TNFRSF1A: Polycystic Ovarian Syndrome Database

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TNFRSF1A

Gene Information

Gene Ontology (GO)

Protein Information

Associated Diseases

Pathways

References

Gene Information

Gene Symbol

TNFRSF1A

Aliases

CD120a, FPF, TBP1, TNF-R, TNF-R-I, TNF-R55, TNFAR, TNFR1, TNFR55, TNFR60, p55, p55-R, p60

Entrez Gene ID

7132

Gene Name

TNF receptor superfamily member 1A

Chromosomal Location

12p13.31

HGNC ID

HGNC:11916

Summary

This gene encodes a member of the TNF receptor superfamily of proteins. The encoded receptor is found in membrane-bound and soluble forms that interact with membrane-bound and soluble forms, respectively, of its ligand, tumor necrosis factor alpha. Binding of membrane-bound tumor necrosis factor alpha to the membrane-bound receptor induces receptor trimerization and activation, which plays a role in cell survival, apoptosis, and inflammation. Proteolytic processing of the encoded receptor results in release of the soluble form of the receptor, which can interact with free tumor necrosis factor alpha to inhibit inflammation. Mutations in this gene underlie tumor necrosis factor receptor-associated periodic syndrome (TRAPS), characterized by fever, abdominal pain and other features. Mutations in this gene may also be associated with multiple sclerosis in human patients. [provided by RefSeq, Sep 2016]

RefSeq DNA

NG_007506.1

RefSeq mRNA

NR_144351.2, NM_001065.4, NM_001346091.2, NM_001346092.2, NM_001065.3

e!Ensembl

Gene	ENSG00000067182
Transcript	ENST00000534885, ENST00000162749, ENST00000543995, ENST00000540022, ENST00000539372, ENST00000366159, ENST00000543048, ENST00000440083, ENST00000536194
Protein	ENSP00000441803, ENSP00000162749, ENSP00000442405, ENSP00000438343, ENSP00000442059, ENSP00000380389, ENSP00000439981, ENSP00000413224, ENSP00000442919

Gene Ontology (GO)

Show/Hide all(27 )

GO ID	Ontology	Function	Evidence	Reference
GO:0006954	Biological process	Inflammatory response	IBA	21873635
GO:0008625	Biological process	Extrinsic apoptotic signaling pathway via death domain receptors	TAS	8612133
GO:0033209	Biological process	Tumor necrosis factor-mediated signaling pathway	IMP	25816133
GO:0033209	Biological process	Tumor necrosis factor-mediated signaling pathway	TAS	24966471
GO:0042531	Biological process	Positive regulation of tyrosine phosphorylation of STAT protein	IMP	21410936
GO:0043123	Biological process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IEP	12761501
GO:0045944	Biological process	Positive regulation of transcription by RNA polymerase II	IMP	21410936
GO:0050728	Biological process	Negative regulation of inflammatory response	IMP	13130484
GO:0071260	Biological process	Cellular response to mechanical stimulus	IEP	19593445
GO:0072659	Biological process	Protein localization to plasma membrane	IMP	25816133
GO:1903140	Biological process	Regulation of establishment of endothelial barrier	IMP	25816133
GO:0000139	Cellular component	Golgi membrane	IDA	22801493
GO:0002947	Cellular component	Tumor necrosis factor receptor superfamily complex	TAS	24966471
GO:0005576	Cellular component	Extracellular region	NAS	12189246
GO:0005615	Cellular component	Extracellular space	IDA	13130484
GO:0005739	Cellular component	Mitochondrion	IBA	21873635
GO:0005887	Cellular component	Integral component of plasma membrane	TAS	1698610
GO:0016020	Cellular component	Membrane	TAS	24966471
GO:0043235	Cellular component	Receptor complex	IBA	21873635
GO:0043235	Cellular component	Receptor complex	IDA	23382219
GO:0045121	Cellular component	Membrane raft	IBA	21873635
GO:0045121	Cellular component	Membrane raft	IDA	17010968
GO:0005031	Molecular function	Tumor necrosis factor-activated receptor activity	IBA	21873635
GO:0005031	Molecular function	Tumor necrosis factor-activated receptor activity	TAS	2158863
GO:0005515	Molecular function	Protein binding	IPI	1087798, 2848815, 7758105, 8565075, 8943045, 8985253, 9115275, 10848577, 11684708, 12887920, 14743216, 15465831, 16611992, 18022363, 19524513, 19641494, 19781631, 20080539, 20103630, 22028622, 22817896, 23955153, 24070898, 24130170, 24440909, 25241761, 25911380, 30561431
GO:0043120	Molecular function	Tumor necrosis factor binding	IBA	21873635
GO:0043120	Molecular function	Tumor necrosis factor binding	IPI	9435233

