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{{Infobox_gene}}
{{PBB_Controls
'''STUB1''' ('''<u>ST</u>IP1 homology and <u>U</u>-<u>B</u>ox containing protein <u>1</u>''') is a human gene that codes for the protein '''CHIP''' ('''<u>C</u> terminus of <u>H</u>SC70-<u>I</u>nteracting <u>P</u>rotein'''). <ref name="entrez">{{cite web | title = Entrez Gene: STUB1 STIP1 homology and U-box containing protein 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10273| accessdate = }}</ref><ref name="pmid10330192">{{cite journal | vauthors = Ballinger CA, Connell P, Wu Y, Hu Z, Thompson LJ, Yin LY, Patterson C | title = Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions | journal = Molecular and Cellular Biology | volume = 19 | issue = 6 | pages = 4535–45 | date = Jun 1999 | pmid = 10330192 | pmc = 104411 | url = http://mcb.asm.org/cgi/content/abstract/19/6/4535 | doi=10.1128/mcb.19.6.4535}}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
The CHIP protein encoded by this gene binds to and inhibits the [[ATPase]] activity of the [[chaperone (protein)|chaperone proteins]] [[HSPA8|HSC70]] and [[Hsp70|HSP70]] and blocks the forward reaction of the HSC70-HSP70 substrate-binding cycle.<ref name="pmid10330192"/> In addition, CHIP possesses [[ubiquitin ligase|E3 ubiquitin ligase]] activity and promotes [[ubiquitylation]]<ref name="pmid11557750">{{cite journal | vauthors = Jiang J, Ballinger CA, Wu Y, Dai Q, Cyr DM, Höhfeld J, Patterson C | title = CHIP is a U-box-dependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation | journal = The Journal of Biological Chemistry | volume = 276 | issue = 46 | pages = 42938–44 | date = Nov 2001 | pmid = 11557750 | doi = 10.1074/jbc.M101968200 }}</ref>, mainly of chaperone-bound misfolded proteins.
| image = PBB_Protein_STUB1_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 2c2l.
| PDB = {{PDB2|2c2l}}, {{PDB2|2c2v}}
| Name = STIP1 homology and U-box containing protein 1
| HGNCid = 11427
| Symbol = STUB1
| AltSymbols =; CHIP; HSPABP2; NY-CO-7; SDCCAG7; UBOX1
| OMIM = 607207
| ECnumber = 
| Homologene = 4281
| MGIid = 1891731
| GeneAtlas_image1 = PBB_GE_STUB1_217934_x_at_tn.png
| Function = {{GNF_GO|id=GO:0004842 |text = ubiquitin-protein ligase activity}} {{GNF_GO|id=GO:0016874 |text = ligase activity}} {{GNF_GO|id=GO:0030544 |text = Hsp70 protein binding}} {{GNF_GO|id=GO:0030674 |text = protein binding, bridging}} {{GNF_GO|id=GO:0042803 |text = protein homodimerization activity}} {{GNF_GO|id=GO:0046332 |text = SMAD binding}} {{GNF_GO|id=GO:0051879 |text = Hsp90 protein binding}}
| Component = {{GNF_GO|id=GO:0000151 |text = ubiquitin ligase complex}} {{GNF_GO|id=GO:0031371 |text = ubiquitin conjugating enzyme complex}}
| Process = {{GNF_GO|id=GO:0000209 |text = protein polyubiquitination}} {{GNF_GO|id=GO:0006457 |text = protein folding}} {{GNF_GO|id=GO:0030579 |text = ubiquitin-dependent SMAD protein catabolic process}} {{GNF_GO|id=GO:0043161 |text = proteasomal ubiquitin-dependent protein catabolic process}} {{GNF_GO|id=GO:0051604 |text = protein maturation}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 10273
    | Hs_Ensembl = ENSG00000103266
    | Hs_RefseqProtein = NP_005852
    | Hs_RefseqmRNA = NM_005861
    | Hs_GenLoc_db =
    | Hs_GenLoc_chr = 16
    | Hs_GenLoc_start = 670116
    | Hs_GenLoc_end = 672768
    | Hs_Uniprot = Q9UNE7
    | Mm_EntrezGene = 56424
    | Mm_Ensembl = ENSMUSG00000039615
    | Mm_RefseqmRNA = NM_019719
    | Mm_RefseqProtein = NP_062693
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 17
    | Mm_GenLoc_start = 25558234
    | Mm_GenLoc_end = 25560961
    | Mm_Uniprot = Q3TYJ0
  }}
}}
'''STIP1 homology and U-box containing protein 1''', also known as '''STUB1''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: STUB1 STIP1 homology and U-box containing protein 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10273| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
CHIP enhances HSP70 induction during acute stress and also mediates its turnover during the stress recovery process. Hence CHIP appears to maintain protein homeostasis by controlling chaperone levels during stress and recovery.<ref name="pmid16554822">{{cite journal | vauthors = Qian SB, McDonough H, Boellmann F, Cyr DM, Patterson C | title = CHIP-mediated stress recovery by sequential ubiquitination of substrates and Hsp70 | journal = Nature | volume = 440 | issue = 7083 | pages = 551–5 | date = Mar 2006 | pmid = 16554822 | doi = 10.1038/nature04600 | pmc = 4112096 }}</ref>
{{PBB_Summary
| section_title =  
| summary_text =  
}}


