Ubiquitin
From Proteopedia
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<StructureSection load='' size='340' side='right' caption='Human ubiquitin (green) complex with ubiquitin-conjugating enzyme E2 (deep sky blue), [[3k9p]]' scene='41/417541/Cv/3' > | <StructureSection load='' size='340' side='right' caption='Human ubiquitin (green) complex with ubiquitin-conjugating enzyme E2 (deep sky blue), [[3k9p]]' scene='41/417541/Cv/3' > | ||
== Function == | == Function == | ||
| - | [[Ubiquitin]] (UBB) is found in almost all cells. It binds to proteins tagging them for destruction in the proteasome. UBB is activated by the UBB-activating enzymes E1, E2 and E3. | + | [[Ubiquitin]] (UBB) is found in almost all cells. It binds to proteins tagging them for destruction in the proteasome. UBB is activated by the UBB-activating enzymes E1, E2 and E3. '''Ubiquitin+1''' is a frameshifted mutant of UBB observed in several diseases. A dimer of UBB (DiUBB) is formed by linkage of K48 to the C-terminus of a second UBB molecule. '''Polyubiquitin''' (polyUBB) is a chain of ubiquitin molecules bound by peptide bonds. PolyUBB can be formed by lysine residues: K6, K11, K27, 29, K33, K48, and K63. Different lysine linkages convey different functions to polyUBB. Lys48- linked polyUBB and LYs11-linked polyUBB are associated with proteasome degradation; Lys63-linked and Lys-6 polyUBB are associated with non-proteolytic functions<ref>PMID:18438605</ref>. At least 4 UBB molecules are needed to tag a protein for the proteasome<ref>PMID:9759494</ref>. <scene name='41/417541/Cv/4'>Human ubiquitin interactions with ubiquitin-conjugating enzyme E2</scene> ([[3k9p]]). For details see<br /> |
* [[Ubiquitin Structure & Function]]<br /> | * [[Ubiquitin Structure & Function]]<br /> | ||
| + | * [[Ubiquitin and Ubiquitination]]<br /> | ||
* [[Ubiquitin salt bridge discussion]]<br /> | * [[Ubiquitin salt bridge discussion]]<br /> | ||
* [[Ubiquitin chains]]. | * [[Ubiquitin chains]]. | ||
| + | |||
| + | Professors Ciechanover, Hershko and Rose received the '''Nobel Prize''' in 2004 for their discovery of the process by which ubiquitin mediates protein proteolysis<ref>PMID:15646859</ref>. | ||
==Additional Resources== | ==Additional Resources== | ||
| - | See: [[ | + | See also: |
| - | + | *[[Tumor susceptibility gene 101]] | |
| + | *[[SUMO]] | ||
== Disease == | == Disease == | ||
The UBB-proteasome system deregulation has been implicated in the pathogenesis of many neurodegenerative disorders like Alzheimer's disease, Parkinson disease, Huntington disease, Prion-like lethal disorders and in genetic diseases like cystic fibrosis, angelman's syndrome, Liddle syndrome and many cancers<ref>PMID:18937370</ref>. | The UBB-proteasome system deregulation has been implicated in the pathogenesis of many neurodegenerative disorders like Alzheimer's disease, Parkinson disease, Huntington disease, Prion-like lethal disorders and in genetic diseases like cystic fibrosis, angelman's syndrome, Liddle syndrome and many cancers<ref>PMID:18937370</ref>. | ||
