FAM149B1

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The Family with sequence similarity 149 member B1 is an uncharacterized protein [1] encoded by the human FAM149B1 gene, with one alias KIAA0974. [2] [3] The protein resides in the nucleus of the cell. The predicted secondary structure of the gene contains multiple alpha-helices, with a few beta-sheet structures. The gene is conserved in mammals, birds, reptiles, fish, and some invertebrates. The protein encoded by this gene contains a DUF3719 protein domain, which is conserved across its orthologues. [3] The protein is expressed at slightly below average levels in most human tissue types, with high expression in brain, kidney, and testes tissues, while showing relatively low expression levels in pancreas tissues. [4] [5]

Contents

Gene

This gene has a possible 14 exons. It is located on the forward strand of chromosome 10 at 10q22.2 on the positive strand. [6] The total span of the gene, including 5' and 3' UTR, is 3149 base pairs. The gene is flanked on the left by NUDT13 (nudix hydrolase 13) and on the right by DNAJC9-AS1 (DNAJC9 antisense RNA 1).

This figure shows the location of the FAM149B1 gene on Chromosome 10, and also displays the genes in the surrounding location. FAM149B1 Chromosome Map.png
This figure shows the location of the FAM149B1 gene on Chromosome 10, and also displays the genes in the surrounding location.

Isoforms

The FAM149B1 protein has a possible 10 isoforms, which are determined through alternative splicing of the gene.

The various isoforms of the FAM149B1 gene NCBI FAM149B1 Gene Isoforms.png
The various isoforms of the FAM149B1 gene
Isoform NameAccessionExonsLength (bp)
Primary TranscriptNM_173348.1All (14)3149
X1XM_005269744.2All (14)3108
X2XM_011539737.2132935
X3XM_005269745.2133006
X4XM_017016164.1122810
X5XM_017016165.1112779
X6*XM_017016166.192816
X6*XM_005269747.392923
X7XM_017016167.191485
X8XM_011539740.291447

Protein

General properties

The primary protein encoded by the FAM149B1 gene is 583 amino acids in length and has a molecular weight of 64 kDal. The protein contains a conserved protein domain, DUF3719 [8] [6] located at the amino acids 115–179. The isoelectric point of the protein before post-translational modifications is 6.3, [9] and this isoelectric point is relatively conserved in the protein's isoforms, especially in those with the most similar composition of exons. This protein is considered serine rich, in that it expresses a higher serine composition relative to the composition of other human proteins. [10] [11] This high serine composition is also seen in the gene's orthologues.

Splice variants

The splice variants of the protein demonstrate some shared qualities of the protein that is translated from the primary transcript. Because each isoform is a different length and contains various combinations of the available exons, there are variances in the isoelectric point and molecular weight. The isoforms closest to the weight and exon composition to the primary transcript generally share these characteristics. The protein isoforms missing the conserved DUF3719 domain are isoforms X5 and X6 because this domain is contained between exons 3–6.

Isoform NameAccessionMolecular Weight (kDal)Length (aa)Isoelectric point
Primary TranscriptNP_775483.1645826.3
X1XP_005269801.163.75746.3
X2XP_011538039.162.65607.5
X3XP_005269802.159.85406.4
X4XP_016871653.157.85187.7
X5XP_016871654.1534766.8
X6*XP_016871655.146.64197.5
X6*XP_005269804.146.64197.5
X7XP_016871656.1413685.1
X8XP_011538042.1383485.2

Structure

There is a negative charge cluster from amino acids 212 to 239. Negative charge clusters often coordinate calcium, or magnesium or zinc ions, mannose-binding protein, or aminopeptidase. [12] The protein contains no positive or mixed charge clusters. The secondary structure of the protein is predicted to be a combination of mostly alpha-helices with a few predicted beta-sheet structures.

This figure shows the predicted 3D structure of the human FAM149B1 protein. The secondary structures contributing to the tertiary structure are alpha-helices and one predicted beta-sheet turn. 3D Structure Prediction.png
This figure shows the predicted 3D structure of the human FAM149B1 protein. The secondary structures contributing to the tertiary structure are alpha-helices and one predicted beta-sheet turn.

Subcellular localization

Immunofluorescent stain shows expression of FAM149B1 to be highly expressed in the nucleus. Immunofluorescent Stain FAM149B1.jpg
Immunofluorescent stain shows expression of FAM149B1 to be highly expressed in the nucleus.

The subcellular location of the protein is the nucleus. [13] There is a leucine zipper pattern in the protein beginning at amino acid 347. [14]

Post-translational modifications

Acetylation

The third amino acid in the protein sequence, serine, is predicted to be acetylated. [15]

Phosphorylation

There are multiple predicted phosphorylation sites on various serine, tyrosine, and threonine amino acids are predicted for this protein sequence. [16] The conserved DUF3719 domain contains 7 predicted phosphorylation sites.

Sumoylation

One predicted sumoylation site was identified in the protein sequence at K267. [17]

A schematic diagram of the FAM149B1 protein after post translational modifications. The DUF3719 domain is also displayed. FAM149B1 Schematic Drawing.png
A schematic diagram of the FAM149B1 protein after post translational modifications. The DUF3719 domain is also displayed.

Expression

Overall in the human body, this gene is expressed at levels slightly below the average human gene expression level. [18] The protein is expressed in most cell types of the human body. [19] Most experimentation shows a higher expression of this protein in kidney, testes, and brain tissues, with very low expression seen in pancreas tissues. [4] [5] The gene is expressed at lower levels than its normal expression in most cancerous tissues. The gene is also seen to be expressed most highly in fetal and infantile tissues. [20]

DNA microarray data

A DNA microarray experiment showing the varying expression levels of FAM149B1 before and after depleting beta-catenin levels in the sample. Beta-catenin GeoProfile.png
A DNA microarray experiment showing the varying expression levels of FAM149B1 before and after depleting beta-catenin levels in the sample.

DNA microarray analysis experiments show expression patterns of FAM149B1 compared to multiple other genes in a sample. FAM149B1 is shown to be at a lower expression level than most other genes in a multiple myeloma cell line and was shown to increase to close to average gene expression levels after the beta-catenin was depleted from the sample. [21]

A microarray experiment displaying lowered gene expression levels of FAM149B1 in an ovarian cancer cell line after the use of NSC319726 anticancer drug. GEOProfile Ovarian Cancer Cell FAM149B1.png
A microarray experiment displaying lowered gene expression levels of FAM149B1 in an ovarian cancer cell line after the use of NSC319726 anticancer drug.

FAM149B1 expression was also shown to decrease to lower than average gene expression levels in an ovarian cancer cell line after the use of an anticancer drug named NSC319726. [13]

Transcriptional regulation

The gene has nine different identified promoter regions, which correlate to the various isoforms of the gene. The promoter for the primary transcript of the gene has binding sites for a variety of different transcription factors.

Interacting proteins

Current data supports the FAM149B1 protein interactions with 6 different proteins.

One protein was determined to be an interacting protein with FAM149B1 through affinity chromatography techniques.

The other five proteins that have been predicted to interact with FAM149B1 protein were found through the process of textmining.

Homology/Evolution

Paralog

There is one known paralog, FAM149A. [27] It is located on the human chromosome 4 at 4q35.1. The function of the protein encoded by this gene is not well understood, but it also contains the DUF3719 protein domain. The protein translated by this gene shares a 21.2% identity [28] with the FAM149B1 protein. The protein sequence is 482 amino acids in length.

Orthologs

An uprooted phylogenetic tree displaying a select number of orthologues and paralog of the FAM149B1 gene, based on the identity of the species to the human protein sequence. FAM149B1 Phylogenetic Tree - Protein Orthologs.jpg
An uprooted phylogenetic tree displaying a select number of orthologues and paralog of the FAM149B1 gene, based on the identity of the species to the human protein sequence.
The graph shows the relative rate of genetic modifications compared to fibrinogen and cytochrome c genes across the orthologs of FAM149B1. Identity versus divergence Graph.png
The graph shows the relative rate of genetic modifications compared to fibrinogen and cytochrome c genes across the orthologs of FAM149B1.

