kallikrein-6; neurosin; protease M; SP59; serine protease 18; serine protease 9; Zyme (KLK6 PRSS18 PRSS9)
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Function
- serine protease
- exhibits a preference for Arg over Lys in the substrate P1 position & for Ser or Pro in the P2 position
- shows activity against
- degrades alpha-synuclein & prevents its polymerization
- may be involved in regulation of axon outgrowth following spinal cord injury
- activated by a range of glycosaminoglycans including chondroitin sulfate, dermatan sulfate, heparan sulfate & heparin
- inactivated by autolytic cleavage after Arg-80
- biomarker of brain aging (negative correlation)
- KM=1562 uM for Tosyl-Gly-Pro-Arg-AMC
- KM=777 uM for Tosyl-Gly-Pro-Lys-AMC
- KM=0.410 mM for Phe-Ser-Arg-AMC
- KM=0.455 mM for Gly-Gly-Arg-AMC
- KM=0.335 mM for Asp-Pro-Arg-AMC
- KM=0.758 mM for Gln-Gly-Arg-AMC
- KM=0.625 mM for Pro-Phe-Arg-AMC
- KM=0.271 mM for Val-Pro-Arg-AMC
- KM=1.72 mM for Val-Leu-Lys-AMC
Inhibition:
- inhibited by a range of serine protease inhibitors including soybean trypsin inhibitor, benzamidine & serpins
Structure
- belongs to the peptidase S1 family, kallikrein subfamily
- contains 1 peptidase S1 domain
Compartment
- secreted
- nucleus, nucleolus
- cytoplasm
- mitochondria, microsome
- in brain, detected in the nucleus of glial cells & in the nucleus & cytoplasm of neurons
- detected in the mitochondrial & microsomal fractions of HEK-293 cells & released into the cytoplasm following cellular stress
Alternative splicing
named isoforms=3
Expression
- in body fluids
- found in milk of lactating women > CSF, nipple aspirate fluid & breast cyst fluid
- also found in serum, seminal plasma & some amniotic fluids & breast tumor cytosolic extracts
- not detected in urine
- in tissue
- found in glandular tissues such as salivary glands > lung, colon, fallopian tube, placenta, breast, pituitary & kidney
- not detected in skin, spleen, bone, thyroid, heart, ureter, liver, muscle, endometrium, testis, pancreas, seminal vesicle, ovary, adrenals & prostate
- in brain, detected in gray matter neurons (at protein level)
- induced by spinal cord injury
- this effect is particularly prominent in macrophages, microglia & reactive astrocytes
Pathology
- degradation of amyloid precursor protein suggests possible role in Alzheimer's disease
- degradation of alpha-synuclein & prevention of its polymerization suggests possible role in Parkinson's disease & other synucleinopathies
- colocalizes with Lewy bodies & glial cytoplasmic inclusions
- tumor cells treated with a neutralizing KLK6 antibody migrate less than control cells, suggesting a role in invasion & metastasis
- overexpressed in primary breast tumors but not expressed in metastatic tumors