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Ubiquitin

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[[Image:1d3z.png|left|200px|thumb|NMR Structure of Ubiquitin, [[1d3z]]]]
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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' >
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{{STRUCTURE_1d3z| PDB=1d3z | SIZE=300| SCENE=Ubiquitin/Cv/1 |right|CAPTION=Ubiquitin, [[1d3z]] }}
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== Function ==
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[[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. UBB+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 />
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* [[Ubiquitin Structure & Function]]<br />
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* [[Ubiquitin and Ubiquitination]]<br />
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* [[Ubiquitin salt bridge discussion]]<br />
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* [[Ubiquitin chains]].
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[[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. UBB+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. At least 4 UBB molecules are needed to tag a protein for the proteasome. The images at the left and at the right correspond to one representative Ubiquitin, ''i.e.'' the NMR structure of human Ubiquitin ([[1d3z]]).
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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>.
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{{TOC limit|limit=2}}
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==Additional Resources==
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See also:
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*[[Tumor susceptibility gene 101]]
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*[[SUMO]]
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== Disease ==
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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>.
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== 3D Structures of Ubiquitin ==
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==[[3D structures of ubiquitin]]==
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</StructureSection>
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==References==
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<references />
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[[Category:Topic Page]]
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=== Ubiquitin ===
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[[2kn5]], [[2klg]], [[2jzz]], [[2pe9]], [[2pea]], [[1g6j]], [[1d3z]] – hUBB – NMR
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[[2ojr]], [[2nr2]], [[2fcq]], [[1ubi]], [[1ubq]] - hUBB
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[[2zcb]], [[2gbj]], [[2gbk]], [[2gbm]], [[2gbn]], [[2gbr]], [[2fcm]], [[2fcn]], [[2fcs]], [[1yiw]], [[1yj1]], [[1sif]], [[1ogw]] - hUBB (mutant)
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[[1c3t]], [[1ud7]] - hUBB (mutant) - NMR
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[[1gjz]] – hUBB N-terminal – NMR
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[[1e0q]] - hUBB N-terminal (mutant) – NMR
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[[2k39]] – UBB – ''Xenopus laevis'' – NMR
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[[2jwz]], [[1zw7]] – yUBB (mutant) – yeast
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[[1cmx]] – yUBB (modified)
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[[2zcc]] – bUBB - bovine
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=== Ubiquitin+UBB-activating enzymes ===
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[[3cmm]] – yUBB+E1
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[[3k9p]], [[3a33]] – hUBB+E2
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[[2gmi]] - hUBB+E2+MMS2
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[[2kjh]], [[1zgu]] – hUBB (mutant)+E2
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[[3jvz]], [[3jw0]] – hUBB+E2+E3
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=== Ubiquitin+1 mutant ===
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[[2kx0]] – hUBB+1 – human – NMR
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[[3k9o]] – hUBB+1+E2
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=== Ubiquitin dimer ===
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[[2xk5]], [[3nob]], [[2xew]], [[3h7p]], [[3h7s]], [[2w9n]], [[2jf5]] – hDiUBB
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[[3m3j]], [[1aar]] – bDiUBB
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[[2bgf]] – hDiUBB – chemical relaxation
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=== Ubiquitin tetramer ===
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[[3alb]], [[3hm3]], [[2o6v]], [[1f9j]], [[1tbe]] – tetra-hUBB
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=== Ubiquitin bound to protein ===
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[[3ofi]] – hUBB+insulin protease
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[[3n3k]], [[3ifw]], [[3kvf]], [[3kw5]], [[3irt]], [[3mtn]], [[3ihp]] – hUBB (mutant)+hUBB carboxyl-terminal esterase catalytic domain
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[[3i3t]], [[2ibi]], [[2ayo]], [[1nbf]] - hUBB+hUBB carboxyl-terminal hydrolase catalytic domain
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[[2hd5]] - bUBB+hUBB carboxyl-terminal hydrolase catalytic domain
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[[3ldz]] – bUBB+signal transducing adapter molecule
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[[2khw]] – hUBB+immunoglobulin G-binding protein G
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[[2kdi]] – yUBB/UIM fusion
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[[1v80]], [[1v81]] – bUBB/L40 ribosomal protein fusion - NMR
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[[1yx5]], [[1yx6]] - hUBB+26S proteasome non-ATPase regulatory subunit – NMR
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[[2k6d]] – hUBB+SH3 domain-containing kinase-binding protein – NMR
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[[2z59]] – hUBB+mProtein Adhesion-regulating molecule 1
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[[2jy6]] – hUBB+hUbiquilin – NMR
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3by4, 3c0r – hUBB+yUBB thioesterase
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2jt4 – yUBB fragment+cytoskeleton assembly control protein
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2hth – hUBB+vacuolar protein sorting protein
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2dx5, 1p3q - bUBB+vacuolar protein sorting protein
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1q0w - yUBB+vacuolar protein sorting protein
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2g3q – yUBB+EDE1 UBA
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2c7m, 2c7n, 2fid, 2fif – bUBB+RAB guanine nucleotide exchange factor
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2d3g – bUBB+HRS-UIM
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1wrd – bUBB+TOM1 GAT domain
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1wr6, 1yd8 - bUBB+GGA3 GAT domain
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1wr1 – yUBB+DSK2P UBA
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1s1q – hUBB+tumor susceptibility gene 101 protein
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1q5w – hUBB+NPL4 zinc-fingers
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1uzx – bUBB+VPS23 UEV
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1otr – yUBB+CUE2
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=== Ubiquitin dimer bound to protein ===
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3a9j, 3a9k, 2wwz, 2wx0, 2wx1 – hDiUBB+mitogen-activated protein kinase
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3jsv, 2zvn, 2zvo – hDiUBB+NF-κ-b essential modulator
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2kde, 2kdf – DiUBB+26S proteasome non-ATPase regulatory subunit – NMR
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3a1q – mDiUBB+UBB interaction motif-containing protein – mouse
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3dvg, 3dvn – hDiUBB+IGG1 fab light&heavy chains
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2znv – mDiUBB+hAMSH-like protease
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=== Ubiquitin + ions ===
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3h1u – bUBB+Cd
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3ehv, 3eec, 3efu – hUBB+ions
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Current revision

Human ubiquitin (green) complex with ubiquitin-conjugating enzyme E2 (deep sky blue), 3k9p

Drag the structure with the mouse to rotate

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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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