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TCID	Name	Domain	Kingdom/Phylum	Protein(s)
8.A.43.1.1	The heme sequestration protein, Shr (Ouattara et al., 2010) (feeds iron into the Shp/SiaABC (HtsABC) ABC uptake system (3.A.1.14.10)). The two NEAT domains are not equivalent (Ouattara et al. 2013).	Bacteria	Firmicutes	Shr of Streptococcus pyogenes (B0LFQ8)
8.A.43.1.2	Chlostridial Shr protein homologue	Bacteria	Firmicutes	Shr homologue of Clostridium botulinum
8.A.43.1.3	InlD protein of 567 aas and 2 TMSs	Bacteria	Firmicutes	InlD of Listeria monocytogenese
8.A.43.1.4	Toll9 of 576 aas and 2 TMSs	Eukaryota	Metazoa	Toll9 of Anopheles gambiae
8.A.43.1.5	Uncharacterized protein of 1349 aas and 2 TMSs.	Bacteria	Firmicutes	UP of Listeria innocua
8.A.43.1.6	Uncharacterized protein of 425 aas and 2 TMSs	Eukaryota	Metazoa	UP of Drosophila melanogaster
8.A.43.1.7	Uncharacterized protein of 1016 aas and 2 or 3 TMSs	Eukaryota	Metazoa	UP of Branchiostoma floridae
8.A.43.1.8	Leucine-rich repeat-containing protein 55. BK channel auxiliary gamma subunit LRRC55. Auxiliary protein of the large-conductance, voltage and calcium-activated potassium channel (BK alpha; TC# 1.A.1.3.2). Modulates gating properties by producing a marked shift in the BK channel's voltage dependence of activation in the hyperpolarizing direction in the absence of calcium (Yan and Aldrich 2012). Only the transmembrane helix modulates channel activity (Li et al. 2016).	Eukaryota	Metazoa	LRRC44 of Homo sapiens
8.A.43.1.9	Toll-like receptor 4, Tlr4, of 839 aas and 0 TMSs. Mediates innate immune and inflamatory responses (Medzhitov et al. 1997). It forms a heterodimer with TLR6, which is rapidly internalized to trigger inflammatory responses (Estruch et al. 2013). Tmbim1 (TC# 1.A.14.3.10) promotes the lysosomal degradation of Tlr4 by cooperating with the ESCRT endosomal sorting complex to facilitate MVB formation, and the ubiquitination of Tmbim1 by the E3 ubiquitin ligase Nedd4l (Zhao et al. 2017).	Eukaryota	Metazoa	Tlr4 of Homo sapiens
8.A.43.1.10	Amphoterin-induced protein 1, AMIGO-1, of 493 aas and 1 TMS. May be involved in fasciculation as well as myelination of developing neural axons, and may also have a role in regeneration as well as neural plasticity in the adult nervous system. It is assembled with KCNB1 to modulate the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1. In mammalian brain neurons, AMIGO-1 is associated with Kv2 alpha subunits, and Kv2 alpha subunits are obligatory in determining the correct pattern of AMIGO-1 expression, plasma membrane trafficking and clustering (Bishop et al. 2018).	Eukaryota	Metazoa	AMIGO-1 of Homo sapiens
8.A.43.1.11	Leucine-rich repeat transmembrane neuronal protein 1, LRRTM1 of 522 aas and 2 TMSs, N- and C-terminal. It exhibits strong synaptogenic activity, and is restricted to excitatory presynaptic differentiation, acting at both pre- and postsynaptic levels. It helps stabilize synaptic AMPA receptors at mature spines during basal synaptic transmission and LTP (Bhouri et al. 2018).	Eukaryota	Metazoa	LRRTM1 of Homo sapiens
8.A.43.1.12	Internalin-A, InlA, of 800 aas and 2 TMSs, N- and C-terminal. L. monocytogenes virulence factors include two surface invasins, InlA and InlB, known to promote bacterial uptake by host cells, and the secreted pore-forming toxin listeriolysin O (LLO), which disrupts the phagosome to allow bacterial proliferation in the cytosol. No role for InlB was detected in any tested cells unless the InlB expression level was substantially enhanced, which was achieved by introducing a mutation (prfA) in the gene encoding the transcription factor PrfA (Phelps et al.* 2018). InlA and LLO were the most critical invasion factors. InlA facilitates both bacterial attachment and internalization in cells that express its receptor, E-cadherin. LLO promotes L. monocytogenes internalization into hepatocytes, but not into cytotrophoblasts and endothelial cells. LLO and InlA cooperate to increase the efficiency of host cell invasion by L. monocytogenes (Phelps et al. 2018).			InlA of Listeria monocytogenes
8.A.43.1.13	Leucine-rich repeat-containing protein 15, LRRC15 of 581 aas and 2 or 3 TMSs, one at the N-terminus and one or two at the C-terminus. LRRC15 is an essential regulator for osteogenesis of mesenchymal stem cells by modulating p65 cytoplasmic/nuclear translocation (Wang et al. 2018).			LRRC15 of Homo sapiens
8.A.43.1.14	Leucine-rich repeat-containing protein 26, LRRC26, of 334 aas. Auxiliary protein of the large-conductance, voltage and calcium-activated potassium channel (BK alpha). LRRC26 is required for the conversion of BK alpha channels from a high-voltage to a low-voltage activated channel type in non-excitable cells. These are characterized by negative membrane voltages and constant low levels of calcium (Yan and Aldrich 2010; Yan and Aldrich 2012).	Eukaryota	Metazoa	LRRC26 of Homo sapiens
8.A.43.1.15	Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1, LINGO1, of 620 aas with two TMSs, one N-terminal and one C-terminal. LINGO1 is a regulator of BK channels, which causes a "functional knockdown" of these currents and may contribute to the tremor associated with increased LINGO1 levels (Dudem et al. 2020).	Eukaryota	Metazoa	LINGO1 of Homo sapiens
8.A.43.1.16	Toll-like receptor 2, TLR2 or TIL4,Lancioni et al. 2011 of 784 aas and 2 TMSs, N- and C-termnal. It cooperates with TLR1 or TLR6 to mediate the innate immune response to bacterial lipoproteins or lipopeptides (Jin et al. 2007; Lancioni et al. 2011). It forms activation clusters composed of several receptors depending on the ligand. These clusters trigger signaling from the cell surface, and subsequently are targeted to the Golgi in a lipid-raft dependent pathway. It also forms the cluster TLR2:TLR6:CD14:CD36 in response to diacylated lipopeptides and TLR2:TLR1:CD14 in response to triacylated lipopeptides (Triantafilou et al. 2006). It is required for normal uptake of M. tuberculosis, a process that is inhibited by M. tuberculosis LppM. Receptor heterodimerization and co-receptor engagement in TLR2 activation is induced by MIC1 and MIC4 from Toxoplasma gondii (Costa Mendonça-Natividade et al. 2019). Association of TMED2 and TMED7 with TLRs facilitates anterograde transport from the ER to the Golgi (Holm et al. 2023).	Eukaryota	Metazoa	TLR2 of Homo sapiens
8.A.43.1.17	CD14 of 375 aas and 2 TMSs, N- and C-terminal. In concert with LBP, it binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating the innate immune response to bacterial lipopolysaccharide (LPS) (Kelley et al. 2013). It acts via MyD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (Haziot et al. 1996). It also acts as a coreceptor for the TLR2:TLR6 heterodimer in response to diacylated lipopeptides, and for the TLR2:TLR1 heterodimer in response to triacylated lipopeptides; these clusters trigger signaling from the cell surface and subsequently are targeted to the Golgi in a lipid-raft dependent pathway (Triantafilou et al. 2006). It binds electronegative LDL (LDL^-) and mediates the cytokine release induced by LDL^- (Estruch et al. 2013).	Eukaryota	Metazoa	CD14 of Homo sapiens
8.A.43.1.18	Monocyte differentiation antigen CD14 of 483 aas and 2 TMSs, N- and C-terminal.	Eukaryota	Metazoa	CD14 of Sparus aurata (gilthead seabream)
8.A.43.1.19	Monocyte differentiation antigen CD14 of 461 aas and 2 TMSs, N- and C-terminal.	Eukaryota	Metazoa	CD14 of Alligator mississippiensis (American alligator)
8.A.43.1.20	Leucine-rich repeat transmembrane neuronal protein 4, LRRTM4, of 590 aas and two TMSs, one at the N-terminus, and one near the C-terminus. It may play a role in the development and maintenance of the vertebrate nervous system. It exhibits strong synaptogenic activity but is restricted to excitatory presynaptic differentiation. It is a member of the transsynaptic complex between rod photoreceptors and bipolar cells (Agosto and Wensel 2020).	Eukaryota	Metazoa	LRRTM4 of Homo sapiens
8.A.43.1.21	Leucine-rich repeats and immunoglobulin-like domains protein 1, LRIG1, of 1093 aas. It consists of a signal peptide, 15 tandem leucine-rich repeats with cysteine-rich N- and C-flanking domains, three immunoglobulin-like domains, a transmembrane domain, and a cytoplasmic tail (Guo et al. 2004). It acts as a feedback negative regulator of signaling by receptor tyrosine kinases, through a mechanism that involves enhancement of receptor ubiquitination and accelerated intracellular degradation (Gur et al. 2004). The functions of LRIG proteins in glioma have been reviewed (Mao et al. 2017).	Eukaryota	Metazoa	LRIG1 of Homo sapiens
8.A.43.1.22	Toll/interleukin-1 receptor domain-containing adapter protein, TIRAP or MAL, of 221 aas. It is an adapter involved in TLR2 and TLR4 signaling pathways in the innate immune response. It acts via IRAK2 and TRAF-6, leading to the activation of NF-kappa-B and resulting in cytokine secretion and the inflammatory response (Nagpal et al. 2009). Toll-like receptors (TLRs) play an essential role in the detection and elimination of invading microbes. They are type-1 transmembrane receptors, containing extracellular leucine rich repeats and an intracellular TIR domain. Upon stimulation, these receptors interact with specific TIR domain-containing adaptor proteins. Five such adaptors are present in mammals (McGettrick and O'Neill 2004).	Eukaryota	Opisthokonta	TIRAP of Homo sapiens
8.A.43.1.23	Kekkon-1, Kek-1 of 880 aas and 1 central TMS. It is a negative regulator of epidermal growth factor-activated receptor activity (Ghiglione et al. 2003).	Eukaryota	Metazoa	Kek-1 of Drosophila melanogaster (Fruit fly)
8.A.43.1.24	Leucine-rich repeat-containing protein 4B, LRRC4B, of 713 aas amd 2 TMSs. one at the N-terminus, and one near the C-terminus. It is a synaptic adhesion protein that regulates the formation of excitatory synapses. The trans-synaptic adhesion between LRRC4B and PTPRF regulates the formation of excitatory synapses in a bidirectional manner. It may be a biomarkers for the diagnosis of encephalitis (Xiong et al. 2021).	Eukaryota	Opisthokonta	LRRC4B of Homo sapiens
8.A.43.1.25	Toll-like receptor 1, TLR1, of 786 aas and 2 TMSs. Toll-like receptors (TLRs) comprise a family of transmembrane receptors whose signaling controls cellular processes of cell proliferation, survival, apoptosis, angiogenesis, remodeling, and repair of tissues. Polymorphisms in TLR genes can change the balance between pro and anti-inflammatory cytokines, modulating the risk of infection, chronic inflammation, and cancer (Quirino et al. 2021). TLR1 participates in the innate immune response to microbial agents, specifically recognizing diacylated and triacylated lipopeptides. It cooperates with TLR2 (TC# 8.A.43.1.16) to mediate the innate immune response to bacterial lipoproteins or lipopeptides (Lancioni et al. 2011), and it forms the activation cluster TLR2:TLR1:CD14 (CD14, TC# 8.A.43.1.17) in response to triacylated lipopeptides. This cluster triggers signaling from the cell surface and subsequently is targeted to the Golgi in a lipid-raft dependent pathway (Triantafilou et al. 2006). Association of TMED2 and TMED7 with TLRs facilitates anterograde transport from the ER to the Golgi (Holm et al. 2023).	Eukaryota	Opisthokonta	TLR1 of Homo sapiens
8.A.43.1.26	P-granule-associated novel protein 1, PAN1, a leucine-rich LRR-TM protein of 594 aas and 2 TMSs, one at the N-terminus and one near the C-terminus. It regulates diverse developmental processes including larval molting and gonad maturation (Gao et al. 2012; Gissendanner and Kelley 2013). The LRR-TM protein PAN-1 interacts with MYRF to promote its nuclear translocation in synaptic remodeling (Xia et al. 2021).	Eukaryota	Opisthokonta	PAN1 of Caenorhabditis elegans
8.A.43.1.27	Leucine-rich repeat transmembrane protein, FLRT3, of 649 aas and 2 TMSs near the N- and C-termini of the protein. The protein mediates cell-cell contacts that promote an increase both in neurite number and in neurite length. It also plays a role in the regulation of the density of glutamaergic synapses (Lu et al. 2015). Variants can give rise to high myopia, an eye disorder (Swierkowska et al. 2021).	Eukaryota	Opisthokonta	FLRT3 of Homo sapiens
8.A.43.1.35	The Toll-like receptor 3, TLR3, of 904 aas and 2 TMSs, one N-terminal and one at about residue 350. A cryoEM structure is available (Cai et al. 2022).	Eukaryota	Opisthokonta	TLR3 of Homo sapiens
8.A.43.1.36	Toll-like receptor 3, TLR3 of 911 aas and two TMSs, one at the N-terminus and one near the C-terminus at about residue 720. Its adaptor protein is the soluble TRIF (TIR-domain-containing adaptor-inducing interferon-beta) protein. The bioinformatics characteristics and expression of TLR3 and its adaptor protein TRIF in largemouth bass (Micropterus salmoides) upon Flavobacterium columnare infection has been described (Zhao et al. 2023).	Eukaryota	Opisthokonta	TLR3 and TRIF of Micropterus salmoides (largemouth bass)
8.A.43.2.1	TIR domain-containing adapter molecule 2, TICAM2 (TIRAP3, TIRP, TRAM) of 235 aas and 3 centrally located peaks of minor hydrophobicity that could be TMSs. It functions as sorting adapter in different signaling pathways to facilitate downstream signaling leading to type I interferon induction (Huai et al. 2015).	Eukaryota	Opisthokonta	TICAM2 of Homo sapiens
8.A.43.2.2	TICAM2 of 243 aas and possibly two TMSs, N- and C-terminal.	Eukaryota	Opisthokonta	TICAM2 of Branchiostoma lanceolatum
8.A.43.2.3	Uncharacterized protein of 497 aas and 0 TMSs.	Eukaryota	Opisthokonta	UP of Asterias rubens (European starfish)
8.A.43.2.4	TIR domain-containing adapter molecule 1 of 696 aas and possibly one TMS at about residue 450.	Eukaryota	Opisthokonta	Adapter of Nannospalax galili (Upper Galilee mountains blind mole rat)