TMEM97
entrez
27346
canonical
uniprot
Q5BJF2
canonical
ensembl
ENSG00000109084
resolver
ensp
ENSP00000226230
resolver
enst
ENST00000226230
resolver
genesymbol
TMEM97
resolver
genesymbol_syn
MAC30
resolver
genesymbol_syn
S2R
resolver
hgnc
HGNC:28106
resolver
uniprot
B4DS02
resolver
uniprot
Q07823
resolver
uniprot_entry
SGMR2_HUMAN
resolver
uniprot_sec
B4DS02
resolver
uniprot_sec
Q07823
resolver
amino_acid_sequence
MGAPATRRCVEWLLGLYFLSHIPITLFMDLQAVLPRELYPVEFRNLLKWYAKEFKDPLLQEPPAWFKSFLFCELVFQLPFFPIATYAFLKGSCKWIRTPAIIYSVHTMTTLIPILSTFLFEDFSKASGFKGQRPETLHERLTLVSVYAPYLLIPFILLIFMLRSPYYKYEEKRKKK
uniprot
proteins
function
FUNCTION: Sigma-2 receptor implicated in the regulation of multiple cellular processes, including cholesterol biosynthesis and trafficking, membrane trafficking, autophagy, lipid membrane-associated protein trafficking, and stabilization of receptors at the cell surface, thereby contributing to the maintenance of cellular homeostasis(PubMed:19583955, PubMed:23922215, PubMed:25620095, PubMed:27378690, PubMed:28559337, PubMed:30443021, PubMed:34233061, PubMed:34799735, PubMed:35970844, PubMed:25566323). Forms a ternary complex with PGRMC1 and LDLR at the plasma membrane, promoting LDLR-mediated internalization of LDL cholesterol (PubMed:30443021). Reduces the availability of the lysosomal sterol transporter NPC1, likely through direct interaction, thereby regulating lipid transport, including cholesterol and LBPA, outside of late endosome/lysosome (PubMed:19583955, PubMed:27378690). Binds the regio- and stereoselective oxysterol 20(S)-hydroxycholesterol (20(S)-OHC). Ligand binding enhances association with NPC1 and modulates TMEM97-containing protein complexes involving PGRMC1 and TSPO, consistent with a role in cholesterol homeostasis (PubMed:34799735, PubMed:37047353). Also able to bind cholesterol (By similarity). Interacts with the salivary peptide histatin 1 (Hst 1/HTN1) at the ER membrane, which is critical for increasing mitochondria-ER contacts and stimulating Hst 1 wound healing properties (PubMed:34233061, PubMed:35970844). May alter the activity of some cytochrome P450 proteins (PubMed:22292588). Although sharing homology with sterol isomerases through the EXPERA domain, lacks sterol isomerase activity; instead, may function as a sterol or oxysterol sensor (PubMed:34880501, PubMed:25566323). Acts as an ER quality control factor by promoting proteolytic degradation of nonproductive and extramitochondrial precursor proteins in the ER membrane, thereby removing them from the ER surface (By similarity). {ECO:0000250|UniProtKB:Q3MHW7, ECO:0000269|PubMed:19583955, ECO:0000269|PubMed:25566323, ECO:0000269|PubMed:27378690, ECO:0000269|PubMed:28559337, ECO:0000269|PubMed:30443021, ECO:0000269|PubMed:34233061, ECO:0000269|PubMed:34799735, ECO:0000269|PubMed:34880501, ECO:0000269|PubMed:35970844, ECO:0000269|PubMed:37047353, ECO:0000303|PubMed:22292588, ECO:0000303|PubMed:23922215, ECO:0000303|PubMed:25620095}.
uniprot
proteins
mass_dalton
20848
uniprot
proteins
mutagenesis
MUTAGEN 11; /note="E->Q: Decreases DTG binding."; /evidence="ECO:0000269|PubMed:28559337"; MUTAGEN 29; /note="D->N: Abolishes DTG binding."; /evidence="ECO:0000269|PubMed:28559337"; MUTAGEN 37; /note="E->Q: No effect on DTG binding."; /evidence="ECO:0000269|PubMed:28559337"; MUTAGEN 42; /note="E->Q: No effect on DTG binding."; /evidence="ECO:0000269|PubMed:28559337"; MUTAGEN 53; /note="E->Q: No effect on DTG binding."; /evidence="ECO:0000269|PubMed:28559337"; MUTAGEN 56; /note="D->N: Abolishes DTG binding."; /evidence="ECO:0000269|PubMed:28559337"; MUTAGEN 61; /note="E->Q: No effect on DTG binding."; /evidence="ECO:0000269|PubMed:28559337"; MUTAGEN 73; /note="E->Q: No effect on DTG binding."; /evidence="ECO:0000269|PubMed:28559337"; MUTAGEN 121; /note="E->Q: No effect on DTG binding."; /evidence="ECO:0000269|PubMed:28559337"; MUTAGEN 122; /note="D->N: Decreases DTG binding."; /evidence="ECO:0000269|PubMed:28559337"; MUTAGEN 135; /note="E->Q: Decreases DTG binding."; /evidence="ECO:0000269|PubMed:28559337"; MUTAGEN 139; /note="E->Q: Decreases DTG binding."; /evidence="ECO:0000269|PubMed:28559337"; MUTAGEN 170; /note="E->Q: Decreases DTG binding."; /evidence="ECO:0000269|PubMed:28559337"; MUTAGEN 171; /note="E->Q: Decreases DTG binding."; /evidence="ECO:0000269|PubMed:28559337"; MUTAGEN 172..176; /note="Missing: Mislocalization to late endosomes and lysosomes."; /evidence="ECO:0000269|PubMed:27378690
uniprot
proteins
protein_family
TMEM97/sigma-2 receptor family
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15375745
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16625196
uniprot
proteins
pubmed
18070364
uniprot
proteins
pubmed
19583955
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22292588
uniprot
proteins
pubmed
23922215
uniprot
proteins
pubmed
25566323
uniprot
proteins
pubmed
25620095
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
27378690
uniprot
proteins
pubmed
28007569
uniprot
proteins
pubmed
28559337
uniprot
proteins
pubmed
30443021
uniprot
proteins
pubmed
34233061
uniprot
proteins
pubmed
34799735
uniprot
proteins
pubmed
34880501
uniprot
proteins
pubmed
35970844
uniprot
proteins
pubmed
37047353
uniprot
proteins
pubmed
7694637
uniprot
proteins
sequence_length
176
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Rough endoplasmic reticulum membrane {ECO:0000269|PubMed:19583955, ECO:0000269|PubMed:34233061, ECO:0000305|PubMed:27378690}; Multi-pass membrane protein {ECO:0000255}. Nucleus membrane {ECO:0000269|PubMed:19583955}; Multi-pass membrane protein {ECO:0000255}. Note=Localized at cell membrane and in lysosomes in sterol-depleted cells when expression of endogenous TMEM97 is stimulated (PubMed:19583955). Localized at cell membrane, probably in lipid rafts, in serum-starved conditions (PubMed:30443021). {ECO:0000269|PubMed:19583955, ECO:0000269|PubMed:30443021}.
uniprot
proteins
transmembrane_region
TRANSMEM 10..30; /note="Helical; Name=1"; /evidence="ECO:0000255"; TRANSMEM 69..89; /note="Helical; Name=2"; /evidence="ECO:0000255"; TRANSMEM 100..120; /note="Helical; Name=3"; /evidence="ECO:0000255"; TRANSMEM 141..161; /note="Helical; Name=4"; /evidence="ECO:0000255
uniprot
proteins