Tclin Sigma non-opioid intracellular receptor 1

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Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane. Involved in the regulation of different receptors it plays a role in BDNF signaling and EGF signaling. Also regulates ion channels like the potassium channel and could modulate neurotransmitter release. Plays a role in calcium signaling through modulation together with ANK2 of the ITP3R-dependent calcium efflux at the endoplasmic reticulum. Plays a role in several other cell functions including proliferation, survival and death. Originally identified for its ability to bind various psychoactive drugs it is involved in learning processes, memory and mood alteration (PubMed:16472803, PubMed:9341151). Necessary for proper mitochondrial axonal transport in motor neurons, in particular the retrograde movement of mitochondria (By similarity).

This gene encodes a receptor protein that interacts with a variety of psychotomimetic drugs, including cocaine and amphetamines. The receptor is believed to play an important role in the cellular functions of various tissues associated with the endocrine, immune, and nervous systems. As indicated by its previous name, opioid receptor sigma 1 (OPRS1), the product of this gene was erroneously thought to function as an opioid receptor; it is now thought to be a non-opioid receptor. Mutations in this gene has been associated with juvenile amyotrophic lateral sclerosis 16. Alternative splicing of this gene results in transcript variants encoding distinct isoforms. [provided by RefSeq, Aug 2013]

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Property Summary

Ligand Count	1,855
NCBI Gene PubMed Count	88
PubMed Score	209.97

PubTator Score	84.16

Knowledge Summary

Patent

No data available

TINX Plot

Disease (7)

Disease	Target Count	Z-score	Confidence
Amyotrophic lateral sclerosis	451	3.958	2.0
AMYOTROPHIC LATERAL SCLEROSIS 16, JUVENILE	1	0.0	0.0
Amnesia	17	0.0	0.0
Cocaine-Related Disorders	92	0.0	0.0
Frontotemporal Lobar Degeneration	6	0.0	0.0
HIV Infections	102	0.0	0.0
Learning Disorders	29	0.0	0.0
Memory Disorders	40	0.0	0.0
Prenatal Exposure Delayed Effects	11	0.0	0.0
Seizures	596	0.0	0.0
Spinal muscular atrophy, Jerash type	2	0.0	0.0

Disease	Target Count
Schizophrenia	1160
Abnormal lower motor neuron morphology	6
Abnormal upper motor neuron morphology	11
Alcoholic Intoxication, Chronic	289
Autosomal recessive predisposition	1442
Babinski Reflex	100
Congenital pes cavus	88
Decreased motor NCV	22
Decreased muscle mass	28
Decreased tendon reflex	122
Distal amyotrophy	51
Distal limb muscle weakness due to peripheral neuropathy	62
Distal muscle weakness	62
Dysarthria	192
Electromyogram abnormal	49
Foot dorsiflexor weakness	27
Foot-drop	27
Gait abnormality	135
Hammer Toe	23
Hyperreflexia	209
Mood Disorders	184
Muscle Spasticity	195
Progressive disorder	142
Pseudobulbar behavioral symptoms	3
Pyramidal sign	29
Slow progression	89
Spinal muscular atrophy	34

Disease	Target Count
General anesthesia	53
Labor pain	4
Local anesthesia	40
Pain	103

Disease	Target Count	P-value
ovarian cancer	8520	3.9e-06
lung cancer	4740	2.3e-03
medulloblastoma, large-cell	6241	2.5e-03
colon cancer	1478	3.0e-03
pancreatic ductal adenocarcinoma liver metastasis	1962	3.7e-02

Disease	Target Count	Z-score	Confidence
Neurodegenerative disease	414	0.0	4.0

Disease	Target Count	Z-score	Confidence
Lateral sclerosis	15	3.042	1.5

Disease	Target Count
Distal hereditary motor neuropathy, Jerash type	1
Juvenile amyotrophic lateral sclerosis	4

Differential Expression (5)

Disease	log2 FC	p
colon cancer	1.600	3.0e-03
lung cancer	1.900	2.3e-03
medulloblastoma, large-cell	1.300	2.5e-03
ovarian cancer	1.400	3.9e-06
pancreatic ductal adenocarcinoma liver m...	-1.255	3.7e-02

