Protein: Q9UNE7

UniprotKB AC UniprotKB ID Gene name Full name Species Curated set
Q9UNE7 (Uniprot) CHIP_HUMAN STUB1 E3 ubiquitin-protein ligase CHIP human No
Uniprot: 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). Negatively regulates TGF-beta signaling by modulating the basal level of SMAD3 via ubiquitin-mediated degradation (PubMed:24613385). more..
GO ID 1 Function 1 Module ID 1 GO ID 2 Function 2 Module ID 2 Association Probability (PrOnto) Interaction Probability (PrOnto)
GO:0009056 catabolic process 125 GO:0009059 macromolecule biosynthetic process 192, 485, 551 6.37e-04 1.88e-40
Module ID (MoonGO) GO ID (BP) GO Name
125 GO:0044248 cellular catabolic process
125 GO:0016567 protein ubiquitination
125 GO:0060255 regulation of macromolecule metabolic process
155 GO:0006464 cellular protein modification process
155 GO:0060255 regulation of macromolecule metabolic process
192 GO:0034645 cellular macromolecule biosynthetic process
192 GO:0006464 cellular protein modification process
192 GO:0010467 gene expression
192 GO:0090304 nucleic acid metabolic process
192 GO:0009893 positive regulation of metabolic process
192 GO:0060255 regulation of macromolecule metabolic process
192 GO:0007165 signal transduction
237 GO:0022607 cellular component assembly
237 GO:0034645 cellular macromolecule biosynthetic process
237 GO:0044271 cellular nitrogen compound biosynthetic process
237 GO:0006464 cellular protein modification process
237 GO:0051649 establishment of localization in cell
237 GO:0010467 gene expression
237 GO:0031324 negative regulation of cellular metabolic process
237 GO:0010605 negative regulation of macromolecule metabolic process
237 GO:0051172 negative regulation of nitrogen compound metabolic process
237 GO:0090304 nucleic acid metabolic process
237 GO:0033365 protein localization to organelle
237 GO:0015031 protein transport
237 GO:0050790 regulation of catalytic activity
237 GO:0051128 regulation of cellular component organization
259 GO:0007165 signal transduction
283 GO:0006464 cellular protein modification process
283 GO:0060255 regulation of macromolecule metabolic process
381 GO:0006464 cellular protein modification process
381 GO:0010467 gene expression
381 GO:0016310 phosphorylation
381 GO:0010604 positive regulation of macromolecule metabolic process
381 GO:0050790 regulation of catalytic activity
381 GO:0032268 regulation of cellular protein metabolic process
381 GO:0007165 signal transduction
410 GO:0010467 gene expression
410 GO:0007165 signal transduction
434 GO:0044267 cellular protein metabolic process
485 GO:0034645 cellular macromolecule biosynthetic process
485 GO:0090304 nucleic acid metabolic process
512 GO:0035556 intracellular signal transduction
512 GO:0006468 protein phosphorylation
512 GO:0060255 regulation of macromolecule metabolic process
534 GO:0007166 cell surface receptor signaling pathway
534 GO:0006464 cellular protein modification process
534 GO:0033554 cellular response to stress
534 GO:0010467 gene expression
534 GO:0006796 phosphate-containing compound metabolic process
534 GO:0060255 regulation of macromolecule metabolic process
534 GO:0009966 regulation of signal transduction
534 GO:0009628 response to abiotic stimulus
545 GO:0044267 cellular protein metabolic process
545 GO:0006139 nucleobase-containing compound metabolic process
551 GO:0034645 cellular macromolecule biosynthetic process
551 GO:0090304 nucleic acid metabolic process
551 GO:0034654 nucleobase-containing compound biosynthetic process
551 GO:0010604 positive regulation of macromolecule metabolic process
551 GO:0051173 positive regulation of nitrogen compound metabolic process
588 GO:0006355 regulation of transcription, DNA-templated
Module ID (MoonGO) GO ID (CC) GO Name
125 GO:0005829 cytosol
125 GO:0005634 nucleus
155 GO:0005634 nucleus
162 GO:0005634 nucleus
192 GO:0005829 cytosol
192 GO:0005654 nucleoplasm
237 GO:0005829 cytosol
237 GO:0012505 endomembrane system
237 GO:0005615 extracellular space
237 GO:0043232 intracellular non-membrane-bounded organelle
237 GO:0070013 intracellular organelle lumen
237 GO:0044428 nuclear part
237 GO:0031982 vesicle
259 GO:0005886 plasma membrane
283 GO:0012505 endomembrane system
283 GO:0044428 nuclear part
381 GO:0005829 cytosol
381 GO:0005634 nucleus
410 GO:0005634 nucleus
434 GO:0005829 cytosol
434 GO:0070062 extracellular exosome
434 GO:0005634 nucleus
485 GO:0043232 intracellular non-membrane-bounded organelle
485 GO:0005634 nucleus
512 GO:0005829 cytosol
534 GO:0005829 cytosol
534 GO:0012505 endomembrane system
534 GO:0005654 nucleoplasm
545 GO:0005829 cytosol
545 GO:0005634 nucleus
545 GO:0031982 vesicle
551 GO:0005829 cytosol
551 GO:0005615 extracellular space
551 GO:0043232 intracellular non-membrane-bounded organelle
551 GO:0005654 nucleoplasm
551 GO:0031982 vesicle
588 GO:0031981 nuclear lumen
GO ID (BP) GO Name Evidence Code (GO EC)
GO:0000209 protein polyubiquitination IMP
GO:0006281 DNA repair IEA
GO:0006511 ubiquitin-dependent protein catabolic process IMP
GO:0006515 protein quality control for misfolded or incompletely synthesized proteins IDA
GO:0016567 protein ubiquitination IMP
GO:0030433 ubiquitin-dependent ERAD pathway IEA
GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway TAS
GO:0030579 ubiquitin-dependent SMAD protein catabolic process IDA
GO:0030968 endoplasmic reticulum unfolded protein response IEA
GO:0031398 positive regulation of protein ubiquitination IDA
GO:0031647 regulation of protein stability IDA
GO:0031943 regulation of glucocorticoid metabolic process IDA
GO:0032091 negative regulation of protein binding IEA
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process IDA
GO:0038128 ERBB2 signaling pathway TAS
GO:0042787 protein ubiquitination involved in ubiquitin-dependent protein catabolic process IMP
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process IDA
GO:0051443 positive regulation of ubiquitin-protein transferase activity IEA
GO:0051604 protein maturation TAS
GO:0051865 protein autoubiquitination IDA
GO:0070534 protein K63-linked ubiquitination IDA
GO:0071218 cellular response to misfolded protein IDA
GO:0090035 positive regulation of chaperone-mediated protein complex assembly IDA
GO ID (CC) GO Name Evidence Code (GO EC)
GO:0000151 ubiquitin ligase complex IDA
GO:0005654 nucleoplasm IDA
GO:0005737 cytoplasm IDA
GO:0005783 endoplasmic reticulum IDA
GO:0005829 cytosol TAS
GO:0030018 Z disc IEA
GO:0031371 ubiquitin conjugating enzyme complex TAS
GO:0042405 nuclear inclusion body IDA
GO:0070062 extracellular exosome IDA
GO ID 1 Component 1 GO ID 2 Component 2 Association Probability (PrOnto) Interaction Probability (PrOnto)
GO:0005654 nucleoplasm GO:0005783 endoplasmic reticulum 1.84e-53 1.21e-118
GO:0005654 nucleoplasm GO:0070062 extracellular exosome 3.37e-20 1.23e-35
Interactor Also a MoonDB EMF protein
BAG3_HUMAN No
RGS17_HUMAN No
CTBP2_HUMAN No
HS90B_HUMAN Yes: P08238 (MoonDB)
E2F8_HUMAN No
ACD_HUMAN Yes: Q96AP0 (MoonDB)
AGO2_HUMAN No
ANDR_HUMAN Yes: P10275 (MoonDB)
ANM5_HUMAN No
ARIP4_HUMAN No
ATCAY_HUMAN No
B4DE84_HUMAN No
BAG1_HUMAN No
BAG2_HUMAN No
BKRB2_HUMAN No
CCL28_HUMAN No
CDK4_HUMAN No
CFLAR_HUMAN No
CLCN2_HUMAN No
CTCFL_HUMAN No
DDIAS_HUMAN No
DDX11_HUMAN No
DNJB1_HUMAN No
DYN3_HUMAN No
EGFR_HUMAN Yes: P00533 (MoonDB)
EIPR1_HUMAN No
EM55_HUMAN No
ERCC3_HUMAN No
FBX24_HUMAN No
FOXP3_HUMAN No
FX4L6_HUMAN No
HCFC1_HUMAN No
HDAC6_HUMAN No
HS71A_HUMAN No
HS90A_HUMAN Yes: P07900 (MoonDB)
HSF1_HUMAN Yes: Q00613 (MoonDB)
HSF2_HUMAN No
HSP74_HUMAN No
HSP7C_HUMAN Yes: P11142 (MoonDB)
HSPB1_HUMAN Yes: P04792 (MoonDB)
HUS1B_HUMAN No
KHDR1_HUMAN No
KLH38_HUMAN No
LBN_HUMAN No
LRRK1_HUMAN No
LRRK2_HUMAN No
MCM5_HUMAN No
MITF_HUMAN No
MLF1_HUMAN Yes: P58340 (MoonDB)
MLF2_HUMAN Yes: Q15773 (MoonDB)
MOONR_HUMAN No
MOS_HUMAN No
NAL12_HUMAN No
NOE3_HUMAN No
P53_HUMAN Yes: P04637 (MoonDB)
POTE1_HUMAN Yes: Q9NUX5 (MoonDB)
PRDM1_HUMAN No
PSMD2_HUMAN Yes: Q13200 (MoonDB)
Q5ULA9_HUMAN No
Q8WYX9_HUMAN No
Q96S08_HUMAN No
RAF1_HUMAN Yes: P04049 (MoonDB)
REC8_HUMAN No
RUNX2_HUMAN No
RUSC1_HUMAN No
SIM2_HUMAN No
SIR6_HUMAN No
SMAD1_HUMAN Yes: Q15797 (MoonDB)
SMRD2_HUMAN No
STIL_HUMAN No
STK11_HUMAN No
TAU_HUMAN No
TERF1_HUMAN No
TET3_HUMAN No
TF3C5_HUMAN No
TFDP3_HUMAN No
THIOM_HUMAN No
TINF2_HUMAN Yes: Q9BSI4 (MoonDB)
UB2D2_HUMAN Yes: P62837 (MoonDB)
UB2Q1_HUMAN No
UB2V1_HUMAN Yes: Q13404 (MoonDB)
UBA1_HUMAN No
UBE2N_HUMAN Yes: P61088 (MoonDB)
UBP49_HUMAN No
PMID Article Title
9610721 Characterization of human colon cancer antigens recognized by autologous antibodies.
10330192 Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions.
11146632 The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins.
11157797 Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16.
11435423 U box proteins as a new family of ubiquitin-protein ligases.
11557750 CHIP is a U-box-dependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation.
12200376 Identification of tumor-associated antigens in chronic lymphocytic leukemia by SEREX.
15215316 The cochaperone HspBP1 inhibits the CHIP ubiquitin ligase and stimulates the maturation of the cystic fibrosis transmembrane conductance regulator.
15466472 Ubiquitylation of neuronal nitric-oxide synthase by CHIP, a chaperone-dependent E3 ligase.
15489334 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15498874 Large-scale cDNA transfection screening for genes related to cancer development and progression.
15616553 The sequence and analysis of duplication-rich human chromosome 16.
16169850 Regulation of the cytoplasmic quality control protein degradation pathway by BAG2.
16307917 Chaperoned ubiquitylation -- crystal structures of the CHIP U box E3 ubiquitin ligase and a CHIP-Ubc13-Uev1a complex.
17081983 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
18042044 Two different classes of E2 ubiquitin-conjugating enzymes are required for the mono-ubiquitination of proteins and elongation by polyubiquitin chains with a specific topology.
18094050 MKKS is a centrosome-shuttling protein degraded by disease-causing mutations via CHIP-mediated ubiquitination.
18669648 A quantitative atlas of mitotic phosphorylation.
18691976 Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
19103148 CYP3A4 ubiquitination by gp78 (the tumor autocrine motility factor receptor, AMFR) and CHIP E3 ligases.
19369195 Large-scale proteomics analysis of the human kinome.
19413330 Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.
19423554 Functional interaction of DYX1C1 with estrogen receptors suggests involvement of hormonal pathways in dyslexia.
19567782 Hsp90 is an essential regulator of EphA2 receptor stability and signaling: implications for cancer cell migration and metastasis.
19690332 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19713937 Ubiquitin ligase ARF-BP1/Mule modulates base excision repair.
20068231 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
21269460 Initial characterization of the human central proteome.
21406692 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
22366786 Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy.
22814378 N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.
23186163 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23560854 Ube2W conjugates ubiquitin to alpha-amino groups of protein N-termini.
23973223 The ubiquitin ligase Stub1 negatively modulates regulatory T cell suppressive activity by promoting degradation of the transcription factor Foxp3.
23990462 Endoplasmic reticulum protein quality control is determined by cooperative interactions between Hsp/c70 protein and the CHIP E3 ligase.
24113144 Ataxia and hypogonadism caused by the loss of ubiquitin ligase activity of the U box protein CHIP.
24275569 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24312598 Identification of CHIP as a novel causative gene for autosomal recessive cerebellar ataxia.
24613385 Hsp70 and Hsp90 oppositely regulate TGF-beta signaling through CHIP/Stub1.
24719489 Autosomal recessive cerebellar ataxia of adult onset due to STUB1 mutations.
24742043 Phenotype and frequency of STUB1 mutations: next-generation screenings in Caucasian ataxia and spastic paraplegia cohorts.
25258038 STUB1 mutations in autosomal recessive ataxias - evidence for mutation-specific clinical heterogeneity.
25944712 N-terminome analysis of the human mitochondrial proteome.
27353360 The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance drug binding.
27708256 ARD1-mediated Hsp70 acetylation balances stress-induced protein refolding and degradation.
OMIM ID Disease Name
615768 Spinocerebellar ataxia, autosomal recessive, 16
Domain Name Domain ID Source
Ubox_domain IPR003613 InterPro
TPR-like_helical_dom_sf IPR011990 InterPro
TPR-contain_dom IPR013026 InterPro
Znf_RING/FYVE/PHD IPR013083 InterPro
TPR_repeat IPR019734 InterPro
U-box PF04564 Pfam
TPR PS50005 PROSITE
TPR_REGION PS50293 PROSITE
U_BOX PS51698 PROSITE
TPR SM00028 SMART
Ubox SM00504 SMART
SSF48452 SSF48452 SUPFAM