| + | |||
| + | ==[[3D structures of ubiquitin]]== | ||
</StructureSection> | </StructureSection> | ||
| - | == 3D Structures of Ubiquitin == | ||
| - | |||
| - | Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} | ||
| - | {{#tree:id=OrganizedByTopic|openlevels=0| | ||
| - | |||
| - | * Ubiquitin | ||
| - | |||
| - | **[[2kn5]], [[2klg]], [[2jzz]], [[2pe9]], [[2pea]], [[1g6j]], [[1d3z]], [[2kox]], [[2ld9]], [[2k25]], [[5ujl]] – hUBB – NMR - human<br /> | ||
| - | **[[2ojr]], [[2nr2]], [[2fcq]], [[1ubi]], [[1ubq]], [[1xqq]], [[3ons]], [[4wzp]], [[5k9p]], [[4zqs]], [[5dk8]], [[4xof]], [[4xok]], [[4xol]], [[4zpz]] - hUBB<br /> | ||
| - | **[[2zcb]], [[2gbj]], [[2gbk]], [[2gbm]], [[2gbn]], [[2gbr]], [[2fcm]], [[2fcn]], [[2fcs]], [[1yiw]], [[1yj1]], [[1sif]], [[1ogw]], [[4hk2]], [[4hjk]], [[4pij]], [[4pih]], [[4pig]] - hUBB (mutant)<br /> | ||
| - | **[[1c3t]], [[1ud7]], [[2mi8]], [[2rsu]], [[2ru6]] - hUBB (mutant) - NMR<br /> | ||
| - | **[[2m0x]] - hUBB - engineered – NMR<br /> | ||
| - | **[[1gjz]], [[2l3z]] – hUBB N-terminal – NMR<br /> | ||
| - | **[[1e0q]] - hUBB N-terminal (mutant) – NMR<br /> | ||
| - | **[[3q3f]] – hUBB/ribonuclease<br /> | ||
| - | **[[4zpz]] – hPolyUBB-B (mutant)<br /> | ||
| - | **[[5af4]], [[4xyz]] – hPolyUBB-C <br /> | ||
| - | **[[5af5]] – hPolyUBB-C (mutant)<br /> | ||
| - | **[[2k39]] – UBB – ''Xenopus laevis'' – NMR<br /> | ||
| - | **[[2jwz]], [[1zw7]] – yUBB (mutant) – yeast<br /> | ||
| - | **[[1cmx]] – yUBB (modified)<br /> | ||
| - | **[[2zcc]] – bUBB - bovine<br /> | ||
| - | |||
| - | * Ubiquitin+1 mutant | ||
| - | |||
| - | **[[2kx0]] – hUBB+1 – human – NMR<br /> | ||
| - | **[[3k9o]] – hUBB+1+E2<br /> | ||
| - | |||
| - | * Ubiquitin dimer | ||
| - | |||
| - | **[[2xk5]], [[3nob]], [[2xew]], [[3h7p]], [[3h7s]], [[2w9n]], [[2jf5]], [[3ns8]], [[3aul]], [[3axc]], [[5gob]], [[5goc]], [[5god]], [[5gog]], [[5goh]], [[5goi]], [[5goj]], [[5j8p]] – hDiUBB<br /> | ||
| - | **[[2mbo]], [[2mbq]] – hDiUBB – NMR<br /> | ||
| - | **[[3m3j]], [[1aar]], [[3aui]] – bDiUBB <br /> | ||
| - | **[[2bgf]] – hDiUBB – chemical relaxation<br /> | ||
| - | **[[4s22]] – bDiUBB <br /> | ||
| - | |||
| - | * Ubiquitin dimer bound to protein | ||
| - | |||
| - | **[[3a9j]], [[3a9k]], [[2wwz]], [[2wx0]], [[2wx1]] – hDiUBB+mitogen-activated protein kinase<br /> | ||
| - | **[[3jsv]], [[2zvn]], [[2zvo]] – hDiUBB+NF-κ-b essential modulator<br /> | ||
| - | **[[2kde]], [[2kdf]] – DiUBB+26S proteasome non-ATPase regulatory subunit – NMR<br /> | ||
