FAM178B

FAM178B is a protein coding gene that is located on the plus strand of chromosome 2.FAM178B - Protein FAM178B - Homo sapiens (Human) - FAM178B gene & protein. (n.d.). Retrieved February 25, 2019, from https://www.uniprot.org/uniprot/Q8IXR5 The locus for the gene is 2q11.2. It is also known by the aliases Family with Sequence Similarity 178, Member B, and HSPC234.RecName: Full=Protein FAM178B - Protein - NCBI. (n.d.). Retrieved February 25, 2019, from https://www.ncbi.nlm.nih.gov/protein/Q8IXR5.2 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.

class="wikitable"

|+FAM178B Isoforms from Splice Variation:

!Isoform:

!Identifier:

!Length in Amino Acids:

!Mass (daltons):

|Q8IXR5-1

|827

|93,514

|Q8IXR5-2

|119

|13,809

|Q8IXR5-3

|679

|76,515

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.{{cite journal | vauthors = 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 | title = DNA repair. Proteomics reveals dynamic assembly of repair complexes during bypass of DNA cross-links | journal = Science | volume = 348 | issue = 6234 | pages = 1253671 | date = May 2015 | pmid = 25931565 | pmc = 5331883 | doi = 10.1126/science.1253671 }}

Protein structure

The molecular weight of the protein is 76.5 kilodaltons,{{Cite web|url=https://www.ebi.ac.uk/Tools/seqstats/saps/|title=SAPS < Sequence Statistics < EMBL-EBI|website=www.ebi.ac.uk|access-date=2019-04-21}} and the isoelectric point is 5.47.The gene has 6 transcript splice variants.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 The protein has been phenotypically associated with bipolar disease due to its locus,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 as well as body mass index (BMI), and cell adhesion.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 A proposed structure for the protein can be found in the images for proposed structures.SWISS-MODEL Repository | Q8IXR5. (n.d.). Retrieved February 25, 2019, from https://swissmodel.expasy.org/repository/uniprot//Q8IXR5 The secondary structure for the FAM178B protein is predicted to be primarily alpha helices.{{Cite web|url=http://www.sbg.bio.ic.ac.uk/phyre2/html/page.cgi?id=index|title=PHYRE2 Protein Fold Recognition Server|website=www.sbg.bio.ic.ac.uk|access-date=2019-04-22}} The tertiary structure of the protein may assume a coiled coil structure.

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Expression

FAM178B is most highly expressed in the skeletal muscle and brain tissues{{Cite web|url=https://www.genomatix.de/|title=Gene2Promoter|last=|first=|date=|website=ExPasy|archive-url=https://web.archive.org/web/20010224072831/http://www.genomatix.de/|archive-date=2001-02-24|access-date=|url-status=dead}}.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,{{Cite web|url=https://www.mouse.brain-map.org/|title=Allen Brain Atlas|last=|first=|date=|website=|archive-url=https://web.archive.org/web/20190419104247/http://mouse.brain-map.org/|archive-date=2019-04-19|access-date=|url-status=dead}} the olfactory regions, and the hippocampus of the mouse brain showed the greatest expressions of the gene when tested experimentally.

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DNA Level Regulation

The proposed promoter region of FAM178B protein is below.{{Cite web|url=https://www.genomatix.de/online_help/help_eldorado/introduction.html|title=ElDorado Introduction|website=www.genomatix.de|access-date=2019-04-29|archive-date=2016-06-02|archive-url=https://web.archive.org/web/20160602041758/https://www.genomatix.de/online_help/help_eldorado/introduction.html|url-status=dead}} A table of relevant transcription factor binding sites that correspond to the sequence and colors highlighted in the promoter region is also included.

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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.{{Cite web|url=https://www.ebi.ac.uk/Tools/msa/clustalo/|title=Clustal Omega < Multiple Sequence Alignment < EMBL-EBI|website=www.ebi.ac.uk|access-date=2019-04-29}}

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:.{{Cite web|url=https://www.expasy.org/proteomics/protein-protein_interaction|title=ExPASy: SIB Bioinformatics Resource Portal - Categories|website=www.expasy.org|access-date=2019-04-29}}

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.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}} 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{{Cite web|url=https://blast.ncbi.nlm.nih.gov/Blast.cgi|title=BLAST: Basic Local Alignment Search Tool|website=blast.ncbi.nlm.nih.gov|access-date=2019-04-21}} and BLAT.{{Cite web|url=https://genome.ucsc.edu/cgi-bin/hgBlat|title=Human BLAT Search|website=genome.ucsc.edu|access-date=2019-04-21}}

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!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{{Cite web|url=http://www.timetree.org/|title=TimeTree :: The Timescale of Life|website=www.timetree.org|access-date=2019-04-29}} for FAM178B

Interacting Proteins

There are 2 proteins that have high predicted values of interaction with FAM178B: LRSAM 1 and ZNF598.{{Cite web|url=https://www.mentha.uniroma2.it/|title=mentha: the interactome browser|website=www.mentha.uniroma2.it|access-date=2019-04-29}} LRSAM1{{Cite web|url=https://www.uniprot.org/uniprot/Q6UWE0|title=LRSAM1 - E3 ubiquitin-protein ligase LRSAM1 - Homo sapiens (Human) - LRSAM1 gene & protein|website=www.uniprot.org|access-date=2019-04-29}} 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.

framelessMENTHA interacting proteins for FAM178B.

alt= STRING{{Cite web|url=https://string-db.org/cgi/network.pl?taskId=mpHKfJap039K|title=FAM178B protein (human) - STRING interaction network|website=string-db.org|access-date=2019-04-29}} interacting proteins for FAM178B.

FAM178B

Forms

Protein structure

Expression

DNA Level Regulation

Protein Level Regulation

Homology and Evolution

Interacting Proteins

References

Further reading