FAM178B

Last updated
FAM178B
Identifiers
Aliases FAM178B , family with sequence similarity 178 member B
External IDs MGI: 3026913; HomoloGene: 87288; GeneCards: FAM178B; OMA:FAM178B - orthologs
Orthologs
SpeciesHumanMouse
Entrez

51252

381337

Ensembl

ENSG00000168754

ENSMUSG00000046337

UniProt

Q8IXR5

Q24JP3

RefSeq (mRNA)

NM_001122646
NM_001172667
NM_016490

NM_001126046
NM_027957
NM_201365
NM_001372416
NM_001372417

Contents

RefSeq (protein)

NP_001116118
NP_001166138
NP_057574

NP_001119518
NP_082233
NP_958753
NP_001359345
NP_001359346

Location (UCSC) Chr 2: 96.88 – 96.99 Mb Chr 1: 36.6 – 36.72 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

FAM178B is a protein coding gene that is located on the plus strand of chromosome 2. [5] The locus for the gene is 2q11.2. It is also known by the aliases Family with Sequence Similarity 178, Member B, and HSPC234. [6] 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. [5]

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. [7]

Protein structure

The molecular weight of the protein is 76.5 kilodaltons, [8] and the isoelectric point is 5.47.The gene has 6 transcript splice variants. [9] The protein has been phenotypically associated with bipolar disease due to its locus, [10] as well as body mass index (BMI), and cell adhesion. [11] A proposed structure for the protein can be found in the images for proposed structures. [12] The secondary structure for the FAM178B protein is predicted to be primarily alpha helices. [13] The tertiary structure of the protein may assume a coiled coil structure. [13]

Tertiary Structure of FAM178B .gif

Expression

FAM178B is most highly expressed in the skeletal muscle and brain tissues [14] .The structure in which it is highly concentrated is in the corpus callosum of the brain. [14] 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, [15] 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. [16] A table of relevant transcription factor binding sites that correspond to the sequence and colors highlighted in the promoter region is also included.


Part 1 of promoter region FAM178B.png

Part 2 promoter region FAM178B.png

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. [17]


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:. [18]


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. [19] There are 74 known orthologs of the protein, and it can be traced back as far back as crustaceans. [5] 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 [20] and BLAT. [21]

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 HumanQ8IXR5.2827------
Macaca Mulatta MacqueXP_01496843370928.18083
Chlorocebus Sabaeus Green MonkeyXP_00800624572428.19194
Cebus Capucinus CapuchinXP_01737941780842.68891
Otolemur Garnettii GalagoXP_01266650267573.07481
Marmota Marmota MarmotXP_01535510969288.07480
Microtus Ochrogaste rVoleXP_02664157956188.06875
Felis Catus CatXP_01968263672094.07177
Equus Caballus HorseXP_02347439565994.07884
Panthera Tigris TigerXP_00709788167494.07580
Miniopterus Natalensis BatXP_01607715164994.07381
Bison Bison BisonXP_01082815766494.06573
Tursiops Truncatus DolphinJH47347382794.06168
Alligator Mississippiensis AlligatorXP_019343229802320.03447
Pogona Vitticeps Bearded DragonXP_0206358801003320.04156
Apteryx Rowi KiwiXP_025941058512320.04258
Gallus Gallus ChickenXP_024998603547320.03750
Rhincodon Typus Whale SharkXP_0203884901155465.03453
Callorhinchus Milii Australian GhostsharkXP_007910600860465.03350
Crassostrea Gigas Pacific OyserEKC429691222794.02438
Pomacea Canaliculta ApplesnailPVD304551229794.02445

Timetree [22] for FAM178B

Interacting Proteins

There are 2 proteins that have high predicted values of interaction with FAM178B: LRSAM 1 and ZNF598. [23] LRSAM1 [24] 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.png MENTHA [23] interacting proteins for FAM178B.

STRING interacting proteins.png STRING [25] interacting proteins for FAM178B.


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References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000168754 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000046337 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 3 FAM178B - Protein FAM178B - Homo sapiens (Human) - FAM178B gene & protein. (n.d.). Retrieved February 25, 2019, from https://www.uniprot.org/uniprot/Q8IXR5
  6. ↑ RecName: Full=Protein FAM178B - Protein - NCBI. (n.d.). Retrieved February 25, 2019, from https://www.ncbi.nlm.nih.gov/protein/Q8IXR5.2
  7. ↑ 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 (May 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. PMC   5331883 . PMID   25931565.
  8. ↑ "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 2019-04-21.
  9. ↑ 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
  10. ↑ 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
  11. ↑ 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
  12. ↑ SWISS-MODEL Repository | Q8IXR5. (n.d.). Retrieved February 25, 2019, from https://swissmodel.expasy.org/repository/uniprot//Q8IXR5
  13. 1 2 "PHYRE2 Protein Fold Recognition Server". www.sbg.bio.ic.ac.uk. Retrieved 2019-04-22.
  14. 1 2 "Gene2Promoter". ExPasy. Archived from the original on 2001-02-24.
  15. ↑ "Allen Brain Atlas". Archived from the original on 2019-04-19.
  16. ↑ "ElDorado Introduction". www.genomatix.de. Archived from the original on 2016-06-02. Retrieved 2019-04-29.
  17. ↑ "Clustal Omega < Multiple Sequence Alignment < EMBL-EBI". www.ebi.ac.uk. Retrieved 2019-04-29.
  18. ↑ "ExPASy: SIB Bioinformatics Resource Portal - Categories". www.expasy.org. Retrieved 2019-04-29.
  19. ↑ 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
  20. ↑ "BLAST: Basic Local Alignment Search Tool". blast.ncbi.nlm.nih.gov. Retrieved 2019-04-21.
  21. ↑ "Human BLAT Search". genome.ucsc.edu. Retrieved 2019-04-21.
  22. ↑ "TimeTree :: The Timescale of Life". www.timetree.org. Retrieved 2019-04-29.
  23. 1 2 "mentha: the interactome browser". www.mentha.uniroma2.it. Retrieved 2019-04-29.
  24. ↑ "LRSAM1 - E3 ubiquitin-protein ligase LRSAM1 - Homo sapiens (Human) - LRSAM1 gene & protein". www.uniprot.org. Retrieved 2019-04-29.
  25. ↑ "FAM178B protein (human) - STRING interaction network". string-db.org. Retrieved 2019-04-29.

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. Bibcode:2005Natur.434..724H. doi: 10.1038/nature03466 . ISSN   1476-4687. PMID   15815621.
  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. doi:10.1016/j.cell.2005.08.029. hdl: 11858/00-001M-0000-0010-8592-0 . ISSN   0092-8674. PMID   16169070. S2CID   8235923.
  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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