FGFR1OP2

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]

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.[10]

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]

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]
• 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[16]
Condition or cell	GEO Profile	Condition or cell	GEO Profile
Pulmonary sarcoidosis	There is a slightly elevated expression level of FGFR1OP2 in pulmonary sarcoidosis.	Monocyte-derived dendritic cell response to VAF347 ligand
Langerhan cells	FGFR1OP2 shows decreased expression in Langerhan cells in Mus musculus.	Autosomal dominant monocytopenia	FGFR1OP2 expression in autosomal dominant monocytopenia.
Septic splenocytes	FGFR1OP2 shows low expression in septic splenocytes	Fetal and adult reticulocytes	FGFR1OP2 expression differs among fetal and adult reticulocytes.

FGFR1OP2 interacting proteins[18]

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]

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]

Wikimedia Commons has media related to FGFR1OP2.

• Homo sapiens FGFR1 oncogene partner 2 (FGFR1OP2), transcript variant 1, mRNA (NCBI)
• Homo sapiens FGFR1 oncogene partner 2 isoform 1 (NCBI)
• FGFR1OP2 human gene location in the UCSC Genome Browser.
• FGFR1OP2 human gene details in the UCSC Genome Browser.