Summary: Ubiquitin family
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Ubiquitin Edit Wikipedia article
|A diagram of ubiquitin. The seven lysine sidechains are shown in orange.|
Ubiquitin is a small regulatory protein that has been found in almost all tissues (ubiquitously) of eukaryotic organisms. It directs proteins to compartments in the cell, including the proteasome which destroys and recycles proteins.
Ubiquitin tags can also direct proteins to other locations in the cell, where they control other protein and cell mechanisms.
Ubiquitin (originally, ubiquitous immunopoietic polypeptide) was first identified in 1975 as an 8.5-kDa protein of unknown function expressed in all eukaryotic cells. The basic functions of ubiquitin and the components of the ubiquitination pathway were elucidated in the early 1980s at Fox Chase Cancer Center by Aaron Ciechanover, Avram Hershko, and Irwin Rose for which the Nobel Prize in Chemistry was awarded in 2004.
The ubiquitylation system was initially characterised as an ATP-dependent proteolytic system present in cellular extracts. A heat-stable polypeptide present in these extracts, ATP-dependent proteolysis factor 1 (APF-1), was found to become covalently attached to the model protein substrate lysozyme in an ATP- and Mg2+-dependent process. Multiple APF-1 molecules were linked to a single substrate molecule by an isopeptide linkage, and conjugates were found to be rapidly degraded with the release of free APF-1. Soon after APF-1-protein conjugation was characterised, APF-1 was identified as ubiquitin. The carboxyl group of the C-terminal glycine residue of ubiquitin (Gly76) was identified as the moiety conjugated to substrate lysine residues.
 The protein
|Number of residues||76|
|Molecular mass||8564.8448 Da|
|Isoelectric point (pI)||6.79|
|Gene names||RPS27A (UBA80, UBCEP1), UBA52 (UBCEP2), UBB, UBC|
Ubiquitin is a small protein that exists in all eukaryotic cells. It performs its myriad functions through conjugation to a large range of target proteins. A variety of different modifications can occur. The ubiquitin protein itself consists of 76 amino acids and has a molecular mass of about 8.5 kDa. Key features include its C-terminal tail and the 7 lysine residues. It is highly conserved among eukaryotic species: Human and yeast ubiquitin share 96% sequence identity. The human ubiquitin sequence in one-letter code (lysine residues in bold):
Ubiquitin is encoded in mammals by 4 different genes. UBA52 and RPS27A genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27a, respectively. The UBB and UBC genes code for polyubiquitin precursor proteins.
No ubiquitin and ubiquitination machinery are known to exist in prokaryotes. However, ubiquitin is believed to have descended from prokaryotic proteins similar to ThiS or MoaD. These prokaryotic proteins, despite having little sequence identity (ThiS has 14% identity to ubiquitin), share the same protein fold. These proteins also share sulfur chemistry with ubiquitin. MoaD, which is involved in molybdenum cofactor biosynthesis, interacts with MoeB, which acts like an E1 ubiquitin-activating enzyme for MoaD, strengthening the link between these prokaryotic proteins and the ubiquitin system. A similar system exists for ThiS, with its E1-like enzyme ThiF. It is also believed that the Saccharomyces cerevisiae protein Urm-1, a ubiquitin-related modifier, is a "molecular fossil" that connects the evolutionary relation with the prokaryotic ubiquitin-like molecules and ubiquitin.
 Ubiquitination (ubiquitylation)
Ubiquitination is an enzymatic, protein post-translational modification (PTM) process in which the carboxylic acid of the terminal glycine from the di-glycine motif in the activated ubiquitin forms an amide bond to the epsilon amine of the lysine in the modified protein.
The process of marking a protein with ubiquitin (ubiquitylation or ubiquitination) consists of a series of steps:
- Activation of ubiquitin: Ubiquitin is activated in a two-step reaction by an E1 ubiquitin-activating enzyme in a process requiring ATP as an energy source. The initial step involves production of a ubiquitin-adenylate intermediate. The second step transfers ubiquitin to the E1 active site cysteine residue, with release of AMP. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.
- Transfer of ubiquitin from E1 to the active site cysteine of a ubiquitin-conjugating enzyme E2 via a trans(thio)esterification reaction. Mammalian genomes contain 30-40 UBCs.
- The final step of the ubiquitylation cascade creates an isopeptide bond between a lysine of the target protein and the C-terminal glycine of ubiquitin. In general, this step requires the activity of one of the hundreds of E3 ubiquitin-protein ligases (often termed simply ubiquitin ligase). E3 enzymes function as the substrate recognition modules of the system and are capable of interaction with both E2 and substrate.
