TAC1 (tachykinin, precursor 1)
| Written | 2009-06 | Philip K Lim, Shyam A Patel, Pranela Rameshwar |
| University of Medicine, Dentistry of New Jersey - New Jersey Medical School,Newark, New Jersey, USA |
(Note : for Links provided by Atlas : click)
1. Identity
| Alias_names | General Information |
| NKNA | |
| tachykinin | |
| Alias_symbol (synonym) | NPK |
| Other alias | NK2 |
| NKA | |
| PPT | |
| HGNC (Hugo) | TAC1 |
| LocusID (NCBI) | 6863 |
| Atlas_Id | 44483 |
| Location | 7q21.3 [Link to chromosome band 7q21] |
| Location_base_pair | Starts at 97731959 and ends at 97740472 bp from pter ( according to hg19-Feb_2009) [Mapping TAC1.png] |
| Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
2. DNA/RNA
| Description | The TAC1 gene maps (Homo sapiens) to NC_000007.12 in the region between 97199311 and 97207720 on the plus strand and spans 8410 bp. |
| Transcription | 4 transcript variants: alpha (1134 bp); open reading frame from bp 247-582 -lacks exon 6 -encodes substance P on exon 3 beta (1188 bp); open reading frame from bp 247-636 -encodes the full-length version of Tac1 -encodes substance P, neurokinin A, neuopeptide K delta (1089 bp); open reading frame from bp 247-537 -lacks exons 4 and 6 -encodes substance P on exon 3 gamma (1143 bp); open reading frame from bp 247-591 -lacks exon 4 -encodes substance P, neurokinin A |
3. Protein
| Note | The TAC1 gene encodes multiple transcripts through post-translational modifications. Each encodes peptides belonging to the tachykinin family of peptides. The major peptides produced from the TAC1 transcripts are substance P and neurokinin A. Others include neuropeptide K, and neuropeptide gamma. The tachykinins exert multiples functions such as neurotransmission, immune modulation and hematopoietic regulation. TAC1 encodes peptides that target nerve receptors, immune cells, stem cells, hematopoietic cells and smooth muscle cells. They function in vasodilatory responses; act as secretagogues and can induce behavioral responses. |
| Description | 4 peptides: alpha: 111 aa -comprises substance P beta: 129 aa -comprises substance P, neurokinin A, neuropeptide K delta: 96 aa -comprises substance P gamma: 114 aa -comprises neuropeptide gamma, substance P, neurokinin A. |
| Expression | Expressed by various immune and neuronal cells. TAC1 expression in the setting of osteoarthritis can be induced by mechanical stimulation (Howard et al., 2008). TAC1 expression is also regulated by microRNAs in neurons derived from human mesenchymal stem cells (Greco et al., 2007). This occurs by binding of miRNA-13-a, miRNA206 and miRNA302a to the Tac1 3'UTR. HIV1 infection resulted in increase production of TAC1 peptide (substance P). The source of substance P has been identified as monocytes-derived macrophages from placenta cord blood and adult peripheral blood. The production of substance P correlates with HIV 1 infection (Douglas et al., 2002). |
| Localisation | Secreted peptide. |
| Function | TAC1 peptides function in both pathologic and physiologic processes. These include hematopoiesis, gastrointestinal secretory processes, respiratory patterns, calcium signaling, neuropeptide signaling, pain, synaptic transmission, insemination (Murthy et al., 2008; David et al., 2009); inflammatory response, autism, and pulmonary infection (Marui et al., 2007; Grissell et al., 2007). In normal respiratory development, TAC1 appears to be a crucial gene, exerting plasticity during development (Berner et al., 2007). TAC1 is involved in hematopoietic regulation. The mRNA is targeted by RNA-binding protein that confers translational control, which could be negatively regulated by cytokines with hematopoietic stimulator properties (Murthy et al., 2008). TAC1 has been implicated in macrophage and monocyte functions (Chernova et al., 2009). |
| Homology | Homo sapiens TAC1 shares sequence homology with mouse and rat sequences. |
4. Implicated in
| Note | |
| Entity | Breast Cancer |
| Note | A gene expression signature for breast cancer has been shown to involve TAC1 (Ellsworth et al., 2009). |
| Prognosis | TAC1 expression occurs in breast cancer and is directly proportional to aggressiveness of the cancer and thus, TAC1 may also be a prognostic factor in breast cancer (Ellsworth et al., 2009; Reddy et al., 2009). |
| Oncogenesis | TAC1 expression favors breast cancer cell entry into the bone marrow during stage IV disease (Reddy et al., 2009). TAC1 regulates the interaction between CXCL12 and its receptor, CXCR4 in the interaction between breast cancer and mesenchymal stem cells (Corcoran et al., 2008). The TAC1 gene products, substance P and neurokinin A, and neurokinin receptor antagonists have been shown to have anti-proliferative effects on breast cancer cells (Rameswhar et al., 1996; Singh et al., 2000). |
| Entity | Colon cancer |
| Note | Substance P, the major peptide encoded by the TAC1 gene, is mitogenic to colon cancer. Its action on the cancer cells appears to be autocrine since NK1 antagonist has been shown to mediate anti-tumor activity (Rosso et al., 2008). On the other hand, Substance P also enhances the expansion of lymphokine-activated killer cells against colon cancer cells (Flageole et al., 1992). These two properties of substance P appear paradoxical. Thus, targeted therapy will need to balance the immune-enhancing effects with the tumor promoting functions of substance. |
| Prognosis | In Dukes stage A/B cancers, TAC1 methylation levels were significantly higher than in Dukes stage C/D cancers (Mori et al., 2006). |
| Oncogenesis | TAC1 was found to be silenced via promoter methylation in primary colon cancer and may lead to early stage carcinogenesis by aiding tumor cells to escape immune surveillance and autocrine growth-inhibitory signaling (Mori et al., 2006). |
| Entity | Esophageal cancer |
| Prognosis | Promoter hypermethylation of TAC1 confers poor prognosis in esophageal cancer (Jin et al., 2007). |
| Oncogenesis | TAC1 promoter hypermethylation has been suggested to be a putative marker for esophageal carcinoma (Jin et al., 2007). |
| Entity | Gastric adenocarcinoma |
| Oncogenesis | Promoter hypermethylation of TAC1 has also been found in gastric adenocarcinoma (David et al., 2009). |
| Entity | Multiple Sclerosis |
| Note | The genetic region surrounding TAC1 may be unstable and has been associated with increased susceptibility to multiple sclerosis (Vandenbroeck et al., 2002). |
| Entity | Narcolepsy |
| Note | TAC1 and other related peptides have been associated with narcolepsy. Stimulation by amphetamines promotes increased TAC1 expression (Lindberg et al., 2007). |
5. Bibliography
| Altered respiratory pattern and hypoxic response in transgenic newborn mice lacking the tachykinin-1 gene. |
| Berner J, Shvarev Y, Lagercrantz H, Bilkei-Gorzo A, Hokfelt T, Wickstrom R. |
| J Appl Physiol. 2007 Aug;103(2):552-9. Epub 2007 May 24. |
| PMID 17525292 |
| Substance P (SP) enhances CCL5-induced chemotaxis and intracellular signaling in human monocytes, which express the truncated neurokinin-1 receptor (NK1R). |
| Chernova I, Lai JP, Li H, Schwartz L, Tuluc F, Korchak HM, Douglas SD, Kilpatrick LE. |
| J Leukoc Biol. 2009 Jan;85(1):154-64. Epub 2008 Oct 3. |
| PMID 18835883 |
| Mesenchymal stem cells in early entry of breast cancer into bone marrow. |
| Corcoran KE, Trzaska KA, Fernandes H, Bryan M, Taborga M, Srinivas V, Packman K, Patel PS, Rameshwar P. |
| PLoS ONE. 2008 Jun 25;3(6):e2563. |
| PMID 18575622 |
| Aberrant silencing of the endocrine peptide gene tachykinin-1 in gastric cancer. |
| David S, Kan T, Cheng Y, Agarwal R, Jin Z, Mori Y. |
| Biochem Biophys Res Commun. 2009 Jan 16;378(3):605-9. Epub 2008 Nov 29. |
| PMID 19046942 |
| A gene expression signature that defines breast cancer metastases. |
| Ellsworth RE, Seebach J, Field LA, Heckman C, Kane J, Hooke JA, Love B, Shriver CD. |
| Clin Exp Metastasis. 2009;26(3):205-13. Epub 2008 Dec 27. |
| PMID 19112599 |
| Substance P increases in vitro lymphokine-activated-killer (LAK) cell cytotoxicity against fresh colorectal cancer cells. |
| Flageole H, Senterman M, Trudel JL. |
| J Surg Res. 1992 Nov;53(5):445-9. |
| PMID 1279274 |
| MicroRNAs regulate synthesis of the neurotransmitter substance P in human mesenchymal stem cell-derived neuronal cells. |
| Greco SJ, Rameshwar P. |
| Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15484-9. Epub 2007 Sep 13. |
| PMID 17855557 |
| Reduced toll-like receptor 4 and substance P gene expression is associated with airway bacterial colonization in children. |
| Grissell TV, Chang AB, Gibson PG. |
| Pediatr Pulmonol. 2007 Apr;42(4):380-5. |
| PMID 17358043 |
| HIV enhances substance P expression in human immune cells. |
| Ho WZ, Lai JP, Li Y, Douglas SD. |
| FASEB J. 2002 Apr;16(6):616-8. |
| PMID 11919172 |
| Mechanical stimulation induces preprotachykinin gene expression in osteoarthritic chondrocytes which is correlated with modulation of the transcription factor neuron restrictive silence factor. |
| Howard MR, Millward-Sadler SJ, Vasilliou AS, Salter DM, Quinn JP. |
| Neuropeptides. 2008 Oct-Dec;42(5-6):681-6. Epub 2008 Nov 5. |
| PMID 18990442 |
| Hypermethylation of tachykinin-1 is a potential biomarker in human esophageal cancer. |
| Jin Z, Olaru A, Yang J, Sato F, Cheng Y, Kan T, Mori Y, Mantzur C, Paun B, Hamilton JP, Ito T, Wang S, David S, Agarwal R, Beer DG, Abraham JM, Meltzer SJ. |
| Clin Cancer Res. 2007 Nov 1;13(21):6293-300. |
| PMID 17975140 |
| Reduced expression of TAC1, PENK and SOCS2 in Hcrtr-2 mutated narcoleptic dog brain. |
| Lindberg J, Saetre P, Nishino S, Mignot E, Jazin E. |
| BMC Neurosci. 2007 May 23;8:34. |
| PMID 17521418 |
| Tachykinin 1 (TAC1) gene SNPs and haplotypes with autism: a case-control study. |
| Marui T, Funatogawa I, Koishi S, Yamamoto K, Matsumoto H, Hashimoto O, Nanba E, Nishida H, Sugiyama T, Kasai K, Watanabe K, Kano Y, Kato N, Sasaki T. |
| Brain Dev. 2007 Sep;29(8):510-3. Epub 2007 Mar 21. |
| PMID 17376622 |
| A genome-wide search identifies epigenetic silencing of somatostatin, tachykinin-1, and 5 other genes in colon cancer. |
| Mori Y, Cai K, Cheng Y, Wang S, Paun B, Hamilton JP, Jin Z, Sato F, Berki AT, Kan T, Ito T, Mantzur C, Abraham JM, Meltzer SJ. |
| Gastroenterology. 2006 Sep;131(3):797-808. |
| PMID 16952549 |
| Tac1 regulation by RNA-binding protein and miRNA in bone marrow stroma: Implication for hematopoietic activity. |
| Murthy RG, Greco SJ, Taborga M, Patel N, Rameshwar P. |
| Brain Behav Immun. 2008 May;22(4):442-50. Epub 2007 Dec 3. |
| PMID 18061399 |
| Induction of negative hematopoietic regulators by neurokinin-A in bone marrow stroma. |
| Rameshwar P, Gascon P. |
| Blood. 1996 Jul 1;88(1):98-106. |
| PMID 8704207 |
| RE-1-silencing transcription factor shows tumor-suppressor functions and negatively regulates the oncogenic TAC1 in breast cancer cells. |
| Reddy BY, Greco SJ, Patel PS, Trzaska KA, Rameshwar P. |
| Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4408-13. Epub 2009 Feb 25. |
| PMID 19246391 |
| The NK-1 receptor is expressed in human primary gastric and colon adenocarcinomas and is involved in the antitumor action of L-733,060 and the mitogenic action of substance P on human gastrointestinal cancer cell lines. |
| Rosso M, Robles-Frias MJ, Covenas R, Salinas-Martin MV, Munoz M. |
| Tumour Biol. 2008;29(4):245-54. Epub 2008 Sep 9. |
| PMID 18781096 |
| Increased expression of preprotachykinin-I and neurokinin receptors in human breast cancer cells: implications for bone marrow metastasis. |
| Singh D, Joshi DD, Hameed M, Qian J, Gascon P, Maloof PB, Mosenthal A, Rameshwar P. |
| Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):388-93. |
| PMID 10618428 |
| Chromosome 7q21-22 and multiple sclerosis: evidence for a genetic susceptibility effect in vicinity to the protachykinin-1 gene. |
| Vandenbroeck K, Fiten P, Heggarty S, Goris A, Cocco E, Hawkins SA, Graham CA, Marrosu MG, Opdenakker G. |
| J Neuroimmunol. 2002 Apr;125(1-2):141-8. |
| PMID 11960650 |
6. Citation
| This paper should be referenced as such : |
| Lim, PK ; Patel, SA ; Rameshwar, P |
| TAC1 (tachykinin, precursor 1) |
| Atlas Genet Cytogenet Oncol Haematol. 2010;14(5):485-487. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://atlasgeneticsoncology.usal.es/classic/Genes/TAC1ID44483ch7q21.html |
7. External links
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Thu Jan 17 19:09:31 CET 2019 |
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