FGFR1 oncogene partner 2 (FGFR1OP2) is a protein that in humans is encoded by the gene FGFR1OP2. It 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.
Function
FGFR1OP2, when fused with the fibroblast growth factor receptor 1 (FGFR1), is shown to cause myeloproliferative syndrome. The protein encoded by the FGFR1 gene belongs to the fibroblast growth factor receptor family. 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. When FGFR1OP2 is fused to FGFR1, it may exhibit constitutive kinase activity. Furthermore, FGFR1OP2 is possibly involved in some steps of the wound healing pathway.
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. Ortholog mRNA and protein sequences were found using NCBI's BLAST and UCSC's BLAT Tool. The accession numbers, as well as the sequence length and the sequence similarity were compiled using BLAST. + mRNA orthologs to Homo sapiens FGFR1OP2 mRNA Genus species Common name Divergence (MYA) Accession number Sequence length (base pairs) Sequence similarity Homo sapiensHuman0NP_056448.13030100% Nomascus leucogenysGibbon20.4XM_003265627.1302096% Bos taurusCow94.2BC148973.1261694% Canis lupus familiarisDog94.2NM_001197313.169494% Loxodonta africanaElephant98.7XM_003405700.176293% Sciurus vulgarisSquirrel92.3NA185992% Mus musculusMouse92.3NM_026218.2282889% Rattus norvegicusRat92.3NM_201421.1286088% Monodelphis domesticaOpossum162.6XM_001362357.176588% Taeniopygia guttataZebra finch296XM_002194575.2107185% Gallus gallusChicken296NM_001007855.1314283% Meleagris gallopavoTurkey296XM_003202514.1127582% Anolis carolinensisAnole296XM_003221530.1196482% Trichechus inunguisManatee98.7NA275281% Oreochromis niloticusTilapia400.1XM_003455706.193779% Xenopus laevisFrog371.2NM_001085932.1127979% Danio rerioZebrafish400.1NM_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.
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 species Common name Divergence (MYA) Accession number Sequence length (amino acids) Sequence similarity Homo sapiensHuman0NP_056448.1253100% Saimiri boliviensis boliviensisSquirrel monkey42.6XP_003926645.125399% Loxodonta africanaElephant98.7XP_003405748.125399% Mus musculusMouse92.3NP_080494.125399% Monodelphis domesticaOpossum162.6XP_001362394.125496% Meleagris gallopavoTurkey296XP_003202562.121583% Anolis carolinensisAnole296XP_003221578.121482% Oreochromis niloticusTilapia400.1XP_003455754.122478% Xenopus laevisFrog371.2NP_001079401.121577% Danio rerioZebrafish400.1NP_956249.121577% Strongylocentrotus purpuratusSea urchin742.9XP_786805.225066% Crassostrea gigasOyster782.7EKC25301.123364% Capitella teletaAnnelid782.7ELU02494.128763% Nematostella vectensisSea anemone855.3XP_001639733.117462% Ciona intestinalisSea squirt722.5XP_002130340.123661% Tribolium castaneumBeetle782.7XP_974301.120157% Loa loaNematode937.5EFO20048.226651% Schistosoma mansoniBlood fluke792.4CCD58880.134251% Amphimedon queenslandicaSponge716.5XP_003387498.122148%
Gene
There are three transcript variants for the FGFR1OP2 gene, with the first being the longest. FGFR1OP2 is also known as HSPC123-like protein (HSPC123L) and wound inducible transcript 3.0 (wit3.0).
Locus
The Homo sapiens FGFR1OP2 gene is located on chromosome 12, with its specific locus being 12p11.23. The Homo sapiens asunder spermatogenesis regulator (ASUN) gene (NCBI Reference Sequence NM_018164.2) is located directly upstream from FGFR1OP2. The ASUN gene is a regulator of development and the mitotic cell cycle. The Homo sapiens transmembrane 7 superfamily member 3 (TM7SF3) gene is located slightly downstream from FGFR1OP2.
