Polyubiquitin-C is a protein encoded by the UBC gene in humans.[5][6][7] Polyubiquitin-C is one of the sources of ubiquitin, along with UBB, UBA52, and RPS27A.[8]
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.[9][10] Defects of UBC gene could lead to mid-gestation embryonic lethality.
UBC gene is located at chromosome 12q24.3, consisting of 2 exons. 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.[9] Nine to ten Ub units were in the UBC gene.
In polyubiquitin-C, the C-terminus of a given ubiquitin molecule is covalently conjugated to either the N-terminal residue or one of seven lysine residues of another ubiquitin molecule.[11] 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.[12][13]
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.[10][14] Polyubiquitin-C has important role in diverse biological processes, such as innate immunity, DNA repair and kinase activity.[15][16][17] Unanchored polyubiquitin-C are also key signaling molecules that connect and coordinate the proteasome and autophagy to eliminate toxic protein aggregates.[18]
Loss of a single UBC allele 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.[10] 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.[19]
Polyubiquitin-C has been shown to interact with:
PDB gallery
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1aar: STRUCTURE OF A DIUBIQUITIN CONJUGATE AND A MODEL FOR INTERACTION WITH UBIQUITIN CONJUGATING ENZYME (E2)
1cmx: STRUCTURAL BASIS FOR THE SPECIFICITY OF UBIQUITIN C-TERMINAL HYDROLASES
1d3z: UBIQUITIN NMR STRUCTURE
1f9j: STRUCTURE OF A NEW CRYSTAL FORM OF TETRAUBIQUITIN
1fxt: STRUCTURE OF A CONJUGATING ENZYME-UBIQUITIN THIOLESTER COMPLEX
1g6j: STRUCTURE OF RECOMBINANT HUMAN UBIQUITIN IN AOT REVERSE MICELLES
1gjz: SOLUTION STRUCTURE OF A DIMERIC N-TERMINAL FRAGMENT OF HUMAN UBIQUITIN
1nbf: Crystal structure of a UBP-family deubiquitinating enzyme in isolation and in complex with ubiquitin aldehyde
1ogw: SYNTHETIC UBIQUITIN WITH FLUORO-LEU AT 50 AND 67
1otr: Solution Structure of a CUE-Ubiquitin Complex
1p3q: Mechanism of Ubiquitin Recognition by the CUE Domain of VPS9
1q0w: Solution structure of Vps27 amino-terminal UIM-ubiquitin complex
1q5w: Ubiquitin Recognition by Npl4 Zinc-Fingers
1s1q: TSG101(UEV) domain in complex with Ubiquitin
1sif: Crystal structure of a multiple hydrophobic core mutant of ubiquitin
1tbe: STRUCTURE OF TETRAUBIQUITIN SHOWS HOW MULTIUBIQUITIN CHAINS CAN BE FORMED
1ubi: SYNTHETIC STRUCTURAL AND BIOLOGICAL STUDIES OF THE UBIQUITIN SYSTEM. PART 1
1ubq: STRUCTURE OF UBIQUITIN REFINED AT 1.8 ANGSTROMS RESOLUTION
1ud7: SOLUTION STRUCTURE OF THE DESIGNED HYDROPHOBIC CORE MUTANT OF UBIQUITIN, 1D7
1uzx: A COMPLEX OF THE VPS23 UEV WITH UBIQUITIN
1v80: Solution structures of ubiquitin at 30 bar and 3 kbar
1v81: Solution structures of ubiquitin at 30 bar and 3 kbar
1wr1: The complex structure of Dsk2p UBA with ubiquitin
1wr6: Crystal structure of GGA3 GAT domain in complex with ubiquitin
1wrd: Crystal structure of Tom1 GAT domain in complex with ubiquitin
1xd3: Crystal structure of UCHL3-UbVME complex
1xqq: Simultaneous determination of protein structure and dynamics
1yd8: COMPLEX OF HUMAN GGA3 GAT DOMAIN AND UBIQUITIN
1yiw: X-ray Crystal Structure of a Chemically Synthesized Ubiquitin
1yj1: X-ray Crystal Structure of a Chemically Synthesized [D-Gln35]Ubiquitin
1yx5: Solution Structure of S5a UIM-1/Ubiquitin Complex
1yx6: Solution Structure of S5a UIM-2/Ubiquitin Complex
1zgu: Solution structure of the human Mms2-Ubiquitin complex
2ayo: Structure of USP14 bound to ubquitin aldehyde
2bgf: NMR STRUCTURE OF LYS48-LINKED DI-UBIQUITIN USING CHEMICAL SHIFT PERTURBATION DATA TOGETHER WITH RDCS AND 15N-RELAXATION DATA
2c7m: HUMAN RABEX-5 RESIDUES 1-74 IN COMPLEX WITH UBIQUITIN
2c7n: HUMAN RABEX-5 RESIDUES 1-74 IN COMPLEX WITH UBIQUITIN
2d3g: Double sided ubiquitin binding of Hrs-UIM
2den: Solution Structure of the Ubiquitin-Associated Domain of Human BMSC-UbP and its Complex with Ubiquitin
2dx5: The complex structure between the mouse EAP45-GLUE domain and ubiquitin
2fcm: X-ray Crystal Structure of a Chemically Synthesized [D-Gln35]Ubiquitin with a Cubic Space Group
2fcn: X-ray Crystal Structure of a Chemically Synthesized [D-Val35]Ubiquitin with a Cubic Space Group
2fcq: X-ray Crystal Structure of a Chemically Synthesized Ubiquitin with a Cubic Space Group
2fcs: X-ray Crystal Structure of a Chemically Synthesized [L-Gln35]Ubiquitin with a Cubic Space Group
2fid: Crystal Structure of a Bovine Rabex-5 fragment complexed with ubiquitin
2fif: Crystal Structure of a Bovine Rabex-5 fragment complexed with ubiquitin
2fuh: Solution Structure of the UbcH5c/Ub Non-covalent Complex
2g3q: Solution Structure of Ede1 UBA-ubiquitin complex
2g45: Co-crystal structure of znf ubp domain from the deubiquitinating enzyme isopeptidase T (isot) in complex with ubiquitin
2gbj: Crystal Structure of the 9-10 8 Glycine Insertion Mutant of Ubiquitin.
2gbk: Crystal Structure of the 9-10 MoaD Insertion Mutant of Ubiquitin
2gbm: Crystal Structure of the 35-36 8 Glycine Insertion Mutant of Ubiquitin
2gbn: Crystal Structure of the 35-36 8 Glycine Insertion Mutant of Ubiquitin
2gbr: Crystal Structure of the 35-36 MoaD Insertion Mutant of Ubiquitin
2gmi: Mms2/Ubc13~Ubiquitin
2hd5: USP2 in complex with ubiquitin
2hth: Structural basis for ubiquitin recognition by the human EAP45/ESCRT-II GLUE domain
2ibi: Covalent Ubiquitin-USP2 Complex
2j7q: CRYSTAL STRUCTURE OF THE UBIQUITIN-SPECIFIC PROTEASE ENCODED BY MURINE CYTOMEGALOVIRUS TEGUMENT PROTEIN M48 IN COMPLEX WITH A UBQUITIN-BASED SUICIDE SUBSTRATE
2nr2: The MUMO (minimal under-restraining minimal over-restraining) method for the determination of native states ensembles of proteins
2o6v: Crystal structure and solution NMR studies of Lys48-linked tetraubiquitin at neutral pH
2oob: crystal structure of the UBA domain from Cbl-b ubiquitin ligase in complex with ubiquitin
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