FGFR1OP2

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Fibroblast growth factor receptor oncogene partner 2 (FGFR1OP2) was identified in a study on myeloproliferative syndrome (EMS). The study aimed to identify the partner genes to the fibroblast growth factor receptor 1 (FGFR1) involved in the syndrome. Using the 5'-RACE PCR technique, FGFR1OP2 was identified as a novel gene with no known function. [1]

Contents

Function

FGFR1OP2, when fused with the fibroblast growth factor receptor 1 (FGFR1), is shown to cause myeloproliferative syndrome. [1] The protein encoded by the FGFR1 gene belongs to the fibroblast growth factor receptor family. [2] FGFRs usually contain an extracellular ligand binding domain, a single transmembrane domain, and an intracellular tyrosine kinase domain. The extracellular domain specifies which ligand the receptor will bind to and mediates ligand-induced receptor dimerization. [3] When FGFR1OP2 is fused to FGFR1, it may exhibit constitutive kinase activity. [4] Furthermore, FGFR1OP2 is possibly involved in some steps of the wound healing pathway. [5]

Evolutionary Biology

The following tables compare the Homo sapiens FGFR1OP2 gene and protein to orthologs. In both of the following tables, the divergence from the Homo sapiens FGFR1OP2 gene or protein to the ortholog was found using TimeTree. [6] Ortholog mRNA and protein sequences were found using NCBI's BLAST [7] and UCSC's BLAT Tool. [8] The accession numbers, as well as the sequence length and the sequence similarity were compiled using BLAST. [7]

mRNA orthologs to Homo sapiens FGFR1OP2 mRNA
Genus speciesCommon nameDivergence (MYA)Accession numberSequence length (base pairs)Sequence similarity
Homo sapiens Human 0NP_056448.13030100%
Nomascus leucogenys Gibbon 20.4XM_003265627.1302096%
Bos taurus Cow 94.2BC148973.1261694%
Canis lupus familiaris Dog 94.2NM_001197313.169494%
Loxodonta africana Elephant 98.7XM_003405700.176293%
Sciurus vulgaris Squirrel 92.3NA185992%
Mus musculus Mouse 92.3NM_026218.2282889%
Rattus norvegicus Rat 92.3NM_201421.1286088%
Monodelphis domestica Opossum 162.6XM_001362357.176588%
Taeniopygia guttata Zebra finch 296XM_002194575.2107185%
Gallus gallus Chicken 296NM_001007855.1314283%
Meleagris gallopavo Turkey 296XM_003202514.1127582%
Anolis carolinensis Anole 296XM_003221530.1196482%
Trichechus inunguis Manatee 98.7NA275281%
Oreochromis niloticus Tilapia 400.1XM_003455706.193779%
Xenopus laevis Frog 371.2NM_001085932.1127979%
Danio rerio Zebrafish 400.1NM_199955150178%

The mRNA orthologs sequence similarity to Homo sapiens FGFR1OP2 was graphed as a function of time in order to show how the FGFR1OP2 gene has changed over time. The graph is depicted on the right.

This graph shows the FGFR1OP2 mRNA sequence identity (% to human) vs. the time since the species diverged (in millions of years) from humans for the mRNA orthologs. MRNAseqID vs divergence.jpg
This graph shows the FGFR1OP2 mRNA sequence identity (% to human) vs. the time since the species diverged (in millions of years) from humans for the mRNA orthologs.

The table below shows the protein orthologs to the Homo sapiens FGFR1OP2 protein. FGFR1OP2 is conserved in all clades of the animal kingdom, as seen in the table below.

Protein orthologs to Homo sapiens FGFR1OP2
Genus speciesCommon nameDivergence (MYA)Accession numberSequence length (amino acids)Sequence similarity
Homo sapiens Human 0NP_056448.1253100%
Saimiri boliviensis boliviensis Squirrel monkey 42.6XP_003926645.125399%
Loxodonta africana Elephant 98.7XP_003405748.125399%
Mus musculus Mouse 92.3NP_080494.125399%
Monodelphis domestica Opossum 162.6XP_001362394.125496%
Meleagris gallopavo Turkey 296XP_003202562.121583%
Anolis carolinensis Anole 296XP_003221578.121482%
Oreochromis niloticus Tilapia 400.1XP_003455754.122478%
Xenopus laevis Frog 371.2NP_001079401.121577%
Danio rerio Zebrafish 400.1NP_956249.121577%
Strongylocentrotus purpuratus Sea urchin 742.9XP_786805.225066%
Crassostrea gigas Oyster 782.7EKC25301.123364%
Capitella teleta Annelid 782.7ELU02494.128763%
Nematostella vectensis Sea anemone 855.3XP_001639733.117462%
Ciona intestinalis Sea squirt 722.5XP_002130340.123661%
Tribolium castaneum Beetle 782.7XP_974301.120157%
Loa loa Nematode 937.5EFO20048.226651%
Schistosoma mansoni Blood fluke 792.4CCD58880.134251%
Amphimedon queenslandica Sponge 716.5XP_003387498.122148%

Gene

ASUN is located downstream and TM7SF3 is located slightly upstream from the FGFR1OP2 gene locus. FGFR1OP2 gene neighborhood.png
ASUN is located downstream and TM7SF3 is located slightly upstream from the FGFR1OP2 gene locus.

