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Protein

Kallikrein-8

Gene

Klk8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.

Enzyme 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

    • cell death Source: UniProtKB
    • keratinocyte proliferation Source: UniProtKB
    • memory Source: UniProtKB
    • negative regulation of axon regeneration Source: UniProtKB
    • negative regulation of myelination Source: UniProtKB
    • neuron projection morphogenesis Source: UniProtKB
    • regulation of synapse organization Source: UniProtKB
    • response to wounding Source: UniProtKB
    • synapse organization Source: MGI
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Chromosome 7

    Organism-specific databases

    MGIiMGI:1343327. Klk8.

    Subcellular locationi

    GO - Cellular componenti

    • cytoplasm Source: UniProtKB
    • extracellular space Source: UniProtKB
    Complete GO annotation...

    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...)Sequence 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.
    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
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi47 – 52Combined sources6
    Beta strandi55 – 64Combined sources10
    Beta strandi67 – 70Combined sources4
    Helixi72 – 74Combined sources3
    Beta strandi80 – 84Combined sources5
    Beta strandi96 – 98Combined sources3
    Beta strandi100 – 105Combined sources6
    Beta strandi122 – 128Combined sources7
    Beta strandi133 – 136Combined sources4
    Beta strandi151 – 158Combined sources8
    Beta strandi160 – 164Combined sources5
    Beta strandi172 – 178Combined sources7
    Helixi181 – 187Combined sources7
    Turni189 – 191Combined sources3
    Beta strandi196 – 200Combined sources5
    Beta strandi215 – 218Combined sources4
    Beta strandi221 – 228Combined sources8
    Beta strandi231 – 233Combined sources3
    Beta strandi240 – 244Combined sources5
    Helixi245 – 256Combined sources12

    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...

    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
    Contains 1 peptidase S1 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal

    Phylogenomic databases

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

    Family and domain databases

    CDDicd00190. Tryp_SPc. 1 hit.
    InterProiIPR009003. Peptidase_S1_PA.
    IPR001314. Peptidase_S1A.
    IPR001254. Trypsin_dom.
    IPR018114. TRYPSIN_HIS.
    IPR033116. TRYPSIN_SER.
    [Graphical view]
    PfamiPF00089. Trypsin. 1 hit.
    [Graphical view]
    PRINTSiPR00722. CHYMOTRYPSIN.
    SMARTiSM00020. Tryp_SPc. 1 hit.
    [Graphical view]
    SUPFAMiSSF50494. SSF50494. 1 hit.
    PROSITEiPS50240. TRYPSIN_DOM. 1 hit.
    PS00134. TRYPSIN_HIS. 1 hit.
    PS00135. TRYPSIN_SER. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    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

    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.

    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.
    OMAiDHSHDIM.
    OrthoDBiEOG091G0DF7.
    PhylomeDBiQ61955.
    TreeFamiTF331065.

    Enzyme and pathway databases

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

    Miscellaneous databases

    EvolutionaryTraceiQ61955.
    PROiQ61955.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSMUSG00000064023.
    CleanExiMM_KLK8.
    ExpressionAtlasiQ61955. baseline and differential.
    GenevisibleiQ61955. MM.

    Family and domain databases

    CDDicd00190. Tryp_SPc. 1 hit.
    InterProiIPR009003. Peptidase_S1_PA.
    IPR001314. Peptidase_S1A.
    IPR001254. Trypsin_dom.
    IPR018114. TRYPSIN_HIS.
    IPR033116. TRYPSIN_SER.
    [Graphical view]
    PfamiPF00089. Trypsin. 1 hit.
    [Graphical view]
    PRINTSiPR00722. CHYMOTRYPSIN.
    SMARTiSM00020. Tryp_SPc. 1 hit.
    [Graphical view]
    SUPFAMiSSF50494. SSF50494. 1 hit.
    PROSITEiPS50240. TRYPSIN_DOM. 1 hit.
    PS00134. TRYPSIN_HIS. 1 hit.
    PS00135. TRYPSIN_SER. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiKLK8_MOUSE
    AccessioniPrimary (citable) accession number: Q61955
    Secondary accession number(s): Q8K5D7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1999
    Last sequence update: November 1, 1996
    Last modified: November 30, 2016
    This is version 140 of the entry and version 1 of the sequence. [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. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. Peptidase families
      Classification of peptidase families and list of entries
    4. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.