Ubiquilin-2 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 ''UBQLN2''
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 ...
.
Function
This gene encodes a
ubiquitin-like protein
Ubiquitin-like proteins (UBLs) are a family of small proteins involved in post-translational modification of other proteins in a cell (biology), cell, usually with a regulatory protein, regulatory function. The UBL protein family derives its name ...
(
ubiquilin) that shares high degree of similarity with related products in yeast, rat and frog. Ubiquilins contain a
N-terminal
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...
ubiquitin-like domain and a
C-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When t ...
ubiquitin-associated domain. They physically associate with both
proteasome
Proteasomes are essential protein complexes responsible for the degradation of proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases. Proteasomes are found inside all e ...
s and
ubiquitin ligase
A ubiquitin ligase (also called an E3 ubiquitin ligase) is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin ...
s, and are thus thought to functionally link the ubiquitination machinery to the proteasome to effect ''in vivo'' protein degradation. This ubiquilin has also been shown to bind the
ATPase
ATPases (, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, ATP hydrolase, adenosine triphosphatase) are a class of enzymes that catalyze the decomposition of ATP into ADP and a free phosphate ion or ...
domain of the
Hsp70
The 70 kilodalton heat shock proteins (Hsp70s or DnaK) are a family of conserved ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms and play crucial roles in the development of can ...
-like
Hspa13 #REDIRECT HSPA13
{{R from alternative capitalization ...
(Stch) protein.
Similarity to other proteins
Human UBQLN2 shares a high degree of similarity with related ubiquilins including
UBQLN1
Ubiquilin-1 is a protein that in humans is encoded by the ''UBQLN1'' gene.
Ubiquilins contain two domains, an N-terminal ubiquitin-like domain and a C-terminal ubiquitin-associated domain. They physically associate with both proteasomes and u ...
and
UBQLN4
Ubiquilin 4 is a protein in humans that is encoded by the UBQLN4 gene. Ubiquilin 4 regulates proteasomal protein degradation.
Similarity to Other Proteins
Human UBQLN4 shares a high degree of similarity with related ubiquilins including UBQLN1 ...
.
Clinical significance
In a small proportion of familial
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 ...
(fALS), the UBQLN2 gene is mutated, causing formation of a non-functional Ubiquilin 2 enzyme. This non-functioning enzyme leads to the accumulation of ubiquinated proteins in the lower motor neurons and upper corticospinal motor neurons, due to the fact that ubiquilin 2 normally degrades these ubiquinated proteins, but cannot if the ALS mutation is present.
[
*] The same accumulations occur in patients without UBQLN2 mutations, but with mutations in other genes, including TDP-43 and
C9ORF72
C9orf72 (chromosome 9 open reading frame 72) is a protein which in humans is encoded by the gene ''C9orf72''.
The human ''C9orf72'' gene is located on the short (p) arm of chromosome 9 open reading frame 72, from base pair 27,546,546 to base pa ...
.
Interactions
UBQLN2 has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...
with
HERPUD1
Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein is a protein that in humans is encoded by the ''HERPUD1'' gene.
The accumulation of unfolded proteins in the endoplasmic reticulum (ER) triggers the ER ...
and
UBE3A
Ubiquitin-protein ligase E3A (UBE3A) also known as E6AP ubiquitin-protein ligase (E6AP) is an enzyme that in humans is encoded by the ''UBE3A'' gene. This enzyme is involved in targeting proteins for degradation within cell (biology), cells.
...
.
References
Further reading
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