In the ubiquitination cascade, E1 can bind with dozens of E2s, which can bind with hundreds of E3s in a hierarchical way. Other ubiquitin-like proteins (ULPs) are also modified via the E1âE2âE3 cascade.
E3 enzymes possess one of two domains:
- The HECT (Homologous to the E6-AP Carboxyl Terminus) domain
- The RING (Really Interesting New Gene) domain (or the closely related U-box domain)
Transfer can occur in two ways:
- Directly from E2, catalysed by RING domain E3s.
- Via an E3 enzyme, catalysed by HECT domain E3s. In this case, a covalent E3-ubiquitin intermediate is formed before transfer of ubiquitin to the substrate protein.
The anaphase-promoting complex (APC) and the SCF complex (for Skp1-Cullin-F-box protein complex) are two examples of multi-subunit E3s involved in recognition and ubiquitination of specific target proteins for degradation by the proteasome.
 Function and variety of ubiquitin modifications
Following addition of a single ubiquitin moiety to a protein substrate (monoubiquitination), further ubiquitin molecules can be added to the first, yielding a polyubiquitin chain. In addition, some substrates are modified by addition of ubiquitin molecules to multiple lysine residues in a process termed multiubiquitination. As discussed, ubiquitin possesses a total of 7 lysine residues. Historically the original type of ubiquitin chains identified were those linked via lysine 48. However, more recent work has uncovered a wide variety of linkages involving all possible lysine residues and in addition chains assembled on the N-terminus of a ubiquitin molecule ("linear chains"). Work published in 2007 has demonstrated the formation of branched ubiquitin chains containing multiple linkage types. "Atypical" (non-lysine 48-linked) ubiquitin chains have been discussed in a review by Ikeda & Dikic.
The ubiquitination system functions in a wide variety of cellular processes, including:
- Antigen processing
- Biogenesis of organelles
- Cell cycle and division
- DNA transcription and repair
- Differentiation and development
- Immune response and inflammation
- Neural and muscular degeneration
- Morphogenesis of neural networks
- Modulation of cell surface receptors, ion channels and the secretory pathway
- Response to stress and extracellular modulators
- Ribosome biogenesis
- Viral infection
The most studied polyubiquitin chains - lysine48-linked - target proteins for destruction, a process known as proteolysis. At least four ubiquitin molecules must be attached to lysine residues on the condemned protein in order for it to be recognised by the 26S. Lysine 63 linked chains direct the localization of proteins. Monoubiquitylation of proteins also targets the localization of proteins -proteasome. The proteasome is a barrel-shaped structure with two chambers, within which proteolysis occurs. Proteins are rapidly degraded into small peptides (usually 3-24 amino acid residues in length). Ubiquitin molecules are cleaved off the protein immediately prior to destruction and are recycled for further use. Although the majority of proteasomal substrates are ubiquitinated, there are examples of non-ubiquitinated proteins targeted to the proteasome.
Ubiquitin can also mark transmembrane proteins (for example, receptors) for removal from membranes and fulfill several signaling roles within the cell. Cell-surface transmembrane molecules that are tagged with ubiquitin are often monoubiquitinated, and this modification alters the subcellular localization of the protein, often targeting the protein for destruction in lysosomes.
 Other chain types
Ubiquitin has seven lysine residues that may serve as points of polyubiquitylation, they are; K48, K63, K6, K11, K27, K29 and K33. These different linkages may define unique signals that are recognized by ubiquitin-binding proteins, which have Ubiquitin interacting motifs (UIMs) that bind to ubiquitin. It is thought that the different linkages are recognized by proteins that are specific for the unique topologies that are intrinsic to the linkage. One example, is the K63 linkage, which is known to be involved in DNA damage recognition of DNA double-strand breaks. The K63 linkage appears to be placed on the H2AX histone by the E2/E3 ligase pair, Ubc13-Mms2/RNF168. This K63 chain appears to recruit RAP80, which contains a UIM, and RAP80 then helps localize BRCA1. This pathway will eventually recruit the necessary proteins for Homologous Recombination Repair.
