The FAM214B, also known as protein family with sequence similarity 214, B (FAM214B) is a protein that, in humans, is encoded by the FAM214B gene located on the human chromosome 9.[5] The protein has 538 amino acids.[6] The gene contain 9 exon.[6] There has been studies that there are low expression of this gene in patients with major depression disorder.[7][8] In most organisms such as mammals, amphibians, reptiles, and birds, there are high levels of gene expression in the bone marrow and blood.[9] For humans in fetal development, FAM214B is mostly expressed in the brains and bone marrow.[9]

FAM214B
Identifiers
AliasesFAM214B, KIAA1539, P1.11659_5, bA182N22.6, family with sequence similarity 214 member B
External IDsMGI: 2441854; HomoloGene: 32625; GeneCards: FAM214B; OMA:FAM214B - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_025182
NM_001317991

NM_001253353
NM_001253354
NM_172691

RefSeq (protein)

NP_001304920
NP_079458

NP_001240282
NP_001240283
NP_766279

Location (UCSC)Chr 9: 35.1 – 35.12 MbChr 4: 43.03 – 43.05 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Gene

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Aliases

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This is also known as KIAA1539, BA182N22.6, FLJ11560, PI.11659_5, LOC80256, and RP11-182N22.6.[10]

Location

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FAM214B is located on human chromosome 9 at the locus position 9p13.3.[11] The gene is 12,229 bp long and it is at position 35,104,112 bp to the 35,116,341 on chromosome 9.[12]

Transcript variants

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There are currently 2 mRNA transcripts variants of FAM214B. Variant 1 encodes the longest transcript and Variant 2 differs in the 5' UTR.[5]

Table 1. Known human mRNA transcript variants for FAM214B
Name Accession Number Number of Exons Size (bp)
Transcript Variant 1 NM_001317991.2 9 3124
Transcript Variant 2 NM_025182.4 9 2999

Protein

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Predicted Secondary Structure using Phyre2
 
Predicted Tertiary Structure I-Tasser (ribbon style)

Isoforms

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There are currently 2 isoforms for FAM214B protein, where isoform 1 encodes for Variant 1 for the longest protein and isoform 2 encoded by Variant 2.[5]

Table 2. Known human protein isoforms for FAM214B
Name Accession Number Size (AA)
Isoform 1 NP_001304920.1 538
Isoform 2 NP_079458.2 514

Composition and characteristics

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The FAM214B protein has a predicted molecular weight of 56.7 kDa and has an isometric point of 9.1.[13] For protein composition, the FAM214B protein contains high amounts of Glycine and Proline, while there was a lack of Isoleucine.[13] There were clusters of positively charged regions on amino acid position 308 to 327 which composed of mostly Leucine and Arginine.[13] There was a repetitive structure of amino acids GPGLG repeat on amino acid position 82 to 86, and 106 to 110.[13] There were repeats of amino acids of Proline in position 10 to 25, and 225 to 265.[13]

Protein Domain

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The FAM214B contains a DUF4210 domain of unknown function at the position 348 to 402, and a chromosome segregation domain at position 480 to 536.[5] The DUF4210 domain is currently has unknown function and predicted to be necessary for chromosome segregation in meiosis.[14]

Secondary structure

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Using Phyre2, Ali2D, and I-TASSER predicted that the FAM214B secondary structure composed of mostly beta sheets and one alpha helix.[15][16][17] Phyre2 prediction is shown on the right.

