Ubiquilin-1 is a
protein that in humans is encoded by the ''UBQLN1''
gene.
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 ami ...
ubiquitin-like domain
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 ...
and a
C-terminal ubiquitin-associated domain
Ubiquitin-associated (UBA) domains are protein domains that non-covalently interact with ubiquitin through protein-protein interactions. Ubiquitin is a small protein that is covalently linked to other proteins as part of intracellular signali ...
. They physically associate with both
proteasome
Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases.
Proteasomes are part of a major mechanism by w ...
s and
ubiquitin ligases, and thus are thought to functionally link the
ubiquitination machinery to the proteasome to effect ''in vivo''
protein degradation.
Functions
Ubiquilin-1 is associated with
protein degradation and aggregation of
misfolded protein
Protein folding is the physical process by which a protein chain is translated to its native three-dimensional structure, typically a "folded" conformation by which the protein becomes biologically functional. Via an expeditious and reproduci ...
s, and may be involved in
neurodegenerative diseases.
Ubiquilin-1 has been reported to act as a
molecular chaperone
In molecular biology, molecular chaperones are proteins that assist the conformational folding or unfolding of large proteins or macromolecular protein complexes. There are a number of classes of molecular chaperones, all of which function to assi ...
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 ...
(APP), a protein associated with
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
.
[
*]
Ubiquilin-1 was first identified through its interactions with
presenilin
Presenilins are a family of related multi-pass transmembrane proteins which constitute the catalytic subunits of the gamma-secretase intramembrane protease protein complex. They were first identified in screens for mutations causing early onset ...
s.
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
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
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
Protein disulfide-isomerase, also known as the beta- subunit of prolyl 4-hydroxylase (P4HB), is an enzyme that in humans encoded by the ''P4HB'' gene. The human ''P4HB'' gene is localized in chromosome 17q25. Unlike other prolyl 4-hydroxylase fami ...
,
*
PSEN1
Presenilin-1 (PS-1) is a presenilin protein that in humans is encoded by the ''PSEN1'' gene. Presenilin-1 is one of the four core proteins in the gamma secretase complex, which is considered to play an important role in generation of amyloid beta ( ...
*
PSEN2
Presenilin-2 is a protein that (in humans) is encoded by the ''PSEN2'' gene.
Function
Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins ( PSEN1; PSEN2) or the amyloid precursor ...
,
[ and
* UBE3A.]TMCO6
Transmembrane and coiled-coil domain 6, TMCO6, is a protein that in humans is encoded by the ''TMCO6'' gene with aliases of PRO1580, HQ1580 or FLJ39769.1.
Gene
The human TMCO6 is found on chromosome 5 (position 5q31.3). The entire gene spans ...
,
References
Further reading
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