| - | **[[3a1q]] – mDiUBB+UBB interaction motif-containing protein <br /> | ||
| - | **[[3dvg]], [[3dvn]] – hDiUBB+IGG1 fab light&heavy chains<br /> | ||
| - | **[[2znv]] – mDiUBB+hAMSH-like protease<br />[[3ptf]] – hDiUBB + UBB conjugating enzyme E2<br /> | ||
| - | **[[3b08]], [[3b0a]] – hDiUBB + HOIL-1<br /> | ||
| - | **[[3u30]] – hDiUBB + antibody<br /> | ||
| - | **[[4hxd]] – hDiUBB + RNA polymerase <br /> | ||
| - | **[[5o6t]] – hDiUBB + E3 UBB protein ligase XIAP<br /> | ||
| - | **[[2lvp]], [[2lvq]] – hDiUBB + E3 UBB protein ligase - NMR<br /> | ||
| - | **[[4ksk]], [[4ksl]] – hDiUBB + Fam105B<br /> | ||
| - | **[[4fjv]] – hDiUBB + UBB thiolesterase <br /> | ||
| - | **[[4bos]] – hDiUBB + UBB thiolesterase + OTUD2<br /> | ||
| - | **[[4s1z]] – hDiUBB + ZranB1<br /> | ||
| - | **[[5e6j]] – hDiUBB (mutant) + replicase polyprotein<br /> | ||
| - | **[[2n13]] – hDiUBB + myosin peptide - NMR<br /> | ||
| - | **[[3wwq]] – hDiUBB + FAAP20 peptide <br /> | ||
| - | **[[5ohp]], [[5ohn]], [[5ohk]] – hDiUBB + USP30<br /> | ||
| - | |||
| - | * Ubiquitin trimer | ||
| - | |||
| - | **[[5go7]], [[5gok]], [[5jby]], [[5jbv]] – hTriUBB <br /> | ||
| - | **[[3zlz]], [[5o44]] – hTriUBB (mutant) <br /> | ||
| - | **[[4boz]] – hTriUBB + UBB thiolesterase <br /> | ||
| - | **[[3vuw]], [[3vux]], [[3vuy]] – hTriUBB + TNF α-induced proitein <br /> | ||
| - | |||
| - | * Ubiquitin tetramer | ||
| - | |||
| - | **[[5go8]] – hTetraUBB <br /> | ||
| - | **[[3tmp]] – hTetraUBB + deubiquitinase<br /> | ||
| - | **[[3alb]], [[3hm3]], [[2o6v]], [[1f9j]], [[1tbe]] – tetra-hUBB<br /> | ||
| - | **[[3zni]] – hTetraUBB + E3 UBB protein ligase + tyrosine protein kinase + UBB conjugating enzyme E2<br /> | ||
| - | **[[5b83]] – hTetraUBB + optineurin<br /> | ||
| - | |||
| - | * Polyubiquitin | ||
| - | |||
| - | **[[4zpz]] – hPolyUBB-B (mutant)<br /> | ||
| - | **[[5af4]], [[4xyz]] – hPolyUBB-C <br /> | ||
| - | **[[5af5]], [[5nl4]] – hPolyUBB-C (mutant)<br /> | ||
| - | **[[5x3o]], [[3x3m]] – hPolyUBB-B + d-ubiquitin <br /> | ||
| - | **[[3phd]] – hPolyUBB+histone deacetylase 6 | ||
| - | **[[3znh]] – hPolyUBB-B + UBB thioesterase<br /> | ||
| - | **[[4uf6]] – hPolyUBB-B + UCH-L5 + NF-κ-b-related protein<br /> | ||
| - | **[[5vf0]] – hPolyUBB-B + RAD18 - NMR<br /> | ||
| - | **[[5vey]] – hPolyUBB-B + RNF169 + Histone H2A-H2B - NMR<br /> | ||
| - | **[[5n38]] , [[5n2w]] – hPolyUBB-B + E3 UBB protein ligase PARKIN<br /> | ||
| - | **[[5mnj]] – hPolyUBB-B + E3 UBB protein ligase MDM2 + UBCH5B<br /> | ||
| - | **[[5l8w]] – hPolyUBB-B + WD repeat-containing protein 48 + USP12<br /> | ||
| - | **[[5l8h]] – hPolyUBB-B + WD repeat-containing protein 48 + USP46<br /> | ||
| - | **[[5kyf]], [[5kye]], [[5kyd]], [[5kyc]] – hPolyUBB-B + USP7<br /> | ||
| - | **[[3znz]] – hPolyUBB-C + otulin<br /> | ||
| - | **[[4jqw]] – hPolyUBB-C + NOD1 CARD<br /> | ||
| - | **[[4k1r]] – hPolyUBB-C + SST2<br /> | ||
| - | **[[5oe7]] – hPolyUBB-C + otulin<br /> | ||
| - | |||
| - | * Ubiquitin monomer bound to protein | ||
| - | |||
| - | **[[3ofi]] – hUBB+insulin protease | ||
| - | **[[3n3k]], [[3ifw]], [[3kvf]], [[3kw5]], [[3irt]], [[3mtn]], [[3ihp]], [[3v6c]], [[3v6e]]– hUBB (mutant)+hUBB carboxyl-terminal esterase catalytic domain<br /> | ||
| - | **[[3i3t]], [[2ibi]], [[2ayo]], [[1nbf]], [[2wdt]], [[4i6l]], [[4i6n]], [[4ig7]], [[5l8h]], [[5jtj]], [[5cvm]] - hUBB+hUBB carboxyl-terminal hydrolase catalytic domain<br /> | ||
| - | **[[5l8w]], [[5cvn]], [[5cvo]] – hUBB + UBB carboxy terminal hydrolase 12 + WD repeat containing protein 48<br /> | ||
| - | **[[2khw]] – hUBB+immunoglobulin G-binding protein G<br /> | ||
| - | **[[1yx5]], [[1yx6]] - hUBB+26S proteasome non-ATPase regulatory subunit – NMR<br /> | ||
| - | **[[2k6d]] – hUBB+SH3 domain-containing kinase-binding protein – NMR<br /> | ||
| - | **[[2z59]] – hUBB+mProtein Adhesion-regulating molecule 1<br /> | ||
| - | **[[2jy6]] – hUBB+hUbiquilin – NMR<br /> | ||
| - | **[[3by4]], [[3c0r]] – hUBB+yUBB thioesterase<br /> | ||
| - | **[[2hth]] – hUBB+vacuolar protein sorting protein<br /> | ||
| - | **[[1s1q]] – hUBB+tumor susceptibility gene 101 protein<br /> | ||
| - | **[[1q5w]] – hUBB+NPL4 zinc-fingers<br /> | ||
| - | **[[2k8b]], [[2k8c]] – hUBB+phospholipase A2-activating protein fragment<br /> | ||
| - | **[[2ktf]] – hUBB+hDNA polymerase IOTA<br /> | ||
| - | **[[2l0f]] – hUBB (mutant)+hDNA polymerase IOTA<br /> | ||
| - | **[[2kwu]], [[2kwv]] - hUBB+mDNA polymerase IOTA – mouse<br /> | ||
| - | **[[2l0t]] – hUBB+signal transducing adapter molecule 2<br /> | ||
| - | **[[3o65]] – hUBB+ataxin-3-like protein josephin domain<br /> | ||
| - | **[[3oj3]] – hUBB+tumor necrosis factor -induced protein 3<br /> | ||
| - | **[[3phd]] – hPolyUBB+histone deacetylase 6<br /> | ||
| - | **[[3znh]] – hPolyUBB-B + UBB thioesterase<br /> | ||
| - | **[[4uf6]] – hPolyUBB-B + UCH-L5 + NF-κ-b-related protein<br /> | ||
| - | **[[3znz]] – hPolyUBB-C + otulin<br /> | ||
| - | **[[4jqw]] – hPolyUBB-C + NOD1 CARD<br /> | ||
| - | **[[4k1r]] – hPolyUBB-C + SST2<br /> | ||
| - | **[[3prm]], [[3prp]] – hUBB+protein L<br /> | ||
| - | **[[3pt2]] – hUBB+RNA polymerase OTU domain<br /> | ||
| - | **[[5v5i]], [[5v5h]], [[5v5g]] - hUBB+RNA polymerase L<br /> | ||
| - | **[[2rr9]] – hUBB + Uimc1<br /> | ||
| - | **[[1fxt]], [[3oj4]], [[3ugb]], [[5dfl]], [[3k9p]], [[3a33]] – hUBB + UBB conjugating enzyme E2<br /> | ||
| - | **[[2fuh]] – hUBB + UBB conjugating enzyme E2 - NMR<br /> | ||
| - | **[[4auq]] – hUBB + UBB conjugating enzyme E2 + livin<br /> | ||
