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Voltage-gated potassium channels (Kv) in GtoPdb v.2025.3
Get PDFThe 6TM family of K channels comprises the voltage-gated KV subfamilies, the EAG subfamily (which includes hERG channels), the Ca2+-activated Slo subfamily (actually with 7TM, termed BK) and the Ca2+-activated SK subfamily. These channels possess a pore-forming α subunit that comprise tetramers of identical subunits (homomeric) or of different subunits (heteromeric). Heteromeric channels can only be formed within subfamilies (e.g. Kv1.1 with Kv1.2; Kv7.2 with Kv7.3). The pharmacology largely reflects the subunit composition of the functional channel.Kv7 channelsKv7.1-Kv7.5 (KCNQ1-5) K+ channels are voltage-gated K+ channels with major roles in neurons, muscle cells and epithelia where they underlie physiologically important K+ currents, such as the neuronal M-current and the cardiac IKs. Genetic deficiencies in all five KCNQ genes result in human excitability disorders, including epilepsy, autism spectrum disorders, cardiac arrhythmias and deafness. Thanks to the recent knowledge of the structure and function of human KCNQ-encoded proteins, these channels are increasingly used as drug targets for treating diseases [333, 2, 777, 294]
SLC39 family of metal ion transporters in GtoPdb v.2025.3
Get PDFAlong with the SLC30 family, SLC39 family members regulate zinc movement in cells. SLC39 metal ion transporters accumulate zinc into the cytosol. Membrane topology modelling suggests the presence of eight TM regions with both termini extracellular or in the lumen of intracellular organelles. The mechanism for zinc transport for many members is unknown but appears to involve co-transport of bicarbonate ions [3, 5]
Adenosine turnover in GtoPdb v.2025.3
Get PDFA multifunctional, ubiquitous molecule, adenosine acts at cell-surface G protein-coupled receptors, as well as numerous enzymes, including protein kinases and adenylyl cyclase. Extracellular adenosine is thought to be produced either by export or by metabolism, predominantly through ecto-5’-nucleotidase activity (also producing inorganic phosphate). It is inactivated either by extracellular metabolism via adenosine deaminase (also producing ammonia) or, following uptake by nucleoside transporters, via adenosine deaminase or adenosine kinase (requiring ATP as co-substrate). Intracellular adenosine may be produced by cytosolic 5’-nucleotidases or through S-adenosylhomocysteine hydrolase (also producing L-homocysteine)
Type XIII RTKs: Ephrin receptor family in GtoPdb v.2025.3
Get PDFEphrin receptors are a family of 15 RTKs - the largest family of RTKs - with two identified subfamilies (EphA and EphB), which have a role in the regulation of neuronal development, cell migration, patterning and angiogenesis. Their ligands are membrane-associated proteins, thought to be glycosylphosphatidylinositol-linked for EphA (ephrin-A1 , ephrin-A2, ephrin-A3, ephrin-A4 and ephrin-A5) and transmembrane proteins for Ephrin B (ENSFM00250000002014: ephrin-B1, ephrin-B2 and ephrin-B3). Ephrin-A3 and ephrin-B3 have also been shown to interact with heparan sulphate proteoglycans [22]
Type XVI RTKs: DDR (collagen receptor) family in GtoPdb v.2025.3
Get PDFThe discoidin domain receptors DDR1 and DDR2 are structurally related receptor tyrosine kinases that function as collagen receptors. The 28 different collagens form the most abundant protein family in man. Collagens are found in the extracellular matrix and are generally deposited there in the form of supramolecular assemblies arranged from triple-helical rope-like structural units. In man, the main collagens include COL1A1, COL2A1, COL3A1 and COL4A1
SLC51 family of steroid-derived molecule transporters in GtoPdb v.2025.3
Get PDFThe SLC51 organic solute transporter family of transporters is a pair of heterodimeric proteins which regulate bile salt movements in the small intestine, bile duct, and liver, as part of the enterohepatic circulation [2, 5, 1]. OSTα/OSTβ is also expressed in steroidogenic cells of the brain and adrenal gland, where it may contribute to neurosteroid and steroid sulphate movement [6]. Bile acid and steroid sulphate transport is suggested to be bidirectional, facilitative and independent of sodium, potassium, chloride ions or protons [5, 2]. OSTα/OSTβ heterodimers have been shown to transport [3H]taurocholic acid, [3H]dehydroepiandrosterone sulphate, [3H]estrone-3-sulphate, [3H]pregnenolone sulphate and [3H]dehydroepiandrosterone sulphate[2, 5, 6]. OSTα/OSTβ-mediated transport is inhibited by clofazimine and fidaxomicin [9, 11]. OSTα is suggested to be a seven TM protein, while OSTβ is a single TM \u27ancillary\u27 protein, both of which are thought to have intracellular C-termini [8]. Both proteins function in solute transport [8, 4]. Inherited mutations in OSTα and OSTβ are associated with liver disease and congenital diarrhea in children [10, 7]
