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Q9WUD1 (CHIP_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
STIP1 homology and U box-containing protein 1

EC=6.3.2.-
Alternative name(s):
Carboxy terminus of Hsp70-interacting protein
E3 ubiquitin-protein ligase CHIP
Gene names
Name:Stub1
Synonyms:Chip
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length304 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.7

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Homodimer. 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 By similarity. Interacts with MKKS By similarity. Interacts with DYX1C1 and POLB By similarity. Interacts (via TPR repeats) with HSP90AA1. Interacts (via the U-box domain) with the UBE2V2-UBE2N heterodimer; the complex has a specific 'Lys-63'-linked polyubiquitination activity. Interacts (when monoubiquitinated) with ATXN3. Interacts with UBE2W. Interacts with DNAJB6 By similarity. Ref.7 Ref.8

Subcellular location

Cytoplasm.

Domain

The TPR domain is essential for ubiquitination mediated by UBE2D1 By similarity.

Post-translational modification

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

Sequence similarities

Contains 3 TPR repeats.

Contains 1 U-box domain.

Ontologies

Keywords
   Biological processDNA damage
DNA repair
Ubl conjugation pathway
   Cellular componentCytoplasm
   DomainRepeat
TPR repeat
   Molecular functionLigase
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA repair

Inferred from electronic annotation. Source: UniProtKB-KW

cellular response to misfolded protein

Inferred from mutant phenotype Ref.7. Source: UniProtKB

misfolded or incompletely synthesized protein catabolic process

Inferred from mutant phenotype Ref.7. Source: UniProtKB

positive regulation of chaperone-mediated protein complex assembly

Inferred from electronic annotation. Source: Ensembl

positive regulation of proteasomal ubiquitin-dependent protein catabolic process

Inferred from sequence or structural similarity Ref.1. Source: HGNC

positive regulation of protein ubiquitination

Inferred from sequence or structural similarity Ref.1. Source: HGNC

proteasome-mediated ubiquitin-dependent protein catabolic process

Inferred from mutant phenotype Ref.7. Source: UniProtKB

protein K63-linked ubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

protein autoubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

protein folding

Traceable author statement Ref.8. Source: HGNC

protein maturation

Traceable author statement Ref.8. Source: HGNC

protein polyubiquitination

Inferred from sequence or structural similarity. Source: HGNC

protein ubiquitination

Traceable author statement Ref.8. Source: HGNC

regulation of glucocorticoid metabolic process

Inferred from sequence or structural similarity Ref.1. Source: HGNC

ubiquitin-dependent SMAD protein catabolic process

Inferred from sequence or structural similarity. Source: HGNC

ubiquitin-dependent protein catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from sequence or structural similarity Ref.1. Source: HGNC

nuclear inclusion body

Inferred from electronic annotation. Source: Ensembl

ubiquitin conjugating enzyme complex

Traceable author statement Ref.8. Source: HGNC

ubiquitin ligase complex

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionHsp70 protein binding

Inferred from sequence or structural similarity Ref.1. Source: HGNC

Hsp90 protein binding

Inferred from sequence or structural similarity. Source: BHF-UCL

SMAD binding

Inferred from sequence or structural similarity. Source: HGNC

TPR domain binding

Inferred from sequence or structural similarity Ref.1. Source: HGNC

heat shock protein binding

Traceable author statement Ref.8. Source: HGNC

protein binding

Inferred from physical interaction Ref.8PubMed 23612611. Source: IntAct

protein binding, bridging

Traceable author statement Ref.8. Source: HGNC

protein homodimerization activity

Inferred from direct assay Ref.8. Source: HGNC

ubiquitin protein ligase binding

Inferred from physical interaction Ref.7. Source: UniProtKB

ubiquitin-protein transferase activity

Inferred from sequence or structural similarity. Source: UniProtKB

ubiquitin-ubiquitin ligase activity

Inferred from direct assay PubMed 11435423. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

IlkO552227EBI-773027,EBI-6690138
UBE2NP610882EBI-773027,EBI-1052908From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 304304STIP1 homology and U box-containing protein 1
PRO_0000106330

Regions

Repeat27 – 6034TPR 1
Repeat61 – 9434TPR 2
Repeat96 – 12833TPR 3
Domain227 – 30175U-box
Compositional bias14 – 196Poly-Gly

Amino acid modifications

Modified residue201Phosphoserine Ref.4 Ref.5
Modified residue241Phosphoserine Ref.6
Modified residue261Phosphoserine Ref.6
Modified residue2741Phosphoserine By similarity
Cross-link2Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.7
Cross-link23Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link222Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link256Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Experimental info

Mutagenesis21K → R: Impaired interaction with ATXN3; when associated with R-4 and R-7. Ref.7
Mutagenesis41K → R: Impaired interaction with ATXN3; when associated with R-2 and R-7. Ref.7
Mutagenesis71K → R: Impaired interaction with ATXN3; when associated with R-2 and R-4. Ref.7
Sequence conflict201S → T in BAB22329. Ref.2

