TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
8.A.93.1.1









TMEM97 protein (the sigma2 receptor (sigma2R); Mac30; S2R) of 176 aas and 4 TMSs in a 1 + 2 + 1 TMS arrangement (Alon et al. 2017).  It is an ER resident protein that regulates the sterol transporter, NPC1 (TC# 2.A.6.6.1). It is involved in diseases as diverse as cancer and neurological disorders (Alon et al. 2017).  TMEM97 possesses the full suite of molecular properties that define the sigma2 receptor, and Asp29 and Asp56 are essential for ligand recognition (Alon et al. 2017). It is regulated by a number of drugs (Intagliata et al. 2020). The highly specific sigma(2)R/TMEM97 ligand, FEM-1689, alleviates neuropathic pain and inhibits the integrated stress response (Yousuf et al. 2023).

Eukaryota
Metazoa, Chordata
Sigma2 receptor of Homo sapiens
8.A.93.1.2









TMEM97 of 184 aas and 4 TMSs

Eukaryota
Metazoa, Chordata
TMEM97 of Gallus gallus (Chicken)
8.A.93.1.3









FM151 protein of 170 aas and 4 TMSs

Eukaryota
Heterolobosea
FM151 of Naegleria gruberi (Amoeba)
8.A.93.1.4









TMEM97 of 167 aas and 4 TMSs

Eukaryota
Discosea
TMEM97 of Acanthamoeba castellanii
8.A.93.2.1









Transmembrane 6 superfamily 2 (TM6SF2) of 377 aas and 9 or 10 TMSs; it regulates plasma lipids. TM6SF2 variants are associated with plasma lipid traits, cardiovascular disease (CVD) and non-alcoholic fatty liver disease (NAFLD) (Li et al. 2018). The mechanisms underlying TM6SF2 regulation of lipid metabolism, involving intestinal cholesterol absorption and hepatic cholesterol biosynthesis and transport, have been discussed (Li et al. 2018). It may be involved in nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) (Di Sessa et al. 2021); Longo et al. 2021). TM6SF2 and SAMM50 are associated with the development and severity of pediatric NAFLD. The impact of genetic variants is greater in overweight children. Four genetic variants have synergetic effects on the severity of pediatric NAFLD (Lee et al. 2022). Genetic polymorphisms in TM6SF2 predispose organisms to a higher risk of liver diseases (Rivera-Iñiguez et al. 2022). It  regulates uptake of sterols via NPC1 (TC# 2.A.6.6.1) and is a neuropathic pain target (Yousuf et al. 2023).

Eukaryota
Metazoa, Chordata
TM6SF2 of Homo sapiens
8.A.93.2.2









TM6SF1 family member of 381 aas and 9 TMSs

Eukaryota
Metazoa, Echinodermata
TM6SF1 protein of Strongylocentrotus purpuratus (Purple sea urchin)
8.A.93.2.3









Uncharacterized TC6SF1 protein of 370 aas and 9 TMSs

Eukaryota
Metazoa, Chordata
UP of Sarcophilus harrisii (Tasmanian devil) (Sarcophilus laniarius)
8.A.93.2.4









The TM6sf1 protein of 377 aas and 9 or 10 TMSs.  Deficiency or overexpression in the liver affects ApoB trafficking and plasma lipid levels, diminished hepatic triglycerides secretion, increased hepatic stestosis and affects atherosclerosis (Ehrhardt et al. 2017).

Eukaryota
Metazoa, Chordata
TM6SF1 of Homo sapiens