 Disease associations
The ubiquitin pathway has been implicated in the pathogenesis of several diseases and genetic disorders:
- Neurodegenerative disorders: Transcript variants encoding different isoforms of ubiquilin-1 are found in lesions associated with Alzheimer's and Parkinson's disease. Higher levels of ubiquilin in the brain have been shown to decrease malformation of amyloid precursor protein (APP), which plays a key role in triggering Alzheimer's disease. Conversely, lower levels of ubiquilin-1 in the brain have been associated with increased malformation of APP. A frameshift mutation in ubiquitin B can result in a truncated peptide missing the C-terminal glycine. This abnormal peptide, known as UBB+1, has been shown to accumulate selectively in Alzheimer's disease and other tauopathies.
- Angelman syndrome is caused by a disruption of UBE3A, which encodes a ubiquitin ligase (E3) enzyme termed E6-AP.
- Von Hippel-Lindau syndrome involves disruption of a ubiquitin E3 ligase termed the VHL tumor suppressor, or VHL gene.
- Fanconi anemia: Eight of the thirteen identified genes whose disruption can cause this disease encode proteins that form a large ubiquitin ligase (E3) complex.
- 3-M syndrome is an autosomal-recessive growth retardation disorder associated with mutations of the Cullin7 E3 ubiquitin ligase.
 Diagnostic use
Immunohistochemistry using antibodies to ubiquitin can identify abnormal accumulations of this protein inside cells, indicating a disease process. These protein accumulations are referred to as inclusion bodies (which is a general term for any microscopically visible collection of abnormal material in a cell). Examples include:
- Neurofibrillary tangles in Alzheimer's disease
- Lewy body in Parkinson's disease
- Pick bodies in Pick's disease
- Inclusions in motor neuron disease and Huntington's Disease
- Mallory bodies in alcoholic liver disease
- Rosenthal fibers in astrocytes
 Ubiquitin-like modifiers
Although ubiquitin is the most well understood post-translation modifier, there is a growing family of ubiquitin-like proteins (UBLs) that modify cellular targets in a pathway that is parallel to, but distinct from, that of ubiquitin. Known UBLs include: small ubiquitin-like modifier (SUMO), ubiquitin cross-reactive protein (UCRP, also known as interferon-stimulated gene-15 ISG15), ubiquitin-related modifier-1 (URM1), neuronal-precursor-cell-expressed developmentally downregulated protein-8 (NEDD8, also called Rub1 in S. cerevisiae), human leukocyte antigen F-associated (FAT10), autophagy-8 (ATG8) and -12 (ATG12), Fau ubiquitin-like protein (FUB1), MUB (membrane-anchored UBL), ubiquitin fold-modifier-1 (UFM1) and ubiquitin-like protein-5 (UBL5, which is but known as homologous to ubiquitin-1 [Hub1] in S. pombe). Whilst these proteins share only modest primary sequence identity with ubiquitin, they are closely related three-dimensionally. For example, SUMO shares only 18% sequence identity, but contain the same structural fold. This fold is called "ubiquitin fold" or sometimes called ubiquiton fold. FAT10 and UCRP contain two. This compact globular beta-grasp fold is found in ubiquitin, UBLs, and proteins that comprise a ubiquitin-like domain e.g. the S. cerevisiae spindle pole body duplication protein, Dsk2, and NER protein, Rad23, both contain N-terminal ubiquitin domains.
These related molecules have novel functions and influence diverse biological processes. There is also cross-regulation between the various conjugation pathways since some proteins can become modified by more than one UBL, and sometimes even at the same lysine residue. For instance, SUMO modification often acts antagonistically to that of ubiquitination and serves to stabilize protein substrates. Proteins conjugated to UBLs are typically not targeted for degradation by the proteasome, but rather function in diverse regulatory activities. Attachment of UBLs might alter substrate conformation, affect the affinity for ligands or other interacting molecules, alter substrate localization and influence protein stability.
UBLs are structurally similar to ubiquitin and are processed, activated, conjugated and released from conjugates by enzymatic steps that are similar to the corresponding mechanisms for ubiquitin. UBLs are also translated with C-terminal extensions that are processed to expose the invariant C-terminal LRGG. These modifiers have their own specific E1 (activating), E2 (conjugating) and E3 (ligating) enzymes that conjugate the UBLs to intracellular targets. These conjugates can be reversed by UBL-specific isopeptidases that have similar mechanisms to that of the deubiquitinating enzymes.
Within some species, the recognition and destruction of sperm mitochondria through a mechanism involving ubiquitin is responsible for sperm mitochondria's disposal after fertilization occurs.
