over-annotated rather than removed. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks |
| 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 a proteome-scale binary (Y2H) interactome map (WITH/FROM PSMB8, P28062-2). Uninformative as a molecular function per curation guidelines. Retained as experimental IPI but marked as over-annotated. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Bare protein binding from a proteome-scale AP-MS interactome study (WITH/FROM FABP1, P07148). Uninformative as a molecular function per curation guidelines. Retained as experimental IPI but marked as over-annotated. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome |
| GO:0042802 identical protein binding | IPI PMID:18675810 Acceptor substrate binding revealed by crystal structure of ... | KEEP AS NON CORE | Summary: Self-interaction (WITH/FROM Q96EK6) reflecting the biologically real homodimer, which the crystal structure work established as the active form of the enzyme. This is a meaningful interaction but supports the catalytic molecular function rather than being a core function in its own right, so keep as non-core. Supporting Evidence: file:human/GNPNAT1/GNPNAT1-uniprot.txt SUBUNIT: Homodimer. |
| GO:0042802 identical protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Self-interaction (WITH/FROM Q96EK6) from a proteome-scale interactome map, consistent with the known homodimer. Meaningful but supports the catalytic function rather than being a core function itself; keep as non-core. Supporting Evidence: file:human/GNPNAT1/GNPNAT1-uniprot.txt SUBUNIT: Homodimer. |
| GO:0006048 UDP-N-acetylglucosamine biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway-based electronic annotation to the core biological process. GNPNAT1 catalyzes step 1 of 2 in the route from glucosamine 6-phosphate to N-acetyl-alpha-D-glucosamine 1-phosphate within UDP-GlcNAc biosynthesis, so this is the correct core process. Supporting Evidence: file:human/GNPNAT1/GNPNAT1-uniprot.txt UDP-N-acetyl-alpha-D- |
| GO:0004343 glucosamine 6-phosphate N-acetyltransferase activity | EXP PMID:18601654 Structural and kinetic differences between human and Aspergi... | ACCEPT | Summary: Direct experimental evidence from crystal structures and kinetic characterization of human GNA1, establishing the EC 2.3.1.4 catalytic activity (KM 26 uM for acetyl-CoA, 97 uM for glucosamine-6-phosphate). This is the definitive core molecular function annotation. Supporting Evidence: PMID:18601654 GNA1 (D-glucosamine-6-phosphate N-acetyltransferase) catalyses the acetylation of GlcN-6P (glucosamine-6-phosphate) to GlcNAc-6P (N-acetylglucosamine-6-phosphate), a key intermediate in the UDP-GlcNAc biosynthetic pathway. |
| GO:0004343 glucosamine 6-phosphate N-acetyltransferase activity | EXP PMID:18675810 Acceptor substrate binding revealed by crystal structure of ... | ACCEPT | Summary: Direct experimental evidence from crystal structures of human GNA1 (apo, GlcN6P complex, and E156A mutant) demonstrating acceptor-substrate binding and the acetyl-CoA-dependent catalytic activity. Confirms the core molecular function. Supporting Evidence: PMID:18675810 GNA1 catalyzes the formation of N-acetylglucosamine-6-phosphate (GlcNAc6P) from acetyl-CoA (AcCoA) and the acceptor substrate GlcN6P. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-449734 | ACCEPT | Summary: Reactome traceable assertion that the GNPNAT1-catalyzed reaction occurs in the cytosol. The hexosamine biosynthetic pathway is cytosolic, so this is the functionally central subcellular location for the enzyme's core activity. Supporting Evidence: Reactome:R-HSA-449734 Cytosolic GNPNAT1 catalyzes the reaction of glucosamine 6-phosphate and acetyl-CoA to form N-acetyl-glucosamine 6-phosphate (GlcNAc6P) and CoA-SH. |
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