Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

TAC1 (tachykinin, precursor 1)

Written2009-06Philip 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)

Identity

Alias_namesTAC2
NKNA
tachykinin
Alias_symbol (synonym)NPK
HGNC (Hugo) TAC1
LocusID (NCBI) 6863
Atlas_Id 44483
Location 7q21.3  [Link to chromosome band 7q21]
Location_base_pair Starts at 97361271 and ends at 97369784 bp from pter ( according to hg19-Feb_2009)  [Mapping TAC1.png]

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

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.

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).
  

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
 

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.org/Genes/TAC1ID44483ch7q21.html


External links

Nomenclature
HGNC (Hugo)TAC1   11517
Cards
AtlasTAC1ID44483ch7q21
Entrez_Gene (NCBI)TAC1  6863  tachykinin precursor 1
AliasesHs.2563; NK2; NKNA; NPK; 
TAC2
GeneCards (Weizmann)TAC1
Ensembl hg19 (Hinxton)ENSG00000006128 [Gene_View]  chr7:97361271-97369784 [Contig_View]  TAC1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000006128 [Gene_View]  chr7:97361271-97369784 [Contig_View]  TAC1 [Vega]
ICGC DataPortalENSG00000006128
TCGA cBioPortalTAC1
AceView (NCBI)TAC1
Genatlas (Paris)TAC1
WikiGenes6863
SOURCE (Princeton)TAC1
Genetics Home Reference (NIH)TAC1
Genomic and cartography
GoldenPath hg19 (UCSC)TAC1  -     chr7:97361271-97369784 +  7q21-q22   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)TAC1  -     7q21-q22   [Description]    (hg38-Dec_2013)
EnsemblTAC1 - 7q21-q22 [CytoView hg19]  TAC1 - 7q21-q22 [CytoView hg38]
Mapping of homologs : NCBITAC1 [Mapview hg19]  TAC1 [Mapview hg38]
OMIM162320   
Gene and transcription
Genbank (Entrez)AF050655 AF050656 AF050657 AF050658 AK222957
RefSeq transcript (Entrez)NM_003182 NM_013996 NM_013997 NM_013998
RefSeq genomic (Entrez)NC_000007 NC_018918 NT_007933 NW_004929332
Consensus coding sequences : CCDS (NCBI)TAC1
Cluster EST : UnigeneHs.2563 [ NCBI ]
CGAP (NCI)Hs.2563
Alternative Splicing GalleryENSG00000006128
Gene ExpressionTAC1 [ NCBI-GEO ]   TAC1 [ EBI - ARRAY_EXPRESS ]   TAC1 [ SEEK ]   TAC1 [ MEM ]
Gene Expression Viewer (FireBrowse)TAC1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6863
GTEX Portal (Tissue expression)TAC1
Protein : pattern, domain, 3D structure
UniProt/SwissProtP20366   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP20366  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP20366
Splice isoforms : SwissVarP20366
PhosPhoSitePlusP20366
Domaine pattern : Prosite (Expaxy)TACHYKININ (PS00267)   
Domains : Interpro (EBI)Tachy_Neuro_lke_CS    Tachykinin_dom    Tachykinin_fam   
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Domain families : Smart (EMBL)TK (SM00203)  
Conserved Domain (NCBI)TAC1
DMDM Disease mutations6863
Blocks (Seattle)TAC1
PDB (SRS)2B19    2KS9    2KSA    2KSB    4HOM   
PDB (PDBSum)2B19    2KS9    2KSA    2KSB    4HOM   
PDB (IMB)2B19    2KS9    2KSA    2KSB    4HOM   
PDB (RSDB)2B19    2KS9    2KSA    2KSB    4HOM   
Structural Biology KnowledgeBase2B19    2KS9    2KSA    2KSB    4HOM   
SCOP (Structural Classification of Proteins)2B19    2KS9    2KSA    2KSB    4HOM   
CATH (Classification of proteins structures)2B19    2KS9    2KSA    2KSB    4HOM   
SuperfamilyP20366
Human Protein AtlasENSG00000006128
Peptide AtlasP20366
HPRD08876
IPIIPI00023571   IPI00219086   IPI00219087   IPI00297740   
Protein Interaction databases
DIP (DOE-UCLA)P20366
IntAct (EBI)P20366
FunCoupENSG00000006128
BioGRIDTAC1
STRING (EMBL)TAC1
ZODIACTAC1
Ontologies - Pathways
QuickGOP20366