This gene has orthologues across mammals, birds, reptiles, fish, and some invertebrates. [3] There is a high conservation in mammals, moderate conservation in many of the other vertebrate orthologues, and a low conservation in its few invertebrate orthologues. [29] [28]

Genus speciesCommon NameTime of Divergence (MYA) [30] Accession NumberLength (aa)Identity [28]
1 Homo sapiens Human-NP_775483.1582100%
2 Pongo abelii Sumatran orangutan15.76XP_009243761.158793.0%
3 Papio anubis Baboon29.4XP_003903829.158293.6%
4 Mus musculus Mouse90XP_006518391.154473.5%
5 Bos mutus Domestic Yak96XP_005910201.158486.0%
6 Orcinus orca Killer whale, Orca96XP_004273176.158587.0%
7 Ailuropoda melanoleuca Giant Panda96XP_011224744.159082.7%
8Orycteropus afer aferAardvark105XP_007938812.158384.0%
9 Monodelphis domestica Short-Tailed Opossum159XP_007478430.158773.5%
10 Sarcophilus harrisii Tasmanian Devil159XP_012396086.158872.0%
11 Ornithorhynchus anatinus Platypus177XP_007658720.150648.1%
12 Gallus gallus Chicken312XP_004942035.160250.4%
13 Lepidothrix coronata Blue-crowned manakin312XP_017688171.157647.5%
14 Haliaeetus albicilla White-tailed eagle312XP_009911204.158949.4%
15 Falco peregrinus Peregrine falcon312XP_005235226.159749.2%
16 Chrysemys picta bellii Western painted turtle312XP_008169104.159656.1%
17 Pelodiscus sinensis Chinese softshell turtle312XP_014433498.148747.1%
18 Alligator mississippiensis American alligator312XP_014464842.159655.0%
19 Xenopus tropicalis Western clawed frog352NP_001278638.156139.8%
20 Danio rerio Zebra fish435NP_001074134.164437.7%
21 Lepisosteus oculatus Spotted gar435XP_015202055.164737.9%
22 Oreochromis niloticus Nile tilapia435XP_005474333.168334.3%
23 Callorhinchus milii Australian ghostshark473XP_007897395.163836.8%
24 Ciona intestinalis Sea squirt676XP_002129894.180724.5%
25 Aplysia californica California sea slug797XP_012945921.131216.9%

Clinical significance

While the gene is largely not well understood by scientists, it is shown to be associated with a wide range of various cancerous tumors. [31] [32]

The FAM149B1 gene is also included in a region of 11 genes that comprises one of 15 regions containing mutations associated with the African Pygmy phenotype. [33] [34]

Related Research Articles

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References

  1. ↑ "Homo sapiens family with sequence similarity 149 member B1 (FAM149B1), mRNA" . Retrieved 6 February 2017.
  2. ↑ "FAM149B1 Family with sequence similarity 149 member B1" . Retrieved 6 February 2017.
  3. 1 2 3 "Gene: FAM149B1". Ensembl. Retrieved 6 February 2017.
  4. 1 2 The Human Protein Atlas, FAM149B1 http://www.proteinatlas.org/ENSG00000138286-FAM149B1/tissue
  5. 1 2 NCBI, National Center for Biotechnology Information, H. sapiens FAM149B1 ETS https://www.ncbi.nlm.nih.gov/gene/317662
  6. 1 2 "FAM149B1 Gene". GeneCards. Retrieved 6 February 2017.
  7. ↑ "FAM149B1 family with sequence similarity 149 member B1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
  8. ↑ "Protein of unknown function DUF3719 (IPR022194)". InterPro.
  9. ↑ PI, Biology Workbench. Program by Dr. Luca Toldo, developed at http://www.embl-heidelberg.de. Changed by Bjoern Kindler to print also the lowest found net charge. Available at EMBL WWW Gateway to Isoelectric Point Service {{cite web |url=http://www.embl-heidelberg.de/cgi/pi-wrapper.pl |title=Archived copy |access-date=2014-05-10 |url-status=dead |archive-url=https://web.archive.org/web/20081026062821/http://www.embl-heidelberg.de/cgi/pi-wrapper.pl |archive-date=2008-10-26 }}
  10. ↑ AASTATS, Biology Workbench. by Jack Kramer, 1990.
  11. ↑ SAPS, Biology Workbench. Algorithm: Brendel, V., Bucher, P., Nourbakhsh, I.R., Blaisdell, B.E. & Karlin, S. (1992) "Methods and algorithms for statistical analysis of protein sequences" Proc. Natl. Acad. Sci. U.S.A. 89, 2002-2006. Program: Volker Brendel, Department of Mathematics, Stanford University, Stanford CA 94305, U.S.A.
  12. ↑ Zhu, Z. Y.; Karlin, S. (1996-08-06). "Clusters of charged residues in protein three-dimensional structures". Proceedings of the National Academy of Sciences. 93 (16): 8350–8355. Bibcode:1996PNAS...93.8350Z. doi: 10.1073/pnas.93.16.8350 . ISSN   0027-8424. PMC   38674 . PMID   8710874.
  13. 1 2 3 4 "GDS4877 / 213463_s_at". www.ncbi.nlm.nih.gov. Retrieved 2017-05-07.
  14. ↑ "PSORT prediction tool". GenScript.
  15. ↑ NetAcet: Prediction of N-terminal acetylation sites., Accessed through Expasy. Lars Kiemer, Jannick Dyrløv Bendtsen and Nikolaj Blom. Accepted in Bioinformatics, 2004.
  16. ↑ NetPhos: Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence. Blom N, Sicheritz-Ponten T, Gupta R, Gammeltoft S, Brunak S. Proteomics: Jun;4(6):1633-49, review 2004.
  17. ↑ SUMOplot Analysis Program, Developed by Abgent, Copyright © 2013 -2017 http://www.abgent.com/sumoplot
  18. ↑ "FAM149B1 search results". pax-db.org. Retrieved 2017-05-07.
  19. ↑ NCBI GeoProfile, Homo sapiens FAM149B1, Profile GDS596 https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS596%3A213463_s_at
  20. ↑ Group, Schuler. "EST Profile - Hs.408577". www.ncbi.nlm.nih.gov. Retrieved 2017-05-07.{{cite web}}: |last= has generic name (help)
  21. 1 2 "GDS3578 / 213463_s_at". www.ncbi.nlm.nih.gov. Retrieved 2017-05-07.
  22. ↑ Huttlin, E., Ting, L., Bruckner, R., Gebreab, F., Gygi, M., Szpyt, J., . . . Gygi, S. (2015). The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell, 162(2), 425-440. doi : 10.1016/j.cell.2015.06.043
  23. ↑ "ABHD8_HUMAN". UniProt.
  24. ↑ "METTL16 Gene". GeneCards. Archived from the original on 2011-11-16.
  25. ↑ "SLC6A17 Gene". GeneCards. Archived from the original on 2011-11-07.
  26. ↑ "TM2D1 Gene". GeneCards. Archived from the original on 2011-11-30.
  27. ↑ "Homo sapiens family with sequence similarity 149 member A (FAM149A), t - Nucleotide - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
  28. 1 2 3 "ALIGN". Biology Workbench. Retrieved 26 February 2017.
  29. ↑ "NCBI BLAST". National Center for Biotechnology Information. Retrieved 26 February 2017.
  30. ↑ "Time Tree". Time Tree. Retrieved 26 February 2017.
  31. ↑ Ikeda, A; Shimizu, T; Matsumoto, Y (19 September 2013). "Leptin receptor somatic mutations are frequent in HCV-infected cirrhotic liver and associated with haptocellular carcinoma". Gastroenterology. 146 (1): 222–32. doi:10.1053/j.gastro.2013.09.025. hdl: 2433/180778 . PMID   24055508.
  32. ↑ Hadj-Hamou, NS; Lae, M; Almeida, A (24 April 2012). "A transcriptome signature of endothelial lymphatic cells coexists with the chronic oxidative stress signature in radiation-induced post-radiotherapy breast angiosarcomas". Carcinogenesis. 33 (7): 1399–405. doi: 10.1093/carcin/bgs155 . PMID   22532251.
  33. ↑ Detection of Convergent Genome-Wide Signals of Adaptation to Tropical Forests in Humans. (Research Article) Amorim, Carlos Eduardo G.; Daub, Josephine T.; Salzano, Francisco M.; Foll, Matthieu; Excoffier, Laurent PLoS ONE, April 7, 2015, Vol.10(4), p.e0121557 [Peer Reviewed Journal]
  34. ↑ Adaptive evolution of loci covarying with the human African Pygmy phenotype Mendizabal, Isabel; Marigorta, Urko; Lao, Oscar; Comas, David Human Genetics, 2012, Vol.131(8), pp.1305-1317 [Peer Reviewed Journal]
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