UniProt functional annotation for Q61955



	UniProt functional annotation for Q61955

UniProt code: Q61955.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Serine protease which is capable of degrading a number of proteins such as casein, fibrinogen, kininogen, fibronectin and collagen type IV. Also cleaves L1CAM in response to increased neural activity. Induces neurite outgrowth and fasciculation of cultured hippocampal neurons. 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. Involved in skin desquamation and keratinocyte proliferation. Plays a role in the secondary phase of pathogenesis following spinal cord injury. {ECO:0000269|PubMed:10762375, ECO:0000269|PubMed:11880192, ECO:0000269|PubMed:12944500, ECO:0000269|PubMed:16308352, ECO:0000269|PubMed:16537644, ECO:0000269|PubMed:17182622, ECO:0000269|PubMed:17629414, ECO:0000269|PubMed:9556608}.

Catalytic activity: Reaction=Cleavage of amide substrates following the basic amino acids Arg or Lys at the P1 position, with a preference for Arg over Lys.; EC=3.4.21.118;

Activity regulation: Strongly inhibited by diisopropyl fluorophosphate, leupeptin and (4-amidinophenyl)methanesulfonyl 1-fluoride. {ECO:0000269|PubMed:9556608}.

Biophysicochemical properties: Kinetic parameters: KM=300 uM for Boc-Val-Pro-Arg-MCA {ECO:0000269|PubMed:9556608}; KM=540 uM for Boc-Phe-Ser-Arg-MCA {ECO:0000269|PubMed:9556608}; KM=280 uM for D-Val-Leu-Arg-MCA {ECO:0000269|PubMed:9556608};

Subunit: Interacts with SPINK9. {ECO:0000250}.

Subcellular location: Secreted. Cytoplasm. Note=Shows a cytoplasmic distribution in the keratinocytes.

Tissue specificity: Expressed in the limbic system of mouse brain and is localized at highest concentration in pyramidal neurons of the hippocampal CA1-3 subfields. Also detected in spinal cord gray matter and in keratinized stratified epithelia of epidermis, hair, tongue, palate, nasal cavity, pharynges, esophagus and forestomach. In skin and mucus membranes, expressed in stratum spinosum and stratum granulosum. Expressed during estrus in vaginal epithelial cells but not stromal cells. Within the vaginal epithelium, expressed in prickle cells, granular cells and parakeratotic cells but not in basal cells. Not expressed in uterus. Expressed in the keratinocytes. {ECO:0000269|PubMed:12354676, ECO:0000269|PubMed:17629414, ECO:0000269|PubMed:17761692, ECO:0000269|PubMed:7623137, ECO:0000269|PubMed:8602273, ECO:0000269|PubMed:9620300, ECO:0000269|PubMed:9749739}.

Developmental stage: Expression is detected in the brain from embryonic day 12 and continues into adulthood. {ECO:0000269|PubMed:8602273}.

Induction: By chemical/incision-induced brain injury which leads to increased expression in axon fiber bundles of the peri-lesioned region, by electrically-induced seizure (kindling) in brain, by UV irradiation in skin and by incisional and chemically-induced skin wounding which causes epidermal proliferation and hyperkeratosis. Induced by chemically-induced oxidative stress which leads to increased expression in the hippocampal pyramidal neurons 2 hours after treatment. Levels then decrease, drop to 60% of pretreated control levels at day 7 when avoidance learning is impaired and return to control levels at day 30. Also induced by spinal crush injury which leads to increased expression in spinal cord white matter adjacent to the lesion. Expression increases between days 1-14 post-injury with a peak at day 4. {ECO:0000269|PubMed:10196465, ECO:0000269|PubMed:10421059, ECO:0000269|PubMed:11274744, ECO:0000269|PubMed:14616360, ECO:0000269|PubMed:17629414, ECO:0000269|PubMed:8864305, ECO:0000269|PubMed:9374276, ECO:0000269|PubMed:9749739}.

Mass spectrometry: Mass=26229; Method=MALDI; Evidence={ECO:0000269|PubMed:9556608};

Disruption phenotype: Mice display marked abnormalities of synapses and neurons in the CA1 subfield of the hippocampus with enlarged and elongated pyramidal cell soma and reduced asymmetrical synapse numbers. Mutants also display impaired spatial memory acquisition, increased hippocampal susceptibility to hyperexcitability in response to repetitive afferent stimulation and prolonged recovery of UV-irradiated skin. Following spinal cord injury, mutants display reduced demyelination, oligodendrocyte death and axonal degeneration, and inproved hind limb recovery, suggesting that attenuation of neuropsin activity may be beneficial in the treatment of spinal cord injury. Blocking of Klk8 activity by intraventricular injection with monoclonal antibodies reduces or eliminates epileptic seizures in kindled mice. {ECO:0000269|PubMed:11273653, ECO:0000269|PubMed:11549709, ECO:0000269|PubMed:14616360, ECO:0000269|PubMed:16308352, ECO:0000269|PubMed:16537644, ECO:0000269|PubMed:17182622, ECO:0000269|PubMed:17629414}.

