General Information

  • ID:  hor006068
  • Uniprot ID:  Q9UHG2
  • Protein name:  PEN
  • Gene name:  PCSK1N
  • Organism:  Homo sapiens (Human)
  • Family:  NA
  • Source:  Human
  • Expression:  Expressed in brain and pancreas.
  • Disease:  Diseases associated with PCSK1N include Amyotrophic Lateral Sclerosis-Parkinsonism/Dementia Complex 1 and Parkinsonism.
  • Comments:  NA
  • Taxonomy:   Homo (genus), Homininae (subfamily), Hominidae (family), Hominoidea (superfamily), Catarrhini (parvorder), Simiiformes (infraorder), Haplorrhini (suborder), Primates (order), Euarchontoglires (superorder), Boreoeutheria , Eutheria , Theria , Mammalia (class), Amniota , Tetrapoda , Dipnotetrapodomorpha , Sarcopterygii (superclass), Euteleostomi , Teleostomi , Gnathostomata , Vertebrata , Craniata (subphylum), Chordata (phylum), Deuterostomia , Bilateria , Eumetazoa , Metazoa (kingdom), Opisthokonta , Eukaryota (superkingdom),cellular organisms
  • GO MF:  GO:0004866 endopeptidase inhibitor activity; GO:0004867 serine-type endopeptidase inhibitor activity; GO:0005102 signaling receptor binding
  • GO BP:  GO:0002021 response to dietary excess; GO:0007218 neuropeptide signaling pathway; GO:0009409 response to cold; GO:0016486 peptide hormone processing
  • GO CC:  GO:0005576 extracellular region; GO:0005615 extracellular space; GO:0005794 Golgi apparatus; GO:0005802 trans-Golgi network; GO:0030141 secretory granule

Sequence Information

  • Sequence:  AADHDVGSELPPEGVLGALLRV
  • Length:  22
  • Propeptide:  MAGSPLLWGPRAGGVGLLVLLLLGLFRPPPALCARPVKEPRGLSAASPPLAETGAPRRFRRSVPRGEAAGAVQELARALAHLLEAERQERARAEAQEAEDQQARVLAQLLRVWGAPRNSDPALGLDDDPDAPAAQLARALLRARLDPAALAAQLVPAPVPAAALRPRPPVYDDGPAGPDAEEAGDETPDVDPELLRYLLGRILAGSADSEGVAAPRRLRRAADHDVGSELPPEGVLGALLRVKRLETPAPQVPARRLLPP
  • Signal peptide:  MAGSPLLWGPRAGGVGLLVLLLLGLFRPPPALC
  • Modification:  NA
  • Glycosylation:  T8 O-linked (GalNAc...) serine
  • Mutagenesis:  15-15V->A: Reduces inhibition of PCSK1.; 16-16V->A: Reduces inhibition of PCSK1.; 17-17V->A: Reduces inhibition of PCSK1.; 20-20V->A: Reduces inhibition of PCSK1.; 21-21V->A: Reduces inhibition of PCSK1.; 22-22V->A: Reduces inhibition of PCSK1.

Activity

  • Function:  May function in the control of the neuroendocrine secretory pathway. Proposed be a specific endogenous inhibitor of PCSK1. ProSAAS and Big PEN-LEN, both containing the C-terminal inhibitory domain, but not the further processed peptides reduce PCSK1 activity in the endoplasmic reticulum and Golgi. It reduces the activity of the 84 kDa form but not the autocatalytically derived 66 kDa form of PCSK1. Subsequent processing of proSAAS may eliminate the inhibition. Slows down convertase-mediated processing of proopiomelanocortin and proenkephalin. May control the intracellular timing of PCSK1 rather than its total level of activity (By similarity).
  • Mechanism:  NA
  • Cross BBB:  NA
  • Target:  PCSK1
  • Target Unid:  P29120
  • IC50: NA
  • EC50: NA
  • ED50: NA
  • kd: NA
  • Half life: NA

Structure

  • Disulfide bond:  NA
  • Structure ID:  AF-Q9UHG2-F1(AlphaFold_DB_ID)

  • Structure: (PDB_ID-from https://www.rcsb.org/; AlphaFold_DB_ID-from https://alphafold.ebi.ac.uk/; hordbxxxxxx_AF2.pdb was predicted structure by AlphaFold2; hordbxxxxxx_ESM.pdb was predicted structure by ESMFold)
    •    hor006068_AF2.pdbhor006068_ESM.pdb

Physical Information

Mass: 259027 Formula: C97H159N27O32
Absent amino acids: CFIKMNQTWY Common amino acids: L
pI: 4.1 Basic residues: 2
Polar residues: 4 Hydrophobic residues: 10
Hydrophobicity: 28.64 Boman Index: -1399
Half-Life: 4.4 hour Half-Life Yeast: >20 hour
Half-Life E.Coli: >10 hour Aliphatic Index 124.09
Instability Index: 4088.64 Extinction Coefficient cystines: 0
Absorbance 280nm: 0

Literature

  • PubMed ID:  10632593
  • Title:  Identification and characterization of proSAAS, a granin-like neuroendocrine peptide precursor that inhibits prohormone processing.
  • PubMed ID:  15489334
  • Title:  The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
  • PubMed ID:  11435430
  • Title:  Inhibitory specificity and potency of proSAAS-derived peptides toward proprotein convertase 1.
  • PubMed ID:  12914799
  • Title:  An N-terminal fragment of ProSAAS (a granin-like neuroendocrine peptide precursor) is associated with tau inclusions in Pick's disease.
  • PubMed ID:  14746899
  • Title:  A human granin-like neuroendocrine peptide precursor (proSAAS) immunoreactivity in tau inclusions of Alzheimer's disease and parkinsonism-dementia complex on Guam.
  • PubMed ID:  19838169
  • Title:  Enrichment of glycopeptides for glycan structure and attachment site identification.
  • PubMed ID:  22171320
  • Title:  Human urinary glycoproteomics; attachment site specific analysis of N- and O-linked glycosylations by CID and ECD.
  • PubMed ID:  23234360
  • Title:  LC-MS/MS characterization of O-glycosylation sites and glycan structures of human cerebrospinal fluid glycoproteins.