TUG1

Summary

TUG1 (taurine up-regulated 1, HGNC:26066) is a protein-coding gene on chromosome 22q12.2, encoding Taurine up-regulated 1 protein (A0A6I8PU40).

Predicted to enable cis-regulatory region sequence-specific DNA binding activity. Predicted to act upstream of or within several processes, including mitochondrion organization; photoreceptor cell development; and spermatogenesis. Predicted to be located in mitochondrial membrane and nuclear membrane. Predicted to be active in nucleus. Biomarker of Huntington’s disease.

Source: NCBI Gene 55000 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_001396518

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26066
Approved symbol	TUG1
Name	taurine up-regulated 1
Location	22q12.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20618, NCRNA00080, LINC00080
Ensembl gene	ENSG00000253352
Ensembl biotype	protein_coding
OMIM	614971
Entrez	55000

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 19 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000519077, ENST00000521091, ENST00000540687, ENST00000563812, ENST00000566220, ENST00000569149, ENST00000569384, ENST00000602393, ENST00000602971, ENST00000643071, ENST00000643077, ENST00000643280, ENST00000643553, ENST00000643877, ENST00000643920, ENST00000644027, ENST00000644773, ENST00000646021, ENST00000646496, ENST00000647354

RefSeq mRNA: 6 — MANE Select: NM_001396518 NM_001396518, NM_001398476, NM_001398477, NM_001398478, NM_001398479, NM_001398480

CCDS: CCDS93148

Canonical transcript exons

ENST00000644773 — 3 exons

Exon	Start	End
ENSE00002123935	30975170	30979395
ENSE00002577457	30972855	30973587
ENSE00003819967	30969265	30971779

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.7971 / max 327.2458, expressed in 1816 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191731	18.4987	1802
191732	6.1819	1676
191730	6.0774	1674
191734	0.9674	554
191733	0.0716	14

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
nipple	UBERON:0002030	98.93	gold quality
cardia of stomach	UBERON:0001162	98.90	gold quality
superficial temporal artery	UBERON:0001614	98.86	gold quality
pylorus	UBERON:0001166	98.69	gold quality
trabecular bone tissue	UBERON:0002483	98.68	gold quality
mammary duct	UBERON:0001765	98.65	gold quality
hair follicle	UBERON:0002073	98.61	gold quality
caput epididymis	UBERON:0004358	98.59	gold quality
male germ cell	CL:0000015	98.58	gold quality
sperm	CL:0000019	98.53	gold quality
lower lobe of lung	UBERON:0008949	98.39	gold quality
cauda epididymis	UBERON:0004360	98.34	gold quality
epithelium of mammary gland	UBERON:0003244	98.32	gold quality
oviduct epithelium	UBERON:0004804	98.28	gold quality
corpus epididymis	UBERON:0004359	98.26	gold quality
tongue squamous epithelium	UBERON:0006919	98.23	gold quality
mammalian vulva	UBERON:0000997	98.20	gold quality
renal medulla	UBERON:0000362	98.19	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.00	gold quality
inferior olivary complex	UBERON:0002127	97.93	gold quality
trigeminal ganglion	UBERON:0001675	97.91	gold quality
superior surface of tongue	UBERON:0007371	97.86	gold quality
embryo	UBERON:0000922	97.83	gold quality
urethra	UBERON:0000057	97.72	gold quality
upper leg skin	UBERON:0004262	97.72	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	97.71	gold quality
cervix epithelium	UBERON:0004801	97.65	gold quality
endometrium	UBERON:0001295	97.62	gold quality
cortical plate	UBERON:0005343	97.60	gold quality
olfactory bulb	UBERON:0002264	97.59	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.60

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): POU5F1, TP53

Literature-anchored findings (GeneRIF, showing 40)

• taurine upregulated gene 1 (TUG1) is necessary for the proper formation of photoreceptors in the developing rodent retina (PMID:15797018)
• Pc2, methylation controls the protein’s interaction with two distinct ncRNAs, TUG1 and NEAT2, which results in the exclusive subnuclear localization of methylated and unmethylated Pc2 in Polycomb bodies and interchromatin granules, respectively. (PMID:22078878)
• High taurine upregulated gene is associated with osteosarcoma. (PMID:23725133)
• Results suggest that p53-regulated TUG1 is a growth regulator, which acts in part through control of HOXB7 in non-small cell lung cancer. (PMID:24853421)
• Study indicates that TUG1 promotes proliferation and migration of ESCC cells and is a potential oncogene of ESCC. (PMID:25366138)
• TUG1 regulates blood brain barrier permeability via miR-144/tight junction protein expression by targeting HSF2. (PMID:26078353)
• Data indicate zinc finger E-box binding homeobox 2 (ZEB2) as a down-stream target of miR-145 and long non-coding RNA TUG1 exerted its function through the microRNA miR-145/ZEB2 axis. (PMID:26318860)
• TUG1 overexpression was induced by nuclear transcription factor SP1 and TUG1 could epigeneticly repress Kruppel-like factor 2 (KLF2) transcription in HCC cells by binding with PRC2 and recruiting it to KLF2 promoter region. (PMID:26336870)
• TUG1 was overexpressed in patients with osteosarcoma and strongly correlated with disease status. (PMID:26499949)
• Moreover, taurine upregulated gene 1 could induce the activation of caspase-3 and-9, with inhibited expression of Bcl-2, implying the mechanism in taurine upregulated gene 1-induced apoptosis. (PMID:26748401)
• tumor expression of lncRNA TUG1 plays a critical role in colorectal cancer metastasis. (PMID:26856330)
• Long noncoding RNA TUG1 was associated with PRC2 and that this association was required for epigenetic repression of cyclin-dependent protein kinase inhibitors thus contributing to the regulation of gastric cancer cell cycle and proliferation. (PMID:26913601)
• TUG1 has a tumor suppressive function and regulates PTEN expression in prostate cancer. (PMID:26975529)
• Its oncogenic activity is partially due to its repression of p21. and it may be a potential target for HCC therapy. (PMID:27154519)
• Our results indicate that TUG1 is identified as a novel oncogene in the morbid state of RCC, which potentially acts as a therapeutic target/biomarker in RCC. The graphic abstract of the present work. (PMID:27323757)
• Our findings suggest that elevated TUG1 expression is related to chemotherapy resistance and may help predict a poor prognostic outcome of esophageal squamous cell carcinoma (PMID:27329359)
• TUG1 is a recently identified oncogenic lncRNA whose aberrant upregulation has been detected in different types of cancer, including B-cell malignancies, oesophageal squamous cell carcinoma, bladder cancer, hepatocellular carcinoma and osteosarcoma. [review] (PMID:27339553)
• Study revealed that TUG1 was upregulated in glioblastoma tissues and cell lines. Its knockdown significantly suppressed glioblastoma induced angiogenesis as well as reduced the secretion and expression of VEGFA. TUG1 influenced tumor angiogenesis though directly binding to the miR-299. (PMID:27345398)
• TUG1 upregulation contributes to unusual hypervascularity of hepatoblastoma. (PMID:27362796)
• TUG1 could serve as a miR-26a sponge in human glioma cells, contributing to the upregulation of PTEN. This study revealed a new TUG1/miR-26a/PTEN regulatory mechanism and provided a further understanding of the tumor-suppressive role of TUG1 in glioma development. (PMID:27363339)
• TUG1 knockdown significantly inhibited cell proliferation, migration and invasion of colorectal cancer (CRC) in vitro. Knockdown of TUG1 may represent a rational therapeutic strategy for CRC patients in future. (PMID:27421138)
• Overexpression of long non-coding RNA TUG1 is associated with high-grade muscle-invasive bladder cancer. (PMID:27460088)
• Results show that LncRNA TUG1 is downregulated in non-small cell lung cancer (NSCLC) and can regulates the expression of CELF1. (PMID:27485439)
• qRT-PCR was used to analyze the expression level of TUG1 and p63 in 75 colon cancer tissues and the matched adjacent non-tumor tissue. p63-siRNA significantly decreased the mRNA level of p63 in HCT-116 and LoVo. The mRNA level of TUG1 was significantly increased in HCT-116 after transfection with p63-siRNA.Among the 75 colon cancer cases, the expression of TUG1 was significantly higher in colon cancer tissues vs. control (PMID:27634385)
• High expression of TUG1 is associated with osteosarcoma. (PMID:27658774)
• knock-down of TUG1 induced cell apoptosis and altered the protein expression levels of apoptosis-related mediators in ovarian cancer cells. (PMID:27693324)
• High TUG1 long noncoding RNA expression is associated with metastasis in breast cancer. (PMID:27848085)
• Notch1 activation in glioma stem cells specifically induces expression of the long noncoding RNA, TUG1. (PMID:27922002)
• LncRNA TUG1 inhibits TGF-beta induction of lung cell proliferation in COPD. (PMID:27932875)
• The results showed that TUG1 was significantly overexpressed and miR-145-5p was dramatically downregulated in GC cell lines. TUG1 knockdown strikingly inhibited cell proliferation and invasion in vitro and markedly suppressed tumor growth in vivo. (PMID:27983921)
• these results suggested that TUG1 mediates cell growth and chemoresistance of SCLC by regulating LIMK2b via EZH2. (PMID:28069000)
• Results show that TUG1 expression is significantly upregulated in cervical cancer, and promotes the proliferation of cervical cancer cells. Its knockdown decreases migration and invasion of cancer cells which provide evidence that TUG1 acts as an oncogene in cervical cancer. (PMID:28088836)
• knock-down of TUG1 suppressed cell growth, proliferation and invasion, and also induced apoptosis of oral squamous cell carcinoma (OSCC) possibly via targeting Wnt/beta-catenin signaling. Our data suggest that knock-down of TUG1 may represent a novel therapeutic target for management of OSCC. (PMID:28119088)
• Increased TUG1 expression was associated with a higher TNM staging and poorer overall survival in tumor patients. (PMID:28164690)
• LncRNA TUG1 promotes gallbladder carcinoma cell proliferation, metastasis and epithelial-mesenchymal transition progression by functioning as a miRNA sponge to abrogate the endogenous effect of miR-300. (PMID:28178615)
• TUG1 affected ROCK1 expression and ROCK1-mediated migration/invasion by working as a competitive endogenous RNA (ceRNA) via miR-335-5p. (PMID:28205334)
• Long non-coding RNA TUG1 mediates methotrexate resistance in colorectal cancer via miR-186/CPEB2 axis. (PMID:28302487)
• LncRNA TUG1 knockdown enhances radiosensitivity of bladder cancer by suppressing HMGB1 expression. (PMID:28376901)
• TUG1 modulated lens epithelial cell apoptosis through miR-421/caspase-3 axis. These findings will offer a novel insight into the pathogenesis of cataract. (PMID:28392351)
• lncRNA-TUG1 enhances the evolution and progression of EC through inhibiting miR-299 and miR-34a-5p. (PMID:28404901)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tug1	ENSMUSG00000056579
rattus_norvegicus	Tug1	ENSRNOG00000064262

Protein

Protein identifiers

Taurine up-regulated 1 protein — A0A6I8PU40 (reviewed: A0A6I8PU40)

All UniProt accessions (1): A0A6I8PU40

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus membrane. Mitochondrion membrane. Cytoplasm.

Tissue specificity. Ubiquitous. Highly expressed in testis.

RefSeq proteins (6): NP_001383447, NP_001385405, NP_001385406, NP_001385407, NP_001385408, NP_001385409 (=MANE)

Domains & families (InterPro)

UniProt features (5 total): topological domain 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0A6I8PU40-F1	43.33	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 158 (showing top): MODULE_97, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GCANCTGNY_MYOD_Q6, CMYB_01, MODULE_182, CAGCTG_AP4_Q5, YY1_Q6, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, YY1_02, NF1_Q6_01, IRF1_Q6, WTGAAAT_UNKNOWN, ZIC1_01, PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP, HFH1_01

GO Biological Process (1): regulation of eye photoreceptor cell development (GO:0042478)

GO Molecular Function (0):

GO Cellular Component (6): nuclear membrane (GO:0031965), mitochondrial membrane (GO:0031966), nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
organelle membrane	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
eye photoreceptor cell development	1
regulation of photoreceptor cell differentiation	1
regulation of cell development	1
nucleus	1
nuclear envelope	1
mitochondrion	1
mitochondrial envelope	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A1W2PPE3, A0A3B3IS91, A0A6I8MX38, A0A6I8PU40, A8MTW9, B1AH88, B3EWF7, C0HLS1, C0HMD6, H3BQW9, I3L0S3, I3L1E1, O70738, O75638, P03289, P0C880, P0DI83, P11300, P13985, P16807, P29164, P33485, P59091, P80612, Q01480, Q01900, Q3SYB3, Q5JLA7, Q5SY85, Q5T4H9, Q63003, Q6EEV4, Q6VB84, Q86SI9, Q8N1I8, Q8N1X5, Q8N319, Q8N6K4, Q8N6U2, Q8N726

Diamond homologs: A0A6I8MX38, A0A6I8PU40

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000116196 (22:30970885 G>T), RS1000284790 (22:30970519 G>C), RS1000333069 (22:30976224 GAA>G), RS1000808730 (22:30975994 C>T), RS1001040346 (22:30967743 A>G,T), RS1001468057 (22:30967468 G>A,C,T), RS1001525510 (22:30976365 G>C), RS1001659924 (22:30976033 T>C), RS1001770801 (22:30970436 A>G), RS1001842969 (22:30976551 C>T), RS1002174710 (22:30976843 C>T), RS1002367208 (22:30971856 C>T), RS1002524412 (22:30967839 T>C), RS1002872141 (22:30971574 C>G,T), RS1003043767 (22:30969253 C>G,T)

Disease associations

OMIM: gene MIM:614971 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

38 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, increases expression, affects cotreatment, decreases expression	2
sodium arsenite	increases abundance, increases expression, affects response to substance	2
Doxorubicin	decreases expression, decreases response to substance, increases expression	2
Cadmium Chloride	increases expression	2
urushiol	increases expression	1
quinone	increases expression, decreases response to substance, decreases expression, decreases reaction, increases cleavage	1
alpha-pinene	increases abundance, affects cotreatment, decreases expression, increases oxidation	1
beta-lapachone	increases expression	1
mono-(2-ethylhexyl)phthalate	affects expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
monomethylarsonic acid	increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression, increases oxidation	1
polydatin	decreases expression	1
monomethylarsonous acid	decreases expression	1
mono(2-ethyl-5-hydroxyhexyl) phthalate	affects expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	decreases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases oxidation	1
Arsenic	increases abundance, affects response to substance, increases expression	1
Benzene	decreases expression	1
Cacodylic Acid	increases expression	1
Coumestrol	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Folic Acid	increases expression	1
Glucose	decreases expression	1
Indomethacin	decreases expression, affects cotreatment	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.