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Q61955 (KLK8_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Kallikrein-8

Short name=mK8
EC=3.4.21.118
Alternative name(s):
Neuropsin
Short name=NP
Serine protease 19
Gene names
Name:Klk8
Synonyms:Nrpn, Prss19
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length260 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.4 Ref.13 Ref.17 Ref.19 Ref.20 Ref.21 Ref.23 Ref.24

Catalytic activity

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

Enzyme regulation

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

Subunit structure

Interacts with SPINK9 By similarity.

Subcellular location

Secreted. Cytoplasm. Note: Shows a cytoplasmic distribution in the keratinocytes. Ref.4 Ref.22

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. Ref.1 Ref.5 Ref.6 Ref.9 Ref.10 Ref.22 Ref.24

Developmental stage

Expression is detected in the brain from embryonic day 12 and continues into adulthood. Ref.6

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. Ref.4 Ref.7 Ref.8 Ref.9 Ref.11 Ref.12 Ref.16 Ref.18 Ref.24

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. Ref.14 Ref.15 Ref.18 Ref.20 Ref.21 Ref.23 Ref.24

Sequence similarities

Belongs to the peptidase S1 family. Kallikrein subfamily.

Contains 1 peptidase S1 domain.

Biophysicochemical properties

Kinetic parameters:

KM=300 µM for Boc-Val-Pro-Arg-MCA Ref.4

KM=540 µM for Boc-Phe-Ser-Arg-MCA

KM=280 µM for D-Val-Leu-Arg-MCA

Mass spectrometry

Molecular mass is 26613 Da from positions 29 - 260. Determined by MALDI. Ref.4

Molecular mass is 26229 Da from positions 33 - 260. Determined by MALDI. Ref.4

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2828 Potential
Propeptide29 – 324
PRO_0000027948
Chain33 – 260228Kallikrein-8
PRO_0000027949

Regions

Domain33 – 257225Peptidase S1

Sites

Active site731Charge relay system By similarity
Active site1201Charge relay system By similarity
Active site2121Charge relay system By similarity

Amino acid modifications

Glycosylation1101N-linked (GlcNAc...) Potential
Disulfide bond39 ↔ 173
Disulfide bond58 ↔ 74
Disulfide bond145 ↔ 246
Disulfide bond152 ↔ 218
Disulfide bond184 ↔ 198
Disulfide bond208 ↔ 233

Secondary structure

........................................ 260
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q61955 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: BE5F6F6BE37CD60E

FASTA26028,524
        10         20         30         40         50         60 
MGRPPPCAIQ PWILLLLFMG AWAGLTRAQG SKILEGRECI PHSQPWQAAL FQGERLICGG 

        70         80         90        100        110        120 
VLVGDRWVLT AAHCKKQKYS VRLGDHSLQS RDQPEQEIQV AQSIQHPCYN NSNPEDHSHD 

       130        140        150        160        170        180 
IMLIRLQNSA NLGDKVKPVQ LANLCPKVGQ KCIISGWGTV TSPQENFPNT LNCAEVKIYS 

       190        200        210        220        230        240 
QNKCERAYPG KITEGMVCAG SSNGADTCQG DSGGPLVCDG MLQGITSWGS DPCGKPEKPG 

