TAC1

Preprotachykinin-1, (abbreviated PPT-1, PPT-I, or PPT-A), is a precursor protein that in humans is encoded by the TAC1 gene.^[5][6]

TAC1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2KS9, 2KSA, 2KSB, 4HOM,%%s2B19,%%s2B19
Identifiers
Aliases	TAC1, Hs.2563, NK2, TAC2, tachykinin precursor 1, NKNA, NPK
External IDs	OMIM: 162320; MGI: 98474; HomoloGene: 2394; GeneCards: TAC1; OMA:TAC1 - orthologs
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7q21.3 Start 97,732,084 bp[1] End 97,740,472 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6 A1|6 3.31 cM Start 7,554,879 bp[2] End 7,565,834 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) 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 BioGPS 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 Species Human Mouse Entrez 6863 21333 Ensembl ENSG00000006128 ENSMUSG00000061762 UniProt P20366 P41539 RefSeq (mRNA) NM_013998 NM_003182 NM_013996 NM_013997 NM_009311 NM_001311060 RefSeq (protein) NP_003173 NP_054702 NP_054703 NP_054704 NP_001297989 NP_033337 Location (UCSC) Chr 7: 97.73 – 97.74 Mb Chr 6: 7.55 – 7.57 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.^[7][8] Alpha- and delta-PPT can only be modified to substance P, whereas beta- and gamma-PPT can produce both substance P and neurokinin A.^[9]

Neurokinin A can also be further modified to produce neuropeptide K (also known as neurokinin K) and neuropeptide gamma.^[10]

These hormones are thought to 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. Alternative splicing of exons 4 and/or 6 produces four known products of undetermined significance.^[6]

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.^[8]

Species comparison

In humans, beta-PPT is the dominant isoform in the brain, which contrasts with rats (predominantly gamma-PPT) and cows (alpha-PPT).^[8]

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.^[8]

References

1. GRCh38: Ensembl release 89: ENSG00000006128 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000061762 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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): 2441–8. doi:10.1210/endo-128-5-2441. PMID 1708336.
6. "Entrez Gene: TAC1 tachykinin, precursor 1 (substance K, substance P, neurokinin 1, neurokinin 2, neuromedin L, neurokinin alpha, neuropeptide K, neuropeptide gamma)".
7. Holzer, P. (1988-03-01). "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.
8. Bannon, Michael J.; Poosch, Michael S.; Haverstick, Doris M.; Anita, Mandal; Xue, Iris C. -H.; Shibata, Kazuhiko; Dragovic, Ljubisa J. (1992-01-01). "Preprotachykinin gene expression in the human basal ganglia: characterization of mRNAs and pre-mRNAs produced by alternate RNA splicing". Molecular Brain Research. 12 (1–3): 225–231. doi:10.1016/0169-328X(92)90088-S. PMID 1312203.
9. "MeSH Supplementary Concept: preprotachykinin". www.mentata.com. Retrieved 2016-05-19.^{[permanent dead link‍]}
10. Takeda, Y; Krause, JE (Jan 1989). "Neuropeptide K potently stimulates salivary gland secretion and potentiates substance P-induced salivation". Proc Natl Acad Sci U S A. 86 (1): 392–396. Bibcode:1989PNAS...86..392T. doi:10.1073/pnas.86.1.392. PMC 286471. PMID 2463627.

Further reading

• McGregor GP, Conlon JM (1991). "Characterization of the C-terminal flanking peptide of human beta-preprotachykinin". Peptides. 11 (5): 907–10. doi:10.1016/0196-9781(90)90007-R. PMID 2284201. S2CID 54246526.
• Harmar AJ, Armstrong A, Pascall JC, et al. (1986). "cDNA sequence of human beta-preprotachykinin, the common precursor to substance P and neurokinin A." FEBS Lett. 208 (1): 67–72. doi:10.1016/0014-5793(86)81534-4. PMID 3770210. S2CID 32411674.
• Zimmer A, Zimmer AM, Baffi J, et al. (1998). "Hypoalgesia in mice with a targeted deletion of the tachykinin 1 gene". Proc. Natl. Acad. Sci. U.S.A. 95 (5): 2630–5. Bibcode:1998PNAS...95.2630Z. doi:10.1073/pnas.95.5.2630. PMC 19441. PMID 9482938.