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Protein

STIP1 homology and U box-containing protein 1

Gene

Stub1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. 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). Acts as a co-chaperone for HSPA1A and HSPA1B chaperone proteins and promotes ubiquitin-mediated protein degradation. Likely mediates polyubiquitination and downregulates plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity. Negatively regulates TGF-beta signaling by modulating the basal level of SMAD3 via ubiquitin-mediated degradation (By similarity).By similarity3 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.2 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.2 Publications
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

GO - Molecular functioni

  • chaperone binding Source: Ensembl
  • enzyme binding Source: MGI
  • G-protein coupled receptor binding Source: MGI
  • heat shock protein binding Source: HGNC
  • Hsp70 protein binding Source: HGNC
  • Hsp90 protein binding Source: BHF-UCL
  • kinase binding Source: MGI
  • misfolded protein binding Source: MGI
  • protein binding, bridging Source: HGNC
  • protein homodimerization activity Source: HGNC
  • SMAD binding Source: HGNC
  • TPR domain binding Source: HGNC
  • ubiquitin protein ligase activity Source: MGI
  • ubiquitin protein ligase binding Source: UniProtKB
  • ubiquitin-protein transferase activity Source: UniProtKB
  • ubiquitin-ubiquitin ligase activity Source: MGI

GO - Biological processi

  • cellular response to heat Source: Ensembl
  • cellular response to hypoxia Source: Ensembl
  • cellular response to misfolded protein Source: UniProtKB
  • DNA repair Source: UniProtKB-KW
  • endoplasmic reticulum unfolded protein response Source: ParkinsonsUK-UCL
  • negative regulation of protein binding Source: ParkinsonsUK-UCL
  • negative regulation of transforming growth factor beta receptor signaling pathway Source: MGI
  • positive regulation of chaperone-mediated protein complex assembly Source: MGI
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: HGNC
  • positive regulation of protein ubiquitination Source: ParkinsonsUK-UCL
  • positive regulation of ubiquitin-protein transferase activity Source: ParkinsonsUK-UCL
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • protein autoubiquitination Source: UniProtKB
  • protein folding Source: HGNC
  • protein K63-linked ubiquitination Source: UniProtKB
  • protein maturation Source: HGNC
  • protein polyubiquitination Source: MGI
  • protein quality control for misfolded or incompletely synthesized proteins Source: UniProtKB
  • protein ubiquitination Source: MGI
  • regulation of glucocorticoid metabolic process Source: HGNC
  • regulation of protein stability Source: MGI
  • response to ischemia Source: Ensembl
  • ubiquitin-dependent ERAD pathway Source: Ensembl
  • ubiquitin-dependent protein catabolic process Source: ARUK-UCL
  • ubiquitin-dependent SMAD protein catabolic process Source: HGNC

Keywordsi

Molecular functionTransferase
Biological processDNA damage, DNA repair, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-MMU-2173788 Downregulation of TGF-beta receptor signaling
R-MMU-8863795 Downregulation of ERBB2 signaling
R-MMU-8939902 Regulation of RUNX2 expression and activity
R-MMU-8948751 Regulation of PTEN stability and activity
R-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
STIP1 homology and U box-containing protein 1Curated (EC:2.3.2.272 Publications)
Alternative name(s):
Carboxy terminus of Hsp70-interacting protein1 Publication
E3 ubiquitin-protein ligase CHIPCurated
RING-type E3 ubiquitin transferase CHIPCurated
Gene namesi
Name:Stub1Imported
Synonyms:Chip1 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:1891731 Stub1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi2K → R: Impaired interaction with ATXN3; when associated with R-4 and R-7. 1 Publication1
Mutagenesisi4K → R: Impaired interaction with ATXN3; when associated with R-2 and R-7. 1 Publication1
Mutagenesisi7K → R: Impaired interaction with ATXN3; when associated with R-2 and R-4. 1 Publication1
Mutagenesisi261H → A: Loss of E3 ubiquitin protein ligase activity. 1 Publication1
Mutagenesisi270P → A: Loss of E3 ubiquitin protein ligase activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001063301 – 304STIP1 homology and U box-containing protein 1Add BLAST304