Ontology : AmiGOresponse to yeast  positive regulation of acute inflammatory response  receptor binding  protein binding  extracellular region  extracellular space  plasma membrane  inflammatory response  positive regulation of cytosolic calcium ion concentration  tachykinin receptor signaling pathway  neuropeptide signaling pathway  cell-cell signaling  synaptic transmission  insemination  long-term memory  regulation of blood pressure  associative learning  detection of abiotic stimulus  response to hormone  negative regulation of heart rate  positive regulation of epithelial cell migration  sensory perception of pain  antibacterial humoral response  antifungal humoral response  axon  substance P receptor binding  positive regulation of synaptic transmission, cholinergic  positive regulation of synaptic transmission, GABAergic  response to lipopolysaccharide  positive regulation of renal sodium excretion  neuronal cell body  response to morphine  innate immune response  positive regulation of action potential  positive regulation of ossification  positive regulation of saliva secretion  response to pain  positive regulation of lymphocyte proliferation  defense response to Gram-negative bacterium  defense response to Gram-positive bacterium  positive regulation of stress fiber assembly  cellular response to nerve growth factor stimulus  positive regulation of corticosterone secretion  
Ontology : EGO-EBIresponse to yeast  positive regulation of acute inflammatory response  receptor binding  protein binding  extracellular region  extracellular space  plasma membrane  inflammatory response  positive regulation of cytosolic calcium ion concentration  tachykinin receptor signaling pathway  neuropeptide signaling pathway  cell-cell signaling  synaptic transmission  insemination  long-term memory  regulation of blood pressure  associative learning  detection of abiotic stimulus  response to hormone  negative regulation of heart rate  positive regulation of epithelial cell migration  sensory perception of pain  antibacterial humoral response  antifungal humoral response  axon  substance P receptor binding  positive regulation of synaptic transmission, cholinergic  positive regulation of synaptic transmission, GABAergic  response to lipopolysaccharide  positive regulation of renal sodium excretion  neuronal cell body  response to morphine  innate immune response  positive regulation of action potential  positive regulation of ossification  positive regulation of saliva secretion  response to pain  positive regulation of lymphocyte proliferation  defense response to Gram-negative bacterium  defense response to Gram-positive bacterium  positive regulation of stress fiber assembly  cellular response to nerve growth factor stimulus  positive regulation of corticosterone secretion  
REACTOMEP20366 [protein]
REACTOME Pathways380095 [pathway]   416476 [pathway]   
NDEx NetworkTAC1
Atlas of Cancer Signalling NetworkTAC1
Wikipedia pathwaysTAC1
Orthology - Evolution
OrthoDB6863
GeneTree (enSembl)ENSG00000006128
Phylogenetic Trees/Animal Genes : TreeFamTAC1
HOVERGENP20366
HOGENOMP20366
Homologs : HomoloGeneTAC1
Homology/Alignments : Family Browser (UCSC)TAC1
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerTAC1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TAC1
dbVarTAC1
ClinVarTAC1
1000_GenomesTAC1 
Exome Variant ServerTAC1
ExAC (Exome Aggregation Consortium)TAC1 (select the gene name)
Genetic variants : HAPMAP6863
Genomic Variants (DGV)TAC1 [DGVbeta]
DECIPHER (Syndromes)7:97361271-97369784  ENSG00000006128
CONAN: Copy Number AnalysisTAC1 
Mutations
ICGC Data PortalTAC1 
TCGA Data PortalTAC1 
Broad Tumor PortalTAC1
OASIS PortalTAC1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICTAC1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDTAC1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch TAC1
DgiDB (Drug Gene Interaction Database)TAC1
DoCM (Curated mutations)TAC1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)TAC1 (select a term)
intoGenTAC1
NCG5 (London)TAC1
Cancer3DTAC1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM162320   
Orphanet
MedgenTAC1
Genetic Testing Registry TAC1
NextProtP20366 [Medical]
TSGene6863
GENETestsTAC1
Huge Navigator TAC1 [HugePedia]
snp3D : Map Gene to Disease6863
BioCentury BCIQTAC1
ClinGenTAC1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD6863
Chemical/Pharm GKB GenePA36297
Clinical trialTAC1
Miscellaneous
canSAR (ICR)TAC1 (select the gene name)
Probes
Litterature
PubMed181 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineTAC1
EVEXTAC1
GoPubMedTAC1
iHOPTAC1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Thu Feb 2 14:11:16 CET 2017

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.