Human Gene STUB1 (ENST00000219548.9_4) from GENCODE V47lift37
  Description: STIP1 homology and U-box containing protein 1, transcript variant 1 (from RefSeq NM_005861.4)
Gencode Transcript: ENST00000219548.9_4
Gencode Gene: ENSG00000103266.11_7
Transcript (Including UTRs)
   Position: hg19 chr16:730,410-732,801 Size: 2,392 Total Exon Count: 7 Strand: +
Coding Region
   Position: hg19 chr16:730,526-732,489 Size: 1,964 Coding Exon Count: 7 

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Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviewsModel Information
Methods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr16:730,410-732,801)mRNA (may differ from genome)Protein (303 aa)
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-  Comments and Description Text from UniProtKB
  ID: CHIP_HUMAN
DESCRIPTION: RecName: Full=E3 ubiquitin-protein ligase CHIP; EC=6.3.2.-; AltName: Full=Antigen NY-CO-7; AltName: Full=CLL-associated antigen KW-8; AltName: Full=Carboxy terminus of Hsp70-interacting protein; AltName: Full=STIP1 homology and U box-containing protein 1;
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.
PATHWAY: Protein modification; protein ubiquitination.
SUBUNIT: Homodimer (By similarity). Interacts with BAG2, and with the E2 ubiquitin conjugating enzymes UBE2D1, UBE2D2 and UBE2D3. Interacts with the C-terminal domains of HSPA8 and HSPA1A. Detected in a ternary complex containing STUB1, HSPA1A and HSPBP1. Interacts with MKKS. Interacts with DYX1C1 and POLB. Interacts (via TPR repeats) with HSP90AA1. Interacts (when monoubiquitinated) with ATXN3. Interacts with UBE2W (By similarity). Interacts (via the U-box domain) with the UBE2V2- UBE2N heterodimer; the complex has a specific 'Lys-63'-linked polyubiquitination activity. Interacts with DNAJB6.
INTERACTION: Q86WG3:ATCAY; NbExp=4; IntAct=EBI-357085, EBI-1783328; P07900:HSP90AA1; NbExp=9; IntAct=EBI-357085, EBI-296047; P08107:HSPA1B; NbExp=3; IntAct=EBI-357085, EBI-629985; P11142:HSPA8; NbExp=3; IntAct=EBI-357085, EBI-351896; P10636:MAPT; NbExp=2; IntAct=EBI-357085, EBI-366182; P61088:UBE2N; NbExp=3; IntAct=EBI-357085, EBI-1052908; Q7Z7E8:UBE2Q1; NbExp=3; IntAct=EBI-357085, EBI-1783287; P12504:vif (xeno); NbExp=2; IntAct=EBI-357085, EBI-779991;
SUBCELLULAR LOCATION: Cytoplasm.
TISSUE SPECIFICITY: Highly expressed in skeletal muscle, heart, pancreas, brain and placenta. Detected in kidney, liver and lung.
DOMAIN: The TPR domain is essential for ubiquitination mediated by UBE2D1.
PTM: Phosphorylated upon DNA damage, probably by ATM or ATR.
PTM: Monoubiquitinated at Lys-2 following cell stress by UBE2W, promoting the interaction with ATXN3 (By similarity). Auto- ubiquitinated; mediated by UBE2D1 and UBE2D2.
MISCELLANEOUS: Antibodies against STUB1 are found in patients with chronic lymphocytic leukemia (CLL) and in colorectal cancer patients.
SIMILARITY: Contains 3 TPR repeats.
SIMILARITY: Contains 1 U-box domain.

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: STUB1
Diseases sorted by gene-association score: spinocerebellar ataxia, autosomal recessive 16* (1692), ataxia (7), autosomal recessive cerebellar ataxia (5), colorectal cancer (2), parkinson disease, late-onset (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 60.03 RPKM in Brain - Frontal Cortex (BA9)
Total median expression: 1917.66 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -73.80116-0.636 Picture PostScript Text
3' UTR -122.50312-0.393 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001440 - TPR-1
IPR013026 - TPR-contain_dom
IPR011990 - TPR-like_helical
IPR019734 - TPR_repeat
IPR003613 - Ubox_domain
IPR013083 - Znf_RING/FYVE/PHD

Pfam Domains:
PF00515 - Tetratricopeptide repeat
PF04564 - U-box domain
PF07719 - Tetratricopeptide repeat
PF12895 - Anaphase-promoting complex, cyclosome, subunit 3
PF13181 - Tetratricopeptide repeat
PF13424 - Tetratricopeptide repeat
PF13432 - Tetratricopeptide repeat
PF14559 - Tetratricopeptide repeat
PF18391 - CHIP N-terminal tetratricopeptide repeat domain

SCOP Domains:
81901 - HCP-like
48439 - Protein prenylyltransferase
48452 - TPR-like
57850 - RING/U-box

ModBase Predicted Comparative 3D Structure on Q9UNE7
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details Gene Details  
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-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0001664 G-protein coupled receptor binding
GO:0004842 ubiquitin-protein transferase activity
GO:0005515 protein binding
GO:0016740 transferase activity
GO:0019899 enzyme binding
GO:0019900 kinase binding
GO:0030544 Hsp70 protein binding
GO:0030674 protein binding, bridging
GO:0030911 TPR domain binding
GO:0031072 heat shock protein binding
GO:0031625 ubiquitin protein ligase binding
GO:0034450 ubiquitin-ubiquitin ligase activity
GO:0042803 protein homodimerization activity
GO:0046332 SMAD binding
GO:0051087 chaperone binding
GO:0051787 misfolded protein binding
GO:0051879 Hsp90 protein binding
GO:0061630 ubiquitin protein ligase activity

Biological Process:
GO:0000209 protein polyubiquitination
GO:0002931 response to ischemia
GO:0006281 DNA repair
GO:0006511 ubiquitin-dependent protein catabolic process
GO:0006515 misfolded or incompletely synthesized protein catabolic process
GO:0006974 cellular response to DNA damage stimulus
GO:0016567 protein ubiquitination
GO:0030433 ER-associated ubiquitin-dependent protein catabolic process
GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway
GO:0030579 ubiquitin-dependent SMAD protein catabolic process
GO:0030968 endoplasmic reticulum unfolded protein response
GO:0031398 positive regulation of protein ubiquitination
GO:0031647 regulation of protein stability
GO:0031943 regulation of glucocorticoid metabolic process
GO:0032091 negative regulation of protein binding
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0034605 cellular response to heat
GO:0038128 ERBB2 signaling pathway
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0051443 positive regulation of ubiquitin-protein transferase activity
GO:0051604 protein maturation
GO:0051865 protein autoubiquitination
GO:0070534 protein K63-linked ubiquitination
GO:0071218 cellular response to misfolded protein
GO:0071456 cellular response to hypoxia
GO:0090035 positive regulation of chaperone-mediated protein complex assembly

Cellular Component:
GO:0000151 ubiquitin ligase complex
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005783 endoplasmic reticulum
GO:0005829 cytosol
GO:0030018 Z disc
GO:0031371 ubiquitin conjugating enzyme complex
GO:0042405 nuclear inclusion body


-  Descriptions from all associated GenBank mRNAs
  AF217968 - Homo sapiens clone PP1131 unknown mRNA.
AF432221 - Homo sapiens CLL-associated antigen KW-8 mRNA, complete cds.
BC007545 - Homo sapiens STIP1 homology and U-box containing protein 1, mRNA (cDNA clone MGC:15444 IMAGE:2959735), complete cds.
BC022788 - Homo sapiens STIP1 homology and U-box containing protein 1, mRNA (cDNA clone MGC:15443 IMAGE:2959735), complete cds.
AF129085 - Homo sapiens carboxy terminus of Hsp70-interacting protein (CHIP) mRNA, complete cds.
BC017178 - Homo sapiens STIP1 homology and U-box containing protein 1, mRNA (cDNA clone MGC:1397 IMAGE:3346811), complete cds.
AF039689 - Homo sapiens antigen NY-CO-7 (NY-CO-7) mRNA, complete cds.
JD478334 - Sequence 459358 from Patent EP1572962.
BC063617 - Homo sapiens STIP1 homology and U-box containing protein 1, mRNA (cDNA clone MGC:70877 IMAGE:3847168), complete cds.
AB587460 - Synthetic construct DNA, clone: pF1KB8203, Homo sapiens STUB1 gene for STIP1 homology and U-box containing protein 1, without stop codon, in Flexi system.
JD456057 - Sequence 437081 from Patent EP1572962.
DQ893185 - Synthetic construct clone IMAGE:100005815; FLH194923.01X; RZPDo839G0680D STIP1 homology and U-box containing protein 1 (STUB1) gene, encodes complete protein.
DQ896502 - Synthetic construct Homo sapiens clone IMAGE:100010962; FLH194919.01L; RZPDo839G0670D STIP1 homology and U-box containing protein 1 (STUB1) gene, encodes complete protein.
KJ892984 - Synthetic construct Homo sapiens clone ccsbBroadEn_02378 STUB1 gene, encodes complete protein.
DQ587701 - Homo sapiens piRNA piR-54813, complete sequence.
JD056299 - Sequence 37323 from Patent EP1572962.
JD419742 - Sequence 400766 from Patent EP1572962.
JD235569 - Sequence 216593 from Patent EP1572962.
BC150144 - Homo sapiens cDNA clone IMAGE:40127981.

-  Biochemical and Signaling Pathways
  BioCyc Knowledge Library
PWY-7511 - protein ubiquitination

Reactome (by CSHL, EBI, and GO)

Protein Q9UNE7 (Reactome details) participates in the following event(s):

R-HSA-2187375 SMAD3 binds STUB1 (CHIP)
R-HSA-9009309 RUNX2 binds STUB1
R-HSA-2187368 STUB1 (CHIP) ubiquitinates SMAD3
R-HSA-9009308 STUB1 polyubiquitinates RUNX2
R-HSA-983157 Interaction of E3 with substrate and E2-Ub complex
R-HSA-983147 Release of E3 from polyubiquitinated substrate
R-HSA-1918092 CHIP (STUB1) mediates ubiquitination of ERBB2
R-HSA-6807134 NEDD4, WWP2, CHIP and XIAP polyubiquitinate PTEN
R-HSA-983140 Transfer of Ub from E2 to substrate and release of E2
R-HSA-2173788 Downregulation of TGF-beta receptor signaling
R-HSA-8939902 Regulation of RUNX2 expression and activity
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-2173789 TGF-beta receptor signaling activates SMADs
R-HSA-8878166 Transcriptional regulation by RUNX2
R-HSA-8863795 Downregulation of ERBB2 signaling
R-HSA-8948751 Regulation of PTEN stability and activity
R-HSA-983169 Class I MHC mediated antigen processing & presentation
R-HSA-170834 Signaling by TGF-beta Receptor Complex
R-HSA-212436 Generic Transcription Pathway
R-HSA-1227986 Signaling by ERBB2
R-HSA-6807070 PTEN Regulation
R-HSA-1280218 Adaptive Immune System
R-HSA-9006936 Signaling by TGF-beta family members
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-168256 Immune System
R-HSA-162582 Signal Transduction
R-HSA-74160 Gene expression (Transcription)
R-HSA-9006925 Intracellular signaling by second messengers

-  Other Names for This Gene
  Alternate Gene Symbols: A2IDB9, CHIP , CHIP_HUMAN, ENST00000219548.1, ENST00000219548.2, ENST00000219548.3, ENST00000219548.4, ENST00000219548.5, ENST00000219548.6, ENST00000219548.7, ENST00000219548.8, NM_005861, O60526, PP1131 , Q969U2, Q9HBT1, Q9UNE7, STUB1 , uc317cxw.1, uc317cxw.2
UCSC ID: ENST00000219548.9_4
RefSeq Accession: NM_005861.4
Protein: Q9UNE7 (aka CHIP_HUMAN)

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene STUB1:
ataxias (Hereditary Ataxia Overview)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.