==References==
Mutations in STUB1 cause spinocerebellar{{SWL|type=mutation_results_in|target=ataxia|label=ataxia}}type 16.<ref name="Synofzik_2014">{{cite journal | vauthors = Synofzik M, Schüle R, Schulze M, Gburek-Augustat J, Schweizer R, Schirmacher A, Krägeloh-Mann I, Gonzalez M, Young P, Züchner S, Schöls L, Bauer P | title = Phenotype and frequency of STUB1 mutations: next-generation screenings in Caucasian ataxia and spastic paraplegia cohorts | journal = Orphanet Journal of Rare Diseases | volume = 9 | issue = 1 | pages = 57 | year = 2014 | pmid = 24742043 | pmc = 4021831 | doi = 10.1186/1750-1172-9-57 }}</ref>
{{reflist|2}}
==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal  | author=Patterson C |title=A new gun in town: the U box is a ubiquitin ligase domain. |journal=Sci. STKE |volume=2002 |issue= 116 |pages= PE4 |year= 2002 |pmid= 11805346 |doi= 10.1126/stke.2002.116.pe4 }}
*{{cite journal  | author=Scanlan MJ, Chen YT, Williamson B, ''et al.'' |title=Characterization of human colon cancer antigens recognized by autologous antibodies. |journal=Int. J. Cancer |volume=76 |issue= 5 |pages= 652-8 |year= 1998 |pmid= 9610721 |doi=  }}
*{{cite journal  | author=Ballinger CA, Connell P, Wu Y, ''et al.'' |title=Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions. |journal=Mol. Cell. Biol. |volume=19 |issue= 6 |pages= 4535-45 |year= 1999 |pmid= 10330192 |doi=  }}
*{{cite journal  | author=Connell P, Ballinger CA, Jiang J, ''et al.'' |title=The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. |journal=Nat. Cell Biol. |volume=3 |issue= 1 |pages= 93-6 |year= 2001 |pmid= 11146632 |doi= 10.1038/35050618 }}
*{{cite journal  | author=Daniels RJ, Peden JF, Lloyd C, ''et al.'' |title=Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16. |journal=Hum. Mol. Genet. |volume=10 |issue= 4 |pages= 339-52 |year= 2001 |pmid= 11157797 |doi=  }}
*{{cite journal | author=Jiang J, Ballinger CA, Wu Y, ''et al.'' |title=CHIP is a U-box-dependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation. |journal=J. Biol. Chem. |volume=276 |issue= 46 |pages= 42938-44 |year= 2001 |pmid= 11557750 |doi= 10.1074/jbc.M101968200 }}
*{{cite journal  | author=Demand J, Alberti S, Patterson C, Höhfeld J |title=Cooperation of a ubiquitin domain protein and an E3 ubiquitin ligase during chaperone/proteasome coupling. |journal=Curr. Biol. |volume=11 |issue= 20 |pages= 1569-77 |year= 2002 |pmid= 11676916 |doi=  }}
*{{cite journal  | author=Imai Y, Soda M, Hatakeyama S, ''et al.'' |title=CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity. |journal=Mol. Cell |volume=10 |issue= 1 |pages= 55-67 |year= 2002 |pmid= 12150907 |doi=  }}
*{{cite journal  | author=Krackhardt AM, Witzens M, Harig S, ''et al.'' |title=Identification of tumor-associated antigens in chronic lymphocytic leukemia by SEREX. |journal=Blood |volume=100 |issue= 6 |pages= 2123-31 |year= 2002 |pmid= 12200376 |doi= 10.1182/blood-2002-02-0513 }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal  | author=Cardozo CP, Michaud C, Ost MC, ''et al.'' |title=C-terminal Hsp-interacting protein slows androgen receptor synthesis and reduces its rate of degradation. |journal=Arch. Biochem. Biophys. |volume=410 |issue= 1 |pages= 134-40 |year= 2003 |pmid= 12559985 |doi=  }}
*{{cite journal  | author=Zhou P, Fernandes N, Dodge IL, ''et al.'' |title=ErbB2 degradation mediated by the co-chaperone protein CHIP. |journal=J. Biol. Chem. |volume=278 |issue= 16 |pages= 13829-37 |year= 2003 |pmid= 12574167 |doi= 10.1074/jbc.M209640200 }}
*{{cite journal  | author=Shimura H, Schwartz D, Gygi SP, Kosik KS |title=CHIP-Hsc70 complex ubiquitinates phosphorylated tau and enhances cell survival. |journal=J. Biol. Chem. |volume=279 |issue= 6 |pages= 4869-76 |year= 2004 |pmid= 14612456 |doi= 10.1074/jbc.M305838200 }}
*{{cite journal  | author=Li L, Xin H, Xu X, ''et al.'' |title=CHIP mediates degradation of Smad proteins and potentially regulates Smad-induced transcription. |journal=Mol. Cell. Biol. |volume=24 |issue= 2 |pages= 856-64 |year= 2004 |pmid= 14701756 |doi=  }}
*{{cite journal  | author=Petrucelli L, Dickson D, Kehoe K, ''et al.'' |title=CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation. |journal=Hum. Mol. Genet. |volume=13 |issue= 7 |pages= 703-14 |year= 2004 |pmid= 14962978 |doi= 10.1093/hmg/ddh083 }}
*{{cite journal  | author=Galigniana MD, Harrell JM, Housley PR, ''et al.'' |title=Retrograde transport of the glucocorticoid receptor in neurites requires dynamic assembly of complexes with the protein chaperone hsp90 and is linked to the CHIP component of the machinery for proteasomal degradation. |journal=Brain Res. Mol. Brain Res. |volume=123 |issue= 1-2 |pages= 27-36 |year= 2004 |pmid= 15046863 |doi= 10.1016/j.molbrainres.2003.12.015 }}
*{{cite journal  | author=He B, Bai S, Hnat AT, ''et al.'' |title=An androgen receptor NH2-terminal conserved motif interacts with the COOH terminus of the Hsp70-interacting protein (CHIP). |journal=J. Biol. Chem. |volume=279 |issue= 29 |pages= 30643-53 |year= 2004 |pmid= 15107424 |doi= 10.1074/jbc.M403117200 }}
*{{cite journal  | author=Alberti S, Böhse K, Arndt V, ''et al.'' |title=The cochaperone HspBP1 inhibits the CHIP ubiquitin ligase and stimulates the maturation of the cystic fibrosis transmembrane conductance regulator. |journal=Mol. Biol. Cell |volume=15 |issue= 9 |pages= 4003-10 |year= 2005 |pmid= 15215316 |doi= 10.1091/mbc.E04-04-0293 }}
*{{cite journal  | author=Beausoleil SA, Jedrychowski M, Schwartz D, ''et al.'' |title=Large-scale characterization of HeLa cell nuclear phosphoproteins. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue= 33 |pages= 12130-5 |year= 2004 |pmid= 15302935 |doi= 10.1073/pnas.0404720101 }}
}}
{{refend}}


