FAM178B explained

FAM178B is a protein coding gene that is located on the plus strand of chromosome 2.[1] The locus for the gene is 2q11.2. It is also known by the aliases Family with Sequence Similarity 178, Member B, and HSPC234.[2] In total there are 24 exons in the gene. FAM178B spans 110,720 base pairs, and contains 827 amino acids.

Forms

There are two isoforms of the gene transcript that exist by alternative splicing, and one gene precursor.

FAM178B Isoforms from Splice Variation:!Isoform:!Identifier:!Length in Amino Acids: !Mass (daltons):
1Q8IXR5-182793,514
2Q8IXR5-211913,809
3Q8IXR5-367976,515
SLF2 (FAM178A) is an important paralog of FAM178B. SLF2 is predicted to play a role in the DNA damage response (DDR) pathway by regulating post-replication repair of UV-damaged DNA, and genomic stability maintenance.[3]

Protein structure

The molecular weight of the protein is 76.5 kilodaltons,[4] and the isoelectric point is 5.47.The gene has 6 transcript splice variants.[5] The protein has been phenotypically associated with bipolar disease due to its locus,[6] as well as body mass index (BMI), and cell adhesion.[7] A proposed structure for the protein can be found in the images for proposed structures.[8] The secondary structure for the FAM178B protein is predicted to be primarily alpha helices.[9] The tertiary structure of the protein may assume a coiled coil structure.

Expression

FAM178B is most highly expressed in the skeletal muscle and brain tissues[10] .The structure in which it is highly concentrated is in the corpus callosum of the brain. Additionally, it is of high levels in the trigeminal nerve and spinal cord. Further, there is also high concentrations of the gene found near the heart, testes and olfactory regions.

According to the Allen Brain Atlas,[11] the olfactory regions, and the hippocampus of the mouse brain showed the greatest expressions of the gene when tested experimentally.

DNA Level Regulation

The proposed promoter region of FAM178B protein is below.[12] A table of relevant transcription factor binding sites that correspond to the sequence and colors highlighted in the promoter region is also included.


The promoter region of FAM178B is highly conserved across its most related orthologs, and is almost identical across the human, gorilla, chimp, bonobo and gibbon organisms.[13]


Protein Level Regulation

Below is a table that shows the protein modifications that could be potentially made to FAM178B, and the potential effects of these modifications on the protein itself:.[14]


Homology and Evolution

An important paralog of the gene is SLF2, which plays a role in the DNA damage response (DDR) pathway by regulating post replication repair of UV-damaged DNA. It also helps maintain genomic stability.[15] There are 74 known orthologs of the protein, and it can be traced back as far back as crustaceans. FAM178B is heavily found in both vertebrates and invertebrates. The ortholog space for the protein FAM178B is quite large as it can be traced back 794 millions of years ago (mya) to mollusks with the apple snail, and Pacific Oyster. There are 134 known orthologs of FAM178B. However, the protein is not found in arthropods, or insects, which is interesting because those organisms also existed in that time period meaning that it was conserved across some taxa, but not others. The protein is most readily found in primates, and other non-primate mammals. The protein is also conserved across reptiles, some bony fish, and cartilaginous fish, and birds.

Below is a table illustrating some of the orthologs for FAM178B using BLAST[16] and BLAT.[17]

!Scientific Name:!Common Name:!Accession Numberfrom NCBI:!Sequence Length:(Amino Acids)!Date of Divergence from Human Lineage:(millions of years ago)!Percent Identity:!Percent Similarity:
Homo SapiensHumanQ8IXR5.2827------
Macaca MulattaMacque XP_01496843370928.18083
Chlorocebus SabaeusGreen MonkeyXP_00800624572428.19194
Cebus CapucinusCapuchinXP_01737941780842.68891
Otolemur GarnettiiGalagoXP_01266650267573.07481
Marmota MarmotaMarmotXP_01535510969288.07480
Microtus OchrogasterVoleXP_02664157956188.06875
Felis Catus CatXP_01968263672094.07177
Equus CaballusHorseXP_02347439565994.07884
Panthera TigrisTigerXP_00709788167494.07580
Miniopterus NatalensisBatXP_01607715164994.07381
Bison BisonBisonXP_01082815766494.06573
Tursiops TruncatusDolphinJH473473 82794.06168
Alligator MississippiensisAlligatorXP_019343229802320.03447
Pogona VitticepsBearded DragonXP_0206358801003320.04156
Apteryx RowiKiwiXP_025941058512320.04258
Gallus GallusChickenXP_024998603547320.03750
Rhincodon TypusWhale SharkXP_0203884901155465.03453
Callorhinchus MiliiAustralian GhostsharkXP_007910600860465.03350
Crassostrea GigasPacific OyserEKC429691222794.02438
Pomacea CanalicultaApplesnailPVD304551229794.02445
Timetree[18] for FAM178B

Interacting Proteins

There are 2 proteins that have high predicted values of interaction with FAM178B: LRSAM 1 and ZNF598.[19] LRSAM1[20] is also known as leucine rich repeat and sterile alpha motif protein 1. The value for the protein is .29 and the evidence is physical from hybrid pooling approaches. LRSAM1 was previously known as Tsg-associated ligase and is located on the LRSAM1 gene. Mutations have been associated with periphery neuropathy, and sensory disorders. It is highly expressed in the spinal cord, as is FAM178B. There is currently no known structure for the protein. ZNF598 is a zinc finger protein and the value is .13. It plays a key role in ribosome quality control. The predicted structures are below for both proteins.

MENTHA interacting proteins for FAM178B.

STRING[21] interacting proteins for FAM178B.


Further reading

  1. Hillier. Ladeana W.. Graves. Tina A.. Fulton. Robert S.. Fulton. Lucinda A.. Pepin. Kymberlie H.. Minx. Patrick. Wagner-McPherson. Caryn. Layman. Dan. Wylie. Kristine. 2005-04-07. Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 434. 7034. 724–731. 10.1038/nature03466. 1476-4687. 15815621. 2005Natur.434..724H . free.
  2. Stelzl. Ulrich. Worm. Uwe. Lalowski. Maciej. Haenig. Christian. Brembeck. Felix H.. Goehler. Heike. Stroedicke. Martin. Zenkner. Martina. Schoenherr. Anke. 2005-09-23. A human protein-protein interaction network: a resource for annotating the proteome. Cell. 122. 6. 957–968. 10.1016/j.cell.2005.08.029. 0092-8674. 16169070. 11858/00-001M-0000-0010-8592-0. 8235923. free.
  3. Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells

Notes and References

  1. FAM178B - Protein FAM178B - Homo sapiens (Human) - FAM178B gene & protein. (n.d.). Retrieved February 25, 2019, from https://www.uniprot.org/uniprot/Q8IXR5
  2. RecName: Full=Protein FAM178B - Protein - NCBI. (n.d.). Retrieved February 25, 2019, from https://www.ncbi.nlm.nih.gov/protein/Q8IXR5.2
  3. Räschle M, Smeenk G, Hansen RK, Temu T, Oka Y, Hein MY, Nagaraj N, Long DT, Walter JC, Hofmann K, Storchova Z, Cox J, Bekker-Jensen S, Mailand N, Mann M . DNA repair. Proteomics reveals dynamic assembly of repair complexes during bypass of DNA cross-links . Science . 348 . 6234 . 1253671 . May 2015 . 25931565 . 5331883 . 10.1126/science.1253671 .
  4. Web site: SAPS < Sequence Statistics < EMBL-EBI. www.ebi.ac.uk. 2019-04-21.
  5. Gene: FAM178B (ENSG00000168754) - Splice variants - Homo sapiens - Ensembl genome browser 95. (n.d.). Retrieved February 25, 2019, from http://useast.ensembl.org/Homo_sapiens/Gene/Splice?db=core;g=ENSG00000168754;r=2:96875882-96986592
  6. Bipolar disorder lithium response (continuous) or schizophrenia - Loci associated with Bipolar disorder lithium response (continuous) or schizophrenia - Homo sapiens - Ensembl genome browser 95. (n.d.). Retrieved February 25, 2019, from http://useast.ensembl.org/Homo_sapiens/Phenotype/Locations?db=core;g=ENSG00000168754;ph=70698;r=2:96875882-96986592
  7. Gene: FAM178B (ENSG00000168754) - Phenotypes - Homo sapiens - Ensembl genome browser 95. (n.d.). Retrieved February 25, 2019, from http://useast.ensembl.org/Homo_sapiens/Gene/Phenotype?db=core;g=ENSG00000168754;r=2:96875882-96986592
  8. SWISS-MODEL Repository | Q8IXR5. (n.d.). Retrieved February 25, 2019, from https://swissmodel.expasy.org/repository/uniprot//Q8IXR5
  9. Web site: PHYRE2 Protein Fold Recognition Server. www.sbg.bio.ic.ac.uk. 2019-04-22.
  10. Web site: Gene2Promoter. ExPasy. https://web.archive.org/web/20010224072831/http://www.genomatix.de/. 2001-02-24. dead.
  11. Web site: Allen Brain Atlas. https://web.archive.org/web/20190419104247/http://mouse.brain-map.org/. 2019-04-19. dead.
  12. Web site: ElDorado Introduction. www.genomatix.de. 2019-04-29. 2016-06-02. https://web.archive.org/web/20160602041758/https://www.genomatix.de/online_help/help_eldorado/introduction.html. dead.
  13. Web site: Clustal Omega < Multiple Sequence Alignment < EMBL-EBI. www.ebi.ac.uk. 2019-04-29.
  14. Web site: ExPASy: SIB Bioinformatics Resource Portal - Categories. www.expasy.org. 2019-04-29.
  15. Räschle, M., Smeenk, G., Hansen, R. K., Temu, T., Oka, Y., Hein, M. Y., … Mann, M. (2015). DNA repair. Proteomics reveals dynamic assembly of repair complexes during bypass of DNA cross-links. Science, 348(6234), 1253671.
  16. Web site: BLAST: Basic Local Alignment Search Tool. blast.ncbi.nlm.nih.gov. 2019-04-21.
  17. Web site: Human BLAT Search. genome.ucsc.edu. 2019-04-21.
  18. Web site: TimeTree :: The Timescale of Life. www.timetree.org. 2019-04-29.
  19. Web site: mentha: the interactome browser. www.mentha.uniroma2.it. 2019-04-29.
  20. Web site: LRSAM1 - E3 ubiquitin-protein ligase LRSAM1 - Homo sapiens (Human) - LRSAM1 gene & protein. www.uniprot.org. 2019-04-29.
  21. Web site: FAM178B protein (human) - STRING interaction network. string-db.org. 2019-04-29.