KLK8 (Kallikrein 8)

KLK8 is serine protease which is capable of degrading a number of proteins such as casein, fibrinogen, kininogen, fibronectin and collagen type IV. KLK8 also cleaves L1CAM in response to increased neural activity. KLK8 induces neurite outgrowth and fasciculation of cultured hippocampal neurons. KLK8 plays a role in the formation and maturation of orphan and small synaptic boutons in the Schaffer-collateral pathway, regulates Schaffer-collateral long-term potentiation in the hippocampus and is required for memory acquisition and synaptic plasticity. KLK8 is involved in skin desquamation and keratinocyte proliferation. KLK8 plays a role in the secondary phase of pathogenesis following spinal cord injury.

KLK8 (Kallikrein 8) Related Areas

Enzyme>>Protease & Regulator>>Serine Protease & Regulator>>Kallikrein>>KLK8/Kallikrein 8

Cancer>>Angiogenesis>>Kallikrein>>KLK8/Kallikrein 8

KLK8 (Kallikrein 8) Alternative Names

KLK8, Kallikrein 8, UNQ283/PRO322, HNP, NP, NRPN, PRSS19, TADG14 [Homo sapiens]

Klk8, Kallikrein 8, BSP1, Nrpn, Prss19 [Mus musculus]

Summaries for KLK8 (Kallikrein 8)

Entrez Gene summary for KLK8:

Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. This KLK8 gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Alternate splicing of this gene results in four transcript variants encoding four different isoforms. The isoforms exhibit distinct patterns of expression that suggest roles in brain plasticity and ovarian cancer. [provided by RefSeq, Jul 2008]

OMIM - description for KLK8:

KLK8 belongs to the kallikrein subgroup of serine proteases, which have diverse physiologic functions in many tissues. For background information on kallikreins, see 147960.

Wikipedia summary for KLK8:

Kallikrein-8 is a protein that in humans is encoded by the KLK8 gene.

Human KLK8 (Kallikrein 8) Protein General Information

 

• Protein names: Kallikrein-8, Short name=hK8
• Sequence length: 260 AA.
• Catalytic activity: Cleavage of amide substrates following the basic amino acids Arg or Lys at the P1 position, with a preference for Arg over Lys.
• Sequence similarities: KLK8 belongs to the peptidase S1 family. Kallikrein subfamily. KLK8 contains 1 peptidase S1 domain.
• Miscellaneous: KLK8 is expressed at high levels in serum, ascites fluid and tumor cytosol of advanced stage ovarian cancer patients and may serve as a marker of ovarian cancer.
• Enzyme regulation: KLK8 is inhibited by a range of serine protease inhibitors including antipain, aprotinin, leupeptin, benzamidine and soybean trypsin inhibitor.
• Subunit structure: KLK8 interacts with SPINK9.
• Subcellular location: Secreted. Cytoplasm. Note: Shows a cytoplasmic distribution in the keratinocytes.
• Tissue specificity: Isoform 1 is predominantly expressed in the pancreas. Isoform 2 is expressed in adult brain and hippocampus. Isoform 1 and isoform 2 are found in fetal brain and placenta. KLK8 is detected in salivary gland, uterus, thymus, breast, testis and kidney but not in spleen, liver, lung or normal ovarian tissue. KLK8 displays an 11.5-fold increase in Alzheimer disease hippocampus compared to controls and is overexpressed in some ovarian carcinomas. KLK8 is expressed at low levels in normal skin while high levels are found in psoriasis vulgaris, seborrheic keratosis, lichen planus and squamous cell carcinoma skin samples. KLK8 is expressed in the keratinocytes.
• Involvement in disease: 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 µmol/min/mg enzyme toward Pro-Phe-Arg-MCA
  Vmax=5.4 µmol/min/mg enzyme toward Z-Val-Val-Arg-MCA
  Vmax=3.9 µmol/min/mg enzyme toward Boc-Val-Pro-Arg-MCA
  Vmax=2.6 µmol/min/mg enzyme toward Boc-Leu-Lys-Arg-MCA
  Vmax=1.9 µmol/min/mg enzyme toward Boc-Val-Leu-Lys-MCA
  Vmax=1.6 µmol/min/mg enzyme toward Boc-Phe-Ser-Arg-MCA
  pH dependence:
  Optimum pH is 8.5. Active from pH 7-10.

General information above from UniProt

Function for KLK8 (Kallikrein 8) Protein

UniProtKB:

KLK8 is serine protease which is capable of degrading a number of proteins such as casein, fibrinogen, kininogen, fibronectin and collagen type IV. KLK8 also cleaves L1CAM in response to increased neural activity. KLK8 induces neurite outgrowth and fasciculation of cultured hippocampal neurons. KLK8 plays a role in the formation and maturation of orphan and small synaptic boutons in the Schaffer-collateral pathway, regulates Schaffer-collateral long-term potentiation in the hippocampus and is required for memory acquisition and synaptic plasticity. KLK8 is involved in skin desquamation and keratinocyte proliferation. KLK8 plays a role in the secondary phase of pathogenesis following spinal cord injury.

Genatlas:

• KLK8 has a trypsin-like activity
• KLK8 is involved in the pathogenesis of inflammatory skin diseases
• KLK8 is involved in desquamation cascade of the skin
• KLK8 is involved in proliferation of keratinocytes and desquamation possibly through other kallikreins
• KLK8 may play a crucial role in promoting cancer-cell invasion in bladder tumor (Pubmed 17459052)
• KLK8 might be involved in desquamation through the degradation of adhesive molecules that connect layers of the epidermis and in tissue development and rearrangement (Pubmed 20180635)
• KLK8 is keratinocyte-specific protease, having an active role for in upper epidermis (Pubmed 20940292)
• active serine protease in stratum corneum and sweat, with potential regulators and targets that augment its involvement in a skin barrier proteolytic cascade (Pubmed 20940292)
• KLK8 is key regulator of the FKBP5 gene and protein expression (Pubmed 21508957)