{{protein-stub}}
== Interactions ==
{{WikiDoc Sources}}
 
STUB1 has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[C-Raf]],<ref name = pmid19011619>{{cite journal | vauthors = Dogan T, Harms GS, Hekman M, Karreman C, Oberoi TK, Alnemri ES, Rapp UR, Rajalingam K | title = X-linked and cellular IAPs modulate the stability of C-RAF kinase and cell motility | journal = Nature Cell Biology | volume = 10 | issue = 12 | pages = 1447–55 | date = Dec 2008 | pmid = 19011619 | doi = 10.1038/ncb1804 }}</ref>
* [[DNAJB1]],<ref name = pmid10330192 />
* [[HSPA1A]],<ref name = pmid10330192/><ref name = pmid12150907/>
* [[HSPA4]],<ref name = pmid10330192/>
* [[HSPA8]],<ref name = pmid10330192/>
* [[Parkin (ligase)]],<ref name = pmid12150907>{{cite journal | vauthors = Imai Y, Soda M, Hatakeyama S, Akagi T, Hashikawa T, Nakayama KI, Takahashi R | title = CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity | journal = Molecular Cell | volume = 10 | issue = 1 | pages = 55–67 | date = Jul 2002 | pmid = 12150907 | doi =  10.1016/s1097-2765(02)00583-x}}</ref>  and
* [[RUNX2]].<ref name = pmid18541707>{{cite journal | vauthors = Li X, Huang M, Zheng H, Wang Y, Ren F, Shang Y, Zhai Y, Irwin DM, Shi Y, Chen D, Chang Z | title = CHIP promotes Runx2 degradation and negatively regulates osteoblast differentiation | journal = The Journal of Cell Biology | volume = 181 | issue = 6 | pages = 959–72 | date = Jun 2008 | pmid = 18541707 | pmc = 2426947 | doi = 10.1083/jcb.200711044 }}</ref>
{{Div col end}}
 