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki2Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei20PhosphoserineCombined sources1
Cross-linki23Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei24PhosphoserineCombined sources1
Modified residuei26PhosphoserineCombined sources1
Modified residuei150PhosphoserineBy similarity1
Cross-linki222Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki256Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei274PhosphoserineBy similarity1

Post-translational modificationi

Auto-ubiquitinated; mediated by UBE2D1 and UBE2D2. Monoubiquitinated at Lys-2 following cell stress by UBE2W, promoting the interaction with ATXN3.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9WUD1
MaxQBiQ9WUD1
PaxDbiQ9WUD1
PeptideAtlasiQ9WUD1
PRIDEiQ9WUD1

PTM databases

iPTMnetiQ9WUD1
PhosphoSitePlusiQ9WUD1

Expressioni

Inductioni

Up-regulated by inflammatory signals in Treg regulatory T-cells (Treg).1 Publication

Gene expression databases

BgeeiENSMUSG00000039615
CleanExiMM_STUB1
GenevisibleiQ9WUD1 MM

Interactioni

Subunit structurei

Homodimer (PubMed:16307917). 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 DNAAF4 and POLB (By similarity). Interacts (via the U-box domain) with the UBE2V2-UBE2N heterodimer; the complex has a specific 'Lys-63'-linked polyubiquitination activity (PubMed:16307917). Interacts (when monoubiquitinated) with ATXN3 (PubMed:21855799). Interacts with UBE2W (PubMed:21855799). Interacts with DNAJB6 (By similarity). Interacts with FOXP3 (PubMed:23973223). Interacts with FLCN and HSP90AA1. Interacts with HSP90. Interacts with UBE2N and UBE2V1. Interacts (via TPR repeats) with the C-terminal domains of HSPA8 and HSPA1A. Interacts with the non-acetylated form of HSPA1A and HSPA1B. Interacts with SMAD3 and HSP90AB1 (By similarity).By similarity3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • chaperone binding Source: Ensembl
  • enzyme binding Source: MGI
  • G-protein coupled receptor binding Source: MGI
  • heat shock protein binding Source: HGNC
  • Hsp70 protein binding Source: HGNC
  • Hsp90 protein binding Source: BHF-UCL
  • kinase binding Source: MGI
  • misfolded protein binding Source: MGI
  • protein binding, bridging Source: HGNC
  • protein homodimerization activity Source: HGNC
  • SMAD binding Source: HGNC
  • TPR domain binding Source: HGNC
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi207969, 46 interactors
DIPiDIP-29751N
IntActiQ9WUD1, 16 interactors
MINTiQ9WUD1
STRINGi10090.ENSMUSP00000040431

Structurei

Secondary structure

1304
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi27 – 39Combined sources13
Helixi43 – 56Combined sources14
Helixi61 – 73Combined sources13
Helixi77 – 90Combined sources14
Helixi95 – 107Combined sources13
Helixi111 – 127Combined sources17
Helixi135 – 152Combined sources18
Helixi161 – 178Combined sources18
Turni179 – 181Combined sources3
Helixi183 – 185Combined sources3
Turni186 – 188Combined sources3
Helixi191 – 194Combined sources4
Helixi196 – 218Combined sources23
Helixi230 – 232Combined sources3
Turni235 – 237Combined sources3
Beta strandi242 – 246Combined sources5
Beta strandi252 – 254Combined sources3
Helixi255 – 264Combined sources10
Turni270 – 272Combined sources3
Helixi278 – 280Combined sources3
Helixi285 – 298Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2C2LX-ray3.30A/B/C/D24-304[»]
2C2VX-ray2.90S/T/U/V227-304[»]
3Q47X-ray1.70B23-155[»]
3Q49X-ray1.54B23-155[»]
3Q4AX-ray1.54B23-155[»]
ProteinModelPortaliQ9WUD1
SMRiQ9WUD1
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9WUD1

