CHIP_MOUSE
ID CHIP_MOUSE Reviewed; 304 AA.
AC Q9WUD1; Q9DCJ0;
DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=E3 ubiquitin-protein ligase CHIP {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000269|PubMed:11435423, ECO:0000269|PubMed:21855799};
DE AltName: Full=Carboxy terminus of Hsp70-interacting protein {ECO:0000303|PubMed:10330192};
DE AltName: Full=RING-type E3 ubiquitin transferase CHIP {ECO:0000305};
DE AltName: Full=STIP1 homology and U box-containing protein 1 {ECO:0000305};
GN Name=Stub1 {ECO:0000303|PubMed:23973223, ECO:0000312|MGI:MGI:1891731};
GN Synonyms=Chip {ECO:0000303|PubMed:10330192};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10330192; DOI=10.1128/mcb.19.6.4535;
RA Ballinger C.A., Connell P., Wu Y., Hu Z., Thompson L.J., Yin L.-Y.,
RA Patterson C.;
RT "Identification of CHIP, a novel tetratricopeptide repeat-containing
RT protein that interacts with heat shock proteins and negatively regulates
RT chaperone functions.";
RL Mol. Cell. Biol. 19:4535-4545(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Corpora quadrigemina, Embryo, and Kidney;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor, and Salivary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, DOMAIN, AND
RP MUTAGENESIS OF HIS-261 AND PRO-270.
RX PubMed=11435423; DOI=10.1074/jbc.m102755200;
RA Hatakeyama S., Yada M., Matsumoto M., Ishida N., Nakayama K.I.;
RT "U box proteins as a new family of ubiquitin-protein ligases.";
RL J. Biol. Chem. 276:33111-33120(2001).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24 AND SER-26, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20 AND SER-24, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, INTERACTION WITH UBE2W AND ATXN3,
RP UBIQUITINATION AT LYS-2, AND MUTAGENESIS OF LYS-2; LYS-4 AND LYS-7.
RX PubMed=21855799; DOI=10.1016/j.molcel.2011.05.036;
RA Scaglione K.M., Zavodszky E., Todi S.V., Patury S., Xu P.,
RA Rodriguez-Lebron E., Fischer S., Konen J., Djarmati A., Peng J.,
RA Gestwicki J.E., Paulson H.L.;
RT "Ube2w and ataxin-3 coordinately regulate the ubiquitin ligase CHIP.";
RL Mol. Cell 43:599-612(2011).
RN [10]
RP FUNCTION, AND INDUCTION.
RX PubMed=23973223; DOI=10.1016/j.immuni.2013.08.006;
RA Chen Z., Barbi J., Bu S., Yang H.Y., Li Z., Gao Y., Jinasena D., Fu J.,
RA Lin F., Chen C., Zhang J., Yu N., Li X., Shan Z., Nie J., Gao Z., Tian H.,
RA Li Y., Yao Z., Zheng Y., Park B.V., Pan Z., Zhang J., Dang E., Li Z.,
RA Wang H., Luo W., Li L., Semenza G.L., Zheng S.G., Loser K., Tsun A.,
RA Greene M.I., Pardoll D.M., Pan F., Li B.;
RT "The ubiquitin ligase Stub1 negatively modulates regulatory T cell
RT suppressive activity by promoting degradation of the transcription factor
RT Foxp3.";
RL Immunity 39:272-285(2013).
RN [11]
RP FUNCTION.
RX PubMed=24043303; DOI=10.1128/mcb.00480-13;
RA Ronnebaum S.M., Wu Y., McDonough H., Patterson C.;
RT "The ubiquitin ligase CHIP prevents SirT6 degradation through noncanonical
RT ubiquitination.";
RL Mol. Cell. Biol. 33:4461-4472(2013).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 24-304 IN COMPLEX WITH UBE2N AND
RP UBE2V1, X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 227-304 IN COMPLEX WITH
RP HSP90AA1, AND HOMODIMERIZATION.
RX PubMed=16307917; DOI=10.1016/j.molcel.2005.09.023;
RA Zhang M., Windheim M., Roe S.M., Peggie M., Cohen P., Prodromou C.,
RA Pearl L.H.;
RT "Chaperoned ubiquitylation -- crystal structures of the CHIP U box E3
RT ubiquitin ligase and a CHIP-Ubc13-Uev1a complex.";
RL Mol. Cell 20:525-538(2005).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which targets misfolded chaperone
CC substrates towards proteasomal degradation (PubMed:11435423,
CC PubMed:21855799). Collaborates with ATXN3 in the degradation of
CC misfolded chaperone substrates: ATXN3 restricting the length of
CC ubiquitin chain attached to STUB1/CHIP substrates and preventing
CC further chain extension (PubMed:11435423, PubMed:21855799).