There are three transcript variants for the FGFR1OP2 gene, with the first being the longest. [9] FGFR1OP2 is also known as HSPC123-like protein (HSPC123L) and wound inducible transcript 3.0 (wit3.0). [9]

The promoter region of the Homo sapiens FGFR1OP2 gene shown with likely binding sites for transcription factors. ElDorado was used to analyze the promoter of FGFR1OP2, and the most likely binding transcription factors are shown. FGFR1OP2 promoter.png
The promoter region of the Homo sapiens FGFR1OP2 gene shown with likely binding sites for transcription factors. ElDorado was used to analyze the promoter of FGFR1OP2, and the most likely binding transcription factors are shown.

Locus

The Homo sapiens FGFR1OP2 gene is located on chromosome 12, with its specific locus being 12p11.23. [9] The Homo sapiens asunder spermatogenesis regulator (ASUN) gene (NCBI Reference Sequence NM_018164.2) is located directly upstream from FGFR1OP2. [11] The ASUN gene is a regulator of development and the mitotic cell cycle. [12] The Homo sapiens transmembrane 7 superfamily member 3 (TM7SF3) gene is located slightly downstream from FGFR1OP2. [13]

Promoter

Transcription factors that bind to the FGFR1OP2 promoter
Transcription factor (T.F.)Full nameFunctionMatrix similarityStrand T.F. bindsSequence T.F. binds
AP1 Activator protein 1Differentiation, proliferation, apoptosis0.874+gggaGAGTcagcg
Smad3 Mothers against decapentaplegic homolog 3TGF-beta signaling factor0.983+agtGTCTggtg
DRE Dioxin response elementBound by AHR/AHRNT heterodimer0.971+gcgcgcgtgcGCGTgcacacacaca
HAS HIF-1 ancillary sequenceInduce vascular endothelial growth0.923+acaCACGcact
RBP2 Retinoblastoma-binding protein 2Demethylase1.000+GCACagcgc
PLAG1 Pleomorphic adenoma gene 1Cell proliferation1.000-gaGGGGgaagggaggcttggccg
KLF7 Kruppel-like factor 7Regulate cell proliferation, differentiation, and survival0.972+ggaagagGGCGgggcca
NFAT Nuclear factor of activated T-cellsImmune response0.994+aaggaGGAAaaaaaaagcc
NFAT Nuclear factor of activated T-cellsImmune response0.955-cgggtGGAAaatctcgagg
Ikaros2Ikaros zinc fingerPotential regulator of lymphocytes0.986+cattGGGAagcag
Ikaros2Ikaros zinc fingerPotential regulator of lymphocytes0.980-gactGGGAaaatt
PLAG1 Pleomorphic adenoma gene 1Cell proliferation1.000-taGGGGgccgtggttggtacttc
WT Wilms tumor suppressorEGR/nerve growth factor0.948-gaccgggTGGGtgggtc
AREB6Atp1a1 regulatory element binding factor 6Negative regulator of IL-20.982+ggccgGTTTcccc
NMP4Nuclear matrix protein 4Cas-interacting zinc finger protein0.994+ggAAAAactcg
SPI1 SPI-1 proto-oncogeneHematopoietic transcription factor0.918+ggaagggaGGAAtagg
KLF7 Kruppel-like factor 7Regulate cell proliferation, differentiation, and survival0.962-aaggcagGGCGgggccc
NFAT Nuclear factor of activated T-cellsImmune response0.989+cgcgaGGAAagaaatctcg
TBX20 Brachyury geneMesoderm developmental factor1.000+ggtcggcggAGGTgtctaccccg
STAT3 Signal transducer and activator of transcription 3Activate transcription0.940+tggcTTCCcggccttccgt

Protein

The protein sequence of FGFR1OP2 was analyzed using PELE, and appears to be made up of mostly alpha helices. FGFR1OP2 sequence analysis for structure.png
The protein sequence of FGFR1OP2 was analyzed using PELE, and appears to be made up of mostly alpha helices.
Mus musculus FGFR1OP2 protein structure from ModBase Mus musculus FGFR1OP2 protein structure from ModBase.png
Mus musculus FGFR1OP2 protein structure from ModBase

