Q9WUD1 (CHIP_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	304 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	E3 ubiquitin-protein ligase which targets misfolded chaperone substrates towards proteasomal degradation. 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 By similarity.
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. Ref.8
Subcellular location	Cytoplasm.
Domain	The TPR domain is essential for ubiquitination mediated by UBE2D1 By similarity.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR By similarity. Ref.4 Ref.5 Ref.6 Ref.7 Auto-ubiquitinated; mediated by UBE2D1 and UBE2D2 By similarity.
Sequence similarities	Contains 3 TPR repeats. Contains 1 U-box domain.

Ontologies

Keywords
Biological process	DNA damage DNA repair Ubl conjugation pathway
Cellular component	Cytoplasm
Domain	Repeat TPR repeat
Molecular function	Ligase
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA repair Inferred from electronic annotation. Source: UniProtKB-KW 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 proteasomal ubiquitin-dependent protein catabolic process Inferred from sequence or structural similarity. Source: HGNC 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 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
Cellular component	cytoplasm Inferred from sequence or structural similarity Ref.1. Source: HGNC ubiquitin conjugating enzyme complex Traceable author statement Ref.8. Source: HGNC ubiquitin ligase complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	Hsp70 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 protein binding, bridging Traceable author statement Ref.8. Source: HGNC protein homodimerization activity Inferred from direct assay Ref.8. Source: HGNC ubiquitin-ubiquitin ligase activity Inferred from direct assay. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
UBE2N	P61088	2	EBI-773027,EBI-1052908	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 304

304

STIP1 homology and U box-containing protein 1

PRO_0000106330

Regions

Repeat

27 – 60

34

TPR 1

Repeat

61 – 94

34

TPR 2

Repeat

96 – 128

33

TPR 3

Domain

227 – 301

75

U-box

Compositional bias

14 – 19

6

Poly-Gly

Amino acid modifications

Modified residue

20

1

Phosphoserine Ref.4 Ref.5 Ref.6

Modified residue

24

1

Phosphoserine Ref.7

Modified residue

26

1

Phosphoserine Ref.7

Modified residue

274

1

Phosphoserine By similarity

Modified residue

277

1

Phosphothreonine By similarity

Cross-link

23

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Cross-link

222

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Cross-link

256

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Experimental info

Sequence conflict

20

1

S → T in BAB22329. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

304

Helix Strand Turn

Details...

Helix

27 – 39

13

Helix

43 – 56

14

Helix

61 – 73

13

Helix

77 – 87

11

Helix

95 – 107

13

Helix

111 – 127

17

Helix

135 – 153

19

Helix

161 – 178

18

Turn

179 – 181

3

Helix

183 – 185

3

Turn

186 – 188

3

Helix

191 – 194

4

Helix

196 – 218

23

Turn

235 – 237

3

Beta strand

242 – 246

5

Beta strand

252 – 254

3

Helix

257 – 264

8

Turn

270 – 272

3

Helix

278 – 280

3

Helix

285 – 295

11

Sequences

	Sequence		Length	Mass (Da)
	Q9WUD1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 18BD2728908025A8	FASTA	304	34,909
	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

References

	« Hide 'large scale' referencesShow '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: 10330192] [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. , 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: 16141072] [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: 15489334] [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: 16452087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, MASS SPECTROMETRY. Tissue: Brain.
[5]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed: 17242355] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, MASS SPECTROMETRY. Tissue: Liver.
[6]	"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: 19144319] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, MASS SPECTROMETRY. Tissue: Macrophage.
[7]	"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: 19131326] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24 AND SER-26, MASS SPECTROMETRY. Tissue: Embryonic fibroblast.
[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: 16307917] [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.

IPI

IPI00471361.

RefSeq

NP_062693.1. NM_019719.3.

UniGene

Mm.277599.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2C2L	X-ray	3.30	A/B/C/D	24-304	[»]
2C2V	X-ray	2.90	S/T/U/V	227-304	[»]
3Q47	X-ray	1.70	B	23-155	[»]
3Q49	X-ray	1.54	B	23-155	[»]
3Q4A	X-ray	1.54	B	23-155	[»]

ProteinModelPortal

Q9WUD1.

SMR

Q9WUD1. Positions 24-304.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29751N.

IntAct

Q9WUD1. 6 interactions.

STRING

Q9WUD1.

PTM databases

PhosphoSite

Q9WUD1.

Proteomic databases

PRIDE

Q9WUD1.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000044911; ENSMUSP00000040431; ENSMUSG00000039615.

GeneID

56424.

KEGG

mmu:56424.

UCSC

uc008bcf.1. mouse.

Organism-specific databases

CTD

10273.

MGI

MGI:1891731. Stub1.

Phylogenomic databases

GeneTree

ENSGT00600000084539.

HOGENOM

HBG378130.

HOVERGEN

HBG053046.

InParanoid

Q9WUD1.

OMA

LHSYLTR.

OrthoDB

EOG4Z36F9.

PhylomeDB

Q9WUD1.

Enzyme and pathway databases

BRENDA

6.3.2.19. 3474.

Gene expression databases

ArrayExpress

Q9WUD1.

Bgee

Q9WUD1.

CleanEx

MM_STUB1.

Genevestigator

Q9WUD1.

GermOnline

ENSMUSG00000039615. Mus musculus.

Family and domain databases

InterPro

IPR013026. TPR-contain.
IPR011990. TPR-like_helical.
IPR019734. TPR_repeat.
IPR003613. Ubox_domain.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]

Gene3D

G3DSA:1.25.40.10. TPR-like_helical. 1 hit.
G3DSA:3.30.40.10. Znf_RING/FYVE/PHD. 1 hit.

KO

K09561.

Pfam

PF04564. U-box. 1 hit.
[Graphical view]

SMART

SM00028. TPR. 3 hits.
SM00504. Ubox. 1 hit.
[Graphical view]

PROSITE

PS50005. TPR. 3 hits.
PS50293. TPR_REGION. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

312582.

SOURCE

Search...

Entry information

Entry name

CHIP_MOUSE

Accession

Primary (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:	November 16, 2011
This is version 107 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program