STUB1 - E3 ubiquitin-protein ligase CHIP - human protein (Function)
 
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STUB1 »  E3 ubiquitin-protein ligase CHIP   [ EC 6.3.2.- ]
 
Protein also known as:  Carboxy terminus of Hsp70-interacting protein.
Gene name:  STUB1
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 159 2
GENE REF ISO

Function

 show evidences
Overview 
E3 ubiquitin-protein ligase which targets misfolded chaperone substrates towards proteasomal degradation. Collaborates with ATXN3 in the degradation of misfolded chaperone substrates: ATXN3 restricting the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension. Ubiquitinates NOS1 in concert with Hsp70 and Hsp40. Modulates the activity of several chaperone complexes, including Hsp70, Hsc70 and Hsp90. Mediates transfer of non-canonical short ubiquitin chains to HSPA8 that have no effect on HSPA8 degradation. Mediates polyubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair: catalyzes polyubiquitination by amplifying the HUWE1/ARF-BP1-dependent monoubiquitination and leading to POLB-degradation by the proteasome. Mediates polyubiquitination of CYP3A4. Ubiquitinates EPHA2 and may regulate the receptor stability and activity through proteasomal degradation. Negatively regulates the suppressive function of regulatory T-cells (Treg) during inflammation by mediating the ubiquitination and degradation of FOXP3 in a HSPA1A/B-dependent manner (PubMed23973223).  
10
  • UniProtKB
GO molecular function 
Enzyme bindingdefinition[GO:0019899]  
1
  • UniProtKB
G-protein coupled receptor bindingdefinition[GO:0001664]  
1
  • ParkinsonsUK-UCL
Hsp70 protein bindingdefinition[GO:0030544]  
1
  • HGNC
Hsp90 protein bindingdefinition[GO:0051879]  
1
  • BHF-UCL
Kinase bindingdefinition[GO:0019900]  
1
  • BHF-UCL
Ligase activitydefinition[GO:0016874]  
1
  • UniProtKB KW
Misfolded protein bindingdefinition[GO:0051787]  
1
  • BHF-UCL
Protein bindingdefinition[GO:0005515]  
17
  • IntAct
  • UniProtKB
  • HGNC
Protein binding, bridgingdefinition[GO:0030674]  
1
  • HGNC
Protein homodimerization activitydefinition[GO:0042803]  
1
  • Ortholog Curator
SMAD bindingdefinition[GO:0046332]  
1
  • HGNC
TPR domain bindingdefinition[GO:0030911]  
1
  • HGNC
Ubiquitin protein ligase activitydefinition[GO:0061630]  
2
  • MGI
  • ParkinsonsUK-UCL
Ubiquitin protein ligase bindingdefinition[GO:0031625]  
1
  • ParkinsonsUK-UCL
Ubiquitin-protein transferase activitydefinition[GO:0004842]  
3
  • UniProtKB
  • HGNC
Ubiquitin-ubiquitin ligase activitydefinition[GO:0034450]  
1
  • Ortholog Curator
GO biological process 
Cellular response to misfolded proteindefinition[GO:0071218]  
1
  • BHF-UCL
DNA repairdefinition[GO:0006281]  
1
  • UniProtKB KW
Endoplasmic reticulum unfolded protein responsedefinition[GO:0030968] silver  
1
  • Ortholog Compara
Misfolded or incompletely synthesized protein catabolic processdefinition[GO:0006515]  
1
  • BHF-UCL
Negative regulation of protein bindingdefinition[GO:0032091] silver  
1
  • Ortholog Compara
Positive regulation of chaperone-mediated protein complex assemblydefinition[GO:0090035]  
1
  • BHF-UCL
Positive regulation of proteasomal ubiquitin-dependent protein catabolic processdefinition[GO:0032436]  
1
  • HGNC
Positive regulation of protein ubiquitinationdefinition[GO:0031398]  
2
  • BHF-UCL
  • HGNC
Positive regulation of ubiquitin-protein transferase activitydefinition[GO:0051443] silver  
1
  • Ortholog Compara
Proteasome-mediated ubiquitin-dependent protein catabolic processdefinition[GO:0043161]  
1
  • HGNC
Protein autoubiquitinationdefinition[GO:0051865]  
2
  • UniProtKB
Protein K63-linked ubiquitinationdefinition[GO:0070534]  
1
  • UniProtKB
Protein maturationdefinition[GO:0051604]  
1
  • HGNC
Protein polyubiquitinationdefinition[GO:0000209]  
3
  • UniProtKB
  • ParkinsonsUK-UCL
  • HGNC
Regulation of glucocorticoid metabolic processdefinition[GO:0031943]  
1
  • HGNC
Ubiquitin-dependent protein catabolic processdefinition[GO:0006511]  
1
  • UniProtKB
Ubiquitin-dependent SMAD protein catabolic processdefinition[GO:0030579]  
1
  • HGNC
Enzymatic activity 
 
More information is available from:
Pathways 
This protein is involved in the following pathway
Protein modification; protein ubiquitination  
3
  • UniProtKB
According to KEGG, this protein belongs to the following pathways:
Protein processing in endoplasmic reticulum  hsa04141+10273  
Ubiquitin mediated proteolysis  hsa04120+10273  
According to Reactome, this protein belongs to the following pathways:
Antigen processing: Ubiquitination & Proteasome degradation  REACT_75842  
Downregulation of TGF-beta receptor signaling  REACT_120727  
Signaling by ERBB2  REACT_115755  
 

Keywords

Biological process 
DNA damage  definition   [KW-0227]
DNA repair  definition   [KW-0234]
Ubl conjugation pathway  definition   [KW-0833]
Molecular function 
Ligase  definition   [KW-0436]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: STUB1
GenomeRNAi: 10273
PRO: PR:Q9UNE7