There are three isoforms of the FGFR1OP2 protein. Transcript variant 1 consists of 253 amino acids and weighs 29.4 kilodaltons. [9] FGFR1OP2's isoelectric point is 5.61. [14] The FGFR1OP2 protein does not have a signal sequences, and therefore is not secreted. [15]

Domains

FGFR1OP2 has a domain of unknown function, designated DUF837. [9]

Protein Structure

Using the PELE program of Biology WorkBench the protein sequence of FGFR1OP2 was analyzed, and FGFR1OP2 appears to be completely composed of alpha helices. [14] No structural models for the Homo sapiens FGFR1OP2 protein could be found, but the Mus musculus FGFR1OP2 protein's structure can be seen below.


Expression

The expression of FGFR1OP2 was analyzed via the Gene Expression Omnibus at NCBI. [16] The following are findings from the Gene Expression Onmibus database:

Interactions

FGFR1OP2 interacting proteins FGFR1OP2 interacting proteins.png
FGFR1OP2 interacting proteins

Using the STRING database and Gene Cards, proteins that possibly interact with FGFR1OP2 were identified, and they are shown in the table below. [5] [18]

FGFR1OP2 Interacting Proteins
InteractantFull nameFunctionSource(s)
STK24 Serine/threonine kinase 24Protein kinaseGene Cards
TRAF3IP3 TRAF3 interacting proteinAdapter moleculeGene Cards, STRING
ZRANB1Zinc finger, RAN-binding domain containing 1Positive regulator of Wnt signaling, cytoskeletal organizationGene Cards
PPP2R1A Protein phosphatase 2Negative control of cell growth and divisionGene Cards
STRN Striatin, calmodulin binding proteinScaffold proteinGene Cards, STRING
FAM40A Family with sequence similarity 40, member ACytoskeletal organizationSTRING
PDCD10 Programmed cell death 10Regulate apoptotic pathwaysSTRING
MST4 Serine/threonine kinase 3Mediator of cell growthSTRING
SIKE1Suppressor of IKBKE1Suppressor of IKK-epsilon and TBK1 inhibitorSTRING
MOBKL3Mps one binder kinase activator-like 3Spindle pole body duplication and mitotic checkpoint regulationSTRING

Clinical Significance

Single-nucleotide polymorphisms (SNPs) in the FGFR1OP2 gene were found to lead to edentulism in the mandible of a small Korean population (134 subjects aged 60–80 years). [19] Also, when FGFR1OP2 is fused to FGFR1, 8p11 myeloproliferative syndrome can result. [1]

Related Research Articles

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Chromosome 4 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 4 spans more than 193 million base pairs and represents between 6 and 6.5 percent of the total DNA in cells.

<span class="mw-page-title-main">Chromosome 8</span> Human chromosome

Chromosome 8 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 8 spans about 146 million base pairs and represents between 4.5 and 5.0% of the total DNA in cells.

<span class="mw-page-title-main">Chromosome 10</span> Human chromosome

Chromosome 10 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 10 spans about 134 million base pairs and represents between 4 and 4.5 percent of the total DNA in cells.

<span class="mw-page-title-main">Chromosome 11</span> Human chromosome

Chromosome 11 is one of the 23 pairs of chromosomes in humans. Humans normally have two copies of this chromosome. Chromosome 11 spans about 135 million base pairs and represents between 4 and 4.5 percent of the total DNA in cells. The shorter arm is termed 11p while the longer arm is 11q. At about 21.5 genes per megabase, chromosome 11 is one of the most gene-rich, and disease-rich, chromosomes in the human genome.

<span class="mw-page-title-main">Fibroblast growth factor receptor 1</span> Protein-coding gene in the species Homo sapiens

Fibroblast growth factor receptor 1 (FGFR-1), also known as basic fibroblast growth factor receptor 1, fms-related tyrosine kinase-2 / Pfeiffer syndrome, and CD331, is a receptor tyrosine kinase whose ligands are specific members of the fibroblast growth factor family. FGFR-1 has been shown to be associated with Pfeiffer syndrome, and clonal eosinophilias.

<span class="mw-page-title-main">GPR113</span> Protein-coding gene in the species Homo sapiens

GPR113 is a gene that encodes the Probable G-protein coupled receptor 113 protein.

<span class="mw-page-title-main">FAM43A</span> Protein-coding gene in the species Homo sapiens

The family with sequence similarity 43 member A (FAM43A) gene, also known as; GCO3P195887, GC03P194406, GC03P191784, and NM_153690.3, codes for a 423 bp protein that is conserved in primates, and orthologs have been found in vertebrate and invertebrate species. Three transcripts have been identified, two protein coding isoforms, and a non-coding transcript (cAug10). Molecular weight of 45.8 kdal in the unphosphorylated state and isoelectric point of 6.1.

