1.C.81 The Arenicin (Arenicin) Family The solution structure and the mode of action of arenicin isoform 1, an antimicrobial peptide with a unique 18-residue loop structure, from the lugworm Arenicola marina have been elucidated (Andra et al., 2007). Arenicin folds into a two-stranded anti-parallel β-sheet. It exhibits high antibacterial activity against Gram-negative and positive bacteria, as well as yeast. Bacterial killing occurs within minutes and is accompanied by membrane permeabilisation, membrane detachment, and release of cytoplasmic constituents (Andra et al., 2007).
Arenicin is a hydrophilic protein, 202 aas long with a single N-terminal hydrophobic region. The last 21 residues (182-202 aas) form the processed active peptide. The protein also contains a BRICHOS domain (pfam 64089) found in proteins involved in dementia and cancer. The full length protein is homologous to the chondromodulin-1 precursor (P17404) also called 'leukocyte cell-derived chemotaxin-1' of H. sapiens.
1.C.81 The Arenicin (Arenicin) Family
The solution structure and the mode of action of arenicin isoform 1, an antimicrobial peptide with a unique 18-residue loop structure, from the lugworm Arenicola marina have been elucidated (Andra et al., 2007). Arenicin folds into a two-stranded anti-parallel β-sheet. It exhibits high antibacterial activity against Gram-negative and positive bacteria, as well as yeast. Bacterial killing occurs within minutes and is accompanied by membrane permeabilisation, membrane detachment, and release of cytoplasmic constituents (Andra et al., 2007).
Arenicin-1 precursor (202 aas). The processed pore-forming β-hairpin antimicrobial peptide corresponds to residues 182-202 (Andrä et al., 2008; Shenkarev et al., 2011). Low-conductivity pores were detected in the phosphatidylethanolamine-containing lipids and high-conductivity pores in anionic lipids. The measured conductivity levels agreed with the model in which arenicin antimicrobial activity was mediated by the formation of toroidal pores assembled of two, three, or four β-structural peptide dimers and lipid molecules (Shenkarev et al., 2011).
Arenicin-1 of Arenicola marina (lugworm) (Q5SC60)
Gastrokine-1, GKN1 of 199 aas and 2 TMSs, one N-terminal and one C-terminal. It has mitogenic activity and may be involved in maintaining the integrity of the gastric mucosal epithelium (Martin et al. 2003).
GKN1 of Homo sapiens
Prepronicomicin-1 of 239 aas
Prepronicomicin-1 of Nicomache minor
Leukocyte cell-derived chemotaxin 1-like protein of 240 aa
Leukocyte cell-derived chemotaxin 1-like peptide of Lingula anatina
Uncharacterized protein of 285 aas and 1 TMS.
UP of Exaiptasia pallida
Leucocyte cell-derived chemotaxin protein 1 of 359 aas
Leucocyte cell-derived chemotaxin protein 1 of Callorhinchus milii
Uncharacteerized protein of 331 aas
UP of Stylophora pistillata
Gastrokine-3-like protein of 181 aas and 1 - 5 TMSs. GKN3 is a host cell receptor for Japanese Encephalitis virus entry into neurons (Mukherjee et al. 2018).
Gastrokine-3-like protein of Xenopus laevis
Leukocyte cell-derived chemotaxin protein 1 isoform 2 precursor of 333 aa
Chemotaxis protein of Homo sapiens
Integral membrane protein 2B, ITM2B or BRI2, of 266 aas and 1 TMS. Binds to and regulates the activity of GLUT9, a sugar/urate transporter (TC# 2.A.1.1.72). ITM2B inhibits urate uptake, but stimulates its efflux (Mandal and Mount 2019). Hyperuricemia plays a critical causative role in gout, but has a protective effect in neurodegenerative disorders, including Alzheimer's disease. Genetic variation in the SLC2A9 gene, encoding GLUT9, exerts the largest single-gene effect on serum uric acid. It plays a regulatory role in the processing of the amyloid-beta A4 precursor protein (APP) and acts as an inhibitor of the amyloid-beta peptide aggregation and fibrils deposition. It also plays a role in the induction of neurite outgrowth and functions as a protease inhibitor by blocking access of secretases to APP cleavage sites. It also facilitates glutamate transmission via both pre- and post-synaptic mechanisms (Yao et al. 2019). It is thus an anti-Alzhemer's disease protein (Matsuda and Senda 2019). The ITM2B interactome in the human retina has been studied (Wohlschlegel et al. 2021). The role of BRI2 in health and disease has been reviewed (Martins et al. 2021).
ITM2B of Homo sapiens
Integral membrane protein, Itm2A, of 263 aas and 1 vey hydrophobic TMS near the N-terminus, plus 3 moderately hydrophobic putative TMSs near the C-terminus of the protein. Constitutive overexpression of Itm2A enhances myogenic differentiation (Van den Plas and Merregaert 2004). Antibodies against ITM2A are internalized in ITM2A-overexpressing HEK293 cells, and ITM2A is expressed in brain microvessels (Cegarra et al. 2022).
Itm2A of Homo sapiens
Integral membrane protein 2C, Itm2C (BRI3, Hucep-14, NPD018), of 267 aas with 1 strongly hydrophobic TMS near the N-terminus. It is a negative regulator of amyloid-beta peptide production, and may inhibit the processing of APP by blocking its access to alpha- and beta-secretase (Gong et al. 2008). Binding to the beta-secretase-cleaved APP C-terminal fragment is negligible, suggesting that ITM2C is a poor gamma-secretase cleavage inhibitor. It may also play a role in TNF-induced cell death and neuronal differentiation (Matsuda et al. 2009).
Itm2C of Homo sapiens