CC Ubiquitinates NOS1 in concert with Hsp70 and Hsp40 (By similarity).
CC Modulates the activity of several chaperone complexes, including Hsp70,
CC Hsc70 and Hsp90 (By similarity). Mediates transfer of non-canonical
CC short ubiquitin chains to HSPA8 that have no effect on HSPA8
CC degradation (By similarity). Mediates polyubiquitination of DNA
CC polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby
CC playing a role in base-excision repair: catalyzes polyubiquitination by
CC amplifying the HUWE1/ARF-BP1-dependent monoubiquitination and leading
CC to POLB-degradation by the proteasome (By similarity). Mediates
CC polyubiquitination of CYP3A4 (By similarity). Ubiquitinates EPHA2 and
CC may regulate the receptor stability and activity through proteasomal
CC degradation (By similarity). Acts as a co-chaperone for HSPA1A and
CC HSPA1B chaperone proteins and promotes ubiquitin-mediated protein
CC degradation. Negatively regulates the suppressive function of
CC regulatory T-cells (Treg) during inflammation by mediating the
CC ubiquitination and degradation of FOXP3 in a HSPA1A/B-dependent manner
CC (PubMed:23973223). Catalyzes monoubiquitination of SIRT6, preventing
CC its degradation by the proteasome (PubMed:24043303). Likely mediates
CC polyubiquitination and down-regulates plasma membrane expression of PD-
CC L1/CD274, an immune inhibitory ligand critical for immune tolerance to
CC self and antitumor immunity (By similarity). Negatively regulates TGF-
CC beta signaling by modulating the basal level of SMAD3 via ubiquitin-
CC mediated degradation (By similarity). May regulate myosin assembly in
CC striated muscles together with UBE4B and VCP/p97 by targeting myosin
CC chaperone UNC45B for proteasomal degradation (By similarity). Mediates
CC ubiquitination of RIPK3 leading to its subsequent proteasome-dependent
CC degradation (By similarity). {ECO:0000250|UniProtKB:Q9UNE7,
CC ECO:0000269|PubMed:11435423, ECO:0000269|PubMed:21855799,
CC ECO:0000269|PubMed:23973223, ECO:0000269|PubMed:24043303}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:11435423,
CC ECO:0000269|PubMed:21855799};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:11435423, ECO:0000269|PubMed:21855799}.
CC -!- SUBUNIT: Homodimer (PubMed:16307917). Interacts with BAG2, and with the
CC E2 ubiquitin conjugating enzymes UBE2D1, UBE2D2 and UBE2D3. Detected in
CC a ternary complex containing STUB1, HSPA1A and HSPBP1. Interacts with
CC MKKS. Interacts with DNAAF4 (By similarity). Interacts (via the U-box
CC domain) with the UBE2V2-UBE2N heterodimer; the complex has a specific
CC 'Lys-63'-linked polyubiquitination activity (PubMed:16307917).
CC Interacts (when monoubiquitinated) with ATXN3 (PubMed:21855799).
CC Interacts with UBE2W (PubMed:21855799). Interacts with DNAJB6 (By
CC similarity). Interacts with FLCN and HSP90AA1. Interacts with HSP90.
CC Interacts with UBE2N and UBE2V1. Interacts (via TPR repeats) with the
CC C-terminal domains of HSPA8 and HSPA1A. Interacts with the non-
CC acetylated form of HSPA1A and HSPA1B. Interacts with SMAD3 and HSP90AB1
CC (By similarity). Interacts with UBE4B (By similarity). Interacts with
CC PRMT5 (By similarity). {ECO:0000250|UniProtKB:Q9UNE7,
CC ECO:0000269|PubMed:16307917, ECO:0000269|PubMed:21855799}.