| - | **[[2g45]] – hUBB + isopeptidase T<br /> | ||
| - | **[[2den]] – hUBB + immunoglobulin G binding protein/ubiquitin-like protein 7 - NMR<br /> | ||
| - | **[[2oob]], [[2qho]] – hUBB + E3 UBB protein ligase<br /> | ||
| - | **[[2lvo]] – hUBB + E3 UBB protein ligase - NMR<br /> | ||
| - | **[[2j7q]] – hUBB + MCMV tegument protein<br /> | ||
| - | **[[4dhj]], [[4dhz]] – hUBB (mutant) + UBB thiolesterase + UBB aldehyde <br /> | ||
| - | **[[3rul]] – hUBB + dalvancin<br /> | ||
| - | **[[3vfk]] – hUBB + monodechloro-teicoplanin <br /> | ||
| - | **[[4ium]], [[4wur]], [[4mm3]] – hUBB+ papain-like protease<br /> | ||
| - | **[[2lz6]], [[2mcn]] – hUBB + CD2-associated protein<br /> | ||
| - | **[[2mbh]] – hUBB + Kreuppel-like factor<br /> | ||
| - | **[[3tbl]] – hUBB + PCNA<br /> | ||
| - | **[[3vht]] – hUBB + GFP<br /> | ||
| - | **[[4jio]] – hUBB + yBRO1<br /> | ||
| - | **[[5af6]] – hUBB + TRABID<br /> | ||
| - | **[[4un2]] – hUBB + Dsk2 peptide<br /> | ||
| - | **[[4msq]], [[4msm]] – hUBB + AMSH-like protease<br /> | ||
| - | **[[5ln1]] – hUBB + RPN10<br /> | ||
| - | **[[5v1z]], [[5v1y]] – hUBB + RPN13 + RPN2<br /> | ||
| - | **[[5jp3]] – hUBB + xanthomonas outer protein<br /> | ||
| - | **[[5lrw]] – hUBB (mutant)+ OUT domain containing protein 7B<br /> | ||
| - | **[[5lrx]] – hUBB (mutant)+ OUT domain containing protein 7C<br /> | ||
| - | **[[5kgf]] – hUBB + nucleosome - Cryo EM<br /> | ||
| - | **[[2nbv]] – hUBB + proteasomal UBB receptor - NMR<br /> | ||
| - | **[[5jg6]] – hUBB + anaphase promoting complex subunit 11<br /> | ||
| - | **[[6eqi]] – hUBB + NB696 + PINK1<br /> | ||
| - | **[[5ohv]] – hUBB + K33-specific affimer<br /> | ||
| - | **[[5af6]] – hUBB + TRABID<br /> | ||
| - | **[[4un2]] – hUBB + Dsk2 peptide<br /> | ||
| - | **[[4msq]], [[4msm]] – hUBB + AMSH-like protease<br /> | ||
| - | **[[4m0w]] – bUBB + replicase polyprotein<br /> | ||
| - | **[[1uzx]] – bUBB+VPS23 UEV<br /> | ||
| - | **[[2hd5]] - bUBB+hUBB carboxyl-terminal hydrolase catalytic domain<br /> | ||
| - | **[[3ldz]] – bUBB+signal transducing adapter molecule<br /> | ||
| - | **[[1v80]], [[1v81]] – bUBB/L40 ribosomal protein fusion - NMR<br /> | ||
| - | **[[2dx5]], [[1p3q]] - bUBB+vacuolar protein sorting protein<br /> | ||
| - | **[[2c7m]], [[2c7n]], [[2fid]], [[2fif]] – bUBB+RAB guanine nucleotide exchange factor<br /> | ||
| - | **[[2d3g]] – bUBB+HRS-UIM<br /> | ||
| - | **[[1wrd]] – bUBB+TOM1 GAT domain<br /> | ||
| - | **[[1wr6]], [[1yd8]] - bUBB+GGA3 GAT domain<br /> | ||
| - | **[[1uzx]] – bUBB+VPS23 UEV<br /> | ||
| - | **[[2kdi]] – yUBB/UIM fusion <br /> | ||
| - | **[[2jt4]] – yUBB fragment+cytoskeleton assembly control protein<br /> | ||
| - | **[[1q0w]] - yUBB+vacuolar protein sorting protein<br /> | ||
| - | **[[2g3q]] – yUBB+EDE1 UBA<br /> | ||
