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]
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]
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.
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.
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.
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
Signal transducer and activator of transcription 3
Activate transcription
0.940
+
tggcTTCCcggccttccgt
Protein
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
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:
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.[17]
Spindle pole body duplication and mitotic checkpoint regulation
STRING
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]
References
1 2 3 Grand, E. K. (2006). "Identification of a novel gene, fgfr1op2, fused to fgfr1 in 8p11 myeloproliferative syndrome". Genes, Chromosomes & Cancer. 40 (1): 78–83. doi:10.1002/gcc.20023. PMID15034873. S2CID511788.
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