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FAM227B

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FAM227B
Identifiers
AliasesFAM227B, C15orf33, family with sequence similarity 227 member B
External IDsMGI: 1923073; HomoloGene: 27384; GeneCards: FAM227B; OMA:FAM227B - orthologs
Orthologs
SpeciesHumanMouse
Entrez

196951

75823

Ensembl

ENSG00000166262

ENSMUSG00000027209

UniProt

Q96M60

Q9D518

RefSeq (mRNA)

NM_152647
NM_001330293

NM_029455

RefSeq (protein)

NP_001317222
NP_689860

NP_083731

Location (UCSC)Chr 15: 49.33 – 49.62 MbChr 2: 125.83 – 125.99 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

FAM227B is a protein that in humans is encoded by FAM227B gene. FAM227B stands for family with sequence similarity 227 member B and encodes protein FAM227B of the same name. Its aliases include C15orf33, MGC57432 and FLJ23800.[5][6]

Gene

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FAM227B is located at 15q21.2 and contains 24 exons. The current size determined for FAM227B is 293,961 base pairs (NCBI). Neighbors of FAM227B on chromosome fifteen include: “ribosomal protein L15 pseudogene”, “galactokinase 2”, “RNA, 7SL, cytoplasmic 307, pseudogene”, “signal peptide peptidase like 2A pseudogene”, “fibroblast growth factor 7”, “uncharacterized LOC105370811”, “DTW domain containing 1”, and “ring finger protein, LIM domain interacting pseudogene 3”.[5]

Transcript

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There are 30 isoforms of FAM227B and one paralog, FAM227A. The conserved domains in these isoforms (as well as the paralog) are of various sizes and encode the protein FWWh (pfam14922) of unknown function, which all contain the distinctive motif FWW with a hydrophobic residue h. The main isoform used for analysis of FAM227B is isoform 1 (NM_152647.3). The next most reliable isoform of FAM227B is isoform 2 ( NM_001330293.2). The second isoform is shorter and has a distinct C-terminus.[5]

Below are cartoons depicting the different lengths and cutting patterns of the isoforms*:

*The cartoons do not precisely depict differences between all the isoforms, but instead act as a simple depiction of a larger pattern between the isoforms.

Protein

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The primary sequence for FAM227B is isoform 1 with accession number: NP_689860.2. It is 508 amino acids long. There are 30 isoforms. The molecular weight is 59.9kD and the isoelectric point is predicted to be high, around 10.[7] Compared to other proteins in humans, FAM227B has high abundance of Phenylalanine and Glycine and low abundance levels of Valine. The protein is predicted to be in the nuclear region of the cell.[8] There is a bipartite nuclear localization signal at RKLERYGEFLKKYHKKK, and three other nuclearization signals at HKKK, KKKK, and PKKTKIK. There is also a vacuolar targeting motif at TLPI.[8][9] An FWWh region, where h signifies hydrophobic, runs from amino acids 135-296 in Homo sapiens FAM227B isoform 1. The function of this region is still unknown.

Secondary structure

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The secondary structure is predicted to be made up of alpha helices mainly and coiled coils[10]

Post translational modifications

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Phosphorylation is the main post-translational modification predicted for FAM227B due to its predicted localization to the nucleus.[8][11] There are many experimentally predicted phosphorylation sites, the most highly rated included in the conceptual translation.[12] Glycosylation sites and SUMOylation sites were also predicted.[13][14]

Expression

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FAM227B is most highly expressed in the testis at 1.983 +/- 0.404 RPKM, in the kidney at 1.408 +/- 0.152 RPKM, in the adrenal at 1.177 +/- 0.088 RPKM, and in the thyroid 1.133 +/- 0.165 RPKM. It is also expressed to a lesser degree in the appendix, bone marrow, brain, colon, duodenum, endometrium, esophagus, fat, gall bladder, heart, liver, lung, lymph node, ovary, pancreas, placenta, prostate, salivary gland, skin, small intestine, spleen, stomach, and urinary bladder[5]

Function

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Currently, the function of FAM227B has not been characterized[15]

Protein-protein interactions

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RNF123 was found to be an interacting protein of FAM227B through Affinity Capture – MS.[16] RAB3A was found to be an interacting protein of FAM227B through tandem affinity purification.[17]

