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{{Infobox_gene}}
'''Preprotachykinin-1''', (abbreviated '''PPT-1, PPT-I,''' or '''PPT-A'''), is a [[Protein precursor|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 | pmc =  | 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/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6863| accessdate = }}</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|url=http://www.sciencedirect.com/science/article/pii/0306452288900644|journal=Neuroscience|volume=24|issue=3|pages=739–768|doi=10.1016/0306-4522(88)90064-4}}</ref><ref name=":0">{{Cite journal|last=Bannon|first=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|url=http://www.sciencedirect.com/science/article/pii/0169328X9290088S|journal=Molecular Brain Research|volume=12|issue=1–3|pages=225–231|doi=10.1016/0169-328X(92)90088-S}}</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}}</ref>
These [[hormone]]s are thought to function as [[neurotransmitter]]s which interact with nerve receptors and [[smooth muscle cells]]. They are known to induce behavioral responses and function as [[Vasodilation|vasodilators]] and [[secretagogue]]s.  [[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 nucleus|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}}
{{PBB_Further_reading
| citations =
*{{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  }}
*{{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  }}
*{{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  }}
}}
{{refend}}
{{PDB Gallery|geneid=6863}}
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
[[Category:Neuropeptides]]
{{GNF_Protein_box
[[Category:Precursor proteins]]
| image = PBB_Protein_TAC1_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 2b19.
| PDB = {{PDB2|2b19}}
| Name = Tachykinin, precursor 1 (substance K, substance P, neurokinin 1, neurokinin 2, neuromedin L, neurokinin alpha, neuropeptide K, neuropeptide gamma)
| HGNCid = 11517
| Symbol = TAC1
| AltSymbols =; Hs.2563; NK2; NKNA; TAC2
| OMIM = 162320
| ECnumber = 
| Homologene = 2394
| MGIid = 98474
| GeneAtlas_image1 = PBB_GE_TAC1_206552_s_at_tn.png
| Function = {{GNF_GO|id=GO:0005102 |text = receptor binding}} {{GNF_GO|id=GO:0005184 |text = neuropeptide hormone activity}}
| Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}} {{GNF_GO|id=GO:0005615 |text = extracellular space}} {{GNF_GO|id=GO:0043025 |text = cell soma}}
| Process = {{GNF_GO|id=GO:0006954 |text = inflammatory response}} {{GNF_GO|id=GO:0007217 |text = tachykinin signaling pathway}} {{GNF_GO|id=GO:0007218 |text = neuropeptide signaling pathway}} {{GNF_GO|id=GO:0007268 |text = synaptic transmission}} {{GNF_GO|id=GO:0007320 |text = insemination}} {{GNF_GO|id=GO:0009582 |text = detection of abiotic stimulus}} {{GNF_GO|id=GO:0019233 |text = sensory perception of pain}} {{GNF_GO|id=GO:0048265 |text = response to pain}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 6863
    | Hs_Ensembl = ENSG00000006128
    | Hs_RefseqProtein = NP_003173
    | Hs_RefseqmRNA = NM_003182
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 7
    | Hs_GenLoc_start = 97199311
    | Hs_GenLoc_end = 97207696
    | Hs_Uniprot = P20366
    | Mm_EntrezGene = 21333
    | Mm_Ensembl = ENSMUSG00000061762
    | Mm_RefseqmRNA = XM_984642
    | Mm_RefseqProtein = XP_989736
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 6
    | Mm_GenLoc_start = 7505071
    | Mm_GenLoc_end = 7512973
    | Mm_Uniprot = Q149W7
  }}
}}
'''Tachykinin, precursor 1 (substance K, substance P, neurokinin 1, neurokinin 2, neuromedin L, neurokinin alpha, neuropeptide K, neuropeptide gamma)''', also known as '''TAC1''', is a human [[gene]].<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 = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6863| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{PBB_Summary
| section_title =
| summary_text = This gene encodes four products of the tachykinin peptide hormone family, substance P and neurokinin A, as well as the related peptides, neuropeptide K and neuropeptide gamma.  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">{{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 = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6863| accessdate = }}</ref>
}}
==References==
{{reflist|2}}
==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal  | author=Kowall NW, Quigley BJ, Krause JE, ''et al.'' |title=Substance P and substance P receptor histochemistry in human neurodegenerative diseases. |journal=Regul. Pept. |volume=46 |issue= 1-2 |pages= 174-85 |year= 1993 |pmid= 7692486 |doi=  }}
*{{cite journal  | author=Advenier C, Lagente V, Boichot E |title=The role of tachykinin receptor antagonists in the prevention of bronchial hyperresponsiveness, airway inflammation and cough. |journal=Eur. Respir. J. |volume=10 |issue= 8 |pages= 1892-906 |year= 1997 |pmid= 9272936 |doi=  }}
*{{cite journal  | author=Rameshwar P, Oh HS, Yook C, ''et al.'' |title=Substance p-fibronectin-cytokine interactions in myeloproliferative disorders with bone marrow fibrosis. |journal=Acta Haematol. |volume=109 |issue= 1 |pages= 1-10 |year= 2003 |pmid= 12486316 |doi=  }}
*{{cite journal  | author=Saito R, Takano Y, Kamiya HO |title=Roles of substance P and NK(1) receptor in the brainstem in the development of emesis. |journal=J. Pharmacol. Sci. |volume=91 |issue= 2 |pages= 87-94 |year= 2003 |pmid= 12686752 |doi=  }}
*{{cite journal  | author=Di Angelantonio S, Giniatullin R, Costa V, ''et al.'' |title=Modulation of neuronal nicotinic receptor function by the neuropeptides CGRP and substance P on autonomic nerve cells. |journal=Br. J. Pharmacol. |volume=139 |issue= 6 |pages= 1061-73 |year= 2004 |pmid= 12871824 |doi= 10.1038/sj.bjp.0705337 }}
*{{cite journal  | author=Bannon MJ, Poosch MS, Haverstick DM, ''et al.'' |title=Preprotachykinin gene expression in the human basal ganglia: characterization of mRNAs and pre-mRNAs produced by alternate RNA splicing. |journal=Brain Res. Mol. Brain Res. |volume=12 |issue= 1-3 |pages= 225-31 |year= 1992 |pmid= 1312203 |doi=  }}
*{{cite journal  | author=Chiwakata C, Brackmann B, Hunt N, ''et al.'' |title=Tachykinin (substance-P) gene expression in Leydig cells of the human and mouse testis. |journal=Endocrinology |volume=128 |issue= 5 |pages= 2441-8 |year= 1991 |pmid= 1708336 |doi=  }}
*{{cite journal  | author=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=  }}
*{{cite journal  | author=Theodorsson-Norheim E, Jörnvall H, Andersson M, ''et al.'' |title=Isolation and characterization of neurokinin A, neurokinin A(3-10) and neurokinin A(4-10) from a neutral water extract of a metastatic ileal carcinoid tumour. |journal=Eur. J. Biochem. |volume=166 |issue= 3 |pages= 693-7 |year= 1987 |pmid= 3038549 |doi=  }}
*{{cite journal  | author=Harmar AJ, Armstrong A, Pascall JC, ''et al.'' |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=  }}
*{{cite journal  | author=Bhogal N, Donnelly D, Findlay JB |title=The ligand binding site of the neurokinin 2 receptor. Site-directed mutagenesis and identification of neurokinin A binding residues in the human neurokinin 2 receptor. |journal=J. Biol. Chem. |volume=269 |issue= 44 |pages= 27269-74 |year= 1994 |pmid= 7961636 |doi=  }}
*{{cite journal  | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171-4 |year= 1994 |pmid= 8125298 |doi=  }}
*{{cite journal  | author=Tian Y, Wu LH, Oxender DL, Chung FZ |title=The unpredicted high affinities of a large number of naturally occurring tachykinins for chimeric NK1/NK3 receptors suggest a role for an inhibitory domain in determining receptor specificity. |journal=J. Biol. Chem. |volume=271 |issue= 34 |pages= 20250-7 |year= 1996 |pmid= 8702757 |doi=  }}
*{{cite journal  | author=Tanabe T, Otani H, Zeng XT, ''et al.'' |title=Inhibitory effects of calcitonin gene-related peptide on substance-P-induced superoxide production in human neutrophils. |journal=Eur. J. Pharmacol. |volume=314 |issue= 1-2 |pages= 175-83 |year= 1997 |pmid= 8957234 |doi=  }}
*{{cite journal  | author=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, ''et al.'' |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149-56 |year= 1997 |pmid= 9373149 |doi=  }}
*{{cite journal  | author=Zimmer A, Zimmer AM, Baffi J, ''et al.'' |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=  }}
*{{cite journal  | author=Ho WZ, Lai JP, Zhu XH, ''et al.'' |title=Human monocytes and macrophages express substance P and neurokinin-1 receptor. |journal=J. Immunol. |volume=159 |issue= 11 |pages= 5654-60 |year= 1998 |pmid= 9548509 |doi=  }}
*{{cite journal  | author=Lai JP, Douglas SD, Ho WZ |title=Human lymphocytes express substance P and its receptor. |journal=J. Neuroimmunol. |volume=86 |issue= 1 |pages= 80-6 |year= 1998 |pmid= 9655475 |doi=  }}
}}
{{refend}}