 
Predicted Tertiary Structure I-Tasser (sphere style)

Tertiary Structure

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Tertiary Structure was predicted using I-Tasser where the purple represents the C-terminal and the red represents the N-terminal shown on the right.[17]

Post-translation modifications

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Phosphorylation

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There are 7 predicted phosphorylation sites on the FAM214B protein which consists of mostly serine and threonine residues.[18]

Table 3. Predicted phosphorylation sites in FAM214B protein
Position Amino Acid
119 Serine
240 Tyrosine
323 Serine
477 Tyrosine
491 Serine
494 Serine
508 Serine

Sub-cellular localization

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Studies of FAM214B protein was determined that the protein is localized in the nucleus.[19]

Expression and regulation

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Promoters

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FAM214B Promoters

Using the Genomatix Gene2Promoter tool, it was determined that the FAM214B has 5 promoters that are found in Homo sapiens.[20] The promoter GXP_38326 has the highest number of encoded transcripts which spans on position 35115811 to 35116911 on the negative strand of human chromosome 9.

Table 4. Promoters for FAM214B gene
Promoter ID Start Position End Position Length (bp) Orientation Number of transcripts supported
GXP_9003729 35111384 35112610 1227 - strand 4
GXP_4436183 35112353 35113392 1040 - strand 1
GXP_38326 35115811 35116911 1101 - strand 9
GXP_9003730 35116054 35117093 1040 - strand 1
GXP_4436184 35116302 35117477 1176 - strand 1

Transcription factors

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FAM214B Promoter Transcription Factors

The table represents a list of predicted transcription factors that bind to the GXP_9003729 promoter using Genomatix MatInspector tool.[20]

Table 5. Predicted transcription factors binding to GXP_9003729
Matrix Family Detail Family Info Matrix Detailed Matrix Info
V$LEFF LEF1/TCF V$LEF1.02 TCF/LEF-1, involved in the Wnt signal transduction pathway
V$HOXF Paralog hox genes 1-8 from the four hox clusters A, B, C, D V$NANOG.01 Homeobox transcription factor Nanog
V$TCFF TCF11 transcription factor V$TCF11.01 TCF11/LCR-F1/Nrf1 homodimers
V$PERO Peroxisome proliferator-activated receptor V$PPAR_RXR.01 PPAR/RXR heterodimers, DR1 sites
V$BCDF Bicoid-like homeodomain transcription factors V$PTX1.01 Pituitary Homeobox 1 (Ptx1, Pitx-1)
V$RUSH SWI/SNF related nucleophosphoproteins with a RING finger DNA binding motif V$SMARCA3.01 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 3
V$ZF42 C2H2 zinc finger transcription factors 42 V$ZNF692.01 Zinc finger protein 692 (AICAR responsive element binding protein - AREBP)
V$EGRF EGR/nerve growth factor induced protein C & related factors V$WT1.02 Wilms Tumor Suppressor
V$SAL4 Spalt-like transcription factor 4 V$SALL4.01 Spalt like 4, DRRS, HSAL4, ZNF797
V$PAX3 PAX-3 binding sites V$PAX3.03 Pax-3 paired domain protein
V$MZF1 Myeloid zinc finger 1 factors V$MZF1.02 Myeloid zinc finger protein MZF1
V$GATA GATA binding factors V$GATA1.01 GATA-binding factor 1
V$AP1R MAF and AP1 related factors V$MARE_ARE.01 Antioxidant response elements
V$TAIP TGF-beta induced apoptosis proteins V$CSRNP1.01 Cysteine-serine-rich nuclear protein 1 (AXUD1, AXIN1 up-regulated 1)
V$STAT Signal transducer and activator of transcription V$STAT5B.01 Signal transducer and activator of transcription 5B
V$ZF03 C2H2 zinc finger transcription factors 3 V$ZNF217.01 Zinc finger protein 217
V$BRNF Brn POU domain factors V$BRN2.03 Brn-2, POU-III protein class
V$GRHL Grainyhead-like transcription factors V$GRHL1.01 Grainyhead-like 1 (LBP32, MGR, TFCP2L2)
V$PERO Peroxisome proliferator-activated receptor V$PPARG.02 Peroxisome proliferator-activated receptor gamma
V$E2FF E2F-myc activator/cell cycle regulator V$E2F.01 E2F, involved in cell cycle regulation, interacts with Rb p107 protein

