Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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PAH Pancreatic hormones / neuropeptide F / peptide YY family

SMART accession number:	SM00309
Description:	Pancreatic hormone is a regulator of pancreatic and gastrointestinal functions.
Interpro abstract (IPR001955):	Pancreatic hormone (PP) [(PUBMED:6107857)] is a peptide synthesized in pancreatic islets of Langherhans, which acts as a regulator of pancreatic and gastrointestinal functions. The hormone is produced as a larger propeptide, which is enzymatically cleaved to yield the mature active peptide: this is 36 amino acids in length [(PUBMED:3031687)] and has an amidated C terminus [(PUBMED:2599092)]. The hormone has a globular structure, residues 2-8 forming a left-handed poly-proline-II-like helix, residues 9-13 a beta turn, and 14-32 an alpha-helix,held close to the first helix by hydrophobic interactions [(PUBMED:3031687)]. Unlike glucagon, another peptide hormone, the structure of pancreatic peptide is preserved in aqueous solution [(PUBMED:2067973)]. Both N and C termini are required for activity: receptor binding and activation functions may reside in the N and C termini respectively [(PUBMED:3031687)]. Pancreatic hormone is part of a wider family of active peptides that includes: Neuropeptide Y (NPY) [(PUBMED:3031687)], one of the most abundant peptides in the mammalian nervous system. NPY is implicated in the control of feeding and the secretion of the gonadotrophin-releasing hormone. Peptide YY (PYY) [(PUBMED:6953409)]. PPY is a gut peptide that inhibits exocrine pancreatic secretion, has a vasoconstrictory action and inhibits jejunal and colonic mobility. Various NPY and PYY-like polypeptides from fish and amphibians [(PUBMED:1459125), (PUBMED:1620652)]. Neuropeptide F (NPF) from invertebrates such as worms and snail. Skin peptide Tyr-Tyr (SPYY) from the frog Phyllomedusa bicolor. SPYY shows a large spectra of antibacterial and antifungal activity. All these peptides are 36 to 39 amino acids long. Like most active peptides, their C-terminal is amidated and they are synthesized as larger protein precursors.
GO component:	extracellular region (GO:0005576)
GO function:	hormone activity (GO:0005179)
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 153 PAH domains in 153 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a PAH domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with PAH domain is also avaliable.

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  Go to specific node: Homo sapiens, Mus musculus, Rattus norvegicus, Takifugu rubripes

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Gehlert DR
  • Multiple receptors for the pancreatic polypeptide (PP-fold) family: physiological implications.
  • Proc Soc Exp Biol Med. 1998; 218: 7-22
  • Display abstract

  • The pancreatic polypeptide (PP-fold) family of peptides consists of the endocrine peptides, pancreatic polypeptide (PP) and peptide YY (PYY), and the neuroneally derived peptide, neuropeptide Y (NPY). All three peptides are found in the circulation, with PP found primarily in the pancreas and PYY found principally in the gut. NPY is released into the circulation from neuroneal stores in response to stress. These peptides have broad peripheral actions on a number of organs. Not surprisingly, PYY and PP are believed to play an important role in the function of the gastrointestinal tract while NPY is a potent vasconstrictor and may have effects on the gut through the enteric nervous system. In the brain, NPY has been implicated in anxiety and depression, feeding and obesity, memory retention, neuroneal excitability, endocrine function, and metabolism. Recent advances in the molecular biology of the receptors for these peptides have resulted in the identification of at least six receptor subtypes with varying peptide pharmacology. Compared to other G-protein coupled receptor families, the PP-fold peptide receptors exhibit a relatively low level of sequence identity. Further advances in the development of selective agonists and antagonists for individual receptor subtypes will be needed to understand further their role in physiological function.

  • Michel MC et al.
  • XVI. International Union of Pharmacology recommendations for the nomenclature of neuropeptide Y, peptide YY, and pancreatic polypeptide receptors.
  • Pharmacol Rev. 1998; 50: 143-50

  • Blundell TL, Humbel RE
  • Hormone families: pancreatic hormones and homologous growth factors.
  • Nature. 1980; 287: 781-7
  • Display abstract

  • The growing realization that biologically active polypeptides can be grouped in families, the members of which show structural and functional relatedness, is illustrated by the four families which are represented in the pancreas by the hormones insulin, glucagon, somatostatin and pancreatic polypeptide.

• Metabolism (metabolic pathways involving proteins which contain this domain)

• % proteins involved KEGG pathway ID Description 72.00 map04080 Neuroactive ligand-receptor interaction 28.00 map04920 Adipocytokine signaling pathway This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with PAH domain which could be assigned to a KEGG orthologous group, and not all proteins containing PAH domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

• Structure (3D structures containing this domain)

• 3D Structures of PAH domains in PDB

  PDB code	Main view	Title
  1bba		Sequence-specific 1h nmr assignments and solution structure of bovine pancreatic polypeptide
  1f8p		Porcine neuropeptide y bound to dpc micelles
  1fvn		[ala31, aib32]-neuropeptide y
  1icy		[ala31,pro32]-pnpy bound to dpc micelles
  1k8v		The nmr-derived conformation of neuropeptide f from moniezia expansa
  1ljv		Bovine pancreatic polypeptide bound to dpc micelles
  1ppt		X-ray analysis (1.4-angstroms resolution) of avian pancreatic polypeptide. small globular protein hormone
  1qbf		Nmr solution structure of porcine peptide yy
  1ron		Nmr solution structure of human neuropeptide y
  1ru5		Solution structure of porcine peptide yy (ppyy)
  1ruu		Solution structure of porcine peptide yy (ppyy) bound to dpc micelles
  1tz4		[hpp19-23]-pnpy bound to dpc micelles
  1tz5		[pnpy19-23]-hpp bound to dpc micelles
  1v1d		Nucleophilic and general acid catalysis at physiological ph by a designed miniature esterase
  2bf9		Anisotropic refinement of avian (turkey) pancreatic polypeptide at 0.99 angstroms resolution.
  2dez		Structure of human pyy
  2df0		Solution structure of human pyy3-36
  2h3s		Cis-azobenzene-avian pancreatic polypeptide bound to dpc micelles
  2h3t		Trans-(4-aminomethyl)phenylazobenzoic acid-app bound to dpc micelles
  2h4b		Cis-4-aminomethylphenylazobenzoic acid-avian pancreatic polypeptide
  2k76		Solution structure of a paralog-specific mena binder by nmr
  2oon		Structure of ala14-pyy in aqueous solution
  2oop		Structure of tyr7-pyy in solution
  2rlk		Refined solution structure of porcine peptide yy (pyy)

• Links (links to other resources describing this domain)

• BLOCKS	PANCREATIC_HORMONE
  PFAM	hormone3
  INTERPRO	IPR001955
  PROSITE	PANCREATIC_HORMONE

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