Biology:FAM178B

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Short description: Protein coding


FAM178B is a protein coding 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.[1]

FAM178B Isoforms from Splice Variation:
Isoform: Identifier: Length in Amino Acids: Mass (daltons):
1 Q8IXR5-1 827 93,514
2 Q8IXR5-2 119 13,809
3 Q8IXR5-3 679 76,515

Protein structure

The molecular weight of the protein is 76.5 kilodaltons,[3] and the isoelectric point is 5.47.The gene has 6 transcript splice variants.[4] The protein has been phenotypically associated with bipolar disease due to its locus,[5] as well as body mass index (BMI), and cell adhesion.[6] A proposed structure for the protein can be found in the images for proposed structures.[7] The secondary structure for the FAM178B protein is predicted to be primarily alpha helices.[8] The tertiary structure of the protein may assume a coiled coil structure.[8]

Expression

FAM178B is most highly expressed in the skeletal muscle and brain tissues[9].The structure in which it is highly concentrated is in the corpus callosum of the brain.[9] 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,[10] the olfactory regions, and the hippocampus of the mouse brain showed the greatest expressions of the gene when tested experimentally.

Gene Expression FAM178B.png

DNA Level Regulation

The proposed promoter region of FAM178B protein is below.[11] 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.[12]


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:.[13]


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.[14] There are 74 known orthologs of the protein, and it can be traced back as far back as crustaceans.[1] 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[15] and BLAT.[16]

Scientific Name: Common Name: Accession Number

from NCBI:

Sequence Length:

(Amino Acids)

Date of Divergence from Human Lineage:

(millions of years ago)

Percent Identity: Percent Similarity:
Homo Sapiens Human Q8IXR5.2 827 -- -- --
Macaca Mulatta Macque XP_014968433 709 28.1 80 83
Chlorocebus Sabaeus Green Monkey XP_008006245 724 28.1 91 94
Cebus Capucinus Capuchin XP_017379417 808 42.6 88 91
Otolemur Garnettii Galago XP_012666502 675 73.0 74 81
Marmota Marmota Marmot XP_015355109 692 88.0 74 80
Microtus Ochrogaster Vole XP_026641579 561 88.0 68 75
Felis Catus Cat XP_019682636 720 94.0 71 77
Equus Caballus Horse XP_023474395 659 94.0 78 84
Panthera Tigris Tiger XP_007097881 674 94.0 75 80
Miniopterus Natalensis Bat XP_016077151 649 94.0 73 81
Bison Bison Bison XP_010828157 664 94.0 65 73
Tursiops Truncatus Dolphin JH473473 827 94.0 61 68
Alligator Mississippiensis Alligator XP_019343229 802 320.0 34 47
Pogona Vitticeps Bearded Dragon XP_020635880 1003 320.0 41 56
Apteryx Rowi Kiwi XP_025941058 512 320.0 42 58
Gallus Gallus Chicken XP_024998603 547 320.0 37 50
Rhincodon Typus Whale Shark XP_020388490 1155 465.0 34 53
Callorhinchus Milii Australian Ghostshark XP_007910600 860 465.0 33 50
Crassostrea Gigas Pacific Oyser EKC42969 1222 794.0 24 38
Pomacea Canaliculta Applesnail PVD30455 1229 794.0 24 45

Timetree[17] for FAM178B

Interacting Proteins

There are 2 proteins that have high predicted values of interaction with FAM178B: LRSAM 1 and ZNF598.[18] LRSAM1[19] 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.

FAM178B Interacting Proteins.pngMENTHA[18] interacting proteins for FAM178B.

STRING[20] interacting proteins for FAM178B.


References

  1. ↑ 1.0 1.1 1.2 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. ↑ "SAPS < Sequence Statistics < EMBL-EBI". https://www.ebi.ac.uk/Tools/seqstats/saps/. 
  4. ↑ 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
  5. ↑ 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
  6. ↑ 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
  7. ↑ SWISS-MODEL Repository | Q8IXR5. (n.d.). Retrieved February 25, 2019, from https://swissmodel.expasy.org/repository/uniprot//Q8IXR5
  8. ↑ 8.0 8.1 "PHYRE2 Protein Fold Recognition Server". http://www.sbg.bio.ic.ac.uk/phyre2/html/page.cgi?id=index. 
  9. ↑ 9.0 9.1 "Gene2Promoter". https://www.genomatix.de/. 
  10. ↑ "Allen Brain Atlas". https://www.mouse.brain-map.org. 
  11. ↑ "ElDorado Introduction". https://www.genomatix.de/online_help/help_eldorado/introduction.html. 
  12. ↑ "Clustal Omega < Multiple Sequence Alignment < EMBL-EBI". https://www.ebi.ac.uk/Tools/msa/clustalo/. 
  13. ↑ "ExPASy: SIB Bioinformatics Resource Portal - Categories". https://www.expasy.org/proteomics/protein-protein_interaction. 
  14. ↑ 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. doi:10.1126/science.1253671
  15. ↑ "BLAST: Basic Local Alignment Search Tool". https://blast.ncbi.nlm.nih.gov/Blast.cgi. 
  16. ↑ "Human BLAT Search". https://genome.ucsc.edu/cgi-bin/hgBlat. 
  17. ↑ "TimeTree :: The Timescale of Life". http://www.timetree.org/. 
  18. ↑ 18.0 18.1 "mentha: the interactome browser". https://www.mentha.uniroma2.it/. 
  19. ↑ "LRSAM1 - E3 ubiquitin-protein ligase LRSAM1 - Homo sapiens (Human) - LRSAM1 gene & protein". https://www.uniprot.org/uniprot/Q6UWE0. 
  20. ↑ "FAM178B protein (human) - STRING interaction network". https://string-db.org/cgi/network.pl?taskId=mpHKfJap039K. 

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 et al. (2005-04-07). "Generation and annotation of the DNA sequences of human chromosomes 2 and 4". Nature 434 (7034): 724–731. doi:10.1038/nature03466. ISSN 1476-4687. PMID 15815621. Bibcode: 2005Natur.434..724H. https://www.ncbi.nlm.nih.gov/pubmed?cmd=search&term=15815621&dopt=b. 
  2. Stelzl, Ulrich; Worm, Uwe; Lalowski, Maciej; Haenig, Christian; Brembeck, Felix H.; Goehler, Heike; Stroedicke, Martin; Zenkner, Martina et al. (2005-09-23). "A human protein-protein interaction network: a resource for annotating the proteome". Cell 122 (6): 957–968. doi:10.1016/j.cell.2005.08.029. ISSN 0092-8674. PMID 16169070. https://www.ncbi.nlm.nih.gov/pubmed?cmd=search&term=16169070&dopt=b. 
  3. Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells
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