Ubiquilin-1 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 ''UBQLN1''
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 ...
.
Ubiquilins contain two
domains, an
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 thus are thought to functionally link the
ubiquitination
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 19 ...
machinery to the proteasome to effect ''in vivo''
protein degradation.
Functions
Ubiquilin-1 is associated with
protein degradation and aggregation of
misfolded proteins, and may be involved in
neurodegenerative disease
A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, mul ...
s.
Ubiquilin-1 has been reported to act as a
molecular chaperone for
amyloid precursor protein
Amyloid-beta precursor protein (APP) is an integral membrane protein expressed in many biological tissue, tissues and concentrated in the synapses of neurons. It functions as a cell surface receptor and has been implicated as a regulator of s ...
(APP), a protein associated with
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
.
[
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Ubiquilin-1 was first identified through its interactions with
presenilins.
Two transcript variants encoding different isoforms have been found for this gene.
Related proteins
Human UBQLN1 shares a high degree of similarity with related ubiquilins including
UBQLN2
Ubiquilin-2 is a protein that in humans is encoded by the ''UBQLN2'' gene.
Function
This gene encodes a ubiquitin-like protein (ubiquilin) that shares high degree of similarity with related products in yeast, rat and frog. Ubiquilins contain ...
and
UBQLN4.
Interactions
UBQLN1 has been shown to
interact 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 ...
,
*
MTOR,
*
P4HB,
*
PSEN1
*
PSEN2,
[ 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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