Similarity: Belongs to the peptidase S1 family. Kallikrein subfamily. {ECO:0000255|PROSITE-ProRule:PRU00274}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Serine protease which is capable of degrading a number of proteins such as casein, fibrinogen, kininogen, fibronectin and collagen type IV. Also cleaves L1CAM in response to increased neural activity. Induces neurite outgrowth and fasciculation of cultured hippocampal neurons. 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. Involved in skin desquamation and keratinocyte proliferation. Plays a role in the secondary phase of pathogenesis following spinal cord injury. {ECO:0000269\|PubMed:10762375, ECO:0000269\|PubMed:11880192, ECO:0000269\|PubMed:12944500, ECO:0000269\|PubMed:16308352, ECO:0000269\|PubMed:16537644, ECO:0000269\|PubMed:17182622, ECO:0000269\|PubMed:17629414, ECO:0000269\|PubMed:9556608}.


Catalytic activity:		Reaction=Cleavage of amide substrates following the basic amino acids Arg or Lys at the P1 position, with a preference for Arg over Lys.; EC=3.4.21.118;
Activity regulation:		Strongly inhibited by diisopropyl fluorophosphate, leupeptin and (4-amidinophenyl)methanesulfonyl 1-fluoride. {ECO:0000269\|PubMed:9556608}.
Biophysicochemical properties:		Kinetic parameters: KM=300 uM for Boc-Val-Pro-Arg-MCA {ECO:0000269\|PubMed:9556608}; KM=540 uM for Boc-Phe-Ser-Arg-MCA {ECO:0000269\|PubMed:9556608}; KM=280 uM for D-Val-Leu-Arg-MCA {ECO:0000269\|PubMed:9556608};
Subunit:		Interacts with SPINK9. {ECO:0000250}.
Subcellular location:		Secreted. Cytoplasm. Note=Shows a cytoplasmic distribution in the keratinocytes.
Tissue specificity:		Expressed in the limbic system of mouse brain and is localized at highest concentration in pyramidal neurons of the hippocampal CA1-3 subfields. Also detected in spinal cord gray matter and in keratinized stratified epithelia of epidermis, hair, tongue, palate, nasal cavity, pharynges, esophagus and forestomach. In skin and mucus membranes, expressed in stratum spinosum and stratum granulosum. Expressed during estrus in vaginal epithelial cells but not stromal cells. Within the vaginal epithelium, expressed in prickle cells, granular cells and parakeratotic cells but not in basal cells. Not expressed in uterus. Expressed in the keratinocytes. {ECO:0000269\|PubMed:12354676, ECO:0000269\|PubMed:17629414, ECO:0000269\|PubMed:17761692, ECO:0000269\|PubMed:7623137, ECO:0000269\|PubMed:8602273, ECO:0000269\|PubMed:9620300, ECO:0000269\|PubMed:9749739}.
Developmental stage:		Expression is detected in the brain from embryonic day 12 and continues into adulthood. {ECO:0000269\|PubMed:8602273}.
Induction:		By chemical/incision-induced brain injury which leads to increased expression in axon fiber bundles of the peri-lesioned region, by electrically-induced seizure (kindling) in brain, by UV irradiation in skin and by incisional and chemically-induced skin wounding which causes epidermal proliferation and hyperkeratosis. Induced by chemically-induced oxidative stress which leads to increased expression in the hippocampal pyramidal neurons 2 hours after treatment. Levels then decrease, drop to 60% of pretreated control levels at day 7 when avoidance learning is impaired and return to control levels at day 30. Also induced by spinal crush injury which leads to increased expression in spinal cord white matter adjacent to the lesion. Expression increases between days 1-14 post-injury with a peak at day 4. {ECO:0000269\|PubMed:10196465, ECO:0000269\|PubMed:10421059, ECO:0000269\|PubMed:11274744, ECO:0000269\|PubMed:14616360, ECO:0000269\|PubMed:17629414, ECO:0000269\|PubMed:8864305, ECO:0000269\|PubMed:9374276, ECO:0000269\|PubMed:9749739}.
Mass spectrometry:		Mass=26229; Method=MALDI; Evidence={ECO:0000269\|PubMed:9556608};
Disruption phenotype:		Mice display marked abnormalities of synapses and neurons in the CA1 subfield of the hippocampus with enlarged and elongated pyramidal cell soma and reduced asymmetrical synapse numbers. Mutants also display impaired spatial memory acquisition, increased hippocampal susceptibility to hyperexcitability in response to repetitive afferent stimulation and prolonged recovery of UV-irradiated skin. Following spinal cord injury, mutants display reduced demyelination, oligodendrocyte death and axonal degeneration, and inproved hind limb recovery, suggesting that attenuation of neuropsin activity may be beneficial in the treatment of spinal cord injury. Blocking of Klk8 activity by intraventricular injection with monoclonal antibodies reduces or eliminates epileptic seizures in kindled mice. {ECO:0000269\|PubMed:11273653, ECO:0000269\|PubMed:11549709, ECO:0000269\|PubMed:14616360, ECO:0000269\|PubMed:16308352, ECO:0000269\|PubMed:16537644, ECO:0000269\|PubMed:17182622, ECO:0000269\|PubMed:17629414}.
Similarity:		Belongs to the peptidase S1 family. Kallikrein subfamily. {ECO:0000255\|PROSITE-ProRule:PRU00274}.