== References ==
{{Reflist|2}}
 
== Further reading ==
{{Refbegin | 2}}
* {{cite journal | vauthors = Patterson C | title = A new gun in town: the U box is a ubiquitin ligase domain | journal = Science's STKE | volume = 2002 | issue = 116 | pages = pe4 | date = Jan 2002 | pmid = 11805346 | doi = 10.1126/stke.2002.116.pe4 }}
* {{cite journal | vauthors = Scanlan MJ, Chen YT, Williamson B, Gure AO, Stockert E, Gordan JD, Türeci O, Sahin U, Pfreundschuh M, Old LJ | title = Characterization of human colon cancer antigens recognized by autologous antibodies | journal = International Journal of Cancer | volume = 76 | issue = 5 | pages = 652–8 | date = May 1998 | pmid = 9610721 | doi = 10.1002/(SICI)1097-0215(19980529)76:5<652::AID-IJC7>3.0.CO;2-P }}
* {{cite journal | vauthors = Ballinger CA, Connell P, Wu Y, Hu Z, Thompson LJ, Yin LY, Patterson C | title = Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions | journal = Molecular and Cellular Biology | volume = 19 | issue = 6 | pages = 4535–45 | date = Jun 1999 | pmid = 10330192 | pmc = 104411 | doi =  10.1128/mcb.19.6.4535}}
* {{cite journal | vauthors = Connell P, Ballinger CA, Jiang J, Wu Y, Thompson LJ, Höhfeld J, Patterson C | title = The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins | journal = Nature Cell Biology | volume = 3 | issue = 1 | pages = 93–6 | date = Jan 2001 | pmid = 11146632 | doi = 10.1038/35050618 }}
* {{cite journal | vauthors = Daniels RJ, Peden JF, Lloyd C, Horsley SW, Clark K, Tufarelli C, Kearney L, Buckle VJ, Doggett NA, Flint J, Higgs DR | title = Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16 | journal = Human Molecular Genetics | volume = 10 | issue = 4 | pages = 339–52 | date = Feb 2001 | pmid = 11157797 | doi = 10.1093/hmg/10.4.339 }}
* {{cite journal | vauthors = Jiang J, Ballinger CA, Wu Y, Dai Q, Cyr DM, Höhfeld J, Patterson C | title = CHIP is a U-box-dependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation | journal = The Journal of Biological Chemistry | volume = 276 | issue = 46 | pages = 42938–44 | date = Nov 2001 | pmid = 11557750 | doi = 10.1074/jbc.M101968200 }}
* {{cite journal | vauthors = Demand J, Alberti S, Patterson C, Höhfeld J | title = Cooperation of a ubiquitin domain protein and an E3 ubiquitin ligase during chaperone/proteasome coupling | journal = Current Biology | volume = 11 | issue = 20 | pages = 1569–77 | date = Oct 2001 | pmid = 11676916 | doi = 10.1016/S0960-9822(01)00487-0 }}
* {{cite journal | vauthors = Imai Y, Soda M, Hatakeyama S, Akagi T, Hashikawa T, Nakayama KI, Takahashi R | title = CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity | journal = Molecular Cell | volume = 10 | issue = 1 | pages = 55–67 | date = Jul 2002 | pmid = 12150907 | doi = 10.1016/S1097-2765(02)00583-X }}
* {{cite journal | vauthors = Krackhardt AM, Witzens M, Harig S, Hodi FS, Zauls AJ, Chessia M, Barrett P, Gribben JG | title = Identification of tumor-associated antigens in chronic lymphocytic leukemia by SEREX | journal = Blood | volume = 100 | issue = 6 | pages = 2123–31 | date = Sep 2002 | pmid = 12200376 | doi = 10.1182/blood-2002-02-0513 }}
* {{cite journal | vauthors = Cardozo CP, Michaud C, Ost MC, Fliss AE, Yang E, Patterson C, Hall SJ, Caplan AJ | title = C-terminal Hsp-interacting protein slows androgen receptor synthesis and reduces its rate of degradation | journal = Archives of Biochemistry and Biophysics | volume = 410 | issue = 1 | pages = 134–40 | date = Feb 2003 | pmid = 12559985 | doi = 10.1016/S0003-9861(02)00680-X }}
