RNA-binding protein EWS is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''EWSR1''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
on human
chromosome 22
Chromosome 22 is one of the 23 pairs of chromosomes in human cells. Humans normally have two copies of chromosome 22 in each cell. Chromosome 22 is the second smallest human chromosome, spanning about 51 million DNA base pairs and representing b ...
, specifically 22q12.2.
It is one of 3 proteins in the
FET protein family
The FET protein family (also known as the TET protein family) consists of three similarly structured and functioning proteins. They and the genes in the FET gene family which encode them (i.e. form the pre-messenger RNAs that are converted to the m ...
.
Clinical significance
The q22.2 region of chromosome 22 encodes the N-terminal transactivation domain of the EWS protein and that region may become joined to one of several other chromosomes which encode various transcription factors; see
EWS/FLI and OMIM-133450.
The expression of a chimeric protein with the EWS transactivation domain fused to the DNA binding region of a transcription factor generates a powerful oncogenic protein causing
Ewing sarcoma and other members of the
Ewing family of tumors
The Ewing family of tumors (EFTs) is a group of small cell sarcomas including Ewing sarcoma of the bone, extra osseous Ewing tumors, and primitive neuroectodermal tumors. They are rare cancers, usually diagnosed in peoples' twenties. The sarcoma of ...
. These translocations can occur due to
chromoplexy Chromoplexy refers to a class of complex DNA rearrangement observed in the genomes of cancer cells. This phenomenon was first identified in prostate cancer by whole genome sequencing of prostate tumors. Chromoplexy causes genetic material from one o ...
, a burst of complex chromosomal rearrangements seen in cancer cells.
The normal EWS gene encodes an RNA binding protein closely related to
FUS (gene)
RNA-binding protein fused in sarcoma/translocated in liposarcoma (FUS/TLS), also known as heterogeneous nuclear ribonucleoprotein P2 is a protein that in humans is encoded by the ''FUS'' gene.
Discovery
FUS/TLS was initially identified as a fus ...
and
TAF15, all of which have been associated to
amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States—Lou Gehrig's disease (LGD), is a rare, Terminal illness, terminal neurodegenerative disease, neurodegenerative disorder that results i ...
.
Interactions
The EWS protein has been shown to
interact with:
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ATF1,
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BARD1
BRCA1-associated RING domain protein 1 is a protein that in humans is encoded by the ''BARD1'' gene. The human BARD1 protein is 777 amino acids long and contains a RING finger domain (residues 46-90), four ankyrin repeats (residues 420-555), and a ...
,
*
ERG
The erg is a unit of energy equal to 10−7joules (100Nano-, nJ). It is not an SI unit, instead originating from the centimetre–gram–second system of units (CGS). Its name is derived from (), a Greek language, Greek word meaning 'work' or ' ...
,
*
POU4F1,
*
PTK2B
Protein tyrosine kinase 2 beta is an enzyme that in humans is encoded by the ''PTK2B'' gene.
Function
This gene encodes a cytoplasmic protein tyrosine kinase that is involved in calcium-induced regulation of ion channels and activation of the ...
*
SF1,
*
SNRPC,
and
*
ZNF165.
References
Further reading
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External links
Ewing sarcoma breakpoint region 1on the
Atlas of Genetics and Oncology
{{PDB Gallery, geneid=2130
Oncogenes