| UIM | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 solution structure of s5a uim-1/ubiquitin complex | |||||||||
| Identifiers | |||||||||
| Symbol | UIM | ||||||||
| Pfam | PF02809 | ||||||||
| InterPro | IPR003903 | ||||||||
| SCOPe | 1p9d / SUPFAM | ||||||||
| |||||||||
In molecular biology, the Ubiquitin-Interacting Motif (UIM), or 'LALAL-motif', is a sequence motif of about 20 amino acid residues, which was first described in the 26S proteasome subunit PSD4/RPN-10 that is known to recognise ubiquitin. [1] [2] In addition, the UIM is found, often in tandem or triplet arrays, in a variety of proteins either involved in ubiquitination and ubiquitin metabolism, or known to interact with ubiquitin-like modifiers. Among the UIM proteins are two different subgroups of the UBP (ubiquitin carboxy-terminal hydrolase) family of deubiquitinating enzymes, one F-box protein, one family of HECT-containing ubiquitin-ligases (E3s) from plants, and several proteins containing ubiquitin-associated UBA and/or UBX domains. [3] In most of these proteins, the UIM occurs in multiple copies and in association with other domains such as UBA (INTERPRO), UBX (INTERPRO), ENTH domain, EH (INTERPRO), VHS (INTERPRO), SH3 domain, HECT, VWFA (INTERPRO), EF-hand calcium-binding, WD-40, F-box (INTERPRO), LIM, protein kinase, ankyrin, PX, phosphatidylinositol 3- and 4-kinase (INTERPRO), C2 domain, OTU (INTERPRO), DnaJ domain (INTERPRO), RING-finger (INTERPRO) or FYVE-finger (INTERPRO). UIMs have been shown to bind ubiquitin and to serve as a specific targeting signal important for monoubiquitination. Thus, UIMs may have several functions in ubiquitin metabolism each of which may require different numbers of UIMs. [4] [5] [6]
In genetics, a sequence motif is a nucleotide or amino-acid sequence pattern that is widespread and has, or is conjectured to have, a biological significance. For proteins, a sequence motif is distinguished from a structural motif, a motif formed by the three-dimensional arrangement of amino acids which may or may not be adjacent.
Amino acids are organic compounds that contain amine (-NH2) and carboxyl (-COOH) functional groups, along with a side chain (R group) specific to each amino acid. The key elements of an amino acid are carbon (C), hydrogen (H), oxygen (O), and nitrogen (N), although other elements are found in the side chains of certain amino acids. About 500 naturally occurring amino acids are known (though only 20 appear in the genetic code) and can be classified in many ways. They can be classified according to the core structural functional groups' locations as alpha- (α-), beta- (β-), gamma- (γ-) or delta- (δ-) amino acids; other categories relate to polarity, pH level, and side chain group type (aliphatic, acyclic, aromatic, containing hydroxyl or sulfur, etc.). In the form of proteins, amino acid residues form the second-largest component (water is the largest) of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis.
Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases.
The UIM is unlikely to form an independent protein domain. Instead, based on the spacing of the conserved residues, the motif probably forms a short alpha-helix that can be embedded into different protein folds. [2] Some proteins known to contain an UIM are listed below:
A protein domain is a conserved part of a given protein sequence and tertiary structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural domains. One domain may appear in a variety of different proteins. Molecular evolution uses domains as building blocks and these may be recombined in different arrangements to create proteins with different functions. In general, domains vary in length from between about 50 amino acids up to 250 amino acids in length. The shortest domains, such as zinc fingers, are stabilized by metal ions or disulfide bridges. Domains often form functional units, such as the calcium-binding EF hand domain of calmodulin. Because they are independently stable, domains can be "swapped" by genetic engineering between one protein and another to make chimeric proteins.
In evolutionary biology, conserved sequences are identical or similar sequences in nucleic acids or proteins across species, or within a genome, or between donor and receptor taxa. Conservation indicates that a sequence has been maintained by natural selection.
- Eukaryotic PSD4/RPN-10/S5, a multi-ubiquitin binding subunit of the 26S proteasome.
- Vertebrate Machado-Joseph disease protein 1 (Ataxin-3), which acts as a histone-binding protein that regulates transcription; defects in Ataxin-3 cause the neurodegenerative disorder Machado-Joseph disease (MJD).
- Vertebrate epsin and epsin2.
- Vertebrate hepatocyte growth factor-regulated tyrosine kinase substrate (HRS).
- Mammalian epidermal growth factor receptor substrate 15 (EPS15), which is involved in cell growth regulation.
- Mammalian epidermal growth factor receptor substrate EPS15R.
- Drosophila melanogaster (Fruit fly) liquid facets (lqf), an epsin.
- Yeast VPS27 vacuolar sorting protein, which is required for membrane traffic to the vacuole.
Vertebrates comprise all species of animals within the subphylum Vertebrata. Vertebrates represent the overwhelming majority of the phylum Chordata, with currently about 69,963 species described. Vertebrates include such groups as the following:
A disease is a particular abnormal condition that negatively affects the structure or function of part or all of an organism, and that is not due to any external injury. Diseases are often known to be medical conditions that are associated with specific symptoms and signs. A disease may be caused by external factors such as pathogens or by internal dysfunctions. For example, internal dysfunctions of the immune system can produce a variety of different diseases, including various forms of immunodeficiency, hypersensitivity, allergies and autoimmune disorders.
In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA (transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from altering the number of copies of RNA that are transcribed, to the temporal control of when the gene is transcribed. This control allows the cell or organism to respond to a variety of intra- and extracellular signals and thus mount a response. Some examples of this include producing the mRNA that encode enzymes to adapt to a change in a food source, producing the gene products involved in cell cycle specific activities, and producing the gene products responsible for cellular differentiation in multicellular eukaryotes, as studied in evolutionary developmental biology.
