CMAS is human N-acylneuraminate cytidylyltransferase (CMP-N-acetylneuraminic acid synthase; EC 2.7.7.43), the enzyme that activates free sialic acid for use in glycoconjugate biosynthesis. It condenses N-acetylneuraminate (Neu5Ac) with CTP to form the sugar-nucleotide donor CMP-N-acetylneuraminate (CMP-Neu5Ac) plus diphosphate; the enzyme also acts on other sialic acids including N-glycolylneuraminate (Neu5Gc) and KDN. CMP-Neu5Ac is the universal donor substrate used by sialyltransferases (after transport into the Golgi by the CMP-sialic acid transporter SLC35A1) to sialylate glycoproteins and glycolipids. The active enzyme is a homotetramer (a dimer of dimers). Unusually among the sialic-acid biosynthetic enzymes, human CMAS localizes at least partly to the nucleus; its basic-cluster (BC2) motif directs nuclear localization and contains the catalytic active site, although nuclear localization is not itself required for catalytic activity. CMAS is ubiquitously expressed.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0008781 N-acylneuraminate cytidylyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core catalytic molecular function. CMAS condenses N-acylneuraminate with CTP to form CMP-N-acyl-beta-neuraminate plus diphosphate (EC 2.7.7.43), the activation step for sialic acid. The phylogenetic (IBA) inference is well supported by the experimentally verified human enzyme activity and by orthologs across fly, mouse and zebrafish. This is the primary function of the gene. Supporting Evidence: file:human/CMAS/CMAS-uniprot.txt Reaction=an N-acylneuraminate + CTP = a CMP-N-acyl-beta-neuraminate + |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic annotation from the UniProt Swiss-Prot subcellular-location mapping. It correctly mirrors the experimentally determined nuclear localization of human CMAS. Redundant with the HDA nucleus annotation (PMID:21630459) but correct. Supporting Evidence: file:human/CMAS/CMAS-uniprot.txt Nucleus {ECO:0000269|PubMed:11602804}. |
| GO:0008781 N-acylneuraminate cytidylyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Automated molecular-function annotation derived from the Rhea/EC mapping (RHEA:11344, EC 2.7.7.43). Identical to the core catalytic function and consistent with the experimentally characterized enzyme. Supporting Evidence: file:human/CMAS/CMAS-uniprot.txt ChEBI:CHEBI:37563, ChEBI:CHEBI:60073, ChEBI:CHEBI:68671; EC=2.7.7.43; |
| GO:0006054 N-acetylneuraminate metabolic process | IEA GO_REF:0000041 | KEEP AS NON CORE | Summary: Correct but a broad parent process. CMAS acts on N-acetylneuraminate, so involvement in its metabolism is accurate. However the specific product of the CMAS reaction is CMP-N-acetylneuraminate, so the more precise process term GO:0006055 (CMP-N-acetylneuraminate biosynthetic process) better captures the core biological role. Retained as non-core (less-precise ancestor). Supporting Evidence: file:human/CMAS/CMAS-uniprot.txt Amino-sugar metabolism; N-acetylneuraminate metabolism. |
| GO:0005730 nucleolus | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Immunofluorescence (HPA) sub-nuclear localization to the nucleolus. Consistent with the established nuclear localization of CMAS, but the nucleolar sub-compartment is not functionally established as the site relevant to catalysis (the enzyme is also seen in nucleoplasm and is active independent of nuclear import). Kept as a valid but non-core localization detail. |
| GO:0006055 CMP-N-acetylneuraminate biosynthetic process | IMP PMID:31121216 Activity of N-acylneuraminate-9-phosphatase (NANP) is not es... | ACCEPT | Summary: Core biological process, experimentally supported. Willems et al. (2019) showed that CMAS-knockout cells have undetectable CMP-sialic acid, directly demonstrating that CMAS is required for CMP-N-acetylneuraminate biosynthesis. This is the precise process term for the CMAS reaction and represents the core biological role of the gene. Supporting Evidence: PMID:31121216 CMP-sialic acid was dramatically reduced in GNE and NANS KO cells and undetectable in CMAS KO. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: Derived from a large-scale membrane-proteome MS survey of an NK-like cell line. CMAS is a soluble nuclear/cytosolic enzyme (homotetramer) with no transmembrane domain or signal peptide, and the study itself notes that a large fraction of identified proteins are only transiently associated with membranes rather than integral. Capture in a membrane preparation is best interpreted as a proteomics artifact, not a functional membrane localization. This is a high-throughput (HDA) dataset annotation, so it is flagged as an over-annotation rather than removed. |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | ACCEPT | Summary: High-throughput MS identification of CMAS in the isolated human sperm nucleus proteome. Corroborates the experimentally established nuclear localization of CMAS (Lawrence et al. 2001). Consistent and correct. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-4084982 | KEEP AS NON CORE | Summary: Reactome traceable-author-statement placing CMAS in the nucleoplasm. Reactome states that CMAS localizes to the nucleus in mammalian cells; nucleoplasm is a reasonable sub-nuclear compartment consistent with the experimental nuclear localization. Kept as a valid but non-core localization detail. Supporting Evidence: Reactome:R-HSA-4084982 CMAS is ubiquitously expressed and localizes to the nucleus in mammalian cells. |
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