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]
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]
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]
Genus species | Common name | Divergence (MYA) | Accession number | Sequence length (base pairs) | Sequence similarity |
---|---|---|---|---|---|
Homo sapiens | Human | 0 | NP_056448.1 | 3030 | 100% |
Nomascus leucogenys | Gibbon | 20.4 | XM_003265627.1 | 3020 | 96% |
Bos taurus | Cow | 94.2 | BC148973.1 | 2616 | 94% |
Canis lupus familiaris | Dog | 94.2 | NM_001197313.1 | 694 | 94% |
Loxodonta africana | Elephant | 98.7 | XM_003405700.1 | 762 | 93% |
Sciurus vulgaris | Squirrel | 92.3 | NA | 1859 | 92% |
Mus musculus | Mouse | 92.3 | NM_026218.2 | 2828 | 89% |
Rattus norvegicus | Rat | 92.3 | NM_201421.1 | 2860 | 88% |
Monodelphis domestica | Opossum | 162.6 | XM_001362357.1 | 765 | 88% |
Taeniopygia guttata | Zebra finch | 296 | XM_002194575.2 | 1071 | 85% |
Gallus gallus | Chicken | 296 | NM_001007855.1 | 3142 | 83% |
Meleagris gallopavo | Turkey | 296 | XM_003202514.1 | 1275 | 82% |
Anolis carolinensis | Anole | 296 | XM_003221530.1 | 1964 | 82% |
Trichechus inunguis | Manatee | 98.7 | NA | 2752 | 81% |
Oreochromis niloticus | Tilapia | 400.1 | XM_003455706.1 | 937 | 79% |
Xenopus laevis | Frog | 371.2 | NM_001085932.1 | 1279 | 79% |
Danio rerio | Zebrafish | 400.1 | NM_199955 | 1501 | 78% |
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.
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.
Genus species | Common name | Divergence (MYA) | Accession number | Sequence length (amino acids) | Sequence similarity |
---|---|---|---|---|---|
Homo sapiens | Human | 0 | NP_056448.1 | 253 | 100% |
Saimiri boliviensis boliviensis | Squirrel monkey | 42.6 | XP_003926645.1 | 253 | 99% |
Loxodonta africana | Elephant | 98.7 | XP_003405748.1 | 253 | 99% |
Mus musculus | Mouse | 92.3 | NP_080494.1 | 253 | 99% |
Monodelphis domestica | Opossum | 162.6 | XP_001362394.1 | 254 | 96% |
Meleagris gallopavo | Turkey | 296 | XP_003202562.1 | 215 | 83% |
Anolis carolinensis | Anole | 296 | XP_003221578.1 | 214 | 82% |
Oreochromis niloticus | Tilapia | 400.1 | XP_003455754.1 | 224 | 78% |
Xenopus laevis | Frog | 371.2 | NP_001079401.1 | 215 | 77% |
Danio rerio | Zebrafish | 400.1 | NP_956249.1 | 215 | 77% |
Strongylocentrotus purpuratus | Sea urchin | 742.9 | XP_786805.2 | 250 | 66% |
Crassostrea gigas | Oyster | 782.7 | EKC25301.1 | 233 | 64% |
Capitella teleta | Annelid | 782.7 | ELU02494.1 | 287 | 63% |
Nematostella vectensis | Sea anemone | 855.3 | XP_001639733.1 | 174 | 62% |
Ciona intestinalis | Sea squirt | 722.5 | XP_002130340.1 | 236 | 61% |
Tribolium castaneum | Beetle | 782.7 | XP_974301.1 | 201 | 57% |
Loa loa | Nematode | 937.5 | EFO20048.2 | 266 | 51% |
Schistosoma mansoni | Blood fluke | 792.4 | CCD58880.1 | 342 | 51% |
Amphimedon queenslandica | Sponge | 716.5 | XP_003387498.1 | 221 | 48% |
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 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]
Transcription factor (T.F.) | Full name | Function | Matrix similarity | Strand T.F. binds | Sequence T.F. binds |
---|---|---|---|---|---|
AP1 | Activator protein 1 | Differentiation, proliferation, apoptosis | 0.874 | + | gggaGAGTcagcg |
Smad3 | Mothers against decapentaplegic homolog 3 | TGF-beta signaling factor | 0.983 | + | agtGTCTggtg |
DRE | Dioxin response element | Bound by AHR/AHRNT heterodimer | 0.971 | + | gcgcgcgtgcGCGTgcacacacaca |
HAS | HIF-1 ancillary sequence | Induce vascular endothelial growth | 0.923 | + | acaCACGcact |
RBP2 | Retinoblastoma-binding protein 2 | Demethylase | 1.000 | + | GCACagcgc |
PLAG1 | Pleomorphic adenoma gene 1 | Cell proliferation | 1.000 | - | gaGGGGgaagggaggcttggccg |
KLF7 | Kruppel-like factor 7 | Regulate cell proliferation, differentiation, and survival | 0.972 | + | ggaagagGGCGgggcca |
NFAT | Nuclear factor of activated T-cells | Immune response | 0.994 | + | aaggaGGAAaaaaaaagcc |
NFAT | Nuclear factor of activated T-cells | Immune response | 0.955 | - | cgggtGGAAaatctcgagg |
Ikaros2 | Ikaros zinc finger | Potential regulator of lymphocytes | 0.986 | + | cattGGGAagcag |
Ikaros2 | Ikaros zinc finger | Potential regulator of lymphocytes | 0.980 | - | gactGGGAaaatt |