Expression

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FAM214B Expression

Tissue Specific Expression

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The RNA-Seq data from NCBI gene and The Human Atlas Protein shows that the FAM214B is highly expressed in the bone marrow, placenta, esophagus, and the brain such as corpus callosum, pons and medulla, and spinal cord.[21][5]

 
RNA-Seq Data FAM214B Expression

Embryonic development

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An in-situ hybridization technique has been conducted on mouse embryos that shows high levels of FAM214B transcript in the hippocampus and neocortex.[22]

Differential expression

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There has been numerous experiments on levels of expression for FAM214B. Patients with diabetic nephropathy express higher levels of FAM214B gene than those who are normal.[23] Patients with bipolar disorders expressed higher levels of FAM214B in the orbitofrontal cortex than those who are normal.[24] Patients with allergic nasal epithelium responses to house dust mites have lower expression of FAM214B than those who did not have allergies to house mites.[25]

3'UTR

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3'UTR

There are 9 stem loops and miRNAs that bind to FAM214B transcript 3'UTR shown on the right.[26][27]

Interacting proteins

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A list of proteins that interact with FAM214B in IntAct and UniProt database.[28][29]

Table 6. List of proteins that interact with FAM214B
Protein Description
IKZF1 DNA-binding protein Ikaros
TRIM27 Zinc finger protein RFP
FHL5 Four and a half LIM domains protein 5
CEP70 Centrosomal protein of 70 kDa
TRAF4 TNF receptor-associated factor 4
KIF20A Kinesin-like protein KIF20A
MDFI MyoD family inhibitor
CYSRT1 Cysteine-rich tail protein 1
MYO1F Unconventional myosin-If
EYA2 Eyes absent homolog 2

Homology and evolution

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Orthologs and paralogs

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FAM214B has orthologs in Mammalia, Aves, Reptilia, Amphibia, Actinopterygii, Arthropodas, Ascomycota, Zygomycota, and Plantae.[30] There is one paralog that is FAM214A.[31] The FAM214A protein has 1076 amino acids and is located on chromosome 13.[32]

Table 6. List of Homo Sapiens FAM214B orthologs
Genus and Species Common Name Taxonomic Group Date of Divergence (MYA) Accession Number Number of Amino Acids Identity
Mus musculus Mouse Rodenta 90 NP_001240282.1 538 91%
Chrysemys picta bellii Painted turtle Testudines 312 XP_005311754.1 646 45%
Gallus gallus Chicken Galliformes 312 XP_004937179.1 606 46%
Nanorana parkeri Himalaya frog Anura 351 XP_018429110.1 702 41%
Acipenser ruthenus Sterlet Acipenseriformes 435 XP_033861969.2 623 41%
Sarcoptes scabiei Itch mite Sarcoptes 797 KAF7489920.1 871 47%
Entomophthora muscae Fly fungus Entomophthoraceae 1105 KAF7753830.1 455 33%
Mikania micrantha Bitter vine Asterales 1496 KAD4889130.1 601 28%

Evolutionary history

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FAM214B Evolution Trend

The most distant species relating to humans was Mikania micrantha which was about 1496 MYA. The most closely related relative for this gene found in mammals comparing to humans was the mouse which was dated about 90 MYA.[33] The FAM214B is conserved in Eukaryota. In terms of the molecular clock analysis, it seems that FAM214B has evolved quicker than Cytochrome c but much slower than Fibrinogen alpha.