       250        260 
VYTKICRYTT WIKKTMDNRD 

« Hide

References

« Hide 'large scale' references
[1]"Expression and activity-dependent changes of a novel limbic-serine protease gene in the hippocampus."
Chen Z.-L., Yoshida S., Kato K., Momota Y., Suzuki J., Tanaka T., Ito J., Nishino H., Aimoto S., Kiyama H., Shiosaka S.
J. Neurosci. 15:5088-5097(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Strain: BALB/c.
Tissue: Hippocampus.
[2]"Assignment of the neuropsin gene (Prss19) to mouse chromosome band 7B4 by in situ hybridization."
Yoshida S., Hirata A., Inoue N., Shiosaka S.
Cytogenet. Cell Genet. 88:97-98(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: Czech II.
Tissue: Mammary gland.
[4]"Characterization of recombinant and brain neuropsin, a plasticity-related serine protease."
Shimizu C., Yoshida S., Shibata M., Kato K., Momota Y., Matsumoto K., Shiosaka T., Midorikawa R., Kamachi T., Kawabe A., Shiosaka S.
J. Biol. Chem. 273:11189-11196(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, MASS SPECTROMETRY.
Strain: BALB/c.
Tissue: Brain.
[5]"Estrogen-independent expression of neuropsin, a serine protease in the vagina of mice exposed neonatally to diethylstilbestrol."
Katsu Y., Takasu E., Iguchi T.
Mol. Cell. Endocrinol. 195:99-107(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 85-260, TISSUE SPECIFICITY.
Strain: C57BL/6.
[6]"Ontogeny of neuropsin mRNA expression in the mouse brain."
Suzuki J., Yoshida S., Chen Z.-L., Momota Y., Kato K., Hirata A., Shiosaka S.
Neurosci. Res. 23:345-351(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[7]"Kindling induces neuropsin mRNA in the mouse brain."
Okabe A., Momota Y., Yoshida S., Hirata A., Ito J., Nishino H., Shiosaka S.
Brain Res. 728:116-120(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[8]"Effects of oxidative stress on the expression of limbic-specific protease neuropsin and avoidance learning in mice."
Akita H., Matsuyama T., Iso H., Sugita M., Yoshida S.
Brain Res. 769:86-96(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[9]"Blockade of neuropsin, a serine protease, ameliorates kindling epilepsy."
Momota Y., Yoshida S., Ito J., Shibata M., Kato K., Sakurai K., Matsumoto K., Shiosaka S.
Eur. J. Neurosci. 10:760-764(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, INDUCTION.
[10]"Expression of neuropsin in the keratinizing epithelial tissue - immunohistochemical analysis of wild-type and nude mice."
Inoue N., Kuwae K., Ishida-Yamamoto A., Iizuka H., Shibata M., Yoshida S., Kato K., Shiosaka S.
J. Invest. Dermatol. 110:923-931(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[11]"Effect of 12-O-tetradecanoyl-phorbol ester and incisional wounding on neuropsin mRNA and its protein expression in murine skin."
Kitayoshi H., Inoue N., Kuwae K., Chen Z.-L., Sato H., Ohta T., Hosokawa K., Itami S., Yoshikawa K., Yoshida S., Shiosaka S.
Arch. Dermatol. Res. 291:333-338(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[12]"Injury induces neuropsin mRNA in the central nervous system."
Tomizawa K., He X.-P., Yamanaka H., Shiosaka S., Yoshida S.
Brain Res. 824:308-311(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[13]"Neuropsin regulates an early phase of Schaffer-collateral long-term potentiation in the murine hippocampus."
Komai S., Matsuyama T., Matsumoto K., Kato K., Kobayashi M., Imamura K., Yoshida S., Ugawa S., Shiosaka S.
Eur. J. Neurosci. 12:1479-1486(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[14]"Loss of hippocampal serine protease BSP1/neuropsin predisposes to global seizure activity."
Davies B., Kearns I.R., Ure J., Davies C.H., Lathe R.
J. Neurosci. 21:6993-7000(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[15]"Abnormalities of synapses and neurons in the hippocampus of neuropsin-deficient mice."
Hirata A., Yoshida S., Inoue N., Matsumoto-Miyai K., Ninomiya A., Taniguchi M., Matsuyama T., Kato K., Iizasa H., Kataoka Y., Yoshida N., Shiosaka S.
Mol. Cell. Neurosci. 17:600-610(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[16]"Expression of neuropsin in oligodendrocytes after injury to the CNS."
He X.-P., Shiosaka S., Yoshida S.
Neurosci. Res. 39:455-462(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[17]"Extracellular serine protease neuropsin (KLK8) modulates neurite outgrowth and fasciculation of mouse hippocampal neurons in culture."
Oka T., Akisada M., Okabe A., Sakurai K., Shiosaka S., Kato K.
Neurosci. Lett. 321:141-144(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[18]"Prolonged recovery of ultraviolet B-irradiated skin in neuropsin (KLK8)-deficient mice."
Kirihara T., Matsumoto-Miyai K., Nakamura Y., Sadayama T., Yoshida S., Shiosaka S.
Br. J. Dermatol. 149:700-706(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION, DISRUPTION PHENOTYPE.
[19]"NMDA-dependent proteolysis of presynaptic adhesion molecule L1 in the hippocampus by neuropsin."
Matsumoto-Miyai K., Ninomiya A., Yamasaki H., Tamura H., Nakamura Y., Shiosaka S.
J. Neurosci. 23:7727-7736(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[20]"Role of neuropsin in formation and maturation of Schaffer-collateral L1cam-immunoreactive synaptic boutons."
Nakamura Y., Tamura H., Horinouchi K., Shiosaka S.
J. Cell Sci. 119:1341-1349(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[21]"Neuropsin is essential for early processes of memory acquisition and Schaffer collateral long-term potentiation in adult mouse hippocampus in vivo."
Tamura H., Ishikawa Y., Hino N., Maeda M., Yoshida S., Kaku S., Shiosaka S.
J. Physiol. (Lond.) 570:541-551(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[22]"SerpinB6 is an inhibitor of kallikrein-8 in keratinocytes."
Scott F.L., Sun J., Whisstock J.C., Kato K., Bird P.I.
J. Biochem. 142:435-442(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[23]"Kallikrein 8 is involved in skin desquamation in cooperation with other kallikreins."
Kishibe M., Bando Y., Terayama R., Namikawa K., Takahashi H., Hashimoto Y., Ishida-Yamamoto A., Jiang Y.-P., Mitrovic B., Perez D., Iizuka H., Yoshida S.
J. Biol. Chem. 282:5834-5841(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[24]"Neuropsin promotes oligodendrocyte death, demyelination and axonal degeneration after spinal cord injury."
Terayama R., Bando Y., Murakami K., Kato K., Kishibe M., Yoshida S.
Neuroscience 148:175-187(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, INDUCTION, DISRUPTION PHENOTYPE.
[25]"Crystal structure of neuropsin, a hippocampal protease involved in kindling epileptogenesis."
Kishi T., Kato M., Shimizu T., Kato K., Matsumoto K., Yoshida S., Shiosaka S., Hakoshima T.
J. Biol. Chem. 274:4220-4224(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 33-257.
Tissue: Hippocampus.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D30785 mRNA. Translation: BAA06451.1.
AB032202 Genomic DNA. Translation: BAA92435.1.
BC055895 mRNA. Translation: AAH55895.1.
AB074296 mRNA. Translation: BAB92021.1.
PIRI56559.
RefSeqNP_032966.1. NM_008940.2.
XP_006540971.1. XM_006540908.1.
UniGeneMm.458023.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1NPMX-ray2.10A/B33-257[»]
ProteinModelPortalQ61955.
SMRQ61955. Positions 33-257.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid234416. 1 interaction.
STRING10090.ENSMUSP00000082588.