{{protein-stub}}
{{gene-7-stub}}
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Latest revision as of 18:09, 10 June 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Preprotachykinin-1, (abbreviated PPT-1, PPT-I, or PPT-A), is a precursor protein that in humans is encoded by the TAC1 gene.[1][2]

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.[3][4] Alpha- and delta-PPT can only be modified to substance P, whereas beta- and gamma-PPT can produce both substance P and neurokinin A.[5]

Neurokinin A can also be further modified to produce neuropeptide K (also known as neurokinin K) and neuropeptide gamma.[6]

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.[2]

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.[4]

Species comparison

In humans, beta-PPT is the dominant isoform in the brain, which contrasts with rats (predominantly gamma-PPT) and cows (alpha-PPT).[4]

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.[4]

References

  1. ↑ 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.
  2. ↑ 2.0 2.1 "Entrez Gene: TAC1 tachykinin, precursor 1 (substance K, substance P, neurokinin 1, neurokinin 2, neuromedin L, neurokinin alpha, neuropeptide K, neuropeptide gamma)".
  3. ↑ 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.
  4. ↑ 4.0 4.1 4.2 4.3 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.
  5. ↑ "MeSH Supplementary Concept: preprotachykinin". www.mentata.com. Retrieved 2016-05-19.[permanent dead link]
  6. ↑ 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. doi:10.1073/pnas.86.1.392. PMC 286471. PMID 2463627.

Further reading


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