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The C16orf13 gene located on Chromosome 16 of the human genome encodes the enzyme LOC84326, a highly conserved putative SAM-dependent methyltransferase. In addition to its protein name, other synonyms for this gene include chromosome 16 open reading frame 13, MGC13114, and JFP2. Bioinformatic analysis yields significant insight into the C16orf13 gene and its corresponding protein, LOC84326.

A methyltransferase is a type of transferase enzyme which transfers a methyl group from a donor to an acceptor. Methylation frequently occurs on nucleic bases in DNA or amino acids in protein structures. Methytransferases use a reactive methyl group bound to sulfur in S-adenosyl methionine (SAM) as the methyl donor.



Overview
C16orf13 is thought to produce 18 spliceoforms ; however, many of these variants remain to be substantially elucidated. The product of this gene is the putative S-adenosyl-L-methionine-dependent methyltransferase, LOC84326. Studies of this gene and its protein's evolutionary origins suggest that it is well conserved in many sequenced species, some as divergent as bacteria. It is notably absent, however, in all sequenced plants and fungi, as well as the genetic model organism E. coli. The predominant form of the protein in all known orthologous species corresponds to LOC84326 isoform 1. There is a high probability that this protein localizes to the cell nucleus, cytoplasm, and perhaps to limited extent with the mitochondria , and exhibits heightened expression in the lungs and other selected tissues. It interacts with SIRT4 and PGD.

Gene neighborhood:

Genes nearby include RAB40C, a member of the RAS oncogene family; WFIKKN1, which encodes a secreted multidomain protein thought to inhibit some proteases; and a few more hypothetical proteins such as LOC100130285 of unknown type and function. Most are oriented in the opposite direction on the chromosome to C16orf13.

Properties
Although 18 splice forms have been observed through EST mapping, only isoforms a, b, c, d, and g currently have reference sequences in the NCBI databases. The raw gene region, GRCGRCh37, is approximately 1.92kb, and the primary gene transcript (splice form 1) is 854 base pairs long, producing a 204 amino-acid (a isoform).

LOC84326 interacts with SIRT4, a mitochondrial ADP-ribosyltransferase that inhibits mitochondrial glutamate dehydrogenase 1 activity, thereby downregulating insulin secretion in response to amino acids. . It also interacts with PGD, which encodes Phosphogluconate dehydrogenase, the second enzyme in the pentose phosphate pathway which forms ribulose 5-phosphate from 6-phosphogluconate, and can be found in the cytosol and the mitochondria. Two additional interaction partners have been identified in mice: GCSH and Hddc2.

LOC84326 encompasses the DUF938 domain and contains a nuclear export signal from amino acids 98-108. It is a member of the S-adenosylmethionine-dependent methyltransferases class I superfamily ; the SAM binding pocket is speculated to be located from amino acids 24-65. It also contains a O-GlcNAc modification at T71 ; this modification is favored among proteins that play a role in nuclear transport. All of these features are conserved in the mouse ortholog.

Homology and Conservation


A multiple sequence alignment shows that C16orf13's predominant protein, LOC84326 isoform a, is very well conserved in various species. Notable exceptions include fungi, plants, and E. coli.

Expression analysis indicates increased level of gene expression in the lung when exposed to asbestos. There is a similar increase in expression when exposed to cigarette smoke. Post-translational modifications are predicted as follows :