FAM78B

Family with Sequence Similarity 78-Member B (FAM78B) is a protein of unknown function in humans that is encoded by the FAM78B gene (1q24.1). It has orthologous genes and predicted proteins in vertebrates and several invertebrates, but not in arthropods. It has a nuclear localization signal in the protein sequence and a miRNA target region in the mRNA sequence.

Evolutionary analysis

Homology FAM78B has one paralog, FAM78A, and is conserved throughout many species. Orthologs can be found throughout all vertebrates excluding arthropods. FAM78B is also found in several invertebrates including the pacific oyster and liver fluke. FAM78A, its paralog, is also found to be conserved in more invertebrates such as the tunicates, worms, and leeches, and make up the distant homologs of FAM78B. The table below contains a list of FAM78B orthologs with percent identity values and time since divergence values relative to the human FAM78B gene or protein.

Genus and species Common name Date of divergence from human lineage (millions of years ago) Accession number Sequence length (bp or aa) Protein/mRNA identity (%) Query cover (%) Crassostrea gigas Pacific oyster 782.7 EKC28338.1 267 48 79 Clonorchis sinensis Liver fluke 792.4 GAA32739.1 295 33 84 Xiphophorus maculatus Platyfish 400.1 XP_005802428.1 285 80 100 Takifugu rubripes Pufferfish 400.1 XP_003975800.1 261 80 100 Danio rerio Zebrafish 400.1 XP_001338241.2 285 80 100 Lepisosteus oculatus Spotted gar 400.1 XP_006635127.1 261 90 100 Xenopus (Silurana) tropicalis Western clawed frog 371.2 XP_002933818.1 263 93 100 Alligator mississippiensis Alligator 296 XP_006276782.1 261 92 100 Anolis carolinensis Anole lizard 296 XP_003219922.1 261 90 100 Gallus gallus Chicken 296 XP_001232254.1 261 90 100 Pseudopodoces humilis Groundpecker 296 XP_005528713.1 261 90 100 Columba livia Rock dove 296 XP_005499081.1 238 86 93 Pelodiscus sinensis Soft shell turtle 296 XP_006128883.1 216 94 72 Trichechus manatus latirostris Manatee 98.7 XP_004385839.1 242 78 100 Camelus ferus Camel 94.2 XP_006194022.1 261 99 100 Mus musculus Mouse 92.3 NP_780670.2 262 98 100 Microtus ochrogaster Prairie vole 92.3 XP_005370139.1 261 99 100 Loxodonta africana Elephant 98.7 XP_003415081.1 999 99 98 Macaca fascicularis Crab eating macaque 42.6 EHH50788.1 233 89 100 Pan paniscus Bonobo 42.6 XP_003824811.1 243 88 100

Structure

Gene

The FAM78B gene is located on the sense (negative) strand of chromosome 1 at location 1q24.1 and spans the chromosomal locus 166039271-166135909, covering a total of 96,638 base pairs along the chromosome, the FAM78B gene has 2 exons in its transcript mRNA of 1,481 bp. FAM78B in humans is separated into two exons that have 95,243 bp of introns between them. The gene is highly conserved in vertebrates (excluding arthropods) and the pacific clam and liver fluke.

mRNA There is one isoform that has been identified in humans and is composed of two exons that composes a mRNA of 1,481 bp.

Protein The FAM78B protein has a calculated molecular weight of 30 kDa, has a higher relative abundance of tryptophan (W), has a more greatly conserved c-terminal region, is composed of both alpha helix and beta strand, and resides in the nucleus of the cell after transcription

General properties The protein FAM78B consists of 254 amino acids with a predicted molecular weight of 30 kDal. The protein has an isoelectric point of 9.6. FAM78B has a highly conserved C terminus among its orthologs and is histidine poor. The highest conserved amino acids are ISDSDG from aa 104-110, WLVA from aa 171-175, VDP---L--R from aa 199-208, and the C' terminus, but especially NADQVLMW from aa 240-247.

Conservation The amino acid sequence for FAM78B is highly conserved in mammals, having around 86% to 100% sequence similarity. Birds, frogs, mammals, and lizards also have a high degree of similarity to the human FAM78B sequence with similarities between 76% and 83%. Fish have between 56% and 66% sequence similarity. The C terminal end is the most highly conserved across ortholog-containing species from mammals to the pacific sea clam.

Regulation

mRNA level There is one miRNA binding site targeted by miR-24 for sequence CUGAGCCA in Homo sapiens located on the 3' end of the mRNA at 88-95 after the stop codon (bp 167,091,390-167,091,397 on chromosome 1). Stem loop from 155-172 of the 3' end of the mRNA matches with the miRNA site.

Protein level Conserved nuclear localization signal (RPKR) from aa 248-252.

Expression FAM78B is generally ubiquitously expressed and is highly expressed in regions of the brain.

Clinical relevance FAM78B is statistically significantly correlated to chronic kidney disease when there is one of three different single nucleotide polymorphisms (SNPs) including two located in the intron (rs2116519 and rs4074897) and one located in the 5' UTR (rs987131).

References

Further reading