Studies of clinical significance

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There are studies that show the gene expression of KIAA1539 in patients with major depression disorders by using biomarkers to detect vulnerability to recurrent depression.[8] Low expression of this gene was common in patients who have MDD and was significantly difference than those who did not have MDD.[7][8] Experiments were conducted in patients with major depression disorders by using biomarkers to detect vulnerability to recurrent depression and is expressed in patients with depressive disorders before and after cognitive behavioral therapy.[34]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000005238Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000036002Ensembl, 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 e "FAM214B family with sequence similarity 214 member B [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-10-26.
  6. ^ a b "KIAA1539 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-10-26.
  7. ^ a b Redei, E E; Andrus, B M; Kwasny, M J; Seok, J; Cai, X; Ho, J; Mohr, D C (September 2014). "Blood transcriptomic biomarkers in adult primary care patients with major depressive disorder undergoing cognitive behavioral therapy". Translational Psychiatry. 4 (9): e442. doi:10.1038/tp.2014.66. ISSN 2158-3188. PMC 4198533. PMID 25226551.
  8. ^ a b c "Patent Database Search Results: kiaa1539 in US Patent Collection". patft.uspto.gov. Retrieved 2020-10-26.
  9. ^ a b "AceView: Gene:KIAA1539, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView". www.ncbi.nlm.nih.gov. Retrieved 2020-10-26.
  10. ^ "FAM214B Gene - GeneCards | F214B Protein | F214B Antibody". www.genecards.org. Retrieved 2020-12-18.
  11. ^ "FAM214A family with sequence similarity 214 member A [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-10-26.
  12. ^ "Gene: FAM214B (ENSG00000005238) - Splice variants - Homo sapiens - Ensembl genome browser 89". may2017.archive.ensembl.org. Retrieved 2020-12-18.
  13. ^ a b c d e "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 2020-12-18.
  14. ^ "SMART: DUF4210 domain annotation". smart.embl-heidelberg.de. Retrieved 2020-12-19.
  15. ^ "PHYRE2 Protein Fold Recognition Server". www.sbg.bio.ic.ac.uk. Retrieved 2020-12-19.
  16. ^ "Bioinformatics Toolkit". toolkit.tuebingen.mpg.de. Retrieved 2020-12-19.
  17. ^ a b "I-TASSER server for protein structure and function prediction". zhanglab.ccmb.med.umich.edu. Retrieved 2020-12-19.
  18. ^ "Motif Scan". myhits.sib.swiss. Retrieved 2020-12-19.
  19. ^ "PSORT II Prediction". psort.hgc.jp. Retrieved 2020-12-19.
  20. ^ a b "Genomatix - NGS Data Analysis & Personalized Medicine". www.genomatix.de. Archived from the original on 2021-08-19. Retrieved 2020-12-19.
  21. ^ "Tissue expression of FAM214B - Summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2020-12-19.
  22. ^ "Genepaint - Home of High Resolution Gene Expression Data". gp3.mpg.de. Retrieved 2020-12-19.
  23. ^ "GDS961 / 33841_at". www.ncbi.nlm.nih.gov. Retrieved 2020-12-19.
  24. ^ "GDS2191 / 207765_s_at". www.ncbi.nlm.nih.gov. Retrieved 2020-12-19.
  25. ^ "GDS3082 / 243543_at". www.ncbi.nlm.nih.gov. Retrieved 2020-12-19.
  26. ^ "RNAfold web server". rna.tbi.univie.ac.at. Retrieved 2020-12-19.
  27. ^ "TargetScanHuman 7.2 predicted targeting of Human FAM214B". www.targetscan.org. Retrieved 2020-12-19.
  28. ^ "Int Act".
  29. ^ "UniProt".
  30. ^ "BLAST: Basic Local Alignment Search Tool". blast.ncbi.nlm.nih.gov. Retrieved 2020-10-26.
  31. ^ "FAM214B Gene - GeneCards | F214B Protein | F214B Antibody". www.genecards.org. Retrieved 2020-10-26.
  32. ^ "FAM214A Gene - GeneCards | F214A Protein | F214A Antibody". www.genecards.org. Retrieved 2020-12-19.
  33. ^ "TimeTree :: The Timescale of Life". www.timetree.org. Retrieved 2020-10-26.
  34. ^ "Patent Database Search Results: kiaa1539 in US Patent Collection". patft.uspto.gov. Retrieved 2020-12-19.