Subcellular localization

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Current studies have determined the location of this gene to be in the nuclear region of the cell.[8][18][11]

Homology and evolution

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Paralogs: FAM227A

Orthologs: FAM227B is present in Deuterostomia and Protostomia, dating as far back as porifera. FAM227B is not present in choanoflagellates, and gene alignment sequences have shown that FAM227B is a rapidly evolving gene due to its evolution trajectory compared to cytochrome c and fibrinogen alpha.[19]

Clinical significance

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The location of FAM227B, 15q21.2, was found to be associated with oral cancer.[20] The 15q21.2 locus is mentioned in other literature as well.[21][22] FGF7 is a neighbour of FAM227B in the 15q21.2 locus (rs10519227), and encodes for the fibroblast growth factor, which is involved in processes such as embryonic development, cell growth, tissue repair, tumor growth, invasion, and morphogenesis. FGF works as a signal for thyroid gland development, and an SNP on intron 2 of FGF7 has been associated with thyroid growth/goiter growth.[21] This association was only significant at the genome level in males.[21] It was found that the abnormal goiter growth is likely due to variant signals that cause increased levels of TSH.[21][22] FAM227B was found to be related to at least some of the 48 significant DMRs (differentially methylated regions) between HF (high fertile) and LF (low fertile) groups in the genome of spermatozoa from boar animal model.[23] FAM227B was found to be upregulated in LOXL2 knockdown.[24] Knocking down LOXL2 results in lower levels of H3K4ox, resulting in chromatin decompaction, thus continuing activation of DNA damage response. This results in anticancer agents being more effective against cancerous cell lines.[24] FAM227B was found to be a genetic risk variant in breast cancer.[25] FAM227B was differentially expressed in prostrate genes of Esr2 knockout rats compared to wildtype rats.[26] Esr2 is involved in anti-proliferation and differentiation.[26] FAM227B was part of 20 upregulated genes in chorionic girdle during trophoblast development in horses.[27] Protein FAM227B was differentially expressed in cardiovascular disease.[28] FAM227B was found to be a candidate causal gene for lung cancer.[29] FAM227B has a predicted p53 binding site.[30]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000166262 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027209 – 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. ^ a b c d "FAM227B family with sequence similarity 227 member B [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2021-07-31.
  6. ^ "FAM227B Gene". www.genecards.org. Retrieved 2021-07-31.
  7. ^ "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 2021-07-31.
  8. ^ a b c d "PSORT: Protein Subcellular Localization Prediction Tool". www.genscript.com. Retrieved 2021-07-31.
  9. ^ "Motif Scan". myhits.sib.swiss. Retrieved 2021-07-31.
  10. ^ "The Yang Zhang Lab". zhanggroup.org. Retrieved 2021-07-31.
  11. ^ a b "Tissue expression of FAM227B - Summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2021-07-31.
  12. ^ "GPS 5.0 - Kinase-specific Phosphorylation Site Prediction". gps.biocuckoo.cn. Retrieved 2021-07-31.
  13. ^ "YinOYang 1.2 Server". www.cbs.dtu.dk. Retrieved 2021-07-31.
  14. ^ "[JASSA] Joined Advanced SUMOylation site and SIM Analyser". www.jassa.fr. Retrieved 2021-07-31.
  15. ^ "Family: FWWh (PF14922)". pfam.xfam.org. Retrieved 2021-07-31.
  16. ^ Khanna R, Krishnamoorthy V, Parnaik VK (June 2018). "E3 ubiquitin ligase RNF123 targets lamin B1 and lamin-binding proteins". The FEBS Journal. 285 (12): 2243–2262. doi:10.1111/febs.14477. PMID 29676528.
