Polyubiquitin-C is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
encoded by the ''UBC''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
in humans.
Polyubiquitin-C is one of the sources of
ubiquitin, along with
UBB,
UBA52, and
RPS27A.
''UBC'' gene is one of the two stress-regulated polyubiquitin genes (''UBB'' and ''UBC'') in mammals. It plays a key role in maintaining cellular
ubiquitin levels under
stress conditions.
Defects of ''UBC'' gene could lead to mid-gestation embryonic lethality.
Structure
Gene
''UBC'' gene is located at
chromosome 12q24.3, consisting of 2
exons
An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding seque ...
. The
promoter of the ''UBC'' gene contains putative heat shock elements (
HSEs), which mediates UBC induction upon stress. ''UBC'' gene differs from ''UBB'' gene in the number of Ub coding units they contain.
Nine to ten Ub units were in the ''UBC'' gene.
Protein
In polyubiquitin-C, the
C-terminus of a given ubiquitin molecule is covalently conjugated to either the
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 ...
residue or one of seven
lysine residues of another ubiquitin molecule.
Different linking of ubiquitin chains results in distinct conformations. There are 8 linkage types of polyubiquitin-C, and each type possesses the linkage-dependent dynamics and a linkage-specific conformation.
Function
The diversity of polyubiquitin-C means that
ubiquitylation contributes to the regulation of many cellular events. Polyubiquitin-C doesn’t activate the heat-shock response, but it plays a key role in sustaining the response. ''UBC'' gene transcription is induced during stress and provides extra ubiquitin necessary to remove damaged/unfolded proteins.
Polyubiquitin-C has important role in diverse biological processes, such as
innate immunity, DNA repair and
kinase
In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...
activity.
Unanchored polyubiquitin-C are also key signaling molecules that connect and coordinate the
proteasome and
autophagy
Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent re ...
to eliminate toxic protein aggregates.
Clinical significance
Loss of a single ''UBC''
allele
An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution.
::"The chrom ...
has no apparent phenotype, while homozygous deletion of UBC gene leads to mid-gestation embryonic lethality due to a defect in fetal liver development, as well as a delay in
cell-cycle progression and increased susceptibility to cellular stress.
It is also reported that homozygous deletion of UBC gene in mouse embryonic fibroblasts will cause decreased cellular Ub level and reduced viability under oxidative stress.
Interactions
Polyubiquitin-C has been shown to
interact
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with:
*
BIRC2
Baculoviral IAP repeat-containing protein 2 (also known as cIAP1) is a protein that in humans is encoded by the ''BIRC2'' gene.
Function
cIAP1 is a member of the Inhibitor of Apoptosis family that inhibit apoptosis by interfering with the act ...
,
* BSG,
* CDC2,[
* ]CFAP298
Cilia- and flagella-associated protein 298 is a protein encoded by ''CFAP298'' gene. It is of interest in part for its association with various diseases. It has been found in high levels in the bone marrow of patients with a negative prognosis of ...
,
* E2F1
Transcription factor E2F1 is a protein that in humans is encoded by the ''E2F1'' gene.
Function
The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of c ...
,
* EGFR,
* HDAC3,
* HIF1A,
* IRAK1,
* KIAA0753.[KIAA0753 Gene - GeneCards , K0753 Protein , K0753 Antibody, (available at https://www.genecards.org/cgi-bin/carddisp.pl?gene=KIAA0753).]
* MARK4,[
* MDM2,]
* NDUFA3,
* NFE2L2,
* NOTCH1
Neurogenic locus notch homolog protein 1 (Notch 1) is a protein encoded in humans by the ''NOTCH1'' gene. Notch 1 is a single-pass transmembrane receptor.
Function
This gene encodes a member of the Notch family. Members of this Type 1 trans ...
,
* NUAK1,
* OPRK1,
* P53,
* PCNA
* PARK2
Parkin is a 465-amino acid residue E3 ubiquitin ligase, a protein that in humans and mice is encoded by the ''PARK2'' gene. Parkin plays a critical role in ubiquitination – the process whereby molecules are covalently labelled with ubiquitin ...
,
* RIPK1,
* RPS6KB1
Ribosomal protein S6 kinase beta-1 (S6K1), also known as p70S6 kinase (p70S6K, p70-S6K), is an enzyme (specifically, a protein kinase) that in humans is encoded by the ''RPS6KB1'' gene. It is a serine/threonine kinase that acts downstream of PIP3 ...
,
* S100A10,
* SCNN1A
The SCNN1A gene encodes for the α subunit of the epithelial sodium channel ENaC in vertebrates. ENaC is assembled as a heterotrimer composed of three homologous subunits α, β, and γ or δ, β, and γ. The other ENAC subunits are encoded by SCN ...
,
* SCNN1G
The SCNN1G gene encodes for the γ subunit of the epithelial sodium channel ENaC in vertebrates. ENaC is assembled as a heterotrimer composed of three homologous subunits α, β, and γ or δ, β, and γ. The other ENAC subunits are encoded by S ...
,[
* SFPQ,]
* SMAD3,
* SMURF2,
* SP1,
* TRAF6, and
* THRA.[
]
References
Further reading
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{{PDB Gallery, geneid=7316
Human proteins