Names & Taxonomy

Uniprot ID:
Q92876
Entry Name:
KLK6_HUMAN
Status:
reviewed
Protein Names:
Kallikrein-6 (EC 3.4.21.-) (Neurosin) (Protease M) (SP59) (Serine protease 18) (Serine protease 9) (Zyme)
Gene Names:
KLK6 PRSS18 PRSS9
Gene Names Primary:
KLK6
Organism:
Homo sapiens (Human)

Structure

Length:
244
Sequence:
MKKLMVVLSLIAAAWAEEQNKLVHGGPCDKTSHPYQAALYTSGHLLCGGVLIHPLWVLTAAHCKKPNLQVFLGKHNLRQRESSQEQSSVVRAVIHPDYDAASHDQDIMLLRLARPAKLSELIQPLPLERDCSANTTSCHILGWGKTADGDFPDTIQCAYIHLVSREECEHAYPGQITQNMLCAGDEKYGKDSCQGDSGGPLVCGDHLRGLVSWGNIPCGSKEKPGVYTNVCRYTNWIQKTIQAK
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Secreted. Nucleus, nucleolus. Cytoplasm. Mitochondrion. Microsome. Note=In brain, detected in the nucleus of glial cells and in the nucleus and cytoplasm of neurons. Detected in the mitochondrial and microsomal fractions of HEK-293 cells and released into the cytoplasm following cell stress.

Function

Function:
Serine protease which exhibits a preference for Arg over Lys in the substrate P1 position and for Ser or Pro in the P2 position. Shows activity against amyloid precursor protein, myelin basic protein, gelatin, casein and extracellular matrix proteins such as fibronectin, laminin, vitronectin and collagen. Degrades alpha-synuclein and prevents its polymerization, indicating that it may be involved in the pathogenesis of Parkinson disease and other synucleinopathies. May be involved in regulation of axon outgrowth following spinal cord injury. Tumor cells treated with a neutralizing KLK6 antibody migrate less than control cells, suggesting a role in invasion and metastasis.
Kinetics:
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=1562 uM for Tosyl-Gly-Pro-Arg-AMC
Enzyme Regulation:
ENZYME REGULATION: Inhibited by a range of serine protease inhibitors including soybean trypsin inhibitor, benzamidine and serpins. Activated by a range of glycosaminoglycans including chondroitin sulfate, dermatan sulfate, heparan sulfate and heparin.
Active Site:
ACT_SITE 62 62 Charge relay system.
Gene Ontology Go:
cytoplasm
endoplasmic reticulum
extracellular region
extracellular space
intercellular bridge
microtubule cytoskeleton
mitochondrion
nuclear membrane
nucleolus
nucleoplasm
serine-type endopeptidase activity
amyloid precursor protein metabolic process
central nervous system development
collagen catabolic process
hormone metabolic process
myelination
neuron death
positive regulation of G-protein coupled receptor protein signaling pathway
protein autoprocessing
protein processing
regulation of cell differentiation
regulation of neuron projection development
response to wounding
tissue regeneration
Gene Ontology Biological Process:
amyloid precursor protein metabolic process
central nervous system development
collagen catabolic process
hormone metabolic process
myelination
neuron death
positive regulation of G-protein coupled receptor protein signaling pathway
protein autoprocessing
protein processing
regulation of cell differentiation
regulation of neuron projection development
response to wounding
tissue regeneration
Gene Ontology Molecular Function:
serine-type endopeptidase activity
Gene Ontology Cellular Component:
cytoplasm
endoplasmic reticulum
extracellular region
extracellular space
intercellular bridge
microtubule cytoskeleton
mitochondrion
nuclear membrane
nucleolus
nucleoplasm
Keywords:
3D-structure
Alternative splicing
Autocatalytic cleavage
Cleavage on pair of basic residues
Complete proteome
Cytoplasm
Direct protein sequencing
Disulfide bond
Endoplasmic reticulum
Glycoprotein
Hydrolase
Microsome
Mitochondrion
Nucleus
Polymorphism
Protease
Reference proteome
Secreted
Serine protease
Signal
Zymogen

Publication

PubMed ID:
8898378 9003450 9312124 10610719 11054574 15207701 16800739 14702039 15057824 15489334 11018688 10997858 11668196 12878203 12928483 15557757 16987227 16321973 17417874 12016211 11983703