Cells - Transformed fibroblasts 17,577

Liver 18,071

Uterus 17,618

Artery - Aorta 17,896

Ovary 17,971

Nerve - Tibial 18,007

Vagina 17,834

Artery - Tibial 17,631

Skin - Sun Exposed (Lower leg) 17,968

Skin - Not Sun Exposed (Suprapubic) 18,081

Artery - Coronary 17,949

Esophagus - Mucosa 18,076

Adipose - Visceral (Omentum) 17,937

Small Intestine - Terminal Ileum 17,954

Thyroid 18,024

Prostate 18,213

Adrenal Gland 18,071

Esophagus - Gastroesophageal Junction 18,000

Adipose - Subcutaneous 18,110

Esophagus - Muscularis 18,017

Colon - Sigmoid 18,089

Cells - EBV-transformed lymphocytes 18,186

Breast - Mammary Tissue 18,103

Brain - Cerebellum 17,983

Brain - Cerebellar Hemisphere 18,015

Stomach 17,879

Testis 18,518

Minor Salivary Gland 18,005

Brain - Hypothalamus 18,169

Spleen 17,614

Colon - Transverse 17,825

Pituitary 18,147

Brain - Frontal Cortex (BA9) 18,069

Brain - Cortex 18,039

Brain - Spinal cord (cervical c-1) 17,973

Lung 18,057

Brain - Nucleus accumbens (basal ganglia... 18,024

Heart - Atrial Appendage 17,896

Brain - Anterior cingulate cortex (BA24) 17,989

Brain - Caudate (basal ganglia) 18,001

Brain - Amygdala 18,006

Brain - Hippocampus 18,011

Pancreas 18,123

Brain - Substantia nigra 17,981

Brain - Putamen (basal ganglia) 17,863

Whole Blood 17,439

Kidney - Cortex 17,329

Heart - Left Ventricle 18,006

Muscle - Skeletal 17,778

Fetal Liver 8,402

Adult Liver 9,113

Adult Adrenal 8,475

Fetal Testis 7,955

Fetal Ovary 9,118

Adult Esophagus 4,936

Adult Ovary 10,192

CD4 Cells 7,773

Fetal Gut 8,640

Adult Urinary Bladder 7,592

Adult Testis 10,836

Adult Retina 10,115

CD8 Cells 9,840

Monocytes 7,422

B Cells 9,086

Adult Prostate 8,952

Fetal Heart 9,228

Adult Gallbladder 7,612

Adult Frontal Cortex 9,048

Adult Colon 7,915

NK Cells 8,475

Adult Lung 6,663

Platelets 6,131

Adult Kidney 6,723

Fetal Brain 7,866

Adult Heart 6,506

Adult Rectum 8,022

Adult Pancreas 9,168

Adult Spinal Cord 7,594

Adrenal gland

Blood platelet

Brain

Colon

Frontal lobe

Gall bladder

Gut

Heart

Kidney

Liver

Lung

B-lymphocyte

Monocyte

Natural killer cell

Esophagus

Ovary

Pancreas

Placenta 6,083

Prostate gland

Rectum

Retina

Spinal cord

Testis

Urinary bladder

BTO:0004410

BTO:0005453

adipose tissue 15,837

adrenal gland 15,963

appendix 16,247

bone marrow 14,571

breast 16,063

cerebral cortex 16,630

cervix, uterine 15,871

colon 15,959

duodenum 15,975

endometrium 16,349

epididymis 15,863

esophagus 15,898

fallopian tube 16,245

gallbladder 16,333

heart muscle 14,972

kidney 15,917

liver 14,587

lung 16,312

lymph node 15,833

ovary 15,408

pancreas 14,070

parathyroid gland 14,769

placenta 15,937

prostate 16,460

rectum 15,705

salivary gland 14,981

seminal vesicle 15,918

skeletal muscle 14,011

skin 16,206

small intestine 16,154

smooth muscle 15,857

spleen 15,972

stomach 16,099

testis 17,936

thyroid gland 15,959

tonsil 15,400

urinary bladder 15,814

Liver and Pancreas 16,750

Digestive Tract 17,369

Urinary Tract 16,678

Endocrine System 18,159

Blood and immune system 16,909

Respiratory system 16,393

Female tissues 17,400

Male tissues 17,142

Skin and soft tissues 17,230

Nervous System 16,725

Cardiovascular System 15,192

Brain 7,346

Breast cancer cell 221

Kidney 1,299

Liver 5,008

Lymphoblast 74

Mammary gland 415

Muscle 725

Thyroid gland 144

Choriocarcinoma cell 33

See source...

Brain 1,516

Nerve 290

Spinal cord 549

Retina 330

RGC-5 cell 11

See source...

Synonym

Accession	Q99720 D3DRM7 O00673 O00725 Q0Z9W6 Q153Z1 Q2TSD1 Q53GN2 Q7Z653 Q8N7H3 Q9NYX0
Symbols	SRBP ALS16 DSMA2 OPRS1 SR-BP SIG-1R SR-BP1 sigma1R hSigmaR1

Gene

SIGMAR1

Ortholog (12)

Species	Source	Disease
Zebrafish 9,725	Inparanoid OMA EggNOG
S.cerevisiae 1,798	Inparanoid EggNOG
Chimp 14,136	OMA EggNOG
Macaque 12,758	Inparanoid OMA EggNOG
Dog 15,069	Inparanoid OMA EggNOG
Horse 14,249	OMA EggNOG
Mouse 16,567	Inparanoid OMA EggNOG
Rat 15,112	Inparanoid OMA EggNOG
Chicken 7,823	Inparanoid OMA
Anole lizard 10,585	Inparanoid OMA EggNOG
Cow 15,316	Inparanoid OMA EggNOG
Opossum 12,223	Inparanoid OMA EggNOG

UniProt Keyword (24)

Complete proteome 20,231

Nucleus 5,259

Polymorphism 12,194

Reference proteome 20,231

Alternative splicing 10,528

Cell projection 826

Disease mutation 2,804

Cell membrane 3,390

Membrane 7,361

Receptor 1,502

See all...

