{{Short description|Protein-coding gene in humans}} {{Infobox_gene}} '''Preprotachykinin-1''', (abbreviated '''PPT-1, PPT-I,''' or '''PPT-A'''), is a precursor protein that in humans is encoded by the ''TAC1'' gene.<ref name="pmid1708336">{{cite journal | vauthors = Chiwakata C, Brackmann B, Hunt N, Davidoff M, Schulze W, Ivell R | title = Tachykinin (substance-P) gene expression in Leydig cells of the human and mouse testis | journal = Endocrinology | volume = 128 | issue = 5 | pages = 2441–8 |date=May 1991 | pmid = 1708336 | doi =10.1210/endo-128-5-2441 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: TAC1 tachykinin, precursor 1 (substance K, substance P, neurokinin 1, neurokinin 2, neuromedin L, neurokinin alpha, neuropeptide K, neuropeptide gamma)| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=6863}}</ref>
== 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.<ref>{{Cite journal|last=Holzer|first=P.|date=1988-03-01|title=Local effector functions of capsaicin-sensitive sensory nerve endings: Involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides|journal=Neuroscience|volume=24|issue=3|pages=739–768|doi=10.1016/0306-4522(88)90064-4|pmid=3288903|s2cid=35325223}}</ref><ref name=":0">{{Cite journal|last1=Bannon|first1=Michael J.|last2=Poosch|first2=Michael S.|last3=Haverstick|first3=Doris M.|last4=Anita|first4=Mandal|last5=Xue|first5=Iris C. -H.|last6=Shibata|first6=Kazuhiko|last7=Dragovic|first7=Ljubisa J.|date=1992-01-01|title=Preprotachykinin gene expression in the human basal ganglia: characterization of mRNAs and pre-mRNAs produced by alternate RNA splicing|journal=Molecular Brain Research|volume=12|issue=1–3|pages=225–231|doi=10.1016/0169-328X(92)90088-S|pmid=1312203}}</ref> Alpha- and delta-PPT can only be modified to substance P, whereas beta- and gamma-PPT can produce both substance P and neurokinin A.<ref>{{Cite web|url=http://www.mentata.com/ds/retrieve/mesh/supplementary/C044206|title=MeSH Supplementary Concept: preprotachykinin|website=www.mentata.com|access-date=2016-05-19}}{{Dead link|date=June 2018 |bot=InternetArchiveBot |fix-attempted=no }}</ref>
Neurokinin A can also be further modified to produce neuropeptide K (also known as neurokinin K) and neuropeptide gamma.<ref>{{cite journal|last1=Takeda|first1=Y|last2=Krause|first2=JE|title=Neuropeptide K potently stimulates salivary gland secretion and potentiates substance P-induced salivation|journal=Proc Natl Acad Sci U S A|date=Jan 1989|volume=86|issue=1|pages=392–396|pmc=286471|doi=10.1073/pnas.86.1.392|pmid=2463627|bibcode=1989PNAS...86..392T|doi-access=free}}</ref>
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.<ref name="entrez" />
== 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.<ref name=":0" />
== Species comparison == In humans, beta-PPT is the dominant isoform in the brain, which contrasts with rats (predominantly gamma-PPT) and cows (alpha-PPT).<ref name=":0" />
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.<ref name=":0" />
==References== {{reflist}}
==Further reading== {{refbegin | 2}} *{{cite journal | vauthors=McGregor GP, Conlon JM |title=Characterization of the C-terminal flanking peptide of human beta-preprotachykinin. |journal=Peptides |volume=11 |issue= 5 |pages= 907–10 |year= 1991 |pmid= 2284201 |doi=10.1016/0196-9781(90)90007-R |s2cid=54246526 }} *{{cite journal |vauthors=Harmar AJ, Armstrong A, Pascall JC, etal |title=cDNA sequence of human beta-preprotachykinin, the common precursor to substance P and neurokinin A. |journal=FEBS Lett. |volume=208 |issue= 1 |pages= 67–72 |year= 1986 |pmid= 3770210 |doi=10.1016/0014-5793(86)81534-4 |s2cid=32411674 |doi-access=free }} *{{cite journal |vauthors=Zimmer A, Zimmer AM, Baffi J, etal |title=Hypoalgesia in mice with a targeted deletion of the tachykinin 1 gene. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=95 |issue= 5 |pages= 2630–5 |year= 1998 |pmid= 9482938 |doi= 10.1073/pnas.95.5.2630| pmc=19441 |bibcode=1998PNAS...95.2630Z |doi-access=free }} {{refend}} {{PDB Gallery|geneid=6863}}
Category:Neuropeptides Category:Precursor proteins
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