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Protein

Sigma intracellular receptor 2

Gene

TMEM97

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).3 Publications1 Publication2 Publications

Miscellaneous

Sigma receptors are classified into two subtypes (Sigma-1 and Sigma-2) based on their different pharmacological profile. Sigma-2 receptors are identified by radioligand-binding studies as a binding site with high affinity for di-o-tolylguanidine (DTG) and haloperidol.1 Publication
Potentially useful for cancer diagnostics or as target for anticancer therapeutics or adjuvant anticancer treatment agents (PubMed:23922215). Some exogenous ligands display a neuroprotective effect (PubMed:25620095).2 Publications

GO - Biological processi

  • cholesterol homeostasis Source: UniProtKB
  • regulation of cell growth Source: UniProtKB

Protein family/group databases

TCDBi8.A.93.1.1. the sigma2 receptor or tmem97 (s2r) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Sigma intracellular receptor 2Curated
Short name:
Sigma-2 receptor1 Publication
Short name:
Sigma2 receptor1 Publication
Alternative name(s):
Meningioma-associated protein 301 Publication
Transmembrane protein 97Imported
Gene namesi
Name:TMEM97Imported
Synonyms:MAC301 Publication, S2R1 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000109084.13.
HGNCiHGNC:28106. TMEM97.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 9CytoplasmicSequence analysis9
Transmembranei10 – 30Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini31 – 68ExtracellularSequence analysisAdd BLAST38
Transmembranei69 – 89Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini90 – 99CytoplasmicSequence analysis10
Transmembranei100 – 120Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini121 – 140ExtracellularSequence analysisAdd BLAST20
Transmembranei141 – 161Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini162 – 176CytoplasmicSequence analysisAdd BLAST15

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi11E → Q: Decreases DTG binding. 1 Publication1
Mutagenesisi29D → N: Abolishes DTG binding. 1 Publication1
Mutagenesisi37E → Q: No effect on DTG binding. 1 Publication1
Mutagenesisi42E → Q: No effect on DTG binding. 1 Publication1
Mutagenesisi53E → Q: No effect on DTG binding. 1 Publication1
Mutagenesisi56D → N: Abolishes DTG binding. 1 Publication1
Mutagenesisi61E → Q: No effect on DTG binding. 1 Publication1
Mutagenesisi73E → Q: No effect on DTG binding. 1 Publication1
Mutagenesisi121E → Q: No effect on DTG binding. 1 Publication1
Mutagenesisi122D → N: Decreases DTG binding. 1 Publication1
Mutagenesisi135E → Q: Decreases DTG binding. 1 Publication1
Mutagenesisi139E → Q: Decreases DTG binding. 1 Publication1
Mutagenesisi170E → Q: Decreases DTG binding. 1 Publication1
Mutagenesisi171E → Q: Decreases DTG binding. 1 Publication1

Organism-specific databases

DisGeNETi27346.
OpenTargetsiENSG00000109084.
PharmGKBiPA143485635.

Polymorphism and mutation databases

BioMutaiTMEM97.
DMDMi74736009.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002545671 – 176Sigma intracellular receptor 2Add BLAST176

Proteomic databases

EPDiQ5BJF2.
MaxQBiQ5BJF2.
PaxDbiQ5BJF2.
PeptideAtlasiQ5BJF2.
PRIDEiQ5BJF2.
TopDownProteomicsiQ5BJF2.

PTM databases

iPTMnetiQ5BJF2.
PhosphoSitePlusiQ5BJF2.
SwissPalmiQ5BJF2.

Expressioni

Tissue specificityi

Widely expressed in normal tissues. Expressed in pancreatic, renal, breast, colon, ovarian surface epithelial (OSE) cells. Highly expressed in various proliferating cancer cells (PubMed:23922215).1 Publication3 Publications

Inductioni

Up-regulated in ovarian surface epithelial (OSE) cells with progesterone.1 Publication

Gene expression databases

BgeeiENSG00000109084.
CleanExiHS_TMEM97.
ExpressionAtlasiQ5BJF2. baseline and differential.
GenevisibleiQ5BJF2. HS.

Organism-specific databases

HPAiHPA044795.

Interactioni

Subunit structurei

Interacts with NPC1.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
ASZ1Q8WWH44EBI-12111910,EBI-12239061

Protein-protein interaction databases

BioGridi118158. 14 interactors.
IntActiQ5BJF2. 10 interactors.
STRINGi9606.ENSP00000226230.

Structurei

3D structure databases

ProteinModelPortaliQ5BJF2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini10 – 158EXPERAPROSITE-ProRule annotationAdd BLAST149

Sequence similaritiesi

Belongs to the TMEM97/sigma-2 receptor family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IX1Z. Eukaryota.
ENOG4111RR6. LUCA.
GeneTreeiENSGT00390000007149.
HOGENOMiHOG000031140.
HOVERGENiHBG079913.
InParanoidiQ5BJF2.
OMAiEWLLGLY.
OrthoDBiEOG091G0P5K.
PhylomeDBiQ5BJF2.
TreeFamiTF300241.

Family and domain databases

InterProiView protein in InterPro
IPR033118. EXPERA.
IPR016964. Transmembrane_97.
PIRSFiPIRSF031032. TMP_97_prd. 1 hit.
PROSITEiView protein in PROSITE
PS51751. EXPERA. 1 hit.

Sequencei

Sequence statusi: Complete.

Q5BJF2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGAPATRRCV EWLLGLYFLS HIPITLFMDL QAVLPRELYP VEFRNLLKWY
60 70 80 90 100
AKEFKDPLLQ EPPAWFKSFL FCELVFQLPF FPIATYAFLK GSCKWIRTPA
110 120 130 140 150
IIYSVHTMTT LIPILSTFLF EDFSKASGFK GQRPETLHER LTLVSVYAPY
160 170
LLIPFILLIF MLRSPYYKYE EKRKKK
Length:176
Mass (Da):20,848
Last modified:April 12, 2005 - v1
Checksum:i685248D421877F84
GO

Sequence cautioni

The sequence AAA16188 differs from that shown. Reason: Frameshift at position 5.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti5A → S in AAA16188 (PubMed:7694637).Curated1
Sequence conflicti34L → V in AAA16188 (PubMed:7694637).Curated1
Sequence conflicti113P → L in AAA16188 (PubMed:7694637).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L19183 mRNA. Translation: AAA16188.1. Frameshift.
AK299511 mRNA. Translation: BAG61464.1.
AC002094 Genomic DNA. No translation available.
BC091504 mRNA. Translation: AAH91504.1.
CCDSiCCDS11226.2.
PIRiI65744.
RefSeqiNP_055388.2. NM_014573.2.
UniGeneiHs.199695.

Genome annotation databases

EnsembliENST00000226230; ENSP00000226230; ENSG00000109084.
GeneIDi27346.
KEGGihsa:27346.
UCSCiuc002hat.3. human.

Similar proteinsi

Entry informationi

Entry nameiSGMR2_HUMAN
AccessioniPrimary (citable) accession number: Q5BJF2
Secondary accession number(s): B4DS02, Q07823
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: April 12, 2005
Last modified: September 27, 2017
This is version 95 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Caution

The molecular identity of the sigma-2 receptor has been unclear for a long time. It is now identified as TMEM97 (PubMed:28559337). Previously identified as PGRMC1 (AC O00264) (PubMed:22292588, PubMed:28007569).1 Publication2 Publications

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families