 Prokaryotic ubiquitin-like protein (Pup)
Recently, a functional analog of ubiquitin has been found in prokaryotes. Prokaryotic ubiquitin-like protein (Pup) serves the same function (targeting proteins for degradations), although the enzymology of ubiquitylation and pupylation is different. In contrast to the three-step reaction of ubiquitylation, pupylation requires two steps, therefore only two enzymes are involved in pupylation.
 Human proteins containing ubiquitin domain
ANUBL1; BAG1; BAT3; DDI1; DDI2; FAU; HERPUD1; HERPUD2; HOPS; IKBKB; ISG15; LOC391257; MIDN; NEDD8; OASL; PARK2; RAD23A; RAD23B; RPS27A; SACS; 8U SF3A1; SUMO1; SUMO2; SUMO3; SUMO4; TMUB1; TMUB2; UBA52; UBB; UBC; UBD; UBFD1; UBL4; UBL4A; UBL4B; UBL7; UBLCP1; UBQLN1; UBQLN2; UBQLN3; UBQLN4; UBQLNL; UBTD1; UBTD2; UHRF1; UHRF2;
 Related proteins
 Prediction of ubiquitination
Currently available prediction programs are:
- UbiPred is a SVM-based prediction server using 31 physicochemical properties for predicting ubiquitylation sites.
- UbPred is a random forest-based predictor of potential ubiquitination sites in proteins. It was trained on a combined set of 266 non-redundant experimentally verified ubiquitination sites available from our experiments and from two large-scale proteomics studies.
- CKSAAP_UbSite is SVM-based prediction which employs the composition of k-spaced amino acid pairs surrounding a query site (i.e. any lysine in a query sequence) as input, usess the same dataset as UbPred.
 See also
- SUMO protein
- SUMO enzymes
- Ubiquitin ligase
- Prokaryotic ubiquitin-like protein
- JUNQ and IPOD
- "The Nobel Prize in Chemistry 2004". Nobelprize.org. Retrieved 2010-10-16.
- "The Nobel Prize in Chemistry 2004: Popular Information". Nobelprize.org. Retrieved 2010-10-16.
- Kimura Y, Tanaka K (2010). "Regulatory mechanisms involved in the control of ubiquitin homeostasis". J Biochem 147 (6): 793â8. doi:10.1093/jb/mvq044. PMID 20418328.
- Wang, Chunyu; Xi, Jun; Begley, Tadhg P.; Nicholson, Linda K. (2001). "Solution structure if ThiS and implications for the evolutionary roots of ubiquitin". Nature Structural Biology 8 (1): 47â51. doi:10.1038/83041. PMID 11135670.
- Lake, Michael W.; Wuebbens, Margot M.; Rajagopalan, K. V.; Schindelin, Hermann (2001). "Mechanism of ubiquitin activation revealed by the structure of a bacterial MoeBâMoaD complex". Nature 414 (6861): 325â329. doi:10.1038/35104586. PMID 11713534.
- Hochstrasser, Mark (2009). "Origin and Function of Ubiquitin-like Protein Conjugation". Nature 458 (7237): 422â429. doi:10.1038/nature07958. PMC 2819001. PMID 19325621.
- Xu, P; Peng (May 2008). "Characterization of Polyubiquitin Chain Structure by Middle-down Mass Spectrometry". Analytical chemistry 80 (9): 3438â44. doi:10.1021/ac800016w. ISSN 0003-2700. PMC 2663523. PMID 18351785.
- Peng, J; Schwartz; Elias; Thoreen; Cheng; Marsischky; Roelofs; Finley et al. (Aug 2003). "A proteomics approach to understanding protein ubiquitination". Nature Biotechnology 21 (8): 921â6. doi:10.1038/nbt849. ISSN 1087-0156. PMID 12872131. Citation uses old-style implicit et al. for authors
- Kirisako, T; Kamei, K; Murata; Kato; Fukumoto; Kanie; Sano; Tokunaga et al. (Oct 2006). "A ubiquitin ligase complex assembles linear polyubiquitin chains" (Free full text). The EMBO Journal 25 (20): 4877â87. doi:10.1038/sj.emboj.7601360. ISSN 0261-4189. PMC 1618115. PMID 17006537. Citation uses old-style implicit et al. for authors
- Kim, HT; Kim; Lledias; Kisselev; Scaglione; Skowyra; Gygi; Goldberg (Jun 2007). "Certain pairs of ubiquitin-conjugating enzymes (E2s) and ubiquitin-protein ligases (E3s) synthesize nondegradable forked ubiquitin chains containing all possible isopeptide linkages" (Free full text). The Journal of Biological Chemistry 282 (24): 17375â86. doi:10.1074/jbc.M609659200. ISSN 0021-9258. PMID 17426036.
- Ikeda, F; Dikic (Jun 2008). "Atypical ubiquitin chains: new molecular signals. 'Protein Modifications: Beyond the Usual Suspects' Review Series" (Free full text). EMBO Reports 9 (6): 536â42. doi:10.1038/embor.2008.93. ISSN 1469-221X. PMC 2427391. PMID 18516089.
- "Ubiquitin Proteasome Pathway Overview". Archived from the original on 2008-03-30. Retrieved 2008-04-30.
- Thrower, JS; Hoffman; Rechsteiner; Pickart (Jan 2000). "Recognition of the polyubiquitin proteolytic signal" (Free full text). The EMBO Journal 19 (1): 94â102. doi:10.1093/emboj/19.1.94. ISSN 0261-4189. PMC 1171781. PMID 10619848.
- Hicke, L. (2001). "Protein regulation by monoubiquitin". Nature Reviews Molecular Cell Biology 2 (3): 195â201. doi:10.1038/35056583. PMID 11265249.
- Hofmann, K. (2009). "Ubiquitin-binding domains and their role in the DNA damage response". DNA Repair 8 (4): 544â556. doi:10.1016/j.dnarep.2009.01.003. PMID 19213613.
- "UBQLN1 ubiquilin 1 [ Homo sapiens ]". Gene. National Center for Biotechnology Information. Retrieved 9 May 2012.
- Stieren ES, El Ayadi A, Xiao Y, Siller E, Landsverk ML, Oberhauser AF, Barral JM, Boehning D (August 2011). "Ubiquilin-1 Is a Molecular Chaperone for the Amyloid Precursor Protein". J Biol Chem 286 (41): 35689â98. doi:10.1074/jbc.M111.243147. PMC 3195644. PMID 21852239. Lay summary â Science Daily.
- Huber, C; Dias-Santagata, ML; Glaser; O'sullivan; Brauner; Wu; Xu; Pearce et al. (Oct 2005). "Identification of mutations in CUL7 in 3-M syndrome". Nature Genetics 37 (10): 1119â24. doi:10.1038/ng1628. ISSN 1061-4036. PMID 16142236. Citation uses old-style implicit et al. for authors
- Downes, Brian P.; Saracco, Scott A.; Lee, Sang Sook; Crowell, Dring N.; Vierstra, Richard D. (July 2006). "MUBs, a Family of Ubiquitin-fold Proteins That Are Plasma Membrane-anchored by Prenylation". Journal of Biological Chemistry 281 (37): 27145â27157. doi:10.1074/jbc.M602283200. ISSN 0021-9258. PMID 16831869.
- Welchman RL, Gordon C, Mayer RJ (2005). "Ubiquitin and ubiquitin-like proteins as multifunctional signals". Nat Rev Mol Cell Biol 6 (8): 599â609. doi:10.1038/nrm1700. PMID 16064136.
- Grabbe C, Dikic I (2009). "Functional roles of ubiquitin-like domain (ULD) and ubiquitin-binding domain (UBD) containing proteins". Chem Rev 109 (4): 1481â94. doi:10.1021/cr800413p. PMID 19253967.
- Ubiquitinated sperm mitochondria, selective proteolysis, and the regulation of mitochondrial inheritance in mammalian embryos. Sutovsky P, Moreno RD, Ramalho-Santos J, Dominko T, Simerly C, Schatten G.
- Tung, C. W.; Ho, S. Y. (2008). "Computational identification of ubiquitylation sites from protein sequences". BMC Bioinformatics 9: 310. doi:10.1186/1471-2105-9-310. PMC 2488362. PMID 18625080.
- Radivojac, P.; Vacic, V.; Haynes, C.; Cocklin, R. R.; Mohan, A.; Heyen, J. W.; Goebl, M. G.; Iakoucheva, L. M. (2010). "Identification, analysis, and prediction of protein ubiquitination sites". Proteins: Structure, Function, and Bioinformatics 78 (2): 365â380. doi:10.1002/prot.22555. PMC 3006176. PMID 19722269.
- Chen, Z.; Chen, Y. Z.; Wang, X. F.; Wang, C.; Yan, R. X.; Zhang, Z. (2011). "Prediction of Ubiquitination Sites by Using the Composition of k-Spaced Amino Acid Pairs". In Fraternali, Franca. PLoS ONE 6 (7): e22930. doi:10.1371/journal.pone.0022930. PMC 3146527. PMID 21829559.
- GeneReviews/NCBI/NIH/UW entry on Angelman syndrome
- OMIM entries on Angelman syndrome
- Ubiquitin at the US National Library of Medicine Medical Subject Headings (MeSH)
Programs for ubiquitination prediction:
- UniProt entry for ubiquitin
- Ubiquitin Web-page
- 7.340 Ubiquitination: The Proteasome and Human Disease MIT OpenCourseWare. Notes from MIT course.
Ubiquitin family Provide feedback
This family contains a number of ubiquitin-like proteins: SUMO (smt3 homologue) (see Q02724), Nedd8 (see P29595), Elongin B (see Q15370), Rub1 (see Q9SHE7), and Parkin (see O60260). A number of them are thought to carry a distinctive five-residue motif termed the proteasome-interacting motif (PIM), which may have a biologically significant role in protein delivery to proteasomes and recruitment of proteasomes to transcription sites .
Bayer P, Arndt A, Metzger S, Mahajan R, Melchior F, Jaenicke R, Becker J; , J Mol Biol 1998;280:275-286.: Structure determination of the small ubiquitin-related modifier SUMO-1. PUBMED:9654451 EPMC:9654451
Whitby FG, Xia G, Pickart CM, Hill CP; , J Biol Chem 1998;273:34983-34991.: Crystal structure of the human ubiquitin-like protein NEDD8 and interactions with ubiquitin pathway enzymes. PUBMED:9857030 EPMC:9857030
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR000626
Ubiquitinylation is an ATP-dependent process that involves the action of at least three enzymes: a ubiquitin-activating enzyme (E1, INTERPRO), a ubiquitin-conjugating enzyme (E2, INTERPRO), and a ubiquitin ligase (E3, INTERPRO, INTERPRO), which work sequentially in a cascade. There are many different E3 ligases, which are responsible for the type of ubiquitin chain formed, the specificity of the target protein, and the regulation of the ubiquitinylation process [PUBMED:12646216]. Ubiquitinylation is an important regulatory tool that controls the concentration of key signalling proteins, such as those involved in cell cycle control, as well as removing misfolded, damaged or mutant proteins that could be harmful to the cell. Several ubiquitin-like molecules have been discovered, such as Ufm1 (INTERPRO), SUMO1 (INTERPRO), NEDD8, Rad23 (INTERPRO), Elongin B and Parkin (INTERPRO), the latter being involved in Parkinson's disease [PUBMED:15564047].
Ubiquitin is a protein of 76 amino acid residues, found in all eukaryotic cells and whose sequence is extremely well conserved from protozoan to vertebrates. Ubiquitin acts through its post-translational attachment (ubiquitinylation) to other proteins, where these modifications alter the function, location or trafficking of the protein, or targets it for destruction by the 26S proteasome [PUBMED:15454246]. The terminal glycine in the C-terminal 4-residue tail of ubiquitin can form an isopeptide bond with a lysine residue in the target protein, or with a lysine in another ubiquitin molecule to form a ubiquitin chain that attaches itself to a target protein. Ubiquitin has seven lysine residues, any one of which can be used to link ubiquitin molecules together, resulting in different structures that alter the target protein in different ways. It appears that Lys(11)-, Lys(29) and Lys(48)-linked poly-ubiquitin chains target the protein to the proteasome for degradation, while mono-ubiquitinylated and Lys(6)- or Lys(63)-linked poly-ubiquitin chains signal reversible modifications in protein activity, location or trafficking [PUBMED:14998368]. For example, Lys(63)-linked poly-ubiquitinylation is known to be involved in DNA damage tolerance, inflammatory response, protein trafficking and signal transduction through kinase activation [PUBMED:15556404]. In addition, the length of the ubiquitin chain alters the fate of the target protein. Regulatory proteins such as transcription factors and histones are frequent targets of ubquitinylation [PUBMED:15525528].
|Molecular function||protein binding (GO:0005515)|
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|Author:||Finn RD, Griffiths-Jones SR|
|Number in seed:||76|
|Number in full:||11560|
|Average length of the domain:||67.10 aa|
|Average identity of full alignment:||44 %|
|Average coverage of the sequence by the domain:||28.05 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||18|
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There are 16 interactions for this family. More...
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the ubiquitin domain has been found. There are 508 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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