STUB1

This gene encodes a protein containing tetratricopeptide repeat and a U-box that functions as a ubiquitin ligase/cochaperone. The encoded protein binds to and ubiquitinates shock cognate 71 kDa protein (Hspa8) and DNA polymerase beta (Polb), among other targets. Mutations in this gene cause spinocerebellar ataxia, autosomal recessive 16. Alternative splicing results in multiple transcript variants. There is a pseudogene for this gene on chromosome 2.

STIP1 homology and U-box containing protein 1

E3 ubiquitin-protein ligase which targets misfolded chaperone substrates towards proteasomal degradation (PubMed:10330192, PubMed:11146632, PubMed:11557750, PubMed:23990462).
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 (PubMed:10330192, PubMed:11146632, PubMed:11557750, PubMed:23990462).
Ubiquitinates NOS1 in concert with Hsp70 and Hsp40 (PubMed:15466472).
Modulates the activity of several chaperone complexes, including Hsp70, Hsc70 and Hsp90 (PubMed:10330192, PubMed:11146632, PubMed:15466472).
Mediates transfer of non-canonical short ubiquitin chains to HSPA8 that have no effect on HSPA8 degradation (PubMed:11557750, PubMed:23990462).
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 (PubMed:19713937).
Mediates polyubiquitination of CYP3A4 (PubMed:19103148).
Ubiquitinates EPHA2 and may regulate the receptor stability and activity through proteasomal degradation (PubMed:19567782).
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).
Catalyzes monoubiquitination of SIRT6, preventing its degradation by the proteasome (PubMed:24043303).
Likely mediates polyubiquitination and down-regulates plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity (PubMed:28813410).
Negatively regulates TGF-beta signaling by modulating the basal level of SMAD3 via ubiquitin-mediated degradation (PubMed:24613385).
May regulate myosin assembly in striated muscles together with UBE4B and VCP/p97 by targeting myosin chaperone UNC45B for proteasomal degradation (PubMed:17369820).
Mediates ubiquitination of RIPK3 leading to its subsequent proteasome-dependent degradation (PubMed:29883609).

Biological Process cellular response to heatISS:ARUK-UCL
Biological Process cellular response to hypoxiaISS:ARUK-UCL
Biological Process cellular response to misfolded proteinManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process chaperone-mediated autophagyIEA:Ensembl
Biological Process DNA repairIEA:UniProtKB-KW
Biological Process endoplasmic reticulum unfolded protein responseIEA:Ensembl
Biological Process ERBB2 signaling pathwayTAS:Reactome
Biological Process negative regulation of protein bindingIEA:Ensembl
Biological Process negative regulation of transforming growth factor beta receptor signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of chaperone-mediated protein complex assemblyManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process positive regulation of proteasomal ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIDA:HGNC-UCL
Biological Process positive regulation of protein ubiquitinationManual Assertion Based On ExperimentIDA:HGNC-UCL
Biological Process positive regulation of proteolysisManual Assertion Based On ExperimentIBA:GO_Central
Biological Process positive regulation of ubiquitin-protein transferase activityIEA:Ensembl
Biological Process proteasome-mediated ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process protein autoubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process protein K63-linked ubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process protein maturationManual Assertion Based On ExperimentTAS:HGNC-UCL
Biological Process protein polyubiquitinationManual Assertion Based On ExperimentIDA:HGNC-UCL
Biological Process protein quality control for misfolded or incompletely synthesized proteinsManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process protein ubiquitinationManual Assertion Based On ExperimentIDA:FlyBase
Biological Process regulation of glucocorticoid metabolic processManual Assertion Based On ExperimentIDA:HGNC-UCL
Biological Process regulation of protein stabilityManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process response to ischemiaISS:ARUK-UCL
Biological Process ubiquitin-dependent ERAD pathwayManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Biological Process ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process ubiquitin-dependent SMAD protein catabolic processManual Assertion Based On ExperimentIDA:HGNC-UCL

Cytoplasm
Nucleus
Translocates to the nucleus in response to inflammatory signals in regulatory T-cells (Treg).

Spinocerebellar ataxia, autosomal recessive, 16 (SCAR16):
A form of spinocerebellar ataxia, 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.
Spinocerebellar ataxia 48 (SCA48):
A form of spinocerebellar ataxia, 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. SCA48 is an autosomal dominant neurodegenerative disease characterized by onset in mid-adulthood of progressive cognitive decline and gait ataxia, and vermian and hemispheric cerebellar atrophy.

Monoubiquitinated at Lys-2 following cell stress by UBE2W, promoting the interaction with ATXN3 (By similarity).
Auto-ubiquitinated; mediated by UBE2D1 and UBE2D2.