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MGP004187

UniProt Annotations

Entry Information
Gene NameSTIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase
Protein EntryCHIP_HUMAN
UniProt IDQ9UNE7
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q9UNE7-1; Sequence=Displayed; Name=2; IsoId=Q9UNE7-2; Sequence=VSP_015947; Note=No experimental confirmation available.;
DiseaseSpinocerebellar 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. {ECO:0000269|PubMed:24113144, ECO:0000269|PubMed:24312598, ECO:0000269|PubMed:24719489, ECO:0000269|PubMed:24742043, ECO:0000269|PubMed:25258038}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DomainThe TPR domain is essential for ubiquitination mediated by UBE2D1. {ECO:0000269|PubMed:18042044}.
DomainThe U-box domain is required for the ubiquitin protein ligase activity. {ECO:0000250|UniProtKB:Q9WUD1}.
FunctionE3 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. {ECO:0000269|PubMed:10330192, ECO:0000269|PubMed:11146632, ECO:0000269|PubMed:11557750, ECO:0000269|PubMed:15466472, ECO:0000269|PubMed:19103148, ECO:0000269|PubMed:19567782, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:23990462}.
InteractionA8K1F4:-; NbExp=2; IntAct=EBI-357085, EBI-9357094; Q86WG3:ATCAY; NbExp=4; IntAct=EBI-357085, EBI-1783328; Q99933:BAG1; NbExp=2; IntAct=EBI-357085, EBI-1030678; O95816:BAG2; NbExp=4; IntAct=EBI-357085, EBI-355275; O95817:BAG3; NbExp=2; IntAct=EBI-357085, EBI-747185; P00533:EGFR; NbExp=3; IntAct=EBI-357085, EBI-297353; P07900:HSP90AA1; NbExp=9; IntAct=EBI-357085, EBI-296047; P08238:HSP90AB1; NbExp=5; IntAct=EBI-357085, EBI-352572; P08107:HSPA1B; NbExp=5; IntAct=EBI-357085, EBI-629985; P11142:HSPA8; NbExp=5; IntAct=EBI-357085, EBI-351896; Q9Y2U5:MAP3K2; NbExp=9; IntAct=EBI-357085, EBI-357393; P10636:MAPT; NbExp=2; IntAct=EBI-357085, EBI-366182; P61088:UBE2N; NbExp=5; IntAct=EBI-357085, EBI-1052908; Q7Z7E8:UBE2Q1; NbExp=3; IntAct=EBI-357085, EBI-1783287; P12504:vif (xeno); NbExp=2; IntAct=EBI-357085, EBI-779991;
MiscellaneousAntibodies against STUB1 are found in patients with chronic lymphocytic leukemia (CLL) and in colorectal cancer patients.
PathwayProtein modification; protein ubiquitination. {ECO:0000269|PubMed:11557750, ECO:0000269|PubMed:15466472}.
PtmMonoubiquitinated at Lys-2 following cell stress by UBE2W, promoting the interaction with ATXN3 (By similarity). Auto- ubiquitinated; mediated by UBE2D1 and UBE2D2. {ECO:0000250, ECO:0000269|PubMed:18042044, ECO:0000269|PubMed:23560854}.
SimilarityContains 1 U-box domain. {ECO:0000305}.
SimilarityContains 3 TPR repeats. {ECO:0000255|PROSITE- ProRule:PRU00339}.
Subcellular LocationCytoplasm {ECO:0000269|PubMed:10330192}.
SubunitHomodimer. Interacts with BAG2, and with the E2 ubiquitin conjugating enzymes UBE2D1, UBE2D2 and UBE2D3. Detected in a ternary complex containing STUB1, HSPA1A and HSPBP1. Interacts with MKKS. Interacts with DYX1C1 and POLB. Interacts (via TPR repeats) with the C-terminal domains of HSP90AA1 and HSPA8. Interacts (when monoubiquitinated) with ATXN3. Interacts with UBE2W. Interacts (via the U-box domain) with the UBE2V2-UBE2N heterodimer; the complex has a specific 'Lys-63'-linked polyubiquitination activity. Interacts with DNAJB6. {ECO:0000250|UniProtKB:Q9WUD1, ECO:0000269|PubMed:10330192, ECO:0000269|PubMed:11146632, ECO:0000269|PubMed:11557750, ECO:0000269|PubMed:15215316, ECO:0000269|PubMed:16169850, ECO:0000269|PubMed:16307917, ECO:0000269|PubMed:18094050, ECO:0000269|PubMed:19423554, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:22366786, ECO:0000269|PubMed:23990462}.
Tissue SpecificityHighly expressed in skeletal muscle, heart, pancreas, brain and placenta. Detected in kidney, liver and lung. {ECO:0000269|PubMed:10330192, ECO:0000269|PubMed:11435423}.
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