| - | **[[1wr1]] – yUBB+DSK2P UBA<br /> | ||
| - | **[[1otr]] – yUBB+CUE2<br /> | ||
| - | **[[2l00]] – yUBB + Zfand5<br /> | ||
| - | **[[4q5h]], [[4q5e]] – yUBB + UBB conjugating enzyme E2 + OspG<br /> | ||
| - | **[[4nql]] – mUBB + AMSH-like protease<br /> | ||
| - | |||
| - | * Ubiquitin complex with ubiquitination enzymes | ||
| - | |||
| - | **[[1fxt]], [[3oj4]], [[3ugb]], [[5dfl]], [[3k9p]], [[3a33]], [[5ulf]], [[5tut]] – hUBB + UBB conjugating enzyme E2<br /> | ||
| - | **[[5bnb]], [[2kjh]], [[1zgu]] – hUBB (mutant) + UBB conjugating enzyme E2<br /> | ||
| - | **[[5edv]], [[4whv]], [[5ait]], [[5aiu]], [[3jvz]], [[3jw0]], [[5udh]], [[5tte]] – hUBB + UBB conjugating enzyme E2 + E3 UBB-protein ligase<br /> | ||
| - | **[[3cmm]] – yUBB + UBB activating enzyme E1<br /> | ||
| - | **[[5knl]] – yUBB (mutant) + UBB activating enzyme E1 + UBB conjugating enzyme E2 <br /> | ||
| - | **[[5tr4]] – bUBB + UBB activating enzyme E1<br /> | ||
| - | **[[2gmi]] – hUBB + UBB conjugating enzyme E2<br /> | ||
| - | **[[5d0k]], [[5d0m]], [[5ulk]], [[5ulh]] – hUBB + UBB conjugating enzyme E2 + RNF165<br /> | ||
| - | **[[4xkl]] – hUBB + NDP52<br /> | ||
| - | **[[4zfr]], [[4zft]] – hUBB + SST2<br /> | ||
| - | **[[5o76]] – hUBB + Zap70 peptide + E3-UBB-protein ligase CBL<br /> | ||
| - | **[[2fuh]] – hUBB + UBB conjugating enzyme E2 - NMR<br /> | ||
| - | **[[4auq]] – hUBB + UBB conjugating enzyme E2 + livin<br /> | ||
| - | **[[4q5h]], [[4q5e]] – yUBB + UBB conjugating enzyme E2 + OspG<br /> | ||
| - | |||
| - | * Ubiquitin + ions | ||
| - | **[[3h1u]] – bUBB+Cd<br /> | ||
| - | **[[3ehv]], [[3eec]], [[3efu]] – hUBB+ions<br /> | ||
| - | **[[3n30]], [[4k7s]], [[4k7u]], [[4k7w]] – hUBB+Zn<br /> | ||
| - | **[[3n32]] – hUBB+Pt<br /> | ||
| - | }} | ||
==References== | ==References== | ||
<references /> | <references /> | ||
[[Category:Topic Page]] | [[Category:Topic Page]] | ||
Current revision
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References
- ↑ Li W, Ye Y. Polyubiquitin chains: functions, structures, and mechanisms. Cell Mol Life Sci. 2008 Aug;65(15):2397-406. PMID:18438605 doi:10.1007/s00018-008-8090-6
- ↑ Hershko A, Ciechanover A. The ubiquitin system. Annu Rev Biochem. 1998;67:425-79. PMID:9759494 doi:http://dx.doi.org/10.1146/annurev.biochem.67.1.425
- ↑ Neefjes J, Groothuis TA, Dantuma NP. [The 2004 Nobel Prize in Chemistry for the discovery of ubiquitin-mediated protein degradation]. Ned Tijdschr Geneeskd. 2004 Dec 25;148(52):2579-82 PMID:15646859
- ↑ Paul S. Dysfunction of the ubiquitin-proteasome system in multiple disease conditions: therapeutic approaches. Bioessays. 2008 Nov;30(11-12):1172-84. doi: 10.1002/bies.20852. PMID:18937370 doi:http://dx.doi.org/10.1002/bies.20852
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