Sigma intracellular receptor 2 (TMEM97)

The protein contains 176 amino acids for an estimated molecular weight of 20848 Da.

 

Intracellular orphan receptor that binds numerous drugs and which is highly expressed in various proliferating cancer cells (PubMed:28559337). Corresponds to the sigma-2 receptor, which is thought to play important role in regulating cell survival, morphology and differentiation (PubMed:23922215, PubMed:25620095). Under investigation for its potential diagnostic and therapeutic uses (PubMed:23922215, PubMed:25620095). May play a role as a regulator of cellular cholesterol homeostasis (PubMed:19583955). May function as sterol isomerase (PubMed:25566323). May alter the activity of some cytochrome P450 proteins (PubMed:22292588). (updated: Nov. 22, 2017)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.


Interpro domains
Total structural coverage: 79%
Model score: 0

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The reference OMIM entry for this protein is 612912

Transmembrane protein 97; tmem97
Mac30

DESCRIPTION

TMEM97 is a conserved integral membrane protein that plays a role in controlling cellular cholesterol levels (Bartz et al., 2009).

CLONING

Using a phage subtraction library to identify genes expressed in normal leptomeningeal cells but not in a meningioma cell line, followed by RT-PCR, Murphy et al. (1993) cloned TMEM97, which they called MAC30. Northern blot analysis detected transcripts of about 2.3 and 2.8 kb in normal leptomeningeal cells and in a cell line derived from these cells. Using differential display RT-PCR to identify genes expressed in fetal but not adult liver, Malhotra et al. (1999) obtained a partial MAC30 clone. Northern blot analysis detected transcripts of about 2.3 and 2.8 kb in 10-, 16-, and 20-week fetal liver, but not in adult liver. Using real-time quantitative PCR, Kayed et al. (2004) found variable MAC30 expression in all normal human tissues examined, with highest expression in testis and stomach and lowest expression in thyroid, thymus, and adipose tissue. In situ hybridization detected MAC30 in normal pancreatic acini, islets, and large ducts. Immunohistochemical analysis showed MAC30 protein in the cytoplasm of peripheral pancreatic islet cells, in endothelial and smooth muscle cells of blood vessels, and in nerves, monocytes, and fibroblasts. In esophagus, MAC30 was detected in cytoplasm of mucosal cells, particularly in the superficial and intermediate epithelial layers. Gastric submucosa and muscularis and normal colonic epithelium exhibited staining patterns similar to that of esophagus. Bartz et al. (2009) reported that the full-length 176-amino acid TMEM97 protein contains an N-terminal signal peptide and 4 transmembrane domains.

GENE FUNCTION

Murphy et al. (1993) found that MAC30 expression was downregulated in meningiomas and Schwann cell tumors compared with normal leptomeningeal cells. Kayed et al. (2004) found that expression of MAC30 was significantly increased in breast and colon cancers and significantly decreased in pancreatic and renal cancers compared with normal tissue. Using microarray analysis, Wilcox et al. (2007) found that TMEM97 and several genes regulating cholesterol and lipid homeostasis were upregulated in cultured ovarian surface epithelial (OSE) cells treated with progesterone. TMEM97 was the most highly upregulated gene identified. Real-time quantitative RT-PCR analysis showed that TMEM97 expression was downregulated in ovarian cancer cells relative to normal OSE cells. Database analysis suggested that expression of TMEM97 is coregulated with that of cholesterol biosynthesis genes in normal human tissues. Wilcox et al. (2007) proposed that TMEM97 may play a role in cholesterol and lipid metabolism. Using genomewide expression profiling and RT-PCR, Bartz et al. (2009) found that TMEM97 was upregulated to an extent similar to that of LDL receptor (LDLR; 606945) following sterol depletion in HeLa cells. TMEM97 expression was also upregulated following knockdown of LDLR via small interfering RNA (siRNA). Bartz et al. (2009) identified a sterol regulatory element-1 (SRE1) consensus sequence upstream of the TMEM97 transcription initiation site, and siRNA-mediated knockdown of SREBP2 (SREBF2; 600481) suppressed TMEM97 expression in sterol-depleted cells. Knockdown of TMEM97 via siRNA reduced the number of LDL-containing endosomes in HeLa cells and reduced cellular uptake of radiolabeled cholesterol. Restoration of TMEM97 expression rescu ... More on the omim web site

Subscribe to this protein entry history

May 12, 2019: Protein entry updated
Automatic update: model status changed

Nov. 17, 2018: Protein entry updated
Automatic update: model status changed

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Oct. 27, 2017: Protein entry updated
Automatic update: model status changed

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 612912 was added.

Feb. 25, 2016: Protein entry updated
Automatic update: model status changed

Feb. 24, 2016: Protein entry updated
Automatic update: model status changed

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed