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
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTAC1, Hs.2563, NK2, TAC2, tachykinin precursor 1, NKNA, NPK
External IDsOMIM: 162320 MGI: 98474 HomoloGene: 2394 GeneCards: TAC1
Orthologs
SpeciesHumanMouse
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 MbChr 6: 7.55 – 7.57 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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.
  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


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