TAC1

TAC1
Identifiers
Aliases	TAC1, Hs.2563, NK2, TAC2, tachykinin precursor 1, NKNA, NPK
External IDs	OMIM: 162320; MGI: 98474; GeneCards: TAC1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2KS9, 2KSA, 2KSB, 4HOM,%%s2B19,%%s2B19
Gene location (Human)
Chr.	Chromosome 7 (human)
End	97,740,472 bp
Gene location (Mouse)
Chr.	Chromosome 6 (mouse)
End	7,565,834 bp
RNA expression pattern
	Top expressed in
	spinal ganglia; ; external globus pallidus; ; endothelial cell; ; putamen; ; dorsal motor nucleus of vagus nerve; ; caudate nucleus; ; nucleus accumbens; ; middle frontal gyrus; ; trigeminal ganglion; ; superior vestibular nucleus;
	Top expressed in
	olfactory tubercle; ; nucleus accumbens; ; ventromedial nucleus; ; ventral tegmental area; ; dorsomedial hypothalamic nucleus; ; mammillary body; ; anterior amygdaloid area; ; globus pallidus; ; habenula; ; superior frontal gyrus;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	protein binding; signaling receptor binding; substance P receptor binding;
Cellular component	plasma membrane; extracellular region; axon; soma; extracellular space;
Biological process	cellular response to nerve growth factor stimulus; response to yeast; associative learning; positive regulation of renal sodium excretion; positive regulation of cytosolic calcium ion concentration; cell-cell signaling; antibacterial humoral response; positive regulation of synaptic transmission, cholinergic; positive regulation of epithelial cell migration; positive regulation of ossification; positive regulation of synaptic transmission, GABAergic; negative regulation of heart rate; positive regulation of corticosterone secretion; regulation of blood pressure; positive regulation of action potential; response to morphine; response to lipopolysaccharide; long-term memory; response to pain; defense response to Gram-negative bacterium; positive regulation of saliva secretion; positive regulation of acute inflammatory response; insemination; response to hormone; sensory perception of pain; detection of abiotic stimulus; innate immune response; neuropeptide signaling pathway; positive regulation of lymphocyte proliferation; positive regulation of stress fiber assembly; antifungal humoral response; defense response to Gram-positive bacterium; chemical synaptic transmission; inflammatory response; tachykinin receptor signaling pathway; antimicrobial humoral immune response mediated by antimicrobial peptide; killing of cells of other organism; G protein-coupled receptor signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	6863
	21333
	ENSG00000006128
	ENSMUSG00000061762
	P20366
	P41539
	NM_013998; NM_003182; NM_013996; NM_013997
	NM_009311; NM_001311060
	NP_003173; NP_054702; NP_054703; NP_054704
	NP_001297989; NP_033337
	Wikidata
View/Edit Human	View/Edit Mouse

Preprotachykinin-1, (abbreviated PPT-1, PPT-I, or PPT-A), is a protein that in humans is encoded by the TAC1 gene. It is a precursor protein that can be cut into a number of smaller peptide hormones including substance P and neurokinin A.

Function

The hormones derived from PPT-1 function as neurotransmitters which interact with nerve receptors and smooth muscle cells. They are known to induce behavioral responses and function as vasodilators and secretagogues.

Isoforms and derivatives

The protein has four isoforms—alpha-, beta-, gamma-, and delta-PPT—which can variably undergo post-translational modification to produce neurokinin A (formerly known as substance K) and substance P. Alpha- and delta-PPT can only be modified to substance P, whereas beta- and gamma-PPT can produce both substance P and neurokinin A. Other produced derivates include neurokinin K and neuropeptide gamma.

Substance P

Substance P is a hormone corresponding to positions 58-68 of preprotachykinin-1. It is released from certain sensory nerves and promotes an inflammatory response that can sensitize pain receptors. It functions through its activation of the receptors TACR1 (G_q- and G_s-type effects) and MRGPRX2. It can also activate TACR3, though it has low affinity.

