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Protein

Kallikrein-8

Gene

Klk8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.8 Publications

Catalytic activityi

Cleavage of amide substrates following the basic amino acids Arg or Lys at the P1 position, with a preference for Arg over Lys.

Activity regulationi

Strongly inhibited by diisopropyl fluorophosphate, leupeptin and (4-amidinophenyl)methanesulfonyl 1-fluoride.1 Publication

Kineticsi

  1. KM=300 µM for Boc-Val-Pro-Arg-MCA1 Publication
  2. KM=540 µM for Boc-Phe-Ser-Arg-MCA1 Publication
  3. KM=280 µM for D-Val-Leu-Arg-MCA1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei73Charge relay systemBy similarity1
    Active sitei120Charge relay systemBy similarity1
    Active sitei212Charge relay systemBy similarity1

    GO - Molecular functioni

    • serine-type endopeptidase activity Source: UniProtKB

    GO - Biological processi

    Keywordsi

    Molecular functionHydrolase, Protease, Serine protease

    Enzyme and pathway databases

    BRENDAi3.4.21.118 3474
    ReactomeiR-MMU-6809371 Formation of the cornified envelope

    Protein family/group databases

    MEROPSiS01.244

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Kallikrein-8 (EC:3.4.21.118)
    Short name:
    mK8
    Alternative name(s):
    Neuropsin
    Short name:
    NP
    Serine protease 19
    Gene namesi
    Name:Klk8
    Synonyms:Nrpn, Prss19
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Chromosome 7

    Organism-specific databases

    MGIiMGI:1343327 Klk8

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm, Secreted

    Pathology & Biotechi

    Disruption phenotypei

    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.7 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Signal peptidei1 – 28Sequence analysisAdd BLAST28
    PropeptideiPRO_000002794829 – 321 Publication4
    ChainiPRO_000002794933 – 260Kallikrein-8Add BLAST228

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Disulfide bondi39 ↔ 173
    Disulfide bondi58 ↔ 74
    Glycosylationi110N-linked (GlcNAc...) asparagineSequence analysis1
    Disulfide bondi145 ↔ 246
    Disulfide bondi152 ↔ 218
    Disulfide bondi184 ↔ 198
    Disulfide bondi208 ↔ 233

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Zymogen

    Proteomic databases

    EPDiQ61955
    PaxDbiQ61955
    PRIDEiQ61955

    PTM databases

    iPTMnetiQ61955
    PhosphoSitePlusiQ61955

    Expressioni

    Tissue specificityi

    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.7 Publications

    Developmental stagei

    Expression is detected in the brain from embryonic day 12 and continues into adulthood.1 Publication

    Inductioni

    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 4.8 Publications

    Gene expression databases

    BgeeiENSMUSG00000064023 Expressed in 190 organ(s), highest expression level in esophagus
    CleanExiMM_KLK8
    ExpressionAtlasiQ61955 baseline and differential
    GenevisibleiQ61955 MM

    Interactioni

    Subunit structurei

    Interacts with SPINK9.By similarity

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000082588

    Structurei

    Secondary structure

    1260
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliQ61955
    SMRiQ61955
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ61955

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini33 – 257Peptidase S1PROSITE-ProRule annotationAdd BLAST225

    Sequence similaritiesi

    Belongs to the peptidase S1 family. Kallikrein subfamily.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiKOG3627 Eukaryota
    COG5640 LUCA
    GeneTreeiENSGT00760000118862
    HOGENOMiHOG000251820
    HOVERGENiHBG013304
    InParanoidiQ61955
    KOiK08650
    OMAiTKLYAEN
    OrthoDBiEOG091G0DF7
    PhylomeDBiQ61955
    TreeFamiTF331065

    Family and domain databases

    CDDicd00190 Tryp_SPc, 1 hit
    InterProiView protein in InterPro
    IPR009003 Peptidase_S1_PA
    IPR001314 Peptidase_S1A
    IPR001254 Trypsin_dom
    IPR018114 TRYPSIN_HIS
    IPR033116 TRYPSIN_SER
    PfamiView protein in Pfam
    PF00089 Trypsin, 1 hit
    PRINTSiPR00722 CHYMOTRYPSIN
    SMARTiView protein in SMART
    SM00020 Tryp_SPc, 1 hit
    SUPFAMiSSF50494 SSF50494, 1 hit
    PROSITEiView protein in PROSITE
    PS50240 TRYPSIN_DOM, 1 hit
    PS00134 TRYPSIN_HIS, 1 hit
    PS00135 TRYPSIN_SER, 1 hit

