Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTBP3XA)

• DTT Name: Polyubiquitin-C (UBC)
• Synonyms: ubiquitin C; HMG20
• Gene Name: UBC
• DTT Type: Patented-recorded target; [1]
• UniProt ID: UBC_HUMAN
• TTD ID: T90167
• Sequence:
  MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYN
  IQKESTLHLVLRLRGGMQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLI
  FAGKQLEDGRTLSDYNIQKESTLHLVLRLRGGMQIFVKTLTGKTITLEVEPSDTIENVKA
  KIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRGGMQIFVKTLTGKT
  ITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLR
  LRGGMQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTL
  SDYNIQKESTLHLVLRLRGGMQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQ
  QRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRGGMQIFVKTLTGKTITLEVEPSDTIE
  NVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRGGMQIFVKTL
  TGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLH
  LVLRLRGGMQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLED
  GRTLSDYNIQKESTLHLVLRLRGGV
• Function: When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling. Ubiquitin: Exists either covalently attached to another protein, or free (unanchored).
• KEGG Pathway: PPAR signaling pathway (hsa03320)
• Reactome Pathway:
  Recognition of DNA damage by PCNA-containing replication complex (R-HSA-110314)
  Translesion Synthesis by POLH (R-HSA-110320)
  Activation of NF-kappaB in B cells (R-HSA-1169091)
  ISG15 antiviral mechanism (R-HSA-1169408)
  Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha (R-HSA-1234176)
  Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants (R-HSA-1236382)
  ER-Phagosome pathway (R-HSA-1236974)
  Downregulation of ERBB4 signaling (R-HSA-1253288)
  Spry regulation of FGF signaling (R-HSA-1295596)
  Downregulation of ERBB2 (R-HSA-1358803)
  Budding and maturation of HIV virion (R-HSA-162588)
  NOD1/2 Signaling Pathway (R-HSA-168638)
  TICAM1, RIP1-mediated IKK complex recruitment (R-HSA-168927)
  DDX58/IFIH1-mediated induction of interferon-alpha/beta (R-HSA-168928)
  APC/C (R-HSA-174048)
  Autodegradation of Cdh1 by Cdh1 (R-HSA-174084)
  SCF-beta-TrCP mediated degradation of Emi1 (R-HSA-174113)
  APC/C (R-HSA-174154)
  APC/C (R-HSA-174178)
  Cdc20 (R-HSA-174184)
  Membrane binding and targetting of GAG proteins (R-HSA-174490)
  Assembly Of The HIV Virion (R-HSA-175474)
  APC-Cdc20 mediated degradation of Nek2A (R-HSA-179409)
  Vpu mediated degradation of CD4 (R-HSA-180534)
  Vif-mediated degradation of APOBEC3G (R-HSA-180585)
  EGFR downregulation (R-HSA-182971)
  SCF(Skp2)-mediated degradation of p27/p21 (R-HSA-187577)
  Degradation of beta-catenin by the destruction complex (R-HSA-195253)
  TCF dependent signaling in response to WNT (R-HSA-201681)
  Downstream TCR signaling (R-HSA-202424)
  NRIF signals cell death from the nucleus (R-HSA-205043)
  p75NTR recruits signalling complexes (R-HSA-209543)
  NF-kB is activated and signals survival (R-HSA-209560)
  Regulation of activated PAK-2p34 by proteasome mediated degradation (R-HSA-211733)
  NOTCH1 Intracellular Domain Regulates Transcription (R-HSA-2122947)
  Activated NOTCH1 Transmits Signal to the Nucleus (R-HSA-2122948)
  Downregulation of TGF-beta receptor signaling (R-HSA-2173788)
  TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) (R-HSA-2173791)
  Downregulation of SMAD2/3 (R-HSA-2173795)
  SMAD2/SMAD3 (R-HSA-2173796)
  Separation of Sister Chromatids (R-HSA-2467813)
  Oxidative Stress Induced Senescence (R-HSA-2559580)
  Senescence-Associated Secretory Phenotype (SASP) (R-HSA-2559582)
  Oncogene Induced Senescence (R-HSA-2559585)
  Regulation of PLK1 Activity at G2/M Transition (R-HSA-2565942)
  Constitutive Signaling by NOTCH1 PEST Domain Mutants (R-HSA-2644606)
  Stimuli-sensing channels (R-HSA-2672351)
  Constitutive Signaling by NOTCH1 HD Domain Mutants (R-HSA-2691232)