  17. ^ Li Y, Wang Y, Zou L, Tang X, Yang Y, Ma L, et al. (February 2016). "Analysis of the Rab GTPase Interactome in Dendritic Cells Reveals Anti-microbial Functions of the Rab32 Complex in Bacterial Containment". Immunity. 44 (2): 422–37. doi:10.1016/j.immuni.2016.01.027. PMID 26885862.
  18. ^ "PredictProtein - Protein Sequence Analysis, Prediction of Structural and Functional Features". predictprotein.org. Retrieved 2021-07-31.
  19. ^ "BLAST: Basic Local Alignment Search Tool". blast.ncbi.nlm.nih.gov. Retrieved 2021-07-31.
  20. ^ Lesseur C, Diergaarde B, Olshan AF, Wünsch-Filho V, Ness AR, Liu G, et al. (December 2016). "Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer". Nature Genetics. 48 (12): 1544–1550. doi:10.1038/ng.3685. PMC 5131845. PMID 27749845.
  21. ^ a b c d Porcu E, Medici M, Pistis G, Volpato CB, Wilson SG, Cappola AR, et al. (2013-02-07). "A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function". PLOS Genetics. 9 (2): e1003266. doi:10.1371/journal.pgen.1003266. PMC 3567175. PMID 23408906.
  22. ^ a b Teumer A, Rawal R, Homuth G, Ernst F, Heier M, Evert M, et al. (May 2011). "Genome-wide association study identifies four genetic loci associated with thyroid volume and goiter risk". American Journal of Human Genetics. 88 (5): 664–73. doi:10.1016/j.ajhg.2011.04.015. PMC 3146733. PMID 21565293.
  23. ^ Pértille F, Alvarez-Rodriguez M, da Silva AN, Barranco I, Roca J, Guerrero-Bosagna C, et al. (March 2021). "Sperm Methylome Profiling Can Discern Fertility Levels in the Porcine Biomedical Model". International Journal of Molecular Sciences. 22 (5): 2679. doi:10.3390/ijms22052679. PMC 7961483. PMID 33800945.
  24. ^ a b Cebrià-Costa JP, Pascual-Reguant L, Gonzalez-Perez A, Serra-Bardenys G, Querol J, Cosín M, et al. (January 2020). "LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells". Oncogene. 39 (1): 79–121. doi:10.1038/s41388-019-0969-1. PMC 6937214. PMID 31462706.
  25. ^ Rashkin SR, Graff RE, Kachuri L, Thai KK, Alexeeff SE, Blatchins MA, et al. (September 2020). "Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts". Nature Communications. 11 (1): 4423. Bibcode:2020NatCo..11.4423R. doi:10.1038/s41467-020-18246-6. PMC 7473862. PMID 32887889.
  26. ^ a b Khristi V, Ghosh S, Chakravarthi VP, Wolfe MW, Rumi MA (June 2019). "Transcriptome data analyses of prostatic hyperplasia in Esr2 knockout rats". Data in Brief. 24: 103826. Bibcode:2019DIB....2403826K. doi:10.1016/j.dib.2019.103826. PMC 6475810. PMID 31016213.
  27. ^ Read JE, Cabrera-Sharp V, Offord V, Mirczuk SM, Allen SP, Fowkes RC, et al. (October 2018). "Dynamic changes in gene expression and signalling during trophoblast development in the horse". Reproduction. 156 (4): 313–330. doi:10.1530/REP-18-0270. PMC 6170800. PMID 30306765.
  28. ^ Lygirou V, Latosinska A, Makridakis M, Mullen W, Delles C, Schanstra JP, et al. (April 2018). "Plasma proteomic analysis reveals altered protein abundances in cardiovascular disease". Journal of Translational Medicine. 16 (1): 104. doi:10.1186/s12967-018-1476-9. PMC 5905170. PMID 29665821.
  29. ^ Bossé Y, Li Z, Xia J, Manem V, Carreras-Torres R, Gabriel A, et al. (April 2020). "Transcriptome-wide association study reveals candidate causal genes for lung cancer". International Journal of Cancer. 146 (7): 1862–1878. doi:10.1002/ijc.32771. PMC 7008463. PMID 31696517.
  30. ^ Hearnes JM, Mays DJ, Schavolt KL, Tang L, Jiang X, Pietenpol JA (November 2005). "Chromatin immunoprecipitation-based screen to identify functional genomic binding sites for sequence-specific transactivators". Molecular and Cellular Biology. 25 (22): 10148–58. doi:10.1128/mcb.25.22.10148-10158.2005. PMC 1280257. PMID 16260627.
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