FAM63A

Family with sequence similarity 63, member A is a is_associated_with::protein that, in humans, is encoded by the FAM63A is_associated_with::gene. It is located on the minus strand of chromosome 1 at locus 1q21.3.

Evolutionarily, FAM63A is_associated_with::orthologs are found in most is_associated_with::vertebrates, and distant is_associated_with::homologs of FAM63A are found in is_associated_with::invertebrates. FAM63A is ubiquitously expressed throughout human tissues, and it is present during all stages of development.

It has been linked to be a potential is_associated_with::biomarker in is_associated_with::Chronic Kidney Disease and is_associated_with::Alzheimer's Disease.

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

Aliases
FAM63A has two aliases KIAA1390 and PR11-316M1.5.

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

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

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

Composition
FAM63A is composed of 469 is_associated_with::amino acids. There is an increased presence of is_associated_with::glutamine found near the is_associated_with::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 is_associated_with::aspartic acid and is_associated_with::glutamic acid are more prevalent than the basic amino acids such as is_associated_with::lysine and is_associated_with::arginine. This overall acidic composition gives FAM63A an acidic is_associated_with::isoelectric point of 4.6.

Post-Translational Modifications
FAM63A contains 25 is_associated_with::phosphorylation sties in humans, including 12 is_associated_with::serine, 10 is_associated_with::threonine, and 3 is_associated_with::tyrosine. Additionally, there are 5 N-is_associated_with::myristoylation sites, and there is 1 is_associated_with::prenylation site. FAM63A contains no is_associated_with::glycosylation sites, is_associated_with::transmembrane domains, or is_associated_with::signal peptides.

Secondary Structure
The is_associated_with::secondary structure for FAM63A has not been explicitly determined. There are, however, predictions for a possible secondary structure. There is a is_associated_with::coiled-coil domain at the end of the protein, and in the predicted secondary structure, there is an is_associated_with::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.

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

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

Protein Expression
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 is_associated_with::heart, is_associated_with::thyroid, is_associated_with::ganglia, and is_associated_with::blood.



Clinical significance
The protein encoded by this gene has been linked to be a potential is_associated_with::biomarker in is_associated_with::Chronic Kidney Disease and is_associated_with::Alzheimer's Disease.

An association between is_associated_with::Alzheimer's Disease and is_associated_with::single nucleotide polymorphisms of FAM63A has been found. Another gene located on 1q21, is_associated_with::Cathepsin S, was also strongly associated with disease duration, the authors believe that there is a strong is_associated_with::linkage disequilibrium between the two genes.