* {{cite journal | vauthors = Zhou P, Fernandes N, Dodge IL, Reddi AL, Rao N, Safran H, DiPetrillo TA, Wazer DE, Band V, Band H | title = ErbB2 degradation mediated by the co-chaperone protein CHIP | journal = The Journal of Biological Chemistry | volume = 278 | issue = 16 | pages = 13829–37 | date = Apr 2003 | pmid = 12574167 | doi = 10.1074/jbc.M209640200 }}
* {{cite journal | vauthors = Shimura H, Schwartz D, Gygi SP, Kosik KS | title = CHIP-Hsc70 complex ubiquitinates phosphorylated tau and enhances cell survival | journal = The Journal of Biological Chemistry | volume = 279 | issue = 6 | pages = 4869–76 | date = Feb 2004 | pmid = 14612456 | doi = 10.1074/jbc.M305838200 }}
* {{cite journal | vauthors = Li L, Xin H, Xu X, Huang M, Zhang X, Chen Y, Zhang S, Fu XY, Chang Z | title = CHIP mediates degradation of Smad proteins and potentially regulates Smad-induced transcription | journal = Molecular and Cellular Biology | volume = 24 | issue = 2 | pages = 856–64 | date = Jan 2004 | pmid = 14701756 | pmc = 343794 | doi = 10.1128/MCB.24.2.856-864.2004 }}
* {{cite journal | vauthors = Petrucelli L, Dickson D, Kehoe K, Taylor J, Snyder H, Grover A, De Lucia M, McGowan E, Lewis J, Prihar G, Kim J, Dillmann WH, Browne SE, Hall A, Voellmy R, Tsuboi Y, Dawson TM, Wolozin B, Hardy J, Hutton M | author18link=Benjamin Wolozin | title = CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation | journal = Human Molecular Genetics | volume = 13 | issue = 7 | pages = 703–14 | date = Apr 2004 | pmid = 14962978 | doi = 10.1093/hmg/ddh083 }}
* {{cite journal | vauthors = Galigniana MD, Harrell JM, Housley PR, Patterson C, Fisher SK, Pratt WB | title = Retrograde transport of the glucocorticoid receptor in neurites requires dynamic assembly of complexes with the protein chaperone hsp90 and is linked to the CHIP component of the machinery for proteasomal degradation | journal = Brain Research. Molecular Brain Research | volume = 123 | issue = 1-2 | pages = 27–36 | date = Apr 2004 | pmid = 15046863 | doi = 10.1016/j.molbrainres.2003.12.015 }}
* {{cite journal | vauthors = He B, Bai S, Hnat AT, Kalman RI, Minges JT, Patterson C, Wilson EM | title = An androgen receptor NH2-terminal conserved motif interacts with the COOH terminus of the Hsp70-interacting protein (CHIP) | journal = The Journal of Biological Chemistry | volume = 279 | issue = 29 | pages = 30643–53 | date = Jul 2004 | pmid = 15107424 | doi = 10.1074/jbc.M403117200 }}
* {{cite journal | vauthors = Alberti S, Böhse K, Arndt V, Schmitz A, Höhfeld J | title = The cochaperone HspBP1 inhibits the CHIP ubiquitin ligase and stimulates the maturation of the cystic fibrosis transmembrane conductance regulator | journal = Molecular Biology of the Cell | volume = 15 | issue = 9 | pages = 4003–10 | date = Sep 2004 | pmid = 15215316 | pmc = 515335 | doi = 10.1091/mbc.E04-04-0293 }}
* {{cite journal | vauthors = Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP | title = Large-scale characterization of HeLa cell nuclear phosphoproteins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 33 | pages = 12130–5 | date = Aug 2004 | pmid = 15302935 | pmc = 514446 | doi = 10.1073/pnas.0404720101 }}
{{Refend}}
 
