TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
8.A.47.1.1









Neuropilin and tolloid-like 1 (Neto1 or BTCL1) protein of 533 aas and 2 TMSs (Copits and Swanson 2012; Howe 2014). It is involved in the development and/or maintenance of neuronal circuitry and is an accessory subunit of the neuronal N-methyl-D-aspartate receptor (NMDAR), critical for maintaining the abundance of GRIN2A-containing NMDARs in the postsynaptic density. It also regulates long-term NMDA receptor-dependent synaptic plasticity and cognition, at least in the context of spatial learning and memory (Howe 2014). It is involved in the development and/or maintenance of neuronal circuitry and is an accessory subunit of the neuronal N-methyl-D-aspartate receptor (NMDAR), critical for maintaining the abundance of GRIN2A-containing NMDARs in the postsynaptic density. It also regulates long-term NMDA receptor-dependent synaptic plasticity and cognition, at least in the context of spatial learning and memory (Michishita et al. 2004).

Eukaryota
Metazoa, Chordata
Neto 1 of Homo sapiens
8.A.47.1.2









Neuropilin and tolloid-like protein 2, Neto2 (Neto-2; Neto 2) or BTCL2, of 525 aas and 2 TMSs, one N-terminal and a second near the C-terminus of the protein (Copits and Swanson 2012). It is an accessory subunit of neuronal kainate-sensitive glutamate receptors, GRIK2 and GRIK3. It increases kainate-receptor channel activity, slowing the decay kinetics of the receptors, without affecting their expression at the cell surface, and increasing the open probability of the receptor channels. It modulates the agonist sensitivity of kainate receptors and slows the decay of kainate receptor-mediated excitatory postsynaptic currents (EPSCs), thus directly influencing synaptic transmission. Neto1 and Neto2 are auxiliary subunits of kainate-type glutamate receptors (KARs) that regulate KAR trafficking and gating (Li et al. 2019). CryoEM structures of homotetrameric GluK2 in complex with NETO2 have been published; NETO2 accesses two broad faces of kainate receptors (He et al. 2021).

 

Eukaryota
Metazoa, Chordata
Neto2 pf Homo sapiens
8.A.47.1.3









Procollagen C-endopeptidase enhancer 1 isoform X2 of 477 aas and 1 N-terminal TMS.

Eukaryota
Metazoa, Chordata
Peptidase of Urocitellus parryii (Arctic ground squirrel)
8.A.47.1.4









Supressor of lurcher protein, Sol-1, of 594 aas and 2 TMSs, one N-terminal and one C-terminal.  Sol1 is an accessory protein required for glutamate-gated currents that participate in the gating of non-NMDA (N-methyl-D-aspartate) ionotropic glutamate receptors such as Glr-1. It is predicted to contain four extracellular beta-barrel-forming domains known as CUB domains. SOL-1 and GLR-1 colocalize to the cell surface and can be co-immunoprecipitated. By recording from neurons expressing GLR-1, SOL-1 is selectively required for glutamate-gated currents (Zheng et al. 2004) and regulates desensitization (Walker et al. 2006).

Eukaryota
Metazoa, Nematoda
Sol-1 of Caenorhabditis elegans
8.A.47.1.5









Neuropilin-1, NRP1, of 923 aas and 2 TMSs, N- and C-terminal. NRP1 localizes to mitochondria and interacts with the mitochondrial transporter, ABCB8 (TC# 3.A.1.201.22). NRP1 loss reduces ABCB8 levels, resulting in iron accumulation, iron-induced mitochondrial superoxide production, and iron-dependent EC senescence. The region of this protein that is homologous to other members of the Neuropilin (Neto) family are residues 26 to 245. Then there is a repeat sequence of about 120 residues, from 278 to 424 and repeated in residues 436 to 583. Residues 601 to the end show similarity to Meprin A (TC#8.A.77.2.1). NRP1 regulates mitochondrial iron transport via interaction with ABCB8/MITOSUR (Issitt et al. 2019). Neuropilin-1 mediates SARS-CoV-2 infection of astrocytes in brain organoids, inducing inflammation leading to dysfunction and death of neurons (Kong et al. 2022). Angiotensin converting enzyme 2 (ACE-2), transmembrane serine protease 2 (TMPRSS-2) and Neuropilin-1 cellular receptors support the entry of SARS-CoV-2 into susceptible human target cells including astrocytes in the blood brain barrier (BBB) (Malik et al. 2023). Neuropilin-1 interacts with VE-cadherin and TGFBR2 to stabilize adherens junctions and prevent activation of an endothelium under flow; it more generally stabilizes protein complexes at cell-cell junctions while supression endothelial inflamation (Bosseboeuf et al. 2023). Neuropilin-1 is essential for vascular endothelial growth factor A-mediated increase of sensory neuron activity and development of pain-like behaviors (Gomez et al. 2023).  Neuropilin 1 promotes unilateral ureteral obstruction-induced renal fibrosis via RACK1 in Renal tubular epithelial cells (Hou and Du 2023).

 

 

Eukaryota
Metazoa, Chordata
NRP1 of Homo sapiens
8.A.47.1.6









Neuropilin-2 of 931 aas and 2 TMSs, N- and C-terminal. It is a high affinity receptor for semaphorins 3C, 3F, VEGF-165 and VEGF-145 isoforms of VEGF, and the PLGF-2 isoform of PGF. It acts as a receptor for human cytomegalovirus pentamer-dependent entry in epithelial and endothelial cells (Martinez-Martin et al. 2018). Neuropilin-2 regulates androgen-receptor transcriptional activity in advanced prostate cancer (Dutta et al. 2022).

Eukaryota
Metazoa, Chordata
Neuropilin-2 of Homo sapiens
8.A.47.1.7









Proteinase R of 665 aas and 1 N-terminal TMS.

Eukaryota
Metazoa, Echinodermata
Proteinase R of Holothuria leucospilota
8.A.47.1.8









Tolloid-like protein 1 isoform X4 of 822 aas and 2 TMSs, N- and C-terminal.

Eukaryota
Metazoa, Arthropoda
Tolloid-like protein of Solenopsis invicta (red fire ant)