Ubiquitin C

UBC
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1C3T, 1CMX, 1D3Z, 1F9J, 1FXT, 1G6J, 1GJZ, 1NBF, 1OGW, 1Q5W, 1S1Q, 1SIF, 1TBE, 1UBI, 1UBQ, 1UD7, 1XD3, 1XQQ, 1YX5, 1YX6, 1ZGU, 2AYO, 2BGF, 2DEN, 2FUH, 2G45, 2GBJ, 2GBK, 2GBM, 2GBN, 2GBR, 2GMI, 2HTH, 2IBI, 2J7Q, 2JF5, 2JRI, 2JY6, 2JZZ, 2K25, 2K6D, 2K8B, 2K8C, 2KDF, 2KJH, 2KLG, 2KN5, 2KX0, 2L3Z, 2LD9, 2LVO, 2LVP, 2LVQ, 2LZ6, 2MBO, 2MBQ, 2MCN, 2MI8, 2MJ5, 2MOR, 2MRE, 2MWS, 2N2K, 2NR2, 2O6V, 2OJR, 2PE9, 2PEA, 2RR9, 2RU6, 2W9N, 2WDT, 2XEW, 2Z59, 2ZCB, 2ZVN, 2ZVO, 3A33, 3ALB, 3AUL, 3B08, 3B0A, 3BY4, 3C0R, 3DVG, 3DVN, 3EEC, 3EFU, 3EHV, 3H7P, 3H7S, 3HM3, 3IFW, 3IHP, 3JSV, 3JVZ, 3JW0, 3K9O, 3K9P, 3KVF, 3KW5, 3LDZ, 3MHS, 3MTN, 3N30, 3N32, 3N3K, 3NS8, 3O65, 3OFI, 3OJ4, 3ONS, 3PRM, 3PT2, 3PTF, 3Q3F, 3RUL, 3TMP, 3U30, 3UGB, 3V6C, 3V6E, 3VFK, 3VUW, 3VUX, 3VUY, 3WXE, 3WXF, 3ZNI, 3ZNZ, 4AUQ, 4BOS, 4BOZ, 4BVU, 4DDG, 4DDI, 4DHJ, 4DHZ, 4FJV, 4HK2, 4HXD, 4I6L, 4I6N, 4IG7, 4IUM, 4JQW, 4K1R, 4K7S, 4K7U, 4K7W, 4KSK, 4KSL, 4LCD, 4LDT, 4MDK, 4MM3, 4MSM, 4MSQ, 4NQK, 4UN2, 4V3K, 4V3L, 5AIU, 4XOK, 5AF6, 5AF5, 5AF4, 4XOL, 5C7J, 5C7M, 5E6J, 4ZQS, 4AP4,%%s4AP4
Identifiers
Aliases	UBC, HMG20, Ubiquitin C
External IDs	MGI: 98889 HomoloGene: 128418 GeneCards: UBC
Gene ontology Molecular function • protease binding • protein binding • poly(A) RNA binding Cellular component • cytoplasm • endocytic vesicle membrane • cytosol • nucleus • extracellular space • extracellular exosome • plasma membrane • nucleoplasm • endosome membrane Biological process • DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest • negative regulation of epidermal growth factor receptor signaling pathway • interstrand cross-link repair • nucleotide-excision repair, DNA damage recognition • positive regulation of canonical Wnt signaling pathway • tumor necrosis factor-mediated signaling pathway • regulation of necrotic cell death • regulation of type I interferon production • TRIF-dependent toll-like receptor signaling pathway • Fc-epsilon receptor signaling pathway • endosomal transport • global genome nucleotide-excision repair • NIK/NF-kappaB signaling • G2/M transition of mitotic cell cycle • stress-activated MAPK cascade • negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle • transforming growth factor beta receptor signaling pathway • macroautophagy • negative regulation of canonical Wnt signaling pathway • DNA damage response, detection of DNA damage • nucleotide-excision repair, DNA gap filling • error-free translesion synthesis • regulation of tumor necrosis factor-mediated signaling pathway • stimulatory C-type lectin receptor signaling pathway • negative regulation of transforming growth factor beta receptor signaling pathway • JNK cascade • regulation of transcription from RNA polymerase II promoter in response to hypoxia • nucleotide-excision repair, DNA incision • I-kappaB kinase/NF-kappaB signaling • innate immune response • positive regulation of ubiquitin-protein ligase activity involved in regulation of mitotic cell cycle transition • Notch signaling pathway • regulation of mRNA stability • protein polyubiquitination • negative regulation of apoptotic process • negative regulation of transcription from RNA polymerase II promoter • virion assembly • activation of MAPK activity • positive regulation of NF-kappaB transcription factor activity • anaphase-promoting complex-dependent catabolic process • negative regulation of type I interferon production • nucleotide-binding oligomerization domain containing signaling pathway • intracellular transport of virus • viral life cycle • MyD88-dependent toll-like receptor signaling pathway • error-prone translesion synthesis • MAPK cascade • fibroblast growth factor receptor signaling pathway • ion transmembrane transport • glycogen biosynthetic process • positive regulation of apoptotic process • positive regulation of I-kappaB kinase/NF-kappaB signaling • translesion synthesis • transcription-coupled nucleotide-excision repair • T cell receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • positive regulation of transcription from RNA polymerase II promoter • nucleotide-excision repair, DNA incision, 5'-to lesion • Wnt signaling pathway • nucleotide-excision repair, DNA duplex unwinding • protein ubiquitination involved in ubiquitin-dependent protein catabolic process • regulation of signal transduction by p53 class mediator • ERBB2 signaling pathway • nucleotide-excision repair, preincision complex assembly • Wnt signaling pathway, planar cell polarity pathway • proteasome-mediated ubiquitin-dependent protein catabolic process • positive regulation of epidermal growth factor receptor signaling pathway • cellular protein metabolic process Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7316	22190
Ensembl	ENSG00000150991	ENSMUSG00000008348
UniProt	P0CG48	P0CG50
RefSeq (mRNA)	NM_021009	NM_019639
RefSeq (protein)	NP_066289.3	NP_062613.3
Location (UCSC)	Chr 12: 124.91 – 124.92 Mb	Chr 5: 125.39 – 125.39 Mb
PubMed search	[1]	[2]
Wikidata

Polyubiquitin-C is a protein encoded by the UBC gene in humans.^[3][4][5] Polyubiquitin-C is one of the sources of ubiquitin, along with UBB, UBA52, and RPS27A.^[6] UBC gene is one of the two stress-regulated polyubiquitin genes (UBU and UBC) in mammals. It plays a key role in maintaining cellular ubiquitin levels under stress conditions.^[7][8] 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. 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. ^[7] 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 residue or one of seven lysine residues of another ubiquitin molecule.^[9] 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. ^[10][11]

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.^[8][12] Polyubiquitin-C has important role in diverse biological processes, such as innate immunity, DNA repair and kinase activity.^[13][14][15] Unanchored polyubiquitin-C are also key signaling molecules that connect and coordinate the proteasome and autophagy to eliminate toxic protein aggregates.^[16]

Clinical significance

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.^[8] 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.^[17]

Interactions

Polyubiquitin-C has been shown to interact with:

References

Further reading

PDB gallery
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