Promoter
+ Transcription factors that bind to the FGFR1OP2 promoter Transcription factor (T.F.) Full name Function Matrix similarity Strand T.F. binds Sequence T.F. binds AP1Activator protein 1Differentiation, proliferation, apoptosis0.874+gggaGAGTcagcg Smad3Mothers against decapentaplegic homolog 3TGF-beta signaling factor0.983+agtGTCTggtg DREDioxin response elementBound by AHR/AHRNT heterodimer0.971+gcgcgcgtgcGCGTgcacacacaca HASHIF-1 ancillary sequenceInduce vascular endothelial growth0.923+acaCACGcact RBP2Retinoblastoma-binding protein 2Demethylase1.000+GCACagcgc PLAG1Pleomorphic adenoma gene 1Cell proliferation1.000-gaGGGGgaagggaggcttggccg KLF7Kruppel-like factor 7Regulate cell proliferation, differentiation, and survival0.972+ggaagagGGCGgggcca NFATNuclear factor of activated T-cellsImmune response0.994+aaggaGGAAaaaaaaagcc NFATNuclear factor of activated T-cellsImmune response0.955-cgggtGGAAaatctcgagg Ikaros2Ikaros zinc fingerPotential regulator of lymphocytes0.986+cattGGGAagcag Ikaros2Ikaros zinc fingerPotential regulator of lymphocytes0.980-gactGGGAaaatt PLAG1Pleomorphic adenoma gene 1Cell proliferation1.000-taGGGGgccgtggttggtacttc WTWilms 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 SPI1SPI-1 proto-oncogeneHematopoietic transcription factor0.918+ggaagggaGGAAtagg KLF7Kruppel-like factor 7Regulate cell proliferation, differentiation, and survival0.962-aaggcagGGCGgggccc NFATNuclear factor of activated T-cellsImmune response0.989+cgcgaGGAAagaaatctcg TBX20Brachyury geneMesoderm developmental factor1.000+ggtcggcggAGGTgtctaccccg STAT3Signal transducer and activator of transcription 3Activate transcription0.940+tggcTTCCcggccttccgt
Protein
There are three isoforms of the FGFR1OP2 protein. Transcript variant 1 consists of 253 amino acids and weighs 29.4 kilodaltons. FGFR1OP2's isoelectric point is 5.61. The FGFR1OP2 protein does not have a signal sequences, and therefore is not secreted.
Domains
FGFR1OP2 has a domain of unknown function, designated DUF837.
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. 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. The following are findings from the Gene Expression Onmibus database: There is a slightly elevated expression level of FGFR1OP2 in pulmonary sarcoidosis, suggesting FGFR1OP2 operates in part of the wound healing pathway. FGFR1OP2 is strongly upregulated when compared to the control in an increased immune response triggered by the VAF347 ligand. FGFR1OP2 is upregulated in the monocyte derived dendritic cell response to the VAF347 ligand. VAF347 activates the aryl hydrocarbon receptor and acts on monocytes and naive CD4+ Th cells to promote development of IL-22 secreting Th cells. Langerhans cells show decreased expression of FGFR1OP2 with the null aryl hydrocarbon receptor (ligand is VAF347) in Mus musculus. The gene is also highly expressed compared to control samples in monocytopenia. It is expressed in cases of leukemia; it may have a linkage to the disease. FGFR1OP2 shows low expression levels in septic splenocytes in Mus musculus. FGFR1OP2 is expressed in fetal reticulocytes but not adult reticulocytes, suggesting it may play a role in the development of red blood cells.
FGFR1OP2 GEO Profiles Condition or cell GEO Profile Condition or cell GEO Profile Pulmonary sarcoidosisMonocyte-derived dendritic cell response to VAF347 ligand Langerhan cellsAutosomal dominant monocytopenia Septic splenocytesFetal and adult reticulocytes
Interactions
Using the STRING database and Gene Cards, proteins that possibly interact with FGFR1OP2 were identified, and they are shown in the table below. + FGFR1OP2 Interacting Proteins Interactant Full name Function Source(s) STK24Serine/threonine kinase 24Protein kinaseGene Cards TRAF3IP3TRAF3 interacting proteinAdapter moleculeGene Cards, STRING ZRANB1Zinc finger, RAN-binding domain containing 1Positive regulator of Wnt signaling, cytoskeletal organizationGene Cards PPP2R1AProtein phosphatase 2Negative control of cell growth and divisionGene Cards STRNStriatin, calmodulin binding proteinScaffold proteinGene Cards, STRING FAM40AFamily with sequence similarity 40, member ACytoskeletal organizationSTRING PDCD10Programmed cell death 10Regulate apoptotic pathwaysSTRING STK26Serine/threonine kinase 26Mediator 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). Also, when FGFR1OP2 is fused to FGFR1, 8p11 myeloproliferative syndrome can result.
References
External links
Homo sapiens FGFR1 oncogene partner 2 (FGFR1OP2), transcript variant 1, mRNA (NCBI) Homo sapiens FGFR1 oncogene partner 2 isoform 1 (NCBI)