STUB1
entrez
10273
canonical
uniprot
Q9UNE7
canonical
ensembl
ENSG00000103266
resolver
ensp
ENSP00000219548
resolver
ensp
ENSP00000457228
resolver
genesymbol
STUB1
resolver
genesymbol_syn
CHIP
resolver
hgnc
HGNC:11427
resolver
uniprot
A2IDB9
resolver
uniprot
O60526
resolver
uniprot
Q969U2
resolver
uniprot
Q9HBT1
resolver
uniprot_entry
CHIP_HUMAN
resolver
uniprot_sec
A2IDB9
resolver
uniprot_sec
O60526
resolver
uniprot_sec
Q969U2
resolver
uniprot_sec
Q9HBT1
resolver
amino_acid_sequence
MKGKEEKEGGARLGAGGGSPEKSPSAQELKEQGNRLFVGRKYPEAAACYGRAITRNPLVAVYYTNRALCYLKMQQHEQALADCRRALELDGQSVKAHFFLGQCQLEMESYDEAIANLQRAYSLAKEQRLNFGDDIPSALRIAKKKRWNSIEERRIHQESELHSYLSRLIAAERERELEECQRNHEGDEDDSHVRAQQACIEAKHDKYMADMDELFSQVDEKRKKRDIPDYLCGKISFELMREPCITPSGITYDRKDIEEHLQRVGHFDPVTRSPLTQEQLIPNLAMKEVIDAFISENGWVEDY
uniprot
proteins
disease_involvement
DISEASE: Spinocerebellar ataxia, autosomal recessive, 16 (SCAR16) [MIM:615768]: 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. {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 variants affecting the gene represented in this entry.; DISEASE: Spinocerebellar ataxia 48 (SCA48) [MIM:618093]: 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. {ECO:0000269|PubMed:30381368}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.3.2.27
uniprot
proteins
function
FUNCTION: E3 ubiquitin-protein ligase which targets misfolded chaperone substrates towards proteasomal degradation (PubMed:10330192, PubMed:11146632, PubMed:11557750, PubMed:23990462, PubMed:26265139). Plays a role in the maintenance of mitochondrial morphology and promotes mitophagic removal of dysfunctional mitochondria; thereby acts as a protector against apoptosis in response to cellular stress (By similarity). Negatively regulates vascular smooth muscle contraction, via degradation of the transcriptional activator MYOCD and subsequent loss of transcription of genes involved in vascular smooth muscle contraction (By similarity). Promotes survival and proliferation of cardiac smooth muscle cells via ubiquitination and degradation of FOXO1, resulting in subsequent repression of FOXO1-mediated transcription of pro-apoptotic genes (PubMed:19483080). Ubiquitinates ICER-type isoforms of CREM and targets them for proteasomal degradation, thereby acts as a positive effector of MAPK/ERK-mediated inhibition of apoptosis in cardiomyocytes (PubMed:20724525). Inhibits lipopolysaccharide-induced apoptosis and hypertrophy in cardiomyocytes, via ubiquitination and subsequent proteasomal degradation of NFATC3 (PubMed:30980393). 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). Ubiquitinates CHRNA3 targeting it for endoplasmic reticulum-associated degradation in cortical neurons, as part of the STUB1-VCP-UBXN2A complex (PubMed:26265139). Ubiquitinates and promotes ESR1 proteasomal degradation in response to age-related circulating estradiol (17-beta-estradiol/E2) decline, thereby promotes neuronal apoptosis in response to ischemic reperfusion injury (By similarity). 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). Plays a role in the degradation of TP53 (PubMed:26634371). Mediates ubiquitination of RIPK3 leading to its subsequent proteasome-dependent degradation (PubMed:29883609). May regulate myosin assembly in striated muscles together with UBE4B and VCP/p97 by targeting myosin chaperone UNC45B for proteasomal degradation (PubMed:17369820). Ubiquitinates PPARG in macrophages playing a role in M2 macrophages polarization and angiogenesis (By similarity). {ECO:0000250|UniProtKB:A6HD62, ECO:0000250|UniProtKB:Q9WUD1, ECO:0000269|PubMed:10330192, ECO:0000269|PubMed:11146632, ECO:0000269|PubMed:11557750, ECO:0000269|PubMed:15466472, ECO:0000269|PubMed:17369820, ECO:0000269|PubMed:19103148, ECO:0000269|PubMed:19483080, ECO:0000269|PubMed:19567782, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20724525, ECO:0000269|PubMed:23973223, ECO:0000269|PubMed:23990462, ECO:0000269|PubMed:24043303, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:26265139, ECO:0000269|PubMed:26634371, ECO:0000269|PubMed:27708256, ECO:0000269|PubMed:28813410, ECO:0000269|PubMed:29883609, ECO:0000269|PubMed:30980393}.
uniprot
proteins
mass_dalton
34856
uniprot
proteins
mutagenesis
MUTAGEN 30; /note="K->A: Loss of interaction with FOXP3 and its ability to ubiquitinate FOXP3. Loss of interaction with SMAD3, HSPA8, HSP90AA1 and HSP90AB1. Reduces interaction, ubiquitination and proteasomal degradation of NFATC3. No effect on localization to the mitochondria following oxygen and glucose deprivation-induced cellular stress."; /evidence="ECO:0000269|PubMed:23973223, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:29934347, ECO:0000269|PubMed:30980393"; MUTAGEN 260; /note="H->Q: Loss of ability to ubiquitinate FOXP3 and SIRT6. Abolishes STUB1-mediated degradation of CHRNA3. Abolishes autoubiquitination and ubiquitination of ICER-type isoforms of CREM. Reduces interaction, ubiquitination and proteasomal degradation of NFATC3. No effect on localization to the mitochondria following oxygen and glucose deprivation-induced cellular stress."; /evidence="ECO:0000269|PubMed:20724525, ECO:0000269|PubMed:23973223, ECO:0000269|PubMed:24043303, ECO:0000269|PubMed:26265139, ECO:0000269|PubMed:29934347, ECO:0000269|PubMed:30980393"; MUTAGEN 269; /note="P->A: Abolishes E3 ligase activity."; /evidence="ECO:0000269|PubMed:23990462
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:11557750, ECO:0000269|PubMed:15466472}.
uniprot
proteins
post_translational_modification
PTM: Monoubiquitinated at Lys-2 following cell stress by UBE2W, promoting the interaction with ATXN3 (By similarity). Auto-ubiquitinated; mediated by UBE2D1 and UBE2D2 and enhanced in the presence of MAP2K5 (PubMed:20724525). {ECO:0000250, ECO:0000250|UniProtKB:Q9WUD1, ECO:0000269|PubMed:18042044, ECO:0000269|PubMed:20724525, ECO:0000269|PubMed:23560854}.
uniprot
proteins
pubmed
10330192
uniprot
proteins
pubmed
11146632
uniprot
proteins
pubmed
11157797
uniprot
proteins
pubmed
11435423
uniprot
proteins
pubmed
11557750
uniprot
proteins
pubmed
12200376
uniprot
proteins
pubmed
15215316
uniprot
proteins
pubmed
15466472
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15498874
uniprot
proteins
pubmed
15616553
uniprot
proteins
pubmed
16169850
uniprot
proteins
pubmed
16307917
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17369820
uniprot
proteins
pubmed
18042044
uniprot
proteins
pubmed
18094050
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19103148
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19423554
uniprot
proteins
pubmed
19483080
uniprot
proteins
pubmed
19567782
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19713937
uniprot
proteins
pubmed
20060297
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20724525
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22366786
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23560854
uniprot
proteins
pubmed
23973223
uniprot
proteins
pubmed
23990462
uniprot
proteins
pubmed
24043303
uniprot
proteins
pubmed
24113144
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24312598
uniprot
proteins
pubmed
24613385
uniprot
proteins
pubmed
24719489
uniprot
proteins
pubmed
24742043
uniprot
proteins
pubmed
25258038
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26265139
uniprot
proteins
pubmed
26634371
uniprot
proteins
pubmed
27353360
uniprot
proteins
pubmed
27708256
uniprot
proteins
pubmed
28813410
uniprot
proteins
pubmed
29883609
uniprot
proteins
pubmed
29934347
uniprot
proteins
pubmed
30381368
uniprot
proteins
pubmed
30980393
uniprot
proteins
pubmed
33376131
uniprot
proteins
pubmed
33798445
uniprot
proteins
pubmed
9610721
uniprot
proteins
sequence_length
303
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10330192, ECO:0000269|PubMed:17369820, ECO:0000269|PubMed:23973223}. Nucleus {ECO:0000269|PubMed:23973223}. Mitochondrion {ECO:0000250|UniProtKB:A6HD62}. Note=Translocates to the nucleus in response to inflammatory signals in regulatory T-cells (Treg). Localizes to mitochondria following oxygen and glucose deprivation-induced cellular stress (By similarity). {ECO:0000250|UniProtKB:A6HD62, ECO:0000269|PubMed:23973223}.
uniprot
proteins