Solute carrier family 6 (neurotransmitter transporter, noradrenalin), member 2 | ||
| Identifiers | ||
| Symbol(s) | SLC6A2; NAT1; NET; NET1; SLC6A5 | |
| External IDs | OMIM: 163970 MGI: 1270850 HomoloGene: 816 | |
| RNA expression pattern | ||
| ||
| Orthologs | ||
| Human | Mouse | |
| Entrez | 6530 | 20538 |
| Ensembl | ENSG00000103546 | ENSMUSG00000055368 |
| Uniprot | P23975 | Q6NZB4 |
| Refseq | NM_001043 (mRNA) NP_001034 (protein) | NM_009209 (mRNA) NP_033235 (protein) |
| Location | Chr 16: 54.25 - 54.3 Mb | Chr 8: 95.85 - 95.89 Mb |
| Pubmed search | [1] | [2] |
The norepinephrine transporter or NET (or noradrenaline transporter (NAT)) is a monoamine transporter that transports the neurotransmitter noradrenaline from the synapse back to its vesicles for storage until later use. The Human Genome Organisation (HUGO is an organization involved in the Human Genome Project, a project about mapping the human genome The Mouse Genome Informatics (MGI website is run by The Jackson Laboratory. HomoloGene, a tool of the National Center for Biotechnology Information (NCBI is a system for automated detection of homologs (similarity attributable to descent The Entrez Global Query Cross-Database Search System is a powerful Federated search engine or Web portal that allows users to search many discrete Health sciences Ensembl is a joint scientific project between the European Bioinformatics Institute and the Wellcome Trust Sanger Institute, which was launched in 1999 in response to the imminent UniProt is the uni versal prot ein resource a central repository of Protein data created by combining Swiss-Prot, TrEMBL PubMed is a free search engine for accessing the MEDLINE database of citations and abstracts of biomedical research articles Norepinephrine ( INN) (abbreviated norepi or NE) or noradrenaline ( BAN) (abbreviated NA or NAd) is a Monoamine transporters are structures in nerve-cell membranes that function as Neurotransmitter transporters transferring Monoamine neurotransmitters See Chemical synapse for an introduction to concepts and terminology used in this article Norepinephrine ( INN) (abbreviated norepi or NE) or noradrenaline ( BAN) (abbreviated NA or NAd) is a Chemical synapses are specialized junctions through which Neurons signal to each other and to non-neuronal cells such as those in Muscles or Glands It also appears to transport the neurotransmitter dopamine in the same way, but to a lesser degree. See Chemical synapse for an introduction to concepts and terminology used in this article Dopamine is a Hormone and Neurotransmitter occurring in a wide variety of animals including both vertebrates and invertebrates "The norepinephrine transporter (NET) protein consists of 617 amino acids and has 12 transmembrane domains"[1] and is encoded by the SLC6A2 gene. History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance
Certain antidepressant medications act to raise noradrenaline, such as the SNRIs and the tricyclic antidepressants (TCAs). An antidepressant is a Psychiatric medication used for alleviating major depression or Dysthymia ('milder' depression Tricyclic antidepressants (abbreviation TCAs) are a class of Antidepressant drugs first used in the 1950s In other words, these medications prevent the noradrenaline transporter from doing its job. Noradrenaline therefore remains in the synapse longer, allowing it to reach more normal levels. Chemical synapses are specialized junctions through which Neurons signal to each other and to non-neuronal cells such as those in Muscles or Glands Since the noradrenaline transporter is also thought to transport dopamine to some extent, SNRIs would also raise dopamine levels in the synapse.
A loss of function mutation in the noradrenaline transporter has been associated with postural orthostatic tachycardia syndrome in one kindred. Postural orthostatic tachycardia syndrome (often referred to as just postural tachycardia syndrome or POTS) is a condition of Dysautonomia, and more specifically [2] An epigenetic mechanism (hypermethylation of CpG islands in the NET gene promoter region)[3] that results in reduced expression of the noradrenaline transporter and consequently a phenotype of impaired neuronal reuptake of noradrenaline has been implicated in both postural orthostatic tachycardia syndrome and panic disorder. In Biology, the term epigenetics refers to changes in Gene expression caused by mechanisms other than changes in the underlying DNA sequence Norepinephrine ( INN) (abbreviated norepi or NE) or noradrenaline ( BAN) (abbreviated NA or NAd) is a Panic Disorder is a Psychological condition characterized by recurring Panic attacks in combination with significant behavioral change lasting at least a month
"The involvement of the norepinephrine transporter (NET) in the pathophysiology and treatment of attention deficit hyperactivity disorder (ADHD), substance abuse, neurodegenerative disorders (e. Pathophysiology is the study of the disturbance of normal Mechanical, Physical, and Biochemical functions either caused by a Disease, or resulting Attention-Deficit Hyperactivity Disorder (ADHD is a neurobehavioral developmental disorder affecting about 3-5% of the world's population Substance abuse is the overindulgence in and dependence of a Drug or other chemical leading to effects that are detrimental to the individual's physical and mental health g. , Alzheimer's disease (AD) and Parkinson's disease (PD)) and clinical depression has long been recognized. Alzheimer's disease ( AD) also called Alzheimer disease or simply Alzheimer's, is the most common form of Dementia. Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the Central nervous system that often impairs the sufferer's Major depressive disorder, also known as major depression, unipolar depression, unipolar disorder, clinical depression, or simply depression [2006]"[4]
Contents |
See also
References
- ^ Tahir Tellioglu and David Robertson, The molecular structure of the norepinephrine transporter protein.
- ^ Shannon J, Flattem N, Jordan J, Jacob G, Black B, Biaggioni I, Blakely R, Robertson D (2000). Neurotransmitter transporters are Proteins that span Cellular membranes and that serve to carry Neurotransmitters across these membranes and to Sodiumneurotransmitter symporters is a family of Neurotransmitter transporters. The SoLute Carrier (SLC group of Membrane transport proteins include over 300 members organized into 47 families "Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency". N Engl J Med 342 (8): 541–9. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 10684912.
- ^ Esler M, Alvarenga M, Pier C, Richards J, El-Osta A, Barton D, Haikerwal D, Kaye D, Schlaich M, Guo L, Jennings G, Socratous F, Lambert G (2006). "The neuronal noradrenaline transporter, anxiety and cardiovascular disease". J Psychopharmacol 20 (4 Suppl): 60–6. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16785272.
- ^ Information Hyperlinked Over Proteins (IHOP)
Further reading
- Eisenhofer G (2001). "The role of neuronal and extraneuronal plasma membrane transporters in the inactivation of peripheral catecholamines. ". Pharmacol. Ther. 91 (1): 35–62. PMID 11707293.
- Pacholczyk T, Blakely RD, Amara SG (1991). "Expression cloning of a cocaine- and antidepressant-sensitive human noradrenaline transporter. ". Nature 350 (6316): 350–4. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 2008212.
- Pörzgen P, Bönisch H, Brüss M (1995). "Molecular cloning and organization of the coding region of the human norepinephrine transporter gene. ". Biochem. Biophys. Res. Commun. 215 (3): 1145–50. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 7488042.
- Gelernter J, Kruger S, Pakstis AJ, et al. (1994). "Assignment of the norepinephrine transporter protein (NET1) locus to chromosome 16. ". Genomics 18 (3): 690–2. PMID 7905857.
- Brüss M, Kunz J, Lingen B, Bönisch H (1993). "Chromosomal mapping of the human gene for the tricyclic antidepressant-sensitive noradrenaline transporter. ". Hum. Genet. 91 (3): 278–80. PMID 8478011.
- Pörzgen P, Bönisch H, Hammermann R, Brüss M (1998). "The human noradrenaline transporter gene contains multiple polyadenylation sites and two alternatively spliced C-terminal exons. ". Biochim. Biophys. Acta 1398 (3): 365–70. PMID 9655936.
- Apparsundaram S, Schroeter S, Giovanetti E, Blakely RD (1998). "Acute regulation of norepinephrine transport: II. PKC-modulated surface expression of human norepinephrine transporter proteins. ". J. Pharmacol. Exp. Ther. 287 (2): 744–51. PMID 9808705.
- Kim CH, Kim HS, Cubells JF, Kim KS (1999). "A previously undescribed intron and extensive 5' upstream sequence, but not Phox2a-mediated transactivation, are necessary for high level cell type-specific expression of the human norepinephrine transporter gene. ". J. Biol. Chem. 274 (10): 6507–18. PMID 10037744.
- Shannon JR, Flattem NL, Jordan J, et al. (2000). "Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency. ". N. Engl. J. Med. 342 (8): 541–9. PMID 10684912.
- Torres GE, Yao WD, Mohn AR, et al. (2001). "Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1. ". Neuron 30 (1): 121–34. PMID 11343649.
- Gu HH, Wu X, Giros B, et al. (2002). "The NH(2)-terminus of norepinephrine transporter contains a basolateral localization signal for epithelial cells. ". Mol. Biol. Cell 12 (12): 3797–807. PMID 11739781.
- Paczkowski FA, Bryan-Lluka LJ (2002). "Tyrosine residue 271 of the norepinephrine transporter is an important determinant of its pharmacology. ". Brain Res. Mol. Brain Res. 97 (1): 32–42. PMID 11744160.
- Paczkowski FA, Bönisch H, Bryan-Lluka LJ (2002). "Pharmacological properties of the naturally occurring Ala(457)Pro variant of the human norepinephrine transporter. ". Pharmacogenetics 12 (2): 165–73. PMID 11875370.
- Barr CL, Kroft J, Feng Y, et al. (2002). "The norepinephrine transporter gene and attention-deficit hyperactivity disorder. ". Am. J. Med. Genet. 114 (3): 255–9. PMID 11920844.
- Zill P, Engel R, Baghai TC, et al. (2002). "Identification of a naturally occurring polymorphism in the promoter region of the norepinephrine transporter and analysis in major depression. ". Neuropsychopharmacology 26 (4): 489–93. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 11927173.
- Leszczyńska-Rodziewicz A, Czerski PM, Kapelski P, et al. (2002). "A polymorphism of the norepinephrine transporter gene in bipolar disorder and schizophrenia: lack of association. ". Neuropsychobiology 45 (4): 182–5. PMID 12097806.
- Bauman PA, Blakely RD (2002). "Determinants within the C-terminus of the human norepinephrine transporter dictate transporter trafficking, stability, and activity. ". Arch. Biochem. Biophys. 404 (1): 80–91. PMID 12127072.
- Urwin RE, Bennetts B, Wilcken B, et al. (2003). "Anorexia nervosa (restrictive subtype) is associated with a polymorphism in the novel norepinephrine transporter gene promoter polymorphic region. ". Mol. Psychiatry 7 (6): 652–7. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 12140790.
- McEvoy B, Hawi Z, Fitzgerald M, Gill M (2003). "No evidence of linkage or association between the norepinephrine transporter (NET) gene polymorphisms and ADHD in the Irish population. ". Am. J. Med. Genet. 114 (6): 665–6. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 12210284.
External links
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