User:1998lulua/sandbox

Protein FAM89A (family with sequence similarity 89, member A) is a protein which in humans is encoded by the FAM89A gene. It is also known as chromosome 1 open reading frame 153 (C1orf153). Highest FAM89A gene expression is observed in the placenta and adipose tissue. Though its function is largely unknown, FAM89A is found to be differentially expressed in response to interleukin exposure, and it is implicated in immune responses pathways and various pathologies.

Gene
The gene FAM89A is a protein-encoding gene in humans, located on minus strand of chromosome 1, map position 1q42.2. It is also known as chromosome 1 open reading frame 153 (C1orf153). The primary mRNA transcript for the FAM89A gene is 1,503 base pairs in length. There are no other transcript variants for FAM89A. The gene is composed of two exons flanking one large intronic region. FAM89A is neighboring the genes TRIM67 (Tripartite Motif Containing 67), located downstream of FAM89A on the plus strand of chromosome 1, and ARV1 (ARV1 Homolog, Fatty Acid Homeostasis Modulator), located upstream of FAM89A on the plus strand of chromosome 1.

Biochemistry
The FAM89A protein is 184 amino acids in length, and it has a predicted molecular mass of 18.6kDa and a predicted isoelectric point of 5.64. FAM89A shows five periodic repeats of leucine residues at every seventh amino acid position at positions 81-115, which is characteristic of its predicted leucine zipper structural motif.

Conserved Domains
FAM89A contains a conserved leucine-rich adapter protein domain (LURAP), located at amino acid positions 84-122. The LURAP superfamily of proteins are activators of the canonical NF-κB pathway, involved in promoting antigen presentation in dendritic cells and the production of pro-inflammatory cytokines.

Secondary Structure
FAM89A is predicted to be 40% alpha helix, 11% extended strand, and 49% random coils. The conserved LURAP domain is predicted to form an alpha helix.

Tertiary Structure
FAM89A tertiary structure has not yet been determined by X-ray crystallography. I-TASSER software predicts dimerization of alpha helix monomers, indicative of the leucine zipper motif.

Promoter
The FAM89A promoter region is 1,104 base pairs in length. It contains binding sites for various transcription factors, including TFIIB (RNA polymerase II transcription factor IIB), PLAG1 (pleomorphic adenoma gene 1), MZF1 (myeloid zinc finger 1 factors), and SP1 (GC-Box factors SP1/GC).

Expression pattern
FAM89A's highest expression is observed in the placenta and adipose tissue. RNA-sequencing data also reveals moderate FAM89A expression in the adrenal gland, lung, skin, spleen, and breast. Microarray hybridization supports high FAM89A expression in the placenta and moderate expression in the lung, spinal cord, skin, adrenal gland, and retina.

Subcellular Localization
The FAM89A protein is suggested to be localized in the nucleoplasm, Golgi apparatus, and/or vesicles.

Phosphorylation/O-Linked β-N-acetylglucosamine
FAM89A has three predicted phosphorylation sites located at amino acid positions 30, 32, and 168 that are conserved in distant orthologs. The predicted phosphorylation site at position 32 is experimentally verified at position 28 in its paralog, FAM89B.

There is a potential competitive binding site for phosphorylation and O-linked β-N-acetylglucosamine (O-GlcNAc) at position 158, supporting localization of FAM89A in the nucleoplasm.

Glycation
NetGlycate 1.0 server predicts two glycation sites at positions 57 and 95. The residues are conserved in distant FAM89A orthologs.

SUMOylation
SUMOplot analysis program predicts SUMO (Small Ubiquitin-like Modifier) protein sites at position 83. The residue is conserved in distant FAM89A orthologs.

Paralogs
An important human paralog of FAM89A is FAM89B, located on human chromosome 11 at map position 11q13.1. FAM89B is also known as, Leucine Repeat Adaptor Protein 25 (LRAP25) and Mammary Tumor Virus Receptor Homolog 1 (MTVR1). Orthologs of FAM89A, but not FAM89B, are present in bivalves, crinoids, hemichordates, starfish, and horseshoe crabs. Orthologs of FAM89B, but not FAM89A, are present in brachiopods and priapulids, The paralogs likely split around 736 million years ago.

Orthologs
FAM89A is largely conserved in Eutelostomi (bony vertebrates). Its orthologs can be found in mammals, amphibians, reptiles, birds, fish, and various insects. Distant FAM89A orthologs are present in octopus, scallop, ants, and bees.

Evolution
The rate of accumulation of amino acid changes relative to the genes Fibrinogen and Cytochrome c indicates that FAM89A is evolving rapidly, using the molecular clock technique.

Interacting Proteins
FAM89A is experimentally determined to interact with the UBXN2B (UBX Domain Protein 2B), an adaptor protein involved in biogenesis in the Golgi apparatus and endoplasmic reticulum (ER) and assembly and maintenance of the ER during the cell cycle

Pathology and Disease Association
FAM89A is suggested to be involved in modulating the effects of smoking on the risk of atherosclerotic plaque burden. In a study conducted in 2014, a cohort of 264 Caribbean Hispanics with varying smoking frequencies were evaluated for carotid plaque burden and 11 single nucleotide polymorphism (SNP) were identified that had a notable interaction with smoking effects on carotid plaque burden, including SNP rs6700792, located within the FAM89A gene.

FAM89A is also suggested to be involved in discriminating viral and bacterial infection in febrile patients. A 2016 study conducted at the Division of Infectious Disease in the Imperial College of London evaluated blood-based transcriptomic biomarkers and revealed that febrile patients with bacterial infection displayed increased expression of FAM89A.

Microarray hybridization data revealed slight decrease in FAM89A expression in response to airway epithelial cell exposure to interleukin 13 and CD8+ T lymphocyte exposure to interleukin 10.