TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
*1.A.54.1.1









Presenilin-1 (PS-1; STM-1; E5-1; AD) Ca2+ leak channel (part of the γ-secretase complex; expression alters the lipid raft composition in neuronal membranes (Eckert and Müller, 2009)). The first 5 TMSs of presenilin-1 are homologous to the 5 TMS CD47 antigenic protein, a constituent of the osteoclast fusion complex (1.N.1.1.1), and CD47 is therefore a presenilin homologue (unpublished observations).  The active site of gamma-secretase resides in an aqueous catalytic pore within the lipid bilayer and is tapered around the catalytic aspartates (Sato et al. 2006). TMS 6 and TMS 7 contribute to the hydrophilic pore. Residues at the luminal portion of TMS 6 are predicted to form a subsite for substrate or inhibitor binding on the α-helix facing the hydrophilic milieu, whereas those around the GxGD catalytic motif within TMS 7 are water accessible (Sato et al. 2006).

Eukaryota
Metazoa
Presenilin-1 of Homo sapiens (467 aas; P49768)
*1.A.54.1.2









Presenilin-2 (PS-2; STM-2; E5-2; AD3 LP; AD5 PSN-2) Ca2+ leak channel
Eukaryota
Metazoa
Presenilin-2 of Homo sapiens (448 aas; P49810)
*1.A.54.2.1









Archaeal presenilin homologue (DUF1119; COG3389; PSN). Members of the peptidase A22B superfamily (found in many archaea, but not bacteria, shows some sequence similarity to members of the LIV-E family, e.g., 2.A.78.2.1))

Archaea
Euryarchaeota
PSN of Haloquadratum walsbyi (339 aas; 9 TMSs; CAJ51633)
*1.A.54.2.2









Presenilin homologue (DUF1119) of 301 aas and 9 TMSs with known 3-d structure. The amino-terminal domain, consisting of TM1-6, forms a horseshoe-shaped structure, surrounding TM7-9 of the carboxy-terminal domain. The two catalytic aspartate residues are located on the cytoplasmic side of TMS 6 and TMS 7, spatially close to each other and approximately 8 Å into the lipid membrane surface. Water molecules gain constant access to the catalytic aspartates through a large cavity between the amino- and carboxy-terminal domains. (Li et al. 2013).  Both protease and ion channel activities have been demostrated, and these two activities share the same active site (Kuo et al. 2015).

Archaea
Euryarchaeota
Presenilin homologue of Methanoculleus marisnigri
*1.A.54.3.1









Signal peptide peptidase-2A (SPP2A; 523 aas; 8TMSs) (no evidence for a transport function).

Eukaryota
Metazoa
SPP2A of Mus musculus (Q9JJF9)
*1.A.54.3.2









Signal peptide peptidase like 2A, SPPL2A

Eukaryota
Metazoa
SPPL2A of Homo sapiens
*1.A.54.3.3









Signal peptide peptidase, SppL3 of 385 aas and 9 TMSs. Cleaves the single TMS in the neuronal ceroid lipofuscinoses (NCLs), a group of proteins causing recessive disorders of childhood with overlapping symptoms including vision loss, ataxia, cognitive regression and premature death (Jules et al. 2017). CLN5 is implicated in the recruitment of the retromer complex to endosomes, which is required to sort the lysosomal sorting receptors from endosomes to the trans-Golgi network. It is initially translated as a type II transmembrane protein and subsequently cleaved by SPPL3 into a mature soluble protein consisting of residues 93-407 and an N-terminal fragment is then further cleaved by SPPL3 and SPPL2b and degraded in the proteasome (Jules et al. 2017).

Eukaryota
Metazoa
Spp of Homo sapiens
*1.A.54.3.4









Signal peptide peptidase, Spp

Eukaryota
Metazoa
Spp of Drosophila melanogaster
*1.A.54.4.1









The pre-flagelin peptidase of 230 aas and 6 TMSs, FlaK, with known 3-d structure (3.6Å resolution) (Hu et al. 2011).  This protein is a member of the presenilin/GxGD membrane protein family; it plays a dual role as protease and ion-conducting channel and is therefore called a "channzyme" (Kuo et al. 2015).

Archaea
Euryarchaeota
FlaK of Methanococcus maripaludis
*1.A.54.4.2









Leader peptidase of 342 aas

Archaea
Euryarchaeota
Leader peptidase of Natrinema pellirubrum
*1.A.54.4.3









Type IV leader peptidase of 289 aas and 7 TMSs.

Archaea
Euryarchaeota
peptidase of Methanobrevibacter smithii
*1.A.54.4.4









Peptidase of 375 aas

Archaea
Euryarchaeota
Peptidase of Thermococcus sibiricus
*1.A.54.4.5









Peptidase of 260 aas

Archaea
Euryarchaeota
Peptidase of Methanosphaerula palustris
*1.A.54.5.1









Prepilliin peptidase A24 of 167 aas and 6 TMSs.

Bacteria
Firmicutes
Peptidase of Desulfotomaculum hydrothermale
*1.A.54.5.2









Peptidase A24 prepilin type IV of 158 aas

Bacteria
Synergistetes
Peptidase of Aminobacterium colombiense
*1.A.54.5.3









Peptidase of 286 aas

Bacteria
Proteobacteria
Peptidase of Acinetobacter pittii
*1.A.54.5.4









Leader peptidase, PppA or YghH of 269 aas and 8 TMSs. May be able to flip phospholipids from one lipid monolayer to another as a scramblase (Smeijers et al. 2006).

Bacteria
Proteobacteria
PppA of E. coli
*1.A.54.6.1









Uncharacterized protein of 229 aas and 6 TMSs.

Archaea
Euryarchaeota
UP of Thermoplasma volcanium