    Sequence (1+)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

    Q61955-1 [UniParc]FASTAAdd to basket
    « Hide
            10         20         30         40         50
    MGRPPPCAIQ PWILLLLFMG AWAGLTRAQG SKILEGRECI PHSQPWQAAL
    60 70 80 90 100
    FQGERLICGG VLVGDRWVLT AAHCKKQKYS VRLGDHSLQS RDQPEQEIQV
    110 120 130 140 150
    AQSIQHPCYN NSNPEDHSHD IMLIRLQNSA NLGDKVKPVQ LANLCPKVGQ
    160 170 180 190 200
    KCIISGWGTV TSPQENFPNT LNCAEVKIYS QNKCERAYPG KITEGMVCAG
    210 220 230 240 250
    SSNGADTCQG DSGGPLVCDG MLQGITSWGS DPCGKPEKPG VYTKICRYTT
    260
    WIKKTMDNRD
    Length:260
    Mass (Da):28,524
    Last modified:November 1, 1996 - v1
    Checksum:iBE5F6F6BE37CD60E
    GO

    Computationally mapped potential isoform sequencesi

    There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    A0A0U1RNI7A0A0U1RNI7_MOUSE
    Kallikrein-8
    Klk8
    228Annotation score:

    Mass spectrometryi

    Molecular mass is 26613 Da from positions 29 - 260. Determined by MALDI. 1 Publication
    Molecular mass is 26229 Da from positions 33 - 260. Determined by MALDI. 1 Publication

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    D30785 mRNA Translation: BAA06451.1
    AB032202 Genomic DNA Translation: BAA92435.1
    BC055895 mRNA Translation: AAH55895.1
    AB074296 mRNA Translation: BAB92021.1
    CCDSiCCDS21182.1
    PIRiI56559
    RefSeqiNP_001311327.1, NM_001324398.1
    NP_032966.1, NM_008940.3
    UniGeneiMm.458023

    Genome annotation databases

    EnsembliENSMUST00000085461; ENSMUSP00000082588; ENSMUSG00000064023
    GeneIDi259277
    KEGGimmu:259277
    UCSCiuc009gns.1 mouse

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    D30785 mRNA Translation: BAA06451.1
    AB032202 Genomic DNA Translation: BAA92435.1
    BC055895 mRNA Translation: AAH55895.1
    AB074296 mRNA Translation: BAB92021.1
    CCDSiCCDS21182.1
    PIRiI56559
    RefSeqiNP_001311327.1, NM_001324398.1
    NP_032966.1, NM_008940.3
    UniGeneiMm.458023

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1NPMX-ray2.10A/B33-257[»]
    ProteinModelPortaliQ61955
    SMRiQ61955
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000082588

    Protein family/group databases

    MEROPSiS01.244

    PTM databases

    iPTMnetiQ61955
    PhosphoSitePlusiQ61955

    Proteomic databases

    EPDiQ61955
    PaxDbiQ61955
    PRIDEiQ61955

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSMUST00000085461; ENSMUSP00000082588; ENSMUSG00000064023
    GeneIDi259277
    KEGGimmu:259277
    UCSCiuc009gns.1 mouse

    Organism-specific databases

    CTDi11202
    MGIiMGI:1343327 Klk8

    Phylogenomic databases

    eggNOGiKOG3627 Eukaryota
    COG5640 LUCA
    GeneTreeiENSGT00760000118862
    HOGENOMiHOG000251820
    HOVERGENiHBG013304
    InParanoidiQ61955
    KOiK08650
    OMAiTKLYAEN
    OrthoDBiEOG091G0DF7
    PhylomeDBiQ61955
    TreeFamiTF331065

    Enzyme and pathway databases

    BRENDAi3.4.21.118 3474
    ReactomeiR-MMU-6809371 Formation of the cornified envelope

    Miscellaneous databases

    EvolutionaryTraceiQ61955
    PROiPR:Q61955
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSMUSG00000064023 Expressed in 190 organ(s), highest expression level in esophagus
    CleanExiMM_KLK8
    ExpressionAtlasiQ61955 baseline and differential
    GenevisibleiQ61955 MM

    Family and domain databases

    CDDicd00190 Tryp_SPc, 1 hit
    InterProiView protein in InterPro
    IPR009003 Peptidase_S1_PA
    IPR001314 Peptidase_S1A
    IPR001254 Trypsin_dom
    IPR018114 TRYPSIN_HIS
    IPR033116 TRYPSIN_SER
    PfamiView protein in Pfam
    PF00089 Trypsin, 1 hit
    PRINTSiPR00722 CHYMOTRYPSIN
    SMARTiView protein in SMART
    SM00020 Tryp_SPc, 1 hit
    SUPFAMiSSF50494 SSF50494, 1 hit
    PROSITEiView protein in PROSITE
    PS50240 TRYPSIN_DOM, 1 hit
    PS00134 TRYPSIN_HIS, 1 hit
    PS00135 TRYPSIN_SER, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiKLK8_MOUSE
    AccessioniPrimary (citable) accession number: Q61955
    Secondary accession number(s): Q8K5D7
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
    Last sequence update: November 1, 1996
    Last modified: November 7, 2018
    This is version 148 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    2. Peptidase families
      Classification of peptidase families and list of entries
    3. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    4. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health

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