GO Function (3)

identical protein binding 1,084

drug binding 75

opioid receptor activity 6

GO Component (13)

integral component of plasma membrane 1,418

integral component of membrane 3,665

cytoplasmic vesicle 217

endoplasmic reticulum 938

endoplasmic reticulum membrane 879

growth cone 116

postsynaptic membrane 210

cell junction 502

postsynaptic density 202

lipid droplet 72

See all...

GO Process (4)

nervous system development 321

lipid transport 46

protein homotrimerization 29

regulation of neuron apoptotic process 18

Compartment GO Term (65)

Asymmetric synapse 140

Bounding membrane of organelle 1,956

Cell 16,178

Cell junction 960

Cell part 16,177

Cell periphery 5,382

Cell projection 1,541

Cell projection part 850

Cytoplasm 10,983

Cytoplasmic part 9,247

Cytoplasmic vesicle 2,218

Endomembrane system 4,237

Endoplasmic reticulum 2,001

Endoplasmic reticulum chaperone complex 24

Endoplasmic reticulum membrane 1,103

See all...

MGI Phenotype (1)

behavior-neurological phenotype 3,401

HCA RNA Cell Line (56)

A-431 16,131

A549 15,174

AF22 16,160

AN3-CA 15,648

ASC TERT1 14,842

BEWO 16,726

BJ 15,448

BJ hTERT+ 15,353

BJ hTERT+ SV40 Large T+ 15,609

BJ hTERT+ SV40 Large T+ RasG12V 15,493

See all...

PDB (2)

...
More...

Drug (40)

pentazocine
pEC50 8.76

cisapride
pIC50 6.00

methysergide
pIC50 6.04

buflomedil
pKi 6.04

tetracaine
pKi 6.15

dexchlorpheniramine
pKi 6.16

raloxifene
pIC50 6.17

mepyramine
pKi 6.18

loperamide
pIC50 6.20

doxepin
pIC50 6.20

terbinafine
pIC50 6.25

phentolamine
pIC50 6.26

buspirone
pIC50 6.30

dimenhydrinate
pKi 6.31

chlorpromazine
pIC50 6.35

ticlopidine
pIC50 6.37

thioridazine
pIC50 6.44

mosapride
pIC50 6.52

promethazine
pIC50 6.54

promazine
pIC50 6.57

See all 40 drugs...

Ligand (1,814)

CHEMBL6224
pIC50 6.00

CHEMBL275528
pIC50 6.00

CHEMBL328986
pIC50 6.00

CHEMBL1089752
pIC50 6.00

CHEMBL557002
pIC50 6.01

CHEMBL285203
pIC50 6.01

CHEMBL336706
pIC50 6.02

CHEMBL320435
pIC50 6.02

CHEMBL2374421
pIC50 6.02

CHEMBL78356
pIC50 6.02

CHEMBL553745
pIC50 6.02

CHEMBL267930
pIC50 6.02

CHEMBL142617
pIC50 6.02

CHEMBL716
pKi 6.02

CHEMBL435046
pKi 6.03

CHEMBL419161
pKi 6.03

CHEMBL607156
pIC50 6.03

CHEMBL2391379
pIC50 6.03

CHEMBL296419
pKi 6.03

CHEMBL2105667
pKi 6.03

See all 1814 ligands...

Gene RIF (79)

AA Sequence

MQWAVGRRWAWAALLLAVAAVLTQVVWLWLGTQSFVFQREEIAQLARQYAGLDHELAFSRLIVELRRLHP      1 - 70
GHVLPDEELQWVFVNAGGWMGAMCLLHASLSEYVLLFGTALGSRGHSGRYWAEISDTIISGTFHQWREGT     71 - 140
TKSEVFYPGETVVHGPGEATAVEWGPNTWMVEYGRGVIPSTLAFALADTVFSTQDFLTLFYTLRSYARGL    141 - 210
RLELTTYLFGQDP                                                             211 - 223
//

Text Mined References (94)

Summary
Details

	PMID	Year	Title

Tclin Sigma non-opioid intracellular receptor 1 Add to cart View Collections Empty Collection

Property Summary

Knowledge Summary

Patent

No data available

TINX Plot

Disease (7)

Expression

Differential Expression (5)

Synonym

Gene

Ortholog (12)

UniProt Keyword (24)

GO Function (3)

GO Component (13)

GO Process (4)

Compartment GO Term (65)

MGI Phenotype (1)

HCA RNA Cell Line (56)

PDB (2)

Drug (40)

Ligand (1,814)

Gene RIF (79)

AA Sequence

Text Mined References (94)

Tclin Sigma non-opioid intracellular receptor 1

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