Peptidyl-prolyl cis/trans isomerases in GtoPdb v.2025.3
Get PDFPeptidyl-prolyl cis/trans isomerases (PPIases) are an enzyme family which catalyse the cis/trans isomerisation of proline peptide bonds to promote the folding and re-folding of peptides and proteins. Three subfamilies have been identified: cyclophilins, FK506-binding proteins and parvulins. Individual PPIases are overexpressed in a number of cancers [65], and family members have been targetted for immunosuppressant effects
Blood coagulation components in GtoPdb v.2025.3
Get PDFCoagulation as a process is interpreted as a mechanism for reducing excessive blood loss through the generation of a gel-like clot local to the site of injury. The process involves the activation, adhesion (see Integrins), degranulation and aggregation of platelets, as well as proteins circulating in the plasma. The coagulation cascade involves multiple proteins being converted to more active forms from less active precursors (for example, prothrombin [Factor II] is converted to thrombin [Factor IIa]), typically through proteolysis (see Proteases). Listed here are the components of the coagulation cascade targeted by agents in current clinical usage or at an advanced level of development
Piezo channels in GtoPdb v.2025.4
Get PDFPIEZO proteins are the pore-forming subunits of trimeric ion channels that open rapidly in response to mechanical stimuli such as membrane stretch, allowing positively charged ions such as the calcium ion to flow into the cell to change cellular structure and function. The proteins are eukaryotic, not prokaryotic, and lack sequence or structural homology to other proteins. There are two main types: In humans, there is PIEZO1 of 2521 amino acids and PIEZO2 of 2752 amino acids, which can form homomeric PIEZO1 and PIEZO2 channels. Membrane stretching causes complex changes in the channels that include a reduced inward curvature, an expansion of the N-terminal transmembrane helical units and an opening of the central ion pore region comprising the last two C-terminal helices. When there is sustained membrane stretching, the channels may adapt by inactivating at various rates depending on the cell type and context. There are many roles of the channels in diverse organ systems including cardiovascular, gastrointestinal, haematological, hepatobiliary, immune, integumental, musculoskeletal, neuronal, reproductive, respiratory and urinary systems as well as adipose tissue and cancers. The expression and functions of PIEZO1 are broad and diverse across many cell types and organs, whereas PIEZO2 is more restricted
Africa, paving the way: Lessons from African actors pushing forward the international community’s role and responsibility in addressing genocide by Iseult Daly
Get PDFCurrently, international collective security and peace institutions are weathering a deep crisis in legitimacy for their systematic inability to protect populations from devastating genocides such as those ongoing Palestine, Sudan and the DRC. This essay examines whether lessons can be extracted from the attitudes of a continent that has historically struggled with high rates of mass atrocity crime, and has thus been driven to innovate in the field of international response.
I find that, in expanding the power and the responsibility of the international community to intervene in protection of targeted peoples, African actors have been seminal in promoting a higher international normative standard of non-indifference towards atrocity.
I look at three different dimensions of international activity to argue this: in a first part, I showcase the African Union’s innovative regional governance framework for identifying risks of mass atrocity and its unique sanctioning of unilateral military intervention in such instances. In a second part, I look at developments in international law concerning mass atrocity driven by African actors, such as their incubation of a regional criminal justice court to address transnational mass atrocity crime, their role in the genesis of the ICC, and finally the activism of both South Africa and The Gambia in expanding the scope of State responsibility before the ICJ. In a final part, I survey the African bloc’s diplomatic posture in the global political arena and show that together they have consistently advocated for larger responsibility of the international community towards victims of genocide. This has been made especially clear recently in light of African attitudes towards the ongoing Palestinian genocide.
I conclude that, despite the persistence of regional challenges, legal and political innovation emanating from the African continent in the area constitutes a ripe field of inspiration in modelling better international protection of targets of mass atrocity.