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati27 – 60TPR 1Add BLAST34
Repeati61 – 94TPR 2Add BLAST34
Repeati96 – 128TPR 3Add BLAST33
Domaini227 – 301U-boxAdd BLAST75

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi14 – 19Poly-Gly6

Domaini

The U-box domain is required for the ubiquitin protein ligase activity.1 Publication
The TPR domain is essential for ubiquitination mediated by UBE2D1.By similarity

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

eggNOGiKOG4642 Eukaryota
ENOG410ZC2R LUCA
GeneTreeiENSGT00730000111218
HOGENOMiHOG000163725
HOVERGENiHBG053046
InParanoidiQ9WUD1
KOiK09561
OMAiTNATYFT
OrthoDBiEOG091G0FJB
PhylomeDBiQ9WUD1
TreeFamiTF313937

Family and domain databases

Gene3Di1.25.40.10, 1 hit
3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR013026 TPR-contain_dom
IPR011990 TPR-like_helical_dom_sf
IPR019734 TPR_repeat
IPR003613 Ubox_domain
IPR013083 Znf_RING/FYVE/PHD
PfamiView protein in Pfam
PF04564 U-box, 1 hit
SMARTiView protein in SMART
SM00028 TPR, 3 hits
SM00504 Ubox, 1 hit
SUPFAMiSSF48452 SSF48452, 1 hit
PROSITEiView protein in PROSITE
PS50005 TPR, 3 hits
PS50293 TPR_REGION, 1 hit
PS51698 U_BOX, 1 hit

Sequencei

Sequence statusi: Complete.

Q9WUD1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKGKEEKEGG ARLGTGGGGS PDKSPSAQEL KEQGNRLFVG RKYPEAAACY
60 70 80 90 100
GRAITRNPLV AVYYTNRALC YLKMQQPEQA LADCRRALEL DGQSVKAHFF
110 120 130 140 150
LGQCQLEMES YDEAIANLQR AYSLAKEQRL NFGDDIPSAL RIAKKKRWNS
160 170 180 190 200
IEERRIHQES ELHSYLTRLI AAERERELEE CQRNHEGHED DGHIRAQQAC
210 220 230 240 250
IEAKHDKYMA DMDELFSQVD EKRKKRDIPD YLCGKISFEL MREPCITPSG
260 270 280 290 300
ITYDRKDIEE HLQRVGHFDP VTRSPLTQEQ LIPNLAMKEV IDAFISENGW

VEDY
Length:304
Mass (Da):34,909
Last modified:November 1, 1999 - v1
Checksum:i18BD2728908025A8
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti20S → T in BAB22329 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF129086 mRNA Translation: AAD33401.1
AK002752 mRNA Translation: BAB22329.1
AK004464 mRNA Translation: BAB23315.1
AK045776 mRNA Translation: BAC32489.1
AK166630 mRNA Translation: BAE38905.1
BC027427 mRNA Translation: AAH27427.1
BC038939 mRNA Translation: AAH38939.1
CCDSiCCDS28533.1
RefSeqiNP_062693.1, NM_019719.3
UniGeneiMm.277599
Mm.491120

Genome annotation databases

EnsembliENSMUST00000044911; ENSMUSP00000040431; ENSMUSG00000039615
GeneIDi56424
KEGGimmu:56424
UCSCiuc008bcf.1 mouse

Similar proteinsi

Entry informationi

Entry nameiCHIP_MOUSE
AccessioniPrimary (citable) accession number: Q9WUD1
Secondary accession number(s): Q9DCJ0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 25, 2005
Last sequence update: November 1, 1999
Last modified: May 23, 2018
This is version 166 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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