Protein family/group databases

MEROPSS01.244.

PTM databases

PhosphoSiteQ61955.

Proteomic databases

PaxDbQ61955.
PRIDEQ61955.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000085461; ENSMUSP00000082588; ENSMUSG00000064023.
GeneID259277.
KEGGmmu:259277.
UCSCuc009gns.1. mouse.

Organism-specific databases

CTD11202.
MGIMGI:1343327. Klk8.

Phylogenomic databases

eggNOGCOG5640.
GeneTreeENSGT00750000117409.
HOGENOMHOG000251820.
HOVERGENHBG013304.
InParanoidQ61955.
KOK08650.
OMACKKPKYT.
OrthoDBEOG75B84T.
PhylomeDBQ61955.
TreeFamTF331065.

Enzyme and pathway databases

BRENDA3.4.21.118. 3474.

Gene expression databases

BgeeQ61955.
CleanExMM_KLK8.
GenevestigatorQ61955.

Family and domain databases

InterProIPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSPR00722. CHYMOTRYPSIN.
SMARTSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMSSF50494. SSF50494. 1 hit.
PROSITEPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ61955.
NextBio392031.
PROQ61955.
SOURCESearch...

Entry information

Entry nameKLK8_MOUSE
AccessionPrimary (citable) accession number: Q61955
Secondary accession number(s): Q8K5D7
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot