| VHS | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 crystal structure of the vhs and fyve tandem domains of hrs, a protein involved in membrane trafficking and signal transduction | |||||||||
| Identifiers | |||||||||
| Symbol | VHS | ||||||||
| Pfam | PF00790 | ||||||||
| Pfam clan | CL0009 | ||||||||
| InterPro | IPR002014 | ||||||||
| SMART | VHS | ||||||||
| SCOP2 | 1elk / SCOPe / SUPFAM | ||||||||
| |||||||||
In molecular biology, the VHS protein domain is approximately 140 residues long. Its name is an acronym derived from its occurrence in VPS-27, Hrs and STAM. It is a domain commonly found in the N-terminus of many proteins. [1]
VHS domains are thought to be very important in vesicular trafficking, in particular, aiding membrane targeting and cargo recognition role. [1]
Resolution of the crystal structure of the VHS domain of Drosophila Hrs and human TOM1 revealed that it consists of eight helices arranged in a double-layer superhelix. [2] The existence of conserved patches of residues on the domain surface suggests that VHS domains may be involved in protein-protein recognition and docking. Overall, sequence similarity is low (approx 25%) amongst domain family members.
Based on regions surrounding the domain, VHS-proteins can be divided into 4 groups: [1]
The VHS domain is always found at the N-terminus of proteins suggesting that such topology is important for function. The domain is considered to have a general membrane targeting/cargo recognition role in vesicular trafficking. [3]
Ubiquitin is a small regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ubiquitously. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Four genes in the human genome code for ubiquitin: UBB, UBC, UBA52 and RPS27A.
A ubiquitin ligase is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin from the E2 to the protein substrate. In simple and more general terms, the ligase enables movement of ubiquitin from a ubiquitin carrier to another thing by some mechanism. The ubiquitin, once it reaches its destination, ends up being attached by an isopeptide bond to a lysine residue, which is part of the target protein. E3 ligases interact with both the target protein and the E2 enzyme, and so impart substrate specificity to the E2. Commonly, E3s polyubiquitinate their substrate with Lys48-linked chains of ubiquitin, targeting the substrate for destruction by the proteasome. However, many other types of linkages are possible and alter a protein's activity, interactions, or localization. Ubiquitination by E3 ligases regulates diverse areas such as cell trafficking, DNA repair, and signaling and is of profound importance in cell biology. E3 ligases are also key players in cell cycle control, mediating the degradation of cyclins, as well as cyclin dependent kinase inhibitor proteins. The human genome encodes over 600 putative E3 ligases, allowing for tremendous diversity in substrates.
The vesicular monoamine transporter (VMAT) is a transport protein integrated into the membranes of synaptic vesicles of presynaptic neurons. It transports monoamine neurotransmitters – such as dopamine, serotonin, norepinephrine, epinephrine, and histamine – into the vesicles, which release the neurotransmitters into synapses as chemical messages to postsynaptic neurons. VMATs utilize a proton gradient generated by V-ATPases in vesicle membranes to power monoamine import.
Vesicular transport adaptor proteins are proteins involved in forming complexes that function in the trafficking of molecules from one subcellular location to another. These complexes concentrate the correct cargo molecules in vesicles that bud or extrude off of one organelle and travel to another location, where the cargo is delivered. While some of the details of how these adaptor proteins achieve their trafficking specificity has been worked out, there is still much to be learned.
Endoplasmic-reticulum-associated protein degradation (ERAD) designates a cellular pathway which targets misfolded proteins of the endoplasmic reticulum for ubiquitination and subsequent degradation by a protein-degrading complex, called the proteasome.
In molecular biology the FYVE zinc finger domain is named after the four cysteine-rich proteins: Fab 1, YOTB, Vac 1, and EEA1, in which it has been found. FYVE domains bind phosphatidylinositol 3-phosphate, in a way dependent on its metal ion coordination and basic amino acids. The FYVE domain inserts into cell membranes in a pH-dependent manner. The FYVE domain has been connected to vacuolar protein sorting and endosome function.
The gene EEA1 encodes for the 1400 amino acid protein, Early Endosome Antigen 1.
ADP-ribosylation factor-binding protein GGA1 is a protein that in humans is encoded by the GGA1 gene.
ADP-ribosylation factor-binding protein GGA3 is a protein that in humans is encoded by the GGA3 gene.
Hepatocyte growth factor-regulated tyrosine kinase substrate is an enzyme that in humans is encoded by the HGS gene.
ADP-ribosylation factor-binding protein GGA2 is a protein that in humans is encoded by the GGA2 gene.
Signal transducing adapter molecule 1 is a protein that in humans is encoded by the STAM gene.
Target of Myb protein 1 is a protein that in humans is encoded by the TOM1 gene.
The endosomal sorting complexes required for transport (ESCRT) machinery is made up of cytosolic protein complexes, known as ESCRT-0, ESCRT-I, ESCRT-II, and ESCRT-III. Together with a number of accessory proteins, these ESCRT complexes enable a unique mode of membrane remodeling that results in membranes bending/budding away from the cytoplasm. These ESCRT components have been isolated and studied in a number of organisms including yeast and humans. A eukaryotic signature protein, the machinery is found in all eukaryotes and some archaea.
The EHD protein family is a relatively small group of proteins which have been shown to play a role in several physiological functions, the most notable being the regulation of endocytotic vesicles. This family is recognized by its highly conserved EH domain, a structural motif that has been shown to facilitate specificity and interaction between protein and ligand. The four mammalian EHD proteins that have been classified are: EHD1, EHD2, EHD3, and EHD4.
In molecular biology, autophagy related 3 (Atg3) is the E2 enzyme for the LC3 lipidation process. It is essential for autophagy. The super protein complex, the Atg16L complex, consists of multiple Atg12-Atg5 conjugates. Atg16L has an E3-like role in the LC3 lipidation reaction. The activated intermediate, LC3-Atg3 (E2), is recruited to the site where the lipidation takes place.
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. 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 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. In most of these proteins, the UIM occurs in multiple copies and in association with other domains such as UBA, UBX, ENTH domain, EH, VHS, SH3 domain, HECT, VWFA, EF-hand calcium-binding, WD-40, F-box, LIM, protein kinase, ankyrin, PX, phosphatidylinositol 3- and 4-kinase, C2 domain, OTU, DnaJ domain, RING-finger or FYVE-finger. 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.
RUN and FYVE domain containing 2 (RUFY2) is a protein that in humans is encoded by the RUFY2 gene. The RUFY2 gene is named for two of its domains, the RUN domain and FYVE domains. RUFY2 is a member of the RUFY family of proteins that include RUFY1, RUFY2, RUFY3, and RUFY4. RUFY2 protein has a dynamic role in endosomal membrane trafficking.
Ubiquitin-binding domains (UBDs) are protein domains that recognise and bind non-covalently to ubiquitin through protein-protein interactions. As of 2019, a total of 29 types of UBDs had been identified in the human proteome. Most UBDs bind to ubiquitin only weakly, with binding affinities in the low to mid μM range. Proteins containing UBDs are known as ubiquitin-binding proteins or sometimes as "ubiquitin receptors".
The muniscin protein family was initially defined in 2009 as proteins having 2 homologous domains that are involved in clathrin mediated endocytosis (CME) and have been reviewed. In addition to FCHO1, FCHO2 and Syp1, SGIP1 is also included in the family because it contains the μ (mu) homology domain and is involved in CME, even though it does not contain the F-BAR domain