Q61955 · KLK8_MOUSE
- ProteinKallikrein-8
- GeneKlk8
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids260 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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.
Catalytic activity
Activity regulation
Strongly inhibited by diisopropyl fluorophosphate, leupeptin and (4-amidinophenyl)methanesulfonyl 1-fluoride.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
300 μM | Boc-Val-Pro-Arg-MCA | |||||
540 μM | Boc-Phe-Ser-Arg-MCA | |||||
280 μM | D-Val-Leu-Arg-MCA |
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 73 | Charge relay system | ||||
Sequence: H | ||||||
Active site | 120 | Charge relay system | ||||
Sequence: D | ||||||
Active site | 212 | Charge relay system | ||||
Sequence: S |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | extracellular space | |
Cellular Component | secretory granule | |
Cellular Component | serine protease inhibitor complex | |
Molecular Function | peptidase activity | |
Molecular Function | serine-type endopeptidase activity | |
Biological Process | keratinocyte proliferation | |
Biological Process | memory | |
Biological Process | neuron projection morphogenesis | |
Biological Process | proteolysis | |
Biological Process | regulation of synapse organization | |
Biological Process | response to wounding | |
Biological Process | synapse organization |
Keywords
- Molecular function
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameKallikrein-8
- EC number
- Short namesmK8
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ61955
- Secondary accessions
Proteomes
Organism-specific databases
Phenotypes & Variants
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.
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 17 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for signal, propeptide, chain, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-28 | |||||
Sequence: MGRPPPCAIQPWILLLLFMGAWAGLTRA | ||||||
Propeptide | PRO_0000027948 | 29-32 | ||||
Sequence: QGSK | ||||||
Chain | PRO_0000027949 | 33-260 | Kallikrein-8 | |||
Sequence: ILEGRECIPHSQPWQAALFQGERLICGGVLVGDRWVLTAAHCKKQKYSVRLGDHSLQSRDQPEQEIQVAQSIQHPCYNNSNPEDHSHDIMLIRLQNSANLGDKVKPVQLANLCPKVGQKCIISGWGTVTSPQENFPNTLNCAEVKIYSQNKCERAYPGKITEGMVCAGSSNGADTCQGDSGGPLVCDGMLQGITSWGSDPCGKPEKPGVYTKICRYTTWIKKTMDNRD | ||||||
Disulfide bond | 39↔173 | |||||
Sequence: CIPHSQPWQAALFQGERLICGGVLVGDRWVLTAAHCKKQKYSVRLGDHSLQSRDQPEQEIQVAQSIQHPCYNNSNPEDHSHDIMLIRLQNSANLGDKVKPVQLANLCPKVGQKCIISGWGTVTSPQENFPNTLNC | ||||||
Disulfide bond | 58↔74 | |||||
Sequence: CGGVLVGDRWVLTAAHC | ||||||
Glycosylation | 110 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 145↔246 | |||||
Sequence: CPKVGQKCIISGWGTVTSPQENFPNTLNCAEVKIYSQNKCERAYPGKITEGMVCAGSSNGADTCQGDSGGPLVCDGMLQGITSWGSDPCGKPEKPGVYTKIC | ||||||
Disulfide bond | 152↔218 | |||||
Sequence: CIISGWGTVTSPQENFPNTLNCAEVKIYSQNKCERAYPGKITEGMVCAGSSNGADTCQGDSGGPLVC | ||||||
Disulfide bond | 184↔198 | |||||
Sequence: CERAYPGKITEGMVC | ||||||
Disulfide bond | 208↔233 | |||||
Sequence: CQGDSGGPLVCDGMLQGITSWGSDPC |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
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.
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.
Developmental stage
Expression is detected in the brain from embryonic day 12 and continues into adulthood.
Gene expression databases
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 33-257 | Peptidase S1 | ||||
Sequence: ILEGRECIPHSQPWQAALFQGERLICGGVLVGDRWVLTAAHCKKQKYSVRLGDHSLQSRDQPEQEIQVAQSIQHPCYNNSNPEDHSHDIMLIRLQNSANLGDKVKPVQLANLCPKVGQKCIISGWGTVTSPQENFPNTLNCAEVKIYSQNKCERAYPGKITEGMVCAGSSNGADTCQGDSGGPLVCDGMLQGITSWGSDPCGKPEKPGVYTKICRYTTWIKKTMD |
Sequence similarities
Belongs to the peptidase S1 family. Kallikrein subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length260
- Mass (Da)28,524
- Last updated1996-11-01 v1
- ChecksumBE5F6F6BE37CD60E
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0U1RNI7 | A0A0U1RNI7_MOUSE | Klk8 | 228 |
Mass Spectrometry
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
D30785 EMBL· GenBank· DDBJ | BAA06451.1 EMBL· GenBank· DDBJ | mRNA | ||
AB032202 EMBL· GenBank· DDBJ | BAA92435.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC055895 EMBL· GenBank· DDBJ | AAH55895.1 EMBL· GenBank· DDBJ | mRNA | ||
AB074296 EMBL· GenBank· DDBJ | BAB92021.1 EMBL· GenBank· DDBJ | mRNA |