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Q9UNE7 Proteins with TPR Repeats
Uniprot ID: Q9UNE7
Protein name : E3 ubiquitin-protein ligase CHIP
Gene : STUB1 CHIP PP1131
Protein Families :
Squence Length : 303
Sequence
>Q9UNE7 304 MKGKEEKEGGARLGAGGGSPEKSPSAQELKEQGNRLFVGRKYPEAAACYGRAITRNPLVAVYYTNRALCYLKMQQHEQALADCRRALELDGQSVKAHFFLGQCQLEMESYDEAIANLQRAYSLAKEQRLNFGDDIPSALRIAKKKRWNSIEERRIHQESELHSYLSRLIAAERERELEECQRNHEGDEDDSHVRAQQACIEAKHDKYMADMDELFSQVDEKRKKRDIPDYLCGKISFELMREPCITPSGITYDRKDIEEHLQRVGHFDPVTRSPLTQEQLIPNLAMKEVIDAFISENGWVEDY
Repeat regions
REPEAT 26 59 TPR 1 REPEAT 60 93 TPR 2 REPEAT 95 127 TPR 3
Sequence region of repeats
26- 59 ELKEQGNRLFVGRKYPEAAACYGRAITRNPLVAV 60- 93 YYTNRALCYLKMQQHEQALADCRRALELDGQSVK 95- 127 HFFLGQCQLEMESYDEAIANLQRAYSLAKEQRL
Domains
DOMAIN 226 300 U-box
Function
"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. Acts as a co-chaperone for HSPA1A and HSPA1B chaperone proteins and promotes ubiquitin-mediated protein degradation (PubMed:27708256). 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 (PubMed:23973223). Likely mediates polyubiquitination and downregulates plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity. Negatively regulates TGF-beta signaling by modulating the basal level of SMAD3 via ubiquitin-mediated degradation (PubMed:24613385)"
Mutation
30 30 K->A: Loss of interaction with FOXP3 and its ability to ubiquitinate FOXP3 260 260 H->Q: Loss of ability to ubiquitinate FOXP3 269 269 P->A: Abolishes E3 ligase activity
Disease
"DISEASE: Spinocerebellar ataxia, autosomal recessive, 16 (SCAR16) [MIM:615768]: Spinocerebellar ataxia defines a clinically and genetically heterogeneous group of cerebellar disorders Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord SCAR16 is characterized by truncal and limb ataxia resulting in gait instability Additionally, patients may show dysarthria, nystagmus, spasticity of the lower limbs, and mild peripheral sensory neuropathy Note=The disease is caused by mutations affecting the gene represented in this entry"