Tdark CMAHP Inactive cytidine monophosphate-N-acetylneuraminic acid hydroxylase

Protein Summary

Description

Sialic acids are components of carbohydrate chains of glycoconjugates and are involved in cell-cell recognition and cell-pathogen interactions. That protein has no CMP-N-acetylneuraminate monooxygenase activity and is not able to convert CMP-N-acetylneuraminic acid (CMP-Neu5Ac) into its hydroxylated derivative CMP-N-glycolylneuraminic acid (CMP-Neu5Gc), a sialic acid abundantly expressed at the surface of many cells in vertebrates (PubMed:9624188). However, it may play a role in Wnt signaling (PubMed:19890979). Sialic acids are terminal components of the carbohydrate chains of glycoconjugates involved in ligand-receptor, cell-cell, and cell-pathogen interactions. The two most common forms of sialic acid found in mammalian cells are N-acetylneuraminic acid (Neu5Ac) and its hydroxylated derivative, N-glycolylneuraminic acid (Neu5Gc). Studies of sialic acid distribution show that Neu5Gc is not detectable in normal human tissues although it was an abundant sialic acid in other mammals. Neu5Gc is, in actuality, immunogenic in humans. The absense of Neu5Gc in humans is due to a deletion within the human gene CMAH encoding cytidine monophosphate-N-acetylneuraminic acid hydroxylase, an enzyme responsible for Neu5Gc biosynthesis. Sequences encoding the mouse, pig, and chimpanzee hydroxylase enzymes were obtained by cDNA cloning and found to be highly homologous. However, the homologous human cDNA differs from these cDNAs by a 92-bp deletion in the 5' region. This deletion, corresponding to exon 6 of the mouse hydroxylase gene, causes a frameshift mutation and premature termination of the polypeptide chain in human. It seems unlikely that the truncated human hydroxylase mRNA encodes for an active enzyme explaining why Neu5Gc is undetectable in normal human tissues. Human genomic DNA also shows evidence of this deletion which does not occur in the genomes of African great apes. Nonetheless, the CMAH gene maps to 6p21.32 in humans and great apes indicating that mutation of the CMAH gene occurred following human divergence from chimpanzees and bonobos. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• Q9Y471
• C1K3L2
• O95250
• Q5TD41
• Q5TD42
• Q5TD43
• Q5TD44
• Q68DC3
• Q9UEE7
• CMP-NeuAc hydroxylase-like protein

Gene Name

• CMAHP

Symbol

• CMAH
• CMAH
• CSAH

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
transcription factor perturbation	0.8
histone modification site profile	0.61
small molecule perturbation	0.53
cell line	0.48
cell type or tissue	0.48

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 0   (req: < 5)

Gene RIFs: 4   (req: <= 3)

Antibodies: 0   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 0   (req: >= 5)

Gene RIFs: 4   (req: > 3)

Antibodies: 0   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 2

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0