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	OMIM: 191340; MGI: 98889; HomoloGene: 128418; GeneCards: UBC; OMA:UBC - orthologs
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q24.31 Start 124,911,604 bp[1] End 124,917,368 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5 G1.1|5 64.18 cM Start 125,463,029 bp[2] End 125,467,266 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in olfactory bulb Brodmann area 46 pericardium vena cava cerebellar vermis postcentral gyrus spinal ganglia trigeminal ganglion lateral nuclear group of thalamus frontal pole Top expressed in granulocyte right kidney endothelial cell of lymphatic vessel temporal muscle dentate gyrus of hippocampal formation granule cell muscle of thigh triceps brachii muscle central gray substance of midbrain sternocleidomastoid muscle calvaria More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protease binding protein binding RNA binding protein tag ubiquitin protein ligase binding Cellular component cytoplasm endocytic vesicle membrane cytosol nucleus extracellular exosome plasma membrane nucleoplasm endosome membrane extracellular space mitochondrial outer membrane endoplasmic reticulum quality control compartment vesicle endoplasmic reticulum membrane host cell 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 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 transforming growth factor beta receptor signaling pathway macroautophagy negative regulation of canonical Wnt signaling pathway 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 Notch signaling pathway regulation of mRNA stability protein polyubiquitination negative regulation of apoptotic process negative regulation of transcription by RNA polymerase II virion assembly 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 by RNA polymerase II nucleotide-excision repair, DNA incision, 5'-to lesion Wnt signaling pathway nucleotide-excision repair, DNA duplex unwinding 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 protein folding negative regulation of G2/M transition of mitotic cell cycle protein ubiquitination protein deubiquitination SCF-dependent proteasomal ubiquitin-dependent protein catabolic process entry of bacterium into host cell transmembrane transport regulation of necroptotic process membrane organization endoplasmic reticulum mannose trimming cellular iron ion homeostasis regulation of hematopoietic stem cell differentiation protein targeting to peroxisome cytokine-mediated signaling pathway modification-dependent protein catabolic process interleukin-1-mediated signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7316 22190 Ensembl ENSG00000150991 ENSMUSG00000008348 UniProt P0CG48 P0CG50 RefSeq (mRNA) NM_021009 NM_019639 RefSeq (protein) NP_066289 NP_062613 Location (UCSC) Chr 12: 124.91 – 124.92 Mb Chr 5: 125.46 – 125.47 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.

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.[9] 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.[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]

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.[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]

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.[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]

Interactions

Polyubiquitin-C has been shown to interact with:

• BIRC2,[20][21][22]
• BSG,[23]
• CDC2,[24]
• CFAP298,[25]
• E2F1,[26]
• EGFR,[27][28][29]
• HDAC3,[24]
• HIF1A,[30][31][32]
• IRAK1,[33][34][35][36]
• KIAA0753.[37]
• MARK4,[38]
• MDM2,[39][40][41]
• NDUFA3,[42]
• NFE2L2,[43][44]
• NOTCH1,[45]
• NUAK1,[38]
• OPRK1,[46]
• P53,[27][39][40][41][47][48][49][50]
• PCNA[51][52][53]
• PARK2,[54][55]
• RIPK1,[20][33][56][57][58]
• RPS6KB1,[59]
• S100A10,[60]
• SCNN1A,[61][62]
• SCNN1G,[61][62]
• SFPQ,[63]
• SMAD3,[64][65]
• SMURF2,[66][67]
• SP1,[68]
• TRAF6,[33][34][56][69][70] and
• THRA.[24]

References

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2. GRCm38: Ensembl release 89: ENSMUSG00000008348 – Ensembl, May 2017
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Further reading

• Mazzé FM, Degrève L (2006). "The role of viral and cellular proteins in the budding of human immunodeficiency virus". Acta Virologica. 50 (2): 75–85. PMID 16808324.
• Kanayama H, Tanaka K, Aki M, Kagawa S, Miyaji H, Satoh M, Okada F, Sato S, Shimbara N, Ichihara A (December 1991). "Changes in expressions of proteasome and ubiquitin genes in human renal cancer cells". Cancer Research. 51 (24): 6677–85. PMID 1660345.
• Baker RT, Board PG (April 1989). "Unequal crossover generates variation in ubiquitin coding unit number at the human UbC polyubiquitin locus". American Journal of Human Genetics. 44 (4): 534–42. PMC 1715567. PMID 2564731.
• Einspanier R, Sharma HS, Scheit KH (September 1987). "Cloning and sequence analysis of a cDNA encoding poly-ubiquitin in human ovarian granulosa cells". Biochemical and Biophysical Research Communications. 147 (2): 581–7. doi:10.1016/0006-291X(87)90970-3. PMID 2820408.
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (April 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
• Nenoi M, Mita K, Ichimura S, Cartwright IL, Takahashi E, Yamauchi M, Tsuji H (October 1996). "Heterogeneous structure of the polyubiquitin gene UbC of HeLa S3 cells". Gene. 175 (1–2): 179–85. doi:10.1016/0378-1119(96)00145-X. PMID 8917096.
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (April 1997). "Large-scale concatenation cDNA sequencing". Genome Research. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
• Nenoi M, Mita K, Ichimura S, Kawano A (February 1998). "Higher frequency of concerted evolutionary events in rodents than in man at the polyubiquitin gene VNTR locus". Genetics. 148 (2): 867–76. doi:10.1093/genetics/148.2.867. PMC 1459823. PMID 9504932.
• Ott DE, Coren LV, Copeland TD, Kane BP, Johnson DG, Sowder RC, Yoshinaka Y, Oroszlan S, Arthur LO, Henderson LE (April 1998). "Ubiquitin is covalently attached to the p6Gag proteins of human immunodeficiency virus type 1 and simian immunodeficiency virus and to the p12Gag protein of Moloney murine leukemia virus". Journal of Virology. 72 (4): 2962–8. doi:10.1128/JVI.72.4.2962-2968.1998. PMC 109742. PMID 9525617.
• Kim NS, Yamaguchi T, Sekine S, Saeki M, Iwamuro S, Kato S (July 1998). "Cloning of human polyubiquitin cDNAs and a ubiquitin-binding assay involving its in vitro translation product". Journal of Biochemistry. 124 (1): 35–9. doi:10.1093/oxfordjournals.jbchem.a022093. PMID 9644242.
• Schubert U, Ott DE, Chertova EN, Welker R, Tessmer U, Princiotta MF, Bennink JR, Krausslich HG, Yewdell JW (November 2000). "Proteasome inhibition interferes with gag polyprotein processing, release, and maturation of HIV-1 and HIV-2". Proceedings of the National Academy of Sciences of the United States of America. 97 (24): 13057–62. Bibcode:2000PNAS...9713057S. doi:10.1073/pnas.97.24.13057. PMC 27177. PMID 11087859.
• Strack B, Calistri A, Accola MA, Palu G, Gottlinger HG (November 2000). "A role for ubiquitin ligase recruitment in retrovirus release". Proceedings of the National Academy of Sciences of the United States of America. 97 (24): 13063–8. Bibcode:2000PNAS...9713063S. doi:10.1073/pnas.97.24.13063. PMC 27178. PMID 11087860.
• Ott DE, Coren LV, Chertova EN, Gagliardi TD, Schubert U (December 2000). "Ubiquitination of HIV-1 and MuLV Gag". Virology. 278 (1): 111–21. doi:10.1006/viro.2000.0648. PMID 11112487.
• Strack B, Calistri A, Göttlinger HG (June 2002). "Late assembly domain function can exhibit context dependence and involves ubiquitin residues implicated in endocytosis". Journal of Virology. 76 (11): 5472–9. doi:10.1128/JVI.76.11.5472-5479.2002. PMC 137019. PMID 11991975.
• Huang L, Feng L, Yang L, Zhou W, Zhao S, Li C (September 2002). "Screen and identification of proteins interacting with ADAM19 cytoplasmic tail". Molecular Biology Reports. 29 (3): 317–23. doi:10.1023/A:1020409217215. PMID 12463424. S2CID 22611084.
• Ott DE, Coren LV, Sowder RC, Adams J, Schubert U (March 2003). "Retroviruses have differing requirements for proteasome function in the budding process". Journal of Virology. 77 (6): 3384–93. doi:10.1128/JVI.77.6.3384-3393.2003. PMC 149504. PMID 12610113.
• Evans PC, Smith TS, Lai MJ, Williams MG, Burke DF, Heyninck K, Kreike MM, Beyaert R, Blundell TL, Kilshaw PJ (June 2003). "A novel type of deubiquitinating enzyme". The Journal of Biological Chemistry. 278 (25): 23180–6. doi:10.1074/jbc.M301863200. PMID 12682062.