kallikrein-8; hK8; neuropsin; NP; ovasin; serine protease 19; serine protease TADG-14; tumor-associated differentially expressed gene 14 protein (KLK8 NRPN PRSS19 TADG14 UNQ283/PRO322)

Function

• serine protease
• capable of degrading a variety of proteins, including
  • casein
  • fibrinogen
  • kininogen
  • fibronectin
  • collagen type IV
• also cleaves L1CAM in response to increased neural activity
• induces neurite outgrowth & fasciculation of cultured hippocampal neurons
• role in the formation & maturation of orphan & small synaptic boutons in the Schaffer-collateral pathway
  • regulates Schaffer-collateral long-term potentiation in the hippocampus
  • required for memory acquisition & synaptic plasticity
• role in skin desquamation & keratinocyte proliferation
• role in the secondary phase of pathogenesis following spinal cord injury
• cleavage of amide substrates following basic amino acids Arg or Lys at the P1 position, with a preference for Arg over Lys
• interacts with SPINK9

Kinetic parameters:

• KM=0.07 mM for Pro-Phe-Arg-MCA
• KM=0.07 mM for Z-Val-Val-Arg-MCA
• KM=0.07 mM for Boc-Val-Pro-Arg-MCA
• KM=0.10 mM for Boc-Leu-Lys-Arg-MCA
• KM=0.10 mM for Boc-Val-Leu-Lys-MCA
• KM=0.07 mM for Boc-Phe-Ser-Arg-MCA
• Vmax=7.1 umol/min/mg enzyme toward Pro-Phe-Arg-MCA
• Vmax=5.4 umol/min/mg enzyme toward Z-Val-Val-Arg-MCA
• Vmax=3.9 umol/min/mg enzyme toward Boc-Val-Pro-Arg-MCA
• Vmax=2.6 umol/min/mg enzyme toward Boc-Leu-Lys-Arg-MCA
• Vmax=1.9 umol/min/mg enzyme toward Boc-Val-Leu-Lys-MCA
• Vmax=1.6 umol/min/mg enzyme toward Boc-Phe-Ser-Arg-MCA
• pH dependence:
  • optimum pH is 8.5
  • active from pH 7-10

Inhibition:

• inhibited by a range of serine protease
• inhibitors including antipain, aprotinin, leupeptin, benzamidine & soybean trypsin inhibitor

Structure

• belongs to the peptidase S1 family, kallikrein subfamily
• contains 1 peptidase S1 domain

Compartment

• secreted. cytoplasm
• cytoplasmic distribution in keratinocytes

Alternative splicing

named isoforms=4

Expression

• isoform 1 is predominantly expressed in the pancreas
• isoform 2 is expressed in adult brain & hippocampus
• isoform 1 & isoform 2 are found in fetal brain & placenta
• detected in salivary gland, uterus, thymus, breast, testis & kidney
• expressed at low levels in normal skin
  • expressed in keratinocytes
• not expressed in spleen, liver, lung or normal ovarian tissue

Pathology

• expression increased 11.5-fold increase in Alzheimer disease hippocampus compared to controls
• overexpressed in some ovarian carcinomas
• overexpressed in psoriasis vulgaris, seborrheic keratosis, lichen planus & squamous cell carcinoma skin samples
• expressed at high levels in serum, ascites fluid & tumor cytosol of advanced stage ovarian cancer patients & may serve as a marker of ovarian cancer

Genetics

• result of a human-specific mutation which is not found in other primates

More general terms

• kallikrein
• glycoprotein
• evolutionary divergent human protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=11202
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:11202
• OMIM: https://mirror.omim.org/entry/605644
• UniProt: http://www.uniprot.org/uniprot/O60259.html