<span class="mw-page-title-main">CCDC94</span> Protein found in humans

Coiled-coil domain containing 94 (CCDC94) is a protein that in humans is encoded by the CCDC94 gene. The CCDC94 protein contains a coiled-coil domain, a domain of unknown function (DUF572), an uncharacterized conserved protein (COG5134), and lacks a transmembrane domain.

TMEM143 is a protein that in humans is encoded by TMEM143 gene. TMEM143, a dual-pass protein, is predicted to reside in the mitochondria and high expression has been found in both human skeletal muscle and the heart. Interaction with other proteins indicate that TMEM143 could potentially play a role in tumor suppression/expression and cancer regulation.

<span class="mw-page-title-main">DMAC1</span> Protein-coding gene in the species Mus musculus

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Chromosome 19 open reading frame 18 (c19orf18) is a protein which in humans is encoded by the c19orf18 gene. The gene is exclusive to mammals and the protein is predicted to have a transmembrane domain and a coiled coil stretch. This protein has a function that is not yet fully understood by the scientific community.

<span class="mw-page-title-main">C22orf23</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">TMEM128</span>

TMEM128, also known as Transmembrane Protein 128, is a protein that in humans is encoded by the TMEM128 gene. TMEM128 has three variants, varying in 5' UTR's and start codon location. TMEM128 contains four transmembrane domains and is localized in the Endoplasmic Reticulum membrane. TMEM128 contains a variety of regulation at the gene, transcript, and protein level. While the function of TMEM128 is poorly understood, it interacts with several proteins associated with the cell cycle, signal transduction, and memory.

<span class="mw-page-title-main">C17orf78</span> Mammalian protein found in Homo sapiens

Uncharacterized protein C17orf78 is a protein encoded by the C17orf78 gene in humans. The name denotes the location of the parent gene, being at the 78th open reading frame, on the 17th human chromosome. The protein is highly expressed in the small intestine, especially the duodenum. The function of C17orf78 is not well defined.

<span class="mw-page-title-main">KIAA2013</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">NOXRED1</span> Human gene

NADP-dependent oxidoreductase domain-containing protein 1 is a protein that in humans is encoded by the NOXRED1 gene. An alias of this gene is Chromosome 14 Open Reading Frame 148 (c14orf148). This gene is located on chromosome 14, at 14q24.3. NOXRED1 is predicted to be involved in pyrroline-5-carboxylate reductase activity as part of the L-proline biosynthetic pathway. It is expressed in a wide variety of tissues at a relatively low level, including the testes, thyroid, skin, small intestine, brain, kidney, colon, and more.

<span class="mw-page-title-main">TMEM248</span> Transmembrane protein 248/TMEM248 gene

Transmembrane protein 248, also known as C7orf42, is a gene that in humans encodes the TMEM248 protein. This gene contains multiple transmembrane domains and is composed of seven exons.TMEM248 is predicted to be a component of the plasma membrane and be involved in vesicular trafficking. It has low tissue specificity, meaning it is ubiquitously expressed in tissues throughout the human body. Orthology analyses determined that TMEM248 is highly conserved, having homology with vertebrates and invertebrates. TMEM248 may play a role in cancer development. It was shown to be more highly expressed in cases of colon, breast, lung, ovarian, brain, and renal cancers.

<span class="mw-page-title-main">EVA1C</span> Transmembrane protein in human

EVA1C is a transmembrane protein in humans that is encoded by the EVA1C gene on Chromosome 21. The EVA1C protein is thought to be involved in herapin binding activity. In addition, the gene is thought to be associated with diseases such as X-Linked Intellectual Disability-Short Stature-Overweight Syndrome.

<span class="mw-page-title-main">BPIFB9P</span> Pseudogene in the species Homo sapiens

Vomeromodulin is a non-human protein also known as BPI fold containing family B, member 9 (BPIFB9) in the rat encoded by the Bpifb9/RYF3 gene, and as BPI fold containing family B, member 9A (BPIFB9A) encoded by the Bpifb9a gene in the mouse. This protein has been characterized in mammals such as rodents, carnivores, even-toed ungulates, insectivores, bats, lagomorphs, and shrews but is apparently absent in primates and other vertebrates such as birds, reptiles, and amphibians. Its function is associated with detection of chemical odorant pheromone molecules.

<span class="mw-page-title-main">TMEM19</span> Protein encoded by the TMEM19 gene

Transmembrane protein 19 is a protein that in humans is encoded by the TMEM19 gene.

References

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