Neurokinin A

Neurokinin A (also called substance K) is a signaling molecule corresponding to positions 98-107 of Preprotachykinin-1. It activates the TACR2 receptor, which causes a G_q-type response.

Neuropeptide K

Neuropeptide K (not to be confused with substance K) is a neurokinin A-like peptide which comes from the beta isoform of PPT-1, and corresponds to positions 72-107 of the (canonical) PPT-1 sequence. In rats, neuropeptide K may interact synergistically with substance P to stimulate saliva release. However, unlike in rats, the main human saliva glands are not innervated by substance P nerves.

Neuropeptide gamma

Neuropeptide gamma is a neurokinin A-like peptide coming from cleavage of the gamma isoform of PPT-1. It corresponds to positions 72-73 and 89-107 of the (canonical) PPT-1 sequence.

Human basal ganglia

The nature and distribution of PPT-1 has been studied in the human basal ganglia. The protein is expressed evenly throughout the caudate and putamen, and 80 to 85% of it exists in the beta-PPT isoform. 15-20% of the protein is in the gamma-PPT isoform, while no alpha-PPT was detected at all.

Species comparison

In humans, beta-PPT is the dominant isoform in the brain, which contrasts with rats (predominantly gamma-PPT) and cows (alpha-PPT).

While both human and rat PPT-1 produce substance P and neurokinin A, humans produce more neuropeptide K, whereas rats produce more neuropeptide gamma. In cow brains, PPT-1 primarily encodes substance P, but not other neurokinin A-derived peptides.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000006128 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000061762 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Chiwakata C, Brackmann B, Hunt N, Davidoff M, Schulze W, Ivell R (May 1991). "Tachykinin (substance-P) gene expression in Leydig cells of the human and mouse testis". Endocrinology. 128 (5): 2441–2448. doi:10.1210/endo-128-5-2441. PMID 1708336.
1 2 "Entrez Gene: TAC1 tachykinin, precursor 1 (substance K, substance P, neurokinin 1, neurokinin 2, neuromedin L, neurokinin alpha, neuropeptide K, neuropeptide gamma)".
1 2 3 4 5 6 "Protachykinin-1". UniProt consortium. Retrieved 2026-10-14.
↑ Holzer P (March 1988). "Local effector functions of capsaicin-sensitive sensory nerve endings: involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides". Neuroscience. 24 (3): 739–768. doi:10.1016/0306-4522(88)90064-4. PMID 3288903. S2CID 35325223.
1 2 3 4 Bannon MJ, Poosch MS, Haverstick DM, Mandal A, Xue IC, Shibata K, et al. (January 1992). "Preprotachykinin gene expression in the human basal ganglia: characterization of mRNAs and pre-mRNAs produced by alternate RNA splicing". Brain Research. Molecular Brain Research. 12 (1–3): 225–231. doi:10.1016/0169-328X(92)90088-S. PMID 1312203.
↑ "MeSH Supplementary Concept: preprotachykinin". www.mentata.com. Retrieved 2016-05-19.^{[permanent dead link]}
↑ Takeda Y, Krause JE (January 1989). "Neuropeptide K potently stimulates salivary gland secretion and potentiates substance P-induced salivation". Proceedings of the National Academy of Sciences of the United States of America. 86 (1): 392–396. Bibcode:1989PNAS...86..392T. doi:10.1073/pnas.86.1.392. PMC 286471. PMID 2463627.
↑ Pedersen AM, Sørensen CE, Proctor GB, Carpenter GH, Ekström J (September 2018). "Salivary secretion in health and disease" (PDF). Journal of oral rehabilitation. 45 (9): 730–46. doi:10.1111/joor.12664.
↑ Nelson DA, Bost KL (2004-09-01). "Non-neuronal mammalian tachykinin expression" (PDF). Front Biosci. 9 (1–3): 2166–76. doi:10.2741/1372.