Secondary structure

........................................ 304
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9WUD1 [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: 18BD2728908025A8

FASTA30434,909
        10         20         30         40         50         60 
MKGKEEKEGG ARLGTGGGGS PDKSPSAQEL KEQGNRLFVG RKYPEAAACY GRAITRNPLV 

        70         80         90        100        110        120 
AVYYTNRALC YLKMQQPEQA LADCRRALEL DGQSVKAHFF LGQCQLEMES YDEAIANLQR 

       130        140        150        160        170        180 
AYSLAKEQRL NFGDDIPSAL RIAKKKRWNS IEERRIHQES ELHSYLTRLI AAERERELEE 

       190        200        210        220        230        240 
CQRNHEGHED DGHIRAQQAC IEAKHDKYMA DMDELFSQVD EKRKKRDIPD YLCGKISFEL 

       250        260        270        280        290        300 
MREPCITPSG ITYDRKDIEE HLQRVGHFDP VTRSPLTQEQ LIPNLAMKEV IDAFISENGW 


VEDY 

« Hide

References

« Hide 'large scale' references
[1]"Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions."
Ballinger C.A., Connell P., Wu Y., Hu Z., Thompson L.J., Yin L.-Y., Patterson C.
Mol. Cell. Biol. 19:4535-4545(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Corpora quadrigemina, Embryo and Kidney.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: FVB/N.
Tissue: Mammary tumor and Salivary gland.
[4]"Comprehensive identification of phosphorylation sites in postsynaptic density preparations."
Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.
Mol. Cell. Proteomics 5:914-922(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Brain.
[5]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[6]"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry."
Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.
Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24 AND SER-26, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
[7]"Ube2w and ataxin-3 coordinately regulate the ubiquitin ligase CHIP."
Scaglione K.M., Zavodszky E., Todi S.V., Patury S., Xu P., Rodriguez-Lebron E., Fischer S., Konen J., Djarmati A., Peng J., Gestwicki J.E., Paulson H.L.
Mol. Cell 43:599-612(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH UBE2W AND ATXN3, UBIQUITINATION AT LYS-2, MUTAGENESIS OF LYS-2; LYS-4 AND LYS-7.
[8]"Chaperoned ubiquitylation -- crystal structures of the CHIP U box E3 ubiquitin ligase and a CHIP-Ubc13-Uev1a complex."
Zhang M., Windheim M., Roe S.M., Peggie M., Cohen P., Prodromou C., Pearl L.H.
Mol. Cell 20:525-538(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 24-304 IN COMPLEX WITH UBE2N AND UBE2V1, X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 227-304 IN COMPLEX WITH HSP90AA1, HOMODIMERIZATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS28533.1.
RefSeqNP_062693.1. NM_019719.3.
UniGeneMm.277599.
Mm.491120.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalQ9WUD1.
SMRQ9WUD1. Positions 24-304.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid207969. 35 interactions.
DIPDIP-29751N.
IntActQ9WUD1. 12 interactions.

PTM databases

PhosphoSiteQ9WUD1.

Proteomic databases

MaxQBQ9WUD1.
PaxDbQ9WUD1.
PRIDEQ9WUD1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000044911; ENSMUSP00000040431; ENSMUSG00000039615.
GeneID56424.
KEGGmmu:56424.
UCSCuc008bcf.1. mouse.

Organism-specific databases

CTD10273.
MGIMGI:1891731. Stub1.

Phylogenomic databases

eggNOGNOG260504.
GeneTreeENSGT00730000111218.
HOGENOMHOG000163725.
HOVERGENHBG053046.
InParanoidQ9WUD1.
KOK09561.
OMAQENELHS.
OrthoDBEOG79W95G.
PhylomeDBQ9WUD1.
TreeFamTF313937.

Enzyme and pathway databases

BRENDA6.3.2.19. 3474.
UniPathwayUPA00143.

Gene expression databases

BgeeQ9WUD1.
CleanExMM_STUB1.
GenevestigatorQ9WUD1.

Family and domain databases

Gene3D1.25.40.10. 1 hit.
3.30.40.10. 1 hit.
InterProIPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical.
IPR001440. TPR_1.
IPR019734. TPR_repeat.
IPR003613. Ubox_domain.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamPF00515. TPR_1. 1 hit.
PF04564. U-box. 1 hit.
[Graphical view]
SMARTSM00028. TPR. 3 hits.
SM00504. Ubox. 1 hit.
[Graphical view]
PROSITEPS50005. TPR. 3 hits.
PS50293. TPR_REGION. 1 hit.
PS51698. U_BOX. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9WUD1.
NextBio312582.
PROQ9WUD1.
SOURCESearch...

Entry information

Entry nameCHIP_MOUSE
AccessionPrimary (citable) accession number: Q9WUD1
Secondary accession number(s): Q9DCJ0
Entry history
Integrated into UniProtKB/Swiss-Prot: October 25, 2005
Last sequence update: November 1, 1999
Last modified: July 9, 2014
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot