TAC1 (tachykinin, precursor 1)

2009-06-01   Philip K Lim , Shyam A Patel , Pranela Rameshwar 

University of Medicine, Dentistry of New Jersey - New Jersey Medical School,Newark, New Jersey, USA





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.


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



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.


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.


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 3UTR.
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).


Secreted peptide.


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).


Homo sapiens TAC1 shares sequence homology with mouse and rat sequences.

Implicated in

Entity name
Breast Cancer
A gene expression signature for breast cancer has been shown to involve TAC1 (Ellsworth et al., 2009).
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).
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 name
Colon cancer
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.
In Dukes stage A/B cancers, TAC1 methylation levels were significantly higher than in Dukes stage C/D cancers (Mori et al., 2006).
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 name
Esophageal cancer
Promoter hypermethylation of TAC1 confers poor prognosis in esophageal cancer (Jin et al., 2007).
TAC1 promoter hypermethylation has been suggested to be a putative marker for esophageal carcinoma (Jin et al., 2007).
Entity name
Gastric adenocarcinoma
Promoter hypermethylation of TAC1 has also been found in gastric adenocarcinoma (David et al., 2009).
Entity name
Multiple Sclerosis
The genetic region surrounding TAC1 may be unstable and has been associated with increased susceptibility to multiple sclerosis (Vandenbroeck et al., 2002).
Entity name
TAC1 and other related peptides have been associated with narcolepsy. Stimulation by amphetamines promotes increased TAC1 expression (Lindberg et al., 2007).


Pubmed IDLast YearTitleAuthors
175252922007Altered respiratory pattern and hypoxic response in transgenic newborn mice lacking the tachykinin-1 gene.Berner J et al
188358832009Substance P (SP) enhances CCL5-induced chemotaxis and intracellular signaling in human monocytes, which express the truncated neurokinin-1 receptor (NK1R).Chernova I et al
185756222008Mesenchymal stem cells in early entry of breast cancer into bone marrow.Corcoran KE et al
190469422009Aberrant silencing of the endocrine peptide gene tachykinin-1 in gastric cancer.David S et al
191125992009A gene expression signature that defines breast cancer metastases.Ellsworth RE et al
12792741992Substance P increases in vitro lymphokine-activated-killer (LAK) cell cytotoxicity against fresh colorectal cancer cells.Flageole H et al
178555572007MicroRNAs regulate synthesis of the neurotransmitter substance P in human mesenchymal stem cell-derived neuronal cells.Greco SJ et al
173580432007Reduced toll-like receptor 4 and substance P gene expression is associated with airway bacterial colonization in children.Grissell TV et al
119191722002HIV enhances substance P expression in human immune cells.Ho WZ et al
189904422008Mechanical stimulation induces preprotachykinin gene expression in osteoarthritic chondrocytes which is correlated with modulation of the transcription factor neuron restrictive silence factor.Howard MR et al
179751402007Hypermethylation of tachykinin-1 is a potential biomarker in human esophageal cancer.Jin Z et al
175214182007Reduced expression of TAC1, PENK and SOCS2 in Hcrtr-2 mutated narcoleptic dog brain.Lindberg J et al
173766222007Tachykinin 1 (TAC1) gene SNPs and haplotypes with autism: a case-control study.Marui T et al
169525492006A genome-wide search identifies epigenetic silencing of somatostatin, tachykinin-1, and 5 other genes in colon cancer.Mori Y et al
180613992008Tac1 regulation by RNA-binding protein and miRNA in bone marrow stroma: Implication for hematopoietic activity.Murthy RG et al
87042071996Induction of negative hematopoietic regulators by neurokinin-A in bone marrow stroma.Rameshwar P et al
192463912009RE-1-silencing transcription factor shows tumor-suppressor functions and negatively regulates the oncogenic TAC1 in breast cancer cells.Reddy BY et al
187810962008The 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 et al
106184282000Increased expression of preprotachykinin-I and neurokinin receptors in human breast cancer cells: implications for bone marrow metastasis.Singh D et al
119606502002Chromosome 7q21-22 and multiple sclerosis: evidence for a genetic susceptibility effect in vicinity to the protachykinin-1 gene.Vandenbroeck K et al

Other Information

Locus ID:

NCBI: 6863
MIM: 162320
HGNC: 11517
Ensembl: ENSG00000006128


dbSNP: 6863
ClinVar: 6863
TCGA: ENSG00000006128


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Signal TransductionREACTOMER-HSA-162582
Signaling by GPCRREACTOMER-HSA-372790
GPCR ligand bindingREACTOMER-HSA-500792
Class A/1 (Rhodopsin-like receptors)REACTOMER-HSA-373076
Peptide ligand-binding receptorsREACTOMER-HSA-375276
Tachykinin receptors bind tachykininsREACTOMER-HSA-380095
GPCR downstream signalingREACTOMER-HSA-388396
G alpha (q) signalling eventsREACTOMER-HSA-416476
Gastrin-CREB signalling pathway via PKC and MAPKREACTOMER-HSA-881907

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
177034122007Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes.100
198745742009Genetical genomic determinants of alcohol consumption in rats and humans.93
195982352009Genes related to sex steroids, neural growth, and social-emotional behavior are associated with autistic traits, empathy, and Asperger syndrome.92
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
169525492006A genome-wide search identifies epigenetic silencing of somatostatin, tachykinin-1, and 5 other genes in colon cancer.69
145322892003Heterodimerization of substance P and mu-opioid receptors regulates receptor trafficking and resensitization.59
210917162011Neurokinin-1 receptor: functional significance in the immune system in reference to selected infections and inflammation.44
178555572007MicroRNAs regulate synthesis of the neurotransmitter substance P in human mesenchymal stem cell-derived neuronal cells.40
172642092007Substance P mediates antiapoptotic responses in human colonocytes by Akt activation.39
196950942009Increased expression of matrix metalloproteinase-10, nerve growth factor and substance P in the painful degenerate intervertebral disc.36


Philip K Lim ; Shyam A Patel ; Pranela Rameshwar

TAC1 (tachykinin, precursor 1)

Atlas Genet Cytogenet Oncol Haematol. 2009-06-01

Online version: http://atlasgeneticsoncology.org/gene/44483/tac1