Protein Information

Protein Name

Tumor necrosis factor receptor superfamily member 1A, TNF-R1, TNF-RI, TNFR-I, tumor necrosis factor binding protein 1, tumor necrosis factor receptor 1A isoform beta, tumor necrosis factor receptor type 1, tumor necrosis factor-alpha receptor

Function

Receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase

Refseq Proteins

, NP_001056.1, NP_001333020.1, NP_001333021.1

UniProt

P19438

PDB

1TNR, 1EXT, 1FT4, 1ICH, 1NCF

Pathways
	KEGG	Reactome
	MAPK signaling pathway Cytokine-cytokine receptor interaction Viral protein interaction with cytokine and cytokine receptor NF-kappa B signaling pathway Sphingolipid signaling pathway mTOR signaling pathway Apoptosis Apoptosis - multiple species Necroptosis Osteoclast differentiation TNF signaling pathway Adipocytokine signaling pathway Insulin resistance Non-alcoholic fatty liver disease (NAFLD) Alzheimer disease Amyotrophic lateral sclerosis (ALS) Chagas disease (American trypanosomiasis) Toxoplasmosis Tuberculosis Hepatitis C Human cytomegalovirus infection Influenza A Human papillomavirus infection Human T-cell leukemia virus 1 infection Kaposi sarcoma-associated herpesvirus infection Herpes simplex virus 1 infection Human immunodeficiency virus 1 infection Fluid shear stress and atherosclerosis	TNFR1-induced proapoptotic signaling Regulation of TNFR1 signaling TNFR1-induced NFkappaB signaling pathway TNFR1-mediated ceramide production TNFs bind their physiological receptors Interleukin-10 signaling TNF signaling

Interactions

STRING	MINT	IntAct
ENSP00000223864		Q9HBL7

View interactions

Associated Diseases

Show/Hide all(13 )

Disease group	Disease Name	References
Cardiovascular Diseases
	Heart Failure	16360360
	Myocardial Failure	16360360
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
	Cystic Fibrosis	16463024
	Genetic Diseases	23965844, 26821543, 26965498, 26299986, 24393624, 27068928, 26598380, 25637003, 26992170
	Fibrocystic Disease of Pancreas	16463024
Digestive System Diseases
	Biliary Cirrhosis	21399635, 28425483, 26394269, 22961000
	Cholangitis	26974007
	Crohn Disease	26974007
	Colitis	26974007
Ear Or Mastoid Diseases
Ear Or Mastoid Diseases	Meniere Disease	28787010
Endocrine System Diseases
	Diabetes Mellitus	11882518
	PCOS	28946816
Immune System Diseases
Immune System Diseases	Autoimmune Diseases	21074606
Musculoskeletal Diseases
Musculoskeletal Diseases	Spondylitis	26974007, 23749187
Neoplasms
Neoplasms	Multiple Sclerosis	19525953, 21833088, 24076602
Nervous System Diseases
Nervous System Diseases	Cerebral Ischemia	15829914
Nutritional and Metabolic Diseases
Nutritional and Metabolic Diseases	TRAPS	14610673, 10199409, 13130484, 10902757, 11443543, 11175303, 9585614, 9529351, 7156325, 1402641
Psychiatric/Brain disorders
	Mental Depression	24094876, 21194425, 21097524, 16458261, 17094069
	Schizophrenia	20659789
Respiratory Tract Diseases
	Pneumonia	21625544
	Chronic Lung Injury	10781441
Skin and Connective Tissue Diseases
Skin and Connective Tissue Diseases	Psoriasis	26974007

References

PMID: 28946816

Effect of TNF-alpha on Molecules Related to the Insulin Action in Endometrial Cells Exposed to Hyperandrogenic and Hyperinsulinic Conditions Characteristics of Polycystic Ovary Syndrome.

Orostica Lorena, Garcia Paula, Vera Carolina, Garcia Victor, Romero Carmen, Vega Margarita

1 Laboratory of Endocrinology and Reproductive Biology, Clinical Hospital, University of Chile, Santiago, Chile.| 1 Laboratory of Endocrinology and Reproductive Biology, Clinical Hospital, University of Chile, Santiago, Chile.| 1 Laboratory of Endocrinology and Reproductive Biology, Clinical Hospital, University of Chile, Santiago, Chile.| 2 Faculty of Health Sciences, University of Antofagasta, Antofagasta, Chile.| 1 Laboratory of Endocrinology and Reproductive Biology, Clinical Hospital, University of Chile, Santiago, Chile.| 3 Department of Obstetrics and Gynecology, Clinical Hospital, Faculty of Medicine, University of Chile, Santiago, Chile.| 1 Laboratory of Endocrinology and Reproductive Biology, Clinical Hospital, University of Chile, Santiago, Chile.| 3 Department of Obstetrics and Gynecology, Clinical Hospital, Faculty of Medicine, University of Chile, Santiago, Chile.

Reprod Sci. 2018 Jul;25(7):1000-1009. doi: 10.1177/1933719117732157. Epub 2017

Abstract

Polycystic ovary syndrome (PCOS) affects not only ovarian functions but is also able to affect endometrium metabolism. Around 80% of women with PCOS are obese. High tumor necrosis factor (TNF)-alpha production and low adiponectin levels are characteristics of obesity. Interestingly, endometrium from obese women with PCOS presents an insulin-resistance condition, high TNF-alpha levels, and low adiponectin levels. However, TNF-alpha effect on molecules associated with insulin action in endometrial cells remains unclear. Therefore, the objective of this work was to evaluate TNF-alpha effect on expression of molecules associated with adiponectin (insulin sensitizing) and TNF-alpha signaling pathways and on Glucose Transporter type 4 (GLUT-4) levels in human endometrial cells under the characteristic conditions of hyperandrogenic/hyperinsulinic (HA/HI) PCOS. Two human endometrial stromal cell lines (T-HESC/St-T1b) under HA/HI conditions were used to assay the effect of high TNF-alpha concentration (100 ng/mL) on adiponectin, AdipoR1-AdipoR2 receptors, Adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1), Phospho-AMP-activated protein kinase T172 (p-AMPKT172), GLUT-4, Tumor necrosis factor receptor 1 (TNFR1)-Tumor necrosis factor receptor 2 (TNFR2) receptors protein levels, and nuclear factor kappaB (NFkappaB) nuclear content, by Western blot or immunocytochemistry. The NFkappaB participation in TNF-alpha effect on adiponectin expression was assayed using an NFkappaB inhibitor (pyrrolidine dithiocarbamate). The TNF-alpha increases the expression of molecules associated with its own signaling pathway ( P < .05) and decreases the protein levels of adiponectin and its associated molecules ( P < .05). Moreover, TNF-alpha increases NFkappaB nuclear content ( P < .001), whereas with NFkappaB inhibition the decrease in adiponectin content induced by TNF-alpha was not observed. GLUT-4 levels were lower with TNF-alpha treatment ( P < .01). Thus, in human endometrial stromal cells, high TNF-alpha levels negatively affect the insulin action through decreased adiponectin signaling and GLUT-4 protein. This could explain the failures observed in endometrial function of obese women with PCOS.

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