Disease relevance of KRT76

• Sustained reflow in dogs with coronary thrombosis with K2P, a novel mutant of tissue-plasminogen activator [1].
• In this study we compared the thrombolytic effect of K2P and rt-PA in dogs with electrically induced coronary artery thrombosis [1].
• MATERIALS AND METHODS: Preoperative bone marrow aspirates of 82 patients with localized (N0) and lymphatically spread (N1) prostate cancer were examined using the monoclonal antibody cytokeratin 2 and the pan-cytokeratin antibody A 45-B/B3, called A 45 [2].
• It begins with an overview of the role of background K+ channels in neuronal excitability and nerve conduction and is followed by a description of the K2P channel family including experimental evidence for the contribution of K2P channels to the mechanism of action and toxicity of local anesthetics [3].

High impact information on KRT76

• The number of neurofilament-positive cells increased with time after initial exposure to retinoic acid, and although 95% of these cells contained cytokeratin initially, less than 5% of the neurofilament-positive cells retained cytokeratin 2 weeks later [4].
• Because this cross-link contains two lysine residues and a dihydropyridinium ring, we assigned it the trivial name of K2P [5].
• We sought to determine the segment-specific expression of transcripts for the 14 known K2P channel genes in human nephron to identify potential correlates of native leak channels [6].
• K2P channels have properties of background or leak K+ channels, and therefore play a crucial role in setting the resting membrane potential and regulating cell excitability [7].
• Some K2P channels are targets of agonists that bind receptors coupled to different types of G proteins, and are probably involved in a variety of neurotransmitter and peptide hormone-mediated signal transduction processes [7].

Biological context of KRT76

• Purification of the kringle 2 domain derived from elastase cleavage of K2P at the Arg275-Ile276 bond revealed that inhibition was mediated by this domain [8].
• In addition, K2P inhibited angiogenesis in vivo and increased endothelial cell apoptosis [8].
• CONCLUSIONS: Wound healing and angiogenesis are severely compromised by K2P [8].
• Glycation breaker discovery would use high-throughput screening and rational drug design to find molecules that are able to break glucosepane crosslinks and K2P crosslinks of extracellular proteins [9].

Anatomical context of KRT76

• Suprabasal marker proteins distinguishing keratinizing squamous epithelia: cytokeratin 2 polypeptides of oral masticatory epithelium and epidermis are different [10].
• CONCLUSION: Human cytotrophoblast cells from term placenta are a site of expression for various K2P genes, two of which, namely, TASK1 and TREK1, are transcribed into protein [11].
• TRESK (TWIK-related spinal cord K+ channel) is the most recently characterized member of the tandem-pore domain potassium channel (K2P) family [12].
• K2P channels are widely expressed in the central nervous system and are involved in the control of the resting membrane potential and the firing pattern of excitable cells [3].
• We investigated effects of H2O2 on various K2P channels expressed in CHO cells [13].

Associations of KRT76 with chemical compounds

• Enzymatically active K2P was liberated from the fusion protein by cleavage at a unique Asn-Gly dipeptide sequence using hydroxylamine [14].
• Human TRESK is potently activated by halothane, isoflurane, sevoflurane, and desflurane, making it the most sensitive volatile anesthetic-activated K2P channel yet described [12].
• Experiments with kringle-2 ligands and a deletion mutant of t-PA (K2P) suggests that glutamic or aspartic acid residues in K2 of t-PA are involved in stimulation of activity, lysine binding and fibrin binding [15].
• The ventilatory stimulant doxapram inhibits TASK tandem pore (K2P) potassium channel function but does not affect minimum alveolar anesthetic concentration [16].

Analytical, diagnostic and therapeutic context of KRT76

• In situ hybridization and real-time PCR studies in wild-type and TASK-1 knock-outs (KOs) demonstrated that the expression of other K2P channels was unaltered in CGNs [17].

References