FAM63A

FAM63A is located on the minus strand of chromosome 1 at band 1q21.3, spanning 11,829 bp. Other genes surrounding FAM63A include ANXA9 and Prune.[9]

FAM63A has two aliases KIAA1390 and PR11-316M1.5.[10]

In humans, there are four isoforms of FAM63A, and there are 10 predicted isoforms. Isoform 1 of FAM63A has a molecular weight of 51.8 kilodaltons, and it contains 11 exons.[11][12] The different isoforms tend to differ at the 5' or 3' end by truncation. Transcription produces 23 introns, 14 spliced variants, and 6 unspliced forms.[13]

FAM63A contains a domain of unknown function (DUF 544). DUF544 contains 125 amino acids, running from Met143 to Thr267.[14] Although not completely conserved, this domain is highly conserved across vertebrates, invertebrates, and plants.[15] FAM63A does not contain a transmembrane domain, and it is found primarily in nuclear regions of the cell. [16]

Two repeats of four glutamines are seen from amino acid 400-403 and from amino acid 426-429, leading to an elevated glutamine composition at the C-terminus.

FAM63A is composed of 469 amino acids.[17] There is an increased presence of glutamine found near the C terminus making FAM63A glutamine rich. FAM63A contains a greater amount of negatively charged (acidic) amino acids than positively charged (basic) amino acids which makes FAM63A a slightly acidic protein. Acidic amino acids such as aspartic acid and glutamic acid are more prevalent than the basic amino acids such as lysine and arginine. This overall acidic composition gives FAM63A an acidic isoelectric point of 4.6.[18]

FAM63A contains 25 phosphorylation sites in humans, including 12 serine, 10 threonine, and 3 tyrosine. Additionally, there are 5 N-myristoylation sites, and there is 1 prenylation site. FAM63A contains no glycosylation sites, transmembrane domains, or signal peptides. [19]

This is a depiction of the posttranslational modifications in FAM63A.

The secondary structure for FAM63A has not been explicitly determined. There are, however, predictions for a possible secondary structure. There is a coiled-coil domain at the end of the protein, and in the predicted secondary structure, there is an alpha helix between amino acids 410 and 436. This helix is conserved throughout more distant orthologs of FAM63A. These data support each other, and it gives a confident prediction of the secondary structure.[20]

The following genes have interactions with FAM63A: GSPT2, NAA38, RNMT, CSNIK1G2, ACOX1, PSMC1, SLC25A37, MMS19, DIAPH1, ME1, GAPDH, UBC. [21] After performing a yeast two-hybrid screen, it was found that NAA38 and FAM63A interact.[22]

The protein FAM63A has several strict orthologs. These strict orthologs are found in organisms ranging from Primates to Fish.[23]

FAM63A evolved through time at a relatively moderate rate.

This shows the protein conservation throughout evolution. FAM63A evolved at a medium rate compared with cytochrome c (fast) and fibrinogen (slow).

The protein FAM63A has only one known paralog: FAM63B. FAM63B is predicted as having a molecular function in the cell.[24] All of the vertebrates for which sequences are available have two copies of the FAM63 gene, both A and B. FAM63A and FAM63B likely split apart around 666 million years ago, as the closest relative to Homo sapiens containing only one FAM63 is a tapeworm, which diverged 666 million years ago.[25]

The promoter region contains a number of transcription factors.[26] Those with high scores include estrogen response elements, TATA boxes, glucocorticoid response elements, and Ccaat/enchancer binding proteins. Experimental data reveals that FAM63A expression decreases when the estrogen receptor is not present, suggesting that the estrogen response elements may serve as an important promoter regulatory mechanism for this protein.[27]

FAM63A is a protein that is ubiquitously expressed across human tissues and throughout development. Although FAM63A is expressed ubiquitously, there are certain tissues that have higher levels of expression including the heart, thyroid, ganglia, and blood.[28]

This is a depiction of the expression levels of FAM63A throughout different human tissues.