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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
General
evolutionary divergent human protein
glycoprotein
kallikrein
Properties
SIZE: entity length = 260 aa
MW = 28 kD
COMPARTMENT: cytoplasm
MOTIF: signal sequence {1-28}
S1 domain {33-257}
MOTIF: cysteine residue {C39}
MODIFICATION: cysteine residue {C173}
cysteine residue {C58}
MODIFICATION: cysteine residue {C74}
histidine residue {H73}
cysteine residue {C74}
MODIFICATION: cysteine residue {C58}
N-glycosylation site {N110}
aspartate residue {D120}
cysteine residue {C145}
MODIFICATION: cysteine residue {C246}
cysteine residue {C152}
MODIFICATION: cysteine residue {C218}
cysteine residue {C173}
MODIFICATION: cysteine residue {C39}
cysteine residue {C184}
MODIFICATION: cysteine residue {C198}
cysteine residue {C198}
MODIFICATION: cysteine residue {C184}
cysteine residue {C208}
MODIFICATION: cysteine residue {C233}
serine residue {S212}
cysteine residue {C218}
MODIFICATION: cysteine residue {C152}
cysteine residue {C233}
MODIFICATION: cysteine residue {C208}
cysteine residue {C246}
MODIFICATION: cysteine residue {C145}
Database Correlations
OMIM 605644
UniProt O60259
Pfam PF00089
Entrez Gene 11202
Kegg hsa:11202
ENZYME 3.4.21.118
References
- UniProt :accession O60259
- Entrez Gene :accession 11202