CC -!- INTERACTION:
CC Q9WUD1; O55222: Ilk; NbExp=7; IntAct=EBI-773027, EBI-6690138;
CC Q9WUD1; Q5S007: LRRK2; Xeno; NbExp=2; IntAct=EBI-773027, EBI-5323863;
CC Q9WUD1; P61088: UBE2N; Xeno; NbExp=2; IntAct=EBI-773027, EBI-1052908;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11435423}. Nucleus
CC {ECO:0000250|UniProtKB:Q9UNE7}. Note=Translocates to the nucleus in
CC response to inflammatory signals in regulatory T-cells (Treg).
CC {ECO:0000250|UniProtKB:Q9UNE7}.
CC -!- INDUCTION: Up-regulated by inflammatory signals in Treg regulatory T-
CC cells (Treg). {ECO:0000269|PubMed:23973223}.
CC -!- DOMAIN: The U-box domain is required for the ubiquitin protein ligase
CC activity. {ECO:0000269|PubMed:11435423}.
CC -!- DOMAIN: The TPR domain is essential for ubiquitination mediated by
CC UBE2D1. {ECO:0000250|UniProtKB:Q9UNE7}.
CC -!- PTM: Auto-ubiquitinated; mediated by UBE2D1 and UBE2D2.
CC Monoubiquitinated at Lys-2 following cell stress by UBE2W, promoting
CC the interaction with ATXN3. {ECO:0000269|PubMed:21855799}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF129086; AAD33401.1; -; mRNA.
DR EMBL; AK002752; BAB22329.1; -; mRNA.
DR EMBL; AK004464; BAB23315.1; -; mRNA.
DR EMBL; AK045776; BAC32489.1; -; mRNA.
DR EMBL; AK166630; BAE38905.1; -; mRNA.
DR EMBL; BC027427; AAH27427.1; -; mRNA.
DR EMBL; BC038939; AAH38939.1; -; mRNA.
DR CCDS; CCDS28533.1; -.
DR RefSeq; NP_062693.1; NM_019719.3.
DR PDB; 2C2L; X-ray; 3.30 A; A/B/C/D=24-304.
DR PDB; 2C2V; X-ray; 2.90 A; S/T/U/V=227-304.
DR PDB; 3Q47; X-ray; 1.70 A; B=23-155.
DR PDB; 3Q49; X-ray; 1.54 A; B=23-155.
DR PDB; 3Q4A; X-ray; 1.54 A; B=23-155.
DR PDBsum; 2C2L; -.
DR PDBsum; 2C2V; -.
DR PDBsum; 3Q47; -.
DR PDBsum; 3Q49; -.
DR PDBsum; 3Q4A; -.
DR AlphaFoldDB; Q9WUD1; -.
DR BMRB; Q9WUD1; -.
DR SMR; Q9WUD1; -.
DR BioGRID; 207969; 72.
DR DIP; DIP-29751N; -.
DR IntAct; Q9WUD1; 17.
DR MINT; Q9WUD1; -.
DR STRING; 10090.ENSMUSP00000040431; -.
DR iPTMnet; Q9WUD1; -.
DR PhosphoSitePlus; Q9WUD1; -.
DR EPD; Q9WUD1; -.
DR jPOST; Q9WUD1; -.
DR MaxQB; Q9WUD1; -.
DR PaxDb; Q9WUD1; -.
DR PeptideAtlas; Q9WUD1; -.
DR PRIDE; Q9WUD1; -.
DR ProteomicsDB; 283905; -.
DR Antibodypedia; 22808; 487 antibodies from 46 providers.
DR DNASU; 56424; -.
DR Ensembl; ENSMUST00000044911; ENSMUSP00000040431; ENSMUSG00000039615.
DR GeneID; 56424; -.
DR KEGG; mmu:56424; -.
DR UCSC; uc008bcf.1; mouse.
DR CTD; 10273; -.
DR MGI; MGI:1891731; Stub1.
DR VEuPathDB; HostDB:ENSMUSG00000039615; -.
DR eggNOG; KOG4642; Eukaryota.
DR GeneTree; ENSGT00930000151045; -.
DR HOGENOM; CLU_056455_1_0_1; -.
DR InParanoid; Q9WUD1; -.
DR OMA; FLEKNGW; -.
DR OrthoDB; 1422450at2759; -.
DR PhylomeDB; Q9WUD1; -.
DR TreeFam; TF313937; -.
DR Reactome; R-MMU-2173788; Downregulation of TGF-beta receptor signaling.
DR Reactome; R-MMU-5675482; Regulation of necroptotic cell death.
DR Reactome; R-MMU-8863795; Downregulation of ERBB2 signaling.