  FCERI mediated NF-kB activation (R-HSA-2871837)
  Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants (R-HSA-2894862)
  NOTCH2 Activation and Transmission of Signal to the Nucleus (R-HSA-2979096)
  Regulation of innate immune responses to cytosolic DNA (R-HSA-3134975)
  Glycogen synthesis (R-HSA-3322077)
  Autodegradation of the E3 ubiquitin ligase COP1 (R-HSA-349425)
  Deactivation of the beta-catenin transactivating complex (R-HSA-3769402)
  Myoclonic epilepsy of Lafora (R-HSA-3785653)
  ABC-family proteins mediated transport (R-HSA-382556)
  Circadian Clock (R-HSA-400253)
  TAK1-dependent IKK and NF-kappa-B activation (R-HSA-445989)
  activated TAK1 mediates p38 MAPK activation (R-HSA-450302)
  JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 (R-HSA-450321)
  AUF1 (hnRNP D0) binds and destabilizes mRNA (R-HSA-450408)
  Asymmetric localization of PCP proteins (R-HSA-4608870)
  Degradation of AXIN (R-HSA-4641257)
  Degradation of DVL (R-HSA-4641258)
  Regulation of FZD by ubiquitination (R-HSA-4641263)
  PINK1-PRKN Mediated Mitophagy (R-HSA-5205685)
  N-glycan trimming in the ER and Calnexin/Calreticulin cycle (R-HSA-532668)
  Regulation of TNFR1 signaling (R-HSA-5357905)
  TNFR1-induced NFkappaB signaling pathway (R-HSA-5357956)
  Hedgehog ligand biogenesis (R-HSA-5358346)
  Hh mutants are degraded by ERAD (R-HSA-5362768)
  Dectin-1 mediated noncanonical NF-kB signaling (R-HSA-5607761)
  CLEC7A (Dectin-1) signaling (R-HSA-5607764)
  Degradation of GLI1 by the proteasome (R-HSA-5610780)
  Degradation of GLI2 by the proteasome (R-HSA-5610783)
  GLI3 is processed to GLI3R by the proteasome (R-HSA-5610785)
  Hedgehog 'on' state (R-HSA-5632684)
  Negative regulation of FGFR1 signaling (R-HSA-5654726)
  Negative regulation of FGFR2 signaling (R-HSA-5654727)
  Negative regulation of FGFR3 signaling (R-HSA-5654732)
  Negative regulation of FGFR4 signaling (R-HSA-5654733)
  Translesion synthesis by POLK (R-HSA-5655862)
  Translesion synthesis by POLI (R-HSA-5656121)
  Termination of translesion DNA synthesis (R-HSA-5656169)
  Regulation of RAS by GAPs (R-HSA-5658442)
  TNFR2 non-canonical NF-kB pathway (R-HSA-5668541)
  Negative regulation of MAPK pathway (R-HSA-5675221)
  Regulation of necroptotic cell death (R-HSA-5675482)
  NIK-->noncanonical NF-kB signaling (R-HSA-5676590)
  Defective CFTR causes cystic fibrosis (R-HSA-5678895)
  MAP3K8 (TPL2)-dependent MAPK1/3 activation (R-HSA-5684264)
  HDR through Homologous Recombination (HRR) (R-HSA-5685942)
  MAPK6/MAPK4 signaling (R-HSA-5687128)
  UCH proteinases (R-HSA-5689603)
  Josephin domain DUBs (R-HSA-5689877)
  Ub-specific processing proteases (R-HSA-5689880)
  Ovarian tumor domain proteases (R-HSA-5689896)
  Metalloprotease DUBs (R-HSA-5689901)
  Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks (R-HSA-5693565)
  Processing of DNA double-strand break ends (R-HSA-5693607)
  DNA Damage Recognition in GG-NER (R-HSA-5696394)
  Formation of Incision Complex in GG-NER (R-HSA-5696395)
  Gap-filling DNA repair synthesis and ligation in GG-NER (R-HSA-5696397)
  Dual Incision in GG-NER (R-HSA-5696400)
  Formation of TC-NER Pre-Incision Complex (R-HSA-6781823)
  Transcription-Coupled Nucleotide Excision Repair (TC-NER) (R-HSA-6781827)
  Dual incision in TC-NER (R-HSA-6782135)
  Gap-filling DNA repair synthesis and ligation in TC-NER (R-HSA-6782210)
  Fanconi Anemia Pathway (R-HSA-6783310)
  Regulation of TP53 Activity through Phosphorylation (R-HSA-6804756)
  Regulation of TP53 Degradation (R-HSA-6804757)
  Regulation of TP53 Activity through Methylation (R-HSA-6804760)
  Negative regulation of MET activity (R-HSA-6807004)
  Assembly of the pre-replicative complex (R-HSA-68867)
  Orc1 removal from chromatin (R-HSA-68949)
  CDK-mediated phosphorylation and removal of Cdc6 (R-HSA-69017)