PLAG1 | Pleomorphic adenoma gene 1 | Cell proliferation | 1.000 | - | taGGGGgccgtggttggtacttc |
WT | Wilms tumor suppressor | EGR/nerve growth factor | 0.948 | - | gaccgggTGGGtgggtc |
AREB6 | Atp1a1 regulatory element binding factor 6 | Negative regulator of IL-2 | 0.982 | + | ggccgGTTTcccc |
NMP4 | Nuclear matrix protein 4 | Cas-interacting zinc finger protein | 0.994 | + | ggAAAAactcg |
SPI1 | SPI-1 proto-oncogene | Hematopoietic transcription factor | 0.918 | + | ggaagggaGGAAtagg |
KLF7 | Kruppel-like factor 7 | Regulate cell proliferation, differentiation, and survival | 0.962 | - | aaggcagGGCGgggccc |
NFAT | Nuclear factor of activated T-cells | Immune response | 0.989 | + | cgcgaGGAAagaaatctcg |
TBX20 | Brachyury gene | Mesoderm developmental factor | 1.000 | + | ggtcggcggAGGTgtctaccccg |
STAT3 | Signal transducer and activator of transcription 3 | Activate transcription | 0.940 | + | tggcTTCCcggccttccgt |
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]
FGFR1OP2 has a domain of unknown function, designated DUF837. [9]
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.
The expression of FGFR1OP2 was analyzed via the Gene Expression Omnibus at NCBI. [16] The following are findings from the Gene Expression Onmibus database:
FGFR1OP2 GEO Profiles [16] | |||
---|---|---|---|
Condition or cell | GEO Profile | Condition or cell | GEO Profile |
Pulmonary sarcoidosis | Monocyte-derived dendritic cell response to VAF347 ligand | ||
Langerhan cells | Autosomal dominant monocytopenia | ||
Septic splenocytes | Fetal and adult reticulocytes | ||
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]
Interactant | Full name | Function | Source(s) |
---|---|---|---|
STK24 | Serine/threonine kinase 24 | Protein kinase | Gene Cards |
TRAF3IP3 | TRAF3 interacting protein | Adapter molecule | Gene Cards, STRING |
ZRANB1 | Zinc finger, RAN-binding domain containing 1 | Positive regulator of Wnt signaling, cytoskeletal organization | Gene Cards |
PPP2R1A | Protein phosphatase 2 | Negative control of cell growth and division | Gene Cards |
STRN | Striatin, calmodulin binding protein | Scaffold protein | Gene Cards, STRING |
FAM40A | Family with sequence similarity 40, member A | Cytoskeletal organization | STRING |
PDCD10 | Programmed cell death 10 | Regulate apoptotic pathways | STRING |
MST4 | Serine/threonine kinase 3 | Mediator of cell growth | STRING |
SIKE1 | Suppressor of IKBKE1 | Suppressor of IKK-epsilon and TBK1 inhibitor | STRING |
MOBKL3 | Mps one binder kinase activator-like 3 | Spindle pole body duplication and mitotic checkpoint regulation | STRING |
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]
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.
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.
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.
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.
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.
GPR113 is a gene that encodes the Probable G-protein coupled receptor 113 protein.
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.
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.
Transmembrane protein 261 is a protein that in humans is encoded by the TMEM261 gene located on chromosome 9. TMEM261 is also known as C9ORF123 and DMAC1, Chromosome 9 Open Reading Frame 123 and Transmembrane Protein C9orf123 and Distal membrane-arm assembly complex protein 1.
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.
C22orf23 is a protein which in humans is encoded by the C22orf23 gene. Its predicted secondary structure consists of alpha helices and disordered/coil regions. It is expressed in many tissues and highest in the testes and it is conserved across many orthologs.
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.
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.
KIAA2013, also known as Q8IYS2 or MGC33867, is a single-pass transmembrane protein encoded by the KIAA2013 gene in humans. The complete function of KIAA2013 has not yet been fully elucidated.
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.
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.
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.
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.
Transmembrane protein 19 is a protein that in humans is encoded by the TMEM19 gene.