== External links ==
* {{UCSC genome browser|STUB1}}
* {{UCSC gene details|STUB1}}
 
{{PDB Gallery|geneid=10273}}

Latest revision as of 09:25, 10 January 2019

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

STUB1 (STIP1 homology and U-Box containing protein 1) is a human gene that codes for the protein CHIP (C terminus of HSC70-Interacting Protein). [1][2]

Function

The CHIP protein encoded by this gene binds to and inhibits the ATPase activity of the chaperone proteins HSC70 and HSP70 and blocks the forward reaction of the HSC70-HSP70 substrate-binding cycle.[2] In addition, CHIP possesses E3 ubiquitin ligase activity and promotes ubiquitylation[3], mainly of chaperone-bound misfolded proteins.

CHIP enhances HSP70 induction during acute stress and also mediates its turnover during the stress recovery process. Hence CHIP appears to maintain protein homeostasis by controlling chaperone levels during stress and recovery.[4]

Mutations in STUB1 cause spinocerebellar ataxia type 16.[5]

Interactions

STUB1 has been shown to interact with:

References

  1. "Entrez Gene: STUB1 STIP1 homology and U-box containing protein 1".
  2. 2.0 2.1 2.2 2.3 2.4 2.5 Ballinger CA, Connell P, Wu Y, Hu Z, Thompson LJ, Yin LY, Patterson C (Jun 1999). "Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions". Molecular and Cellular Biology. 19 (6): 4535–45. doi:10.1128/mcb.19.6.4535. PMC 104411. PMID 10330192.
  3. Jiang J, Ballinger CA, Wu Y, Dai Q, Cyr DM, Höhfeld J, Patterson C (Nov 2001). "CHIP is a U-box-dependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation". The Journal of Biological Chemistry. 276 (46): 42938–44. doi:10.1074/jbc.M101968200. PMID 11557750.
  4. Qian SB, McDonough H, Boellmann F, Cyr DM, Patterson C (Mar 2006). "CHIP-mediated stress recovery by sequential ubiquitination of substrates and Hsp70". Nature. 440 (7083): 551–5. doi:10.1038/nature04600. PMC 4112096. PMID 16554822.
  5. Synofzik M, Schüle R, Schulze M, Gburek-Augustat J, Schweizer R, Schirmacher A, Krägeloh-Mann I, Gonzalez M, Young P, Züchner S, Schöls L, Bauer P (2014). "Phenotype and frequency of STUB1 mutations: next-generation screenings in Caucasian ataxia and spastic paraplegia cohorts". Orphanet Journal of Rare Diseases. 9 (1): 57. doi:10.1186/1750-1172-9-57. PMC 4021831. PMID 24742043.
  6. Dogan T, Harms GS, Hekman M, Karreman C, Oberoi TK, Alnemri ES, Rapp UR, Rajalingam K (Dec 2008). "X-linked and cellular IAPs modulate the stability of C-RAF kinase and cell motility". Nature Cell Biology. 10 (12): 1447–55. doi:10.1038/ncb1804. PMID 19011619.
  7. 7.0 7.1 Imai Y, Soda M, Hatakeyama S, Akagi T, Hashikawa T, Nakayama KI, Takahashi R (Jul 2002). "CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity". Molecular Cell. 10 (1): 55–67. doi:10.1016/s1097-2765(02)00583-x. PMID 12150907.
  8. Li X, Huang M, Zheng H, Wang Y, Ren F, Shang Y, Zhai Y, Irwin DM, Shi Y, Chen D, Chang Z (Jun 2008). "CHIP promotes Runx2 degradation and negatively regulates osteoblast differentiation". The Journal of Cell Biology. 181 (6): 959–72. doi:10.1083/jcb.200711044. PMC 2426947. PMID 18541707.

Further reading

External links