  Cyclin D associated events in G1 (R-HSA-69231)
  G2/M Checkpoints (R-HSA-69481)
  Stabilization of p53 (R-HSA-69541)
  Ubiquitin Mediated Degradation of Phosphorylated Cdc25A (R-HSA-69601)
  Ubiquitin-dependent degradation of Cyclin D (R-HSA-75815)
  PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 (R-HSA-8849469)
  The role of GTSE1 in G2/M progression after G2 checkpoint (R-HSA-8852276)
  FBXL7 down-regulates AURKA during mitotic entry and in early mitosis (R-HSA-8854050)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Downregulation of ERBB2 signaling (R-HSA-8863795)
  VLDLR internalisation and degradation (R-HSA-8866427)
  Synthesis of active ubiquitin (R-HSA-8866652)
  E3 ubiquitin ligases ubiquitinate target proteins (R-HSA-8866654)
  InlB-mediated entry of Listeria monocytogenes into host cell (R-HSA-8875360)
  InlA-mediated entry of Listeria monocytogenes into host cells (R-HSA-8876493)
  RUNX1 regulates transcription of genes involved in differentiation of HSCs (R-HSA-8939236)
  Regulation of RUNX2 expression and activity (R-HSA-8939902)
  Regulation of RUNX3 expression and activity (R-HSA-8941858)
  Regulation of PTEN localization (R-HSA-8948747)
  Regulation of PTEN stability and activity (R-HSA-8948751)
  Neddylation (R-HSA-8951664)
  ER Quality Control Compartment (ERQC) (R-HSA-901032)
  Regulation of expression of SLITs and ROBOs (R-HSA-9010553)
  NOTCH3 Activation and Transmission of Signal to the Nucleus (R-HSA-9013507)
  TICAM1-dependent activation of IRF3/IRF7 (R-HSA-9013973)
  TICAM1,TRAF6-dependent induction of TAK1 complex (R-HSA-9014325)
  Interleukin-1 signaling (R-HSA-9020702)
  Peroxisomal protein import (R-HSA-9033241)
  Regulation of signaling by CBL (R-HSA-912631)
  Endosomal Sorting Complex Required For Transport (ESCRT) (R-HSA-917729)
  Iron uptake and transport (R-HSA-917937)
  Negative regulators of DDX58/IFIH1 signaling (R-HSA-936440)
  Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon (R-HSA-936964)
  IRAK1 recruits IKK complex (R-HSA-937039)
  IKK complex recruitment mediated by RIP1 (R-HSA-937041)
  IRAK2 mediated activation of TAK1 complex (R-HSA-937042)
  TRAF6-mediated induction of TAK1 complex within TLR4 complex (R-HSA-937072)
  Negative regulation of NOTCH4 signaling (R-HSA-9604323)
  Chaperone Mediated Autophagy (R-HSA-9613829)
  Late endosomal microautophagy (R-HSA-9615710)
  Prevention of phagosomal-lysosomal fusion (R-HSA-9636383)
  Modulation by Mtb of host immune system (R-HSA-9637628)
  Alpha-protein kinase 1 signaling pathway (R-HSA-9645460)
  Aggrephagy (R-HSA-9646399)
  RAS processing (R-HSA-9648002)
  Pexophagy (R-HSA-9664873)
  Maturation of protein E (R-HSA-9683683)
  Maturation of protein E (R-HSA-9694493)
  Inactivation of CSF3 (G-CSF) signaling (R-HSA-9705462)
  SARS-CoV-2 activates/modulates innate and adaptive immune responses (R-HSA-9705671)
  Negative regulation of FLT3 (R-HSA-9706369)
  FLT3 signaling by CBL mutants (R-HSA-9706377)
  Regulation of BACH1 activity (R-HSA-9708530)
  TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling (R-HSA-975110)
  IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation (R-HSA-975144)
  IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation (R-HSA-975163)
  KEAP1-NFE2L2 pathway (R-HSA-9755511)
  GSK3B and BTRC (R-HSA-9762114)
  Amyloid fiber formation (R-HSA-977225)
  Antigen processing (R-HSA-983168)
  Translesion synthesis by REV1 (R-HSA-110312)
• BioCyc Pathway: MetaCyc:ENSG00000150991-MON

Molecular Interaction Atlas (MIA) of This DTT

2 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID25553724-Compound-US20130237529 35	DMYGB2O	N. A.	N. A.	Patented	[1]
PMID25553724-Compound-US20130237529 36	DM9NGDI	N. A.	N. A.	Patented	[1]

References

• [1] Novel NF-B inhibitors: a patent review (2011 - 2014).Expert Opin Ther Pat. 2015 Mar;25(3):319-34.