DR Reactome; R-MMU-8939902; Regulation of RUNX2 expression and activity.
DR Reactome; R-MMU-8948751; Regulation of PTEN stability and activity.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 56424; 20 hits in 113 CRISPR screens.
DR ChiTaRS; Stub1; mouse.
DR EvolutionaryTrace; Q9WUD1; -.
DR PRO; PR:Q9WUD1; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q9WUD1; protein.
DR Bgee; ENSMUSG00000039615; Expressed in embryonic facial prominence and 62 other tissues.
DR ExpressionAtlas; Q9WUD1; baseline and differential.
DR Genevisible; Q9WUD1; MM.
DR GO; GO:0101031; C:chaperone complex; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:ARUK-UCL.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0042405; C:nuclear inclusion body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0031371; C:ubiquitin conjugating enzyme complex; TAS:HGNC-UCL.
DR GO; GO:0000151; C:ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0030018; C:Z disc; IDA:MGI.
DR GO; GO:0051087; F:chaperone binding; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0001664; F:G protein-coupled receptor binding; ISO:MGI.
DR GO; GO:0031072; F:heat shock protein binding; ISO:MGI.
DR GO; GO:0030544; F:Hsp70 protein binding; ISS:HGNC-UCL.
DR GO; GO:0051879; F:Hsp90 protein binding; ISS:BHF-UCL.
DR GO; GO:0019900; F:kinase binding; ISO:MGI.
DR GO; GO:0051787; F:misfolded protein binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:HGNC-UCL.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; TAS:HGNC-UCL.
DR GO; GO:0046332; F:SMAD binding; ISS:HGNC-UCL.
DR GO; GO:0030911; F:TPR domain binding; ISS:HGNC-UCL.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0034450; F:ubiquitin-ubiquitin ligase activity; IDA:MGI.
DR GO; GO:0034605; P:cellular response to heat; ISO:MGI.
DR GO; GO:0071456; P:cellular response to hypoxia; ISO:MGI.
DR GO; GO:0071218; P:cellular response to misfolded protein; IMP:UniProtKB.
DR GO; GO:0061684; P:chaperone-mediated autophagy; ISO:MGI.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IDA:ParkinsonsUK-UCL.
DR GO; GO:0032091; P:negative regulation of protein binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:MGI.
DR GO; GO:0090035; P:positive regulation of chaperone-mediated protein complex assembly; ISO:MGI.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISS:HGNC-UCL.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:ParkinsonsUK-UCL.
DR GO; GO:0045862; P:positive regulation of proteolysis; IBA:GO_Central.
DR GO; GO:0051443; P:positive regulation of ubiquitin-protein transferase activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; ISS:UniProtKB.
DR GO; GO:0006457; P:protein folding; TAS:HGNC-UCL.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0051604; P:protein maturation; TAS:HGNC-UCL.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:MGI.
DR GO; GO:0006515; P:protein quality control for misfolded or incompletely synthesized proteins; IMP:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:MGI.
DR GO; GO:0031943; P:regulation of glucocorticoid metabolic process; ISS:HGNC-UCL.
DR GO; GO:0031647; P:regulation of protein stability; ISO:MGI.
DR GO; GO:0002931; P:response to ischemia; ISO:MGI.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; ISO:MGI.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:MGI.
DR GO; GO:0030579; P:ubiquitin-dependent SMAD protein catabolic process; ISS:HGNC-UCL.
DR CDD; cd16654; RING-Ubox_CHIP; 1.
DR Gene3D; 1.25.40.10; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR045200; CHIP/LubX.
DR InterPro; IPR045202; CHIP/LubX_RING-Ubox.
DR InterPro; IPR041312; CHIP_TPR_N.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR019734; TPR_repeat.
DR InterPro; IPR003613; Ubox_domain.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR46803; PTHR46803; 1.
DR Pfam; PF18391; CHIP_TPR_N; 1.
DR Pfam; PF04564; U-box; 1.
DR SMART; SM00028; TPR; 3.
DR SMART; SM00504; Ubox; 1.
DR SUPFAM; SSF48452; SSF48452; 1.
DR PROSITE; PS50005; TPR; 3.
DR PROSITE; PS50293; TPR_REGION; 1.
DR PROSITE; PS51698; U_BOX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; DNA damage; DNA repair; Isopeptide bond; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; TPR repeat; Transferase;
KW Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..304
FT /note="E3 ubiquitin-protein ligase CHIP"
FT /id="PRO_0000106330"
FT REPEAT 27..60
FT /note="TPR 1"
FT REPEAT 61..94
FT /note="TPR 2"
FT REPEAT 96..128
FT /note="TPR 3"
FT DOMAIN 227..301
FT /note="U-box"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16452087,
FT ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19131326,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 26
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19131326"
FT MOD_RES 150
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UNE7"
FT MOD_RES 274
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UNE7"
FT CROSSLNK 2
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:21855799"
FT CROSSLNK 23
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9UNE7"
FT CROSSLNK 222
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9UNE7"
FT CROSSLNK 256
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9UNE7"
FT MUTAGEN 2
FT /note="K->R: Impaired interaction with ATXN3; when
FT associated with R-4 and R-7."
FT /evidence="ECO:0000269|PubMed:21855799"
FT MUTAGEN 4
FT /note="K->R: Impaired interaction with ATXN3; when
FT associated with R-2 and R-7."
FT /evidence="ECO:0000269|PubMed:21855799"
FT MUTAGEN 7
FT /note="K->R: Impaired interaction with ATXN3; when
FT associated with R-2 and R-4."
FT /evidence="ECO:0000269|PubMed:21855799"
FT MUTAGEN 261
FT /note="H->A: Loss of E3 ubiquitin protein ligase activity."
FT /evidence="ECO:0000269|PubMed:11435423"
FT MUTAGEN 270
FT /note="P->A: Loss of E3 ubiquitin protein ligase activity."
FT /evidence="ECO:0000269|PubMed:11435423"
FT CONFLICT 20
FT /note="S -> T (in Ref. 2; BAB22329)"
FT /evidence="ECO:0000305"
FT HELIX 27..39
FT /evidence="ECO:0007829|PDB:3Q4A"
FT HELIX 43..56
FT /evidence="ECO:0007829|PDB:3Q4A"
FT HELIX 61..73
FT /evidence="ECO:0007829|PDB:3Q4A"
FT HELIX 77..90
FT /evidence="ECO:0007829|PDB:3Q4A"
FT HELIX 95..107
FT /evidence="ECO:0007829|PDB:3Q4A"
FT HELIX 111..127
FT /evidence="ECO:0007829|PDB:3Q4A"
FT HELIX 135..152
FT /evidence="ECO:0007829|PDB:3Q4A"
FT HELIX 161..178
FT /evidence="ECO:0007829|PDB:2C2L"
FT TURN 179..181
FT /evidence="ECO:0007829|PDB:2C2L"
FT HELIX 183..185
FT /evidence="ECO:0007829|PDB:2C2L"
FT TURN 186..188
FT /evidence="ECO:0007829|PDB:2C2L"
FT HELIX 191..194
FT /evidence="ECO:0007829|PDB:2C2L"
FT HELIX 196..218
FT /evidence="ECO:0007829|PDB:2C2L"
FT HELIX 230..232
FT /evidence="ECO:0007829|PDB:2C2V"
FT TURN 235..237
FT /evidence="ECO:0007829|PDB:2C2V"
FT STRAND 242..246
FT /evidence="ECO:0007829|PDB:2C2V"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:2C2V"
FT HELIX 255..264
FT /evidence="ECO:0007829|PDB:2C2V"
FT TURN 270..272
FT /evidence="ECO:0007829|PDB:2C2V"
FT HELIX 278..280
FT /evidence="ECO:0007829|PDB:2C2V"
FT HELIX 285..298
FT /evidence="ECO:0007829|PDB:2C2V"
SQ SEQUENCE 304 AA; 34909 MW; 18BD2728908025A8 CRC64;
MKGKEEKEGG ARLGTGGGGS PDKSPSAQEL KEQGNRLFVG RKYPEAAACY GRAITRNPLV
AVYYTNRALC YLKMQQPEQA LADCRRALEL DGQSVKAHFF LGQCQLEMES YDEAIANLQR
AYSLAKEQRL NFGDDIPSAL RIAKKKRWNS IEERRIHQES ELHSYLTRLI AAERERELEE
CQRNHEGHED DGHIRAQQAC IEAKHDKYMA DMDELFSQVD EKRKKRDIPD YLCGKISFEL
MREPCITPSG ITYDRKDIEE HLQRVGHFDP VTRSPLTQEQ LIPNLAMKEV IDAFISENGW
VEDY
