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Q61955

- KLK8_MOUSE

UniProt

Q61955 - KLK8_MOUSE

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Protein
Kallikrein-8
Gene
Klk8, Nrpn, Prss19
Organism
Mus musculus (Mouse)
Status
Reviewed - 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-MCA
  3. KM=280 µM for D-Val-Leu-Arg-MCA

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei73 – 731Charge relay system By similarity
Active sitei120 – 1201Charge relay system By similarity
Active sitei212 – 2121Charge relay system By similarity

GO - Molecular functioni

  1. serine-type endopeptidase activity Source: UniProtKB

GO - Biological processi

  1. cell death Source: UniProtKB
  2. keratinocyte proliferation Source: UniProtKB
  3. memory Source: UniProtKB
  4. negative regulation of axon regeneration Source: UniProtKB
  5. negative regulation of myelination Source: UniProtKB
  6. neuron projection morphogenesis Source: UniProtKB
  7. regulation of synapse organization Source: UniProtKB
  8. response to wounding Source: UniProtKB
  9. synapse organization Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Enzyme and pathway databases

BRENDAi3.4.21.118. 3474.

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
ProteomesiUP000000589: Chromosome 7

Organism-specific databases

MGIiMGI:1343327. Klk8.

Subcellular locationi

Secreted. Cytoplasm
Note: Shows a cytoplasmic distribution in the keratinocytes.2 Publications

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. 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)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2828 Reviewed prediction
Add
BLAST
Propeptidei29 – 324
PRO_0000027948
Chaini33 – 260228Kallikrein-8
PRO_0000027949Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi39 ↔ 173
Disulfide bondi58 ↔ 74
Glycosylationi110 – 1101N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi145 ↔ 246
Disulfide bondi152 ↔ 218
Disulfide bondi184 ↔ 198
Disulfide bondi208 ↔ 233

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiQ61955.
PRIDEiQ61955.

PTM databases

PhosphoSiteiQ61955.

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 4.9 Publications

Gene expression databases

BgeeiQ61955.
CleanExiMM_KLK8.
GenevestigatoriQ61955.

Interactioni

Subunit structurei

Interacts with SPINK9 By similarity.

Protein-protein interaction databases

BioGridi234416. 1 interaction.
STRINGi10090.ENSMUSP00000082588.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi47 – 526
Beta strandi55 – 6410
Beta strandi67 – 704
Helixi72 – 743
Beta strandi80 – 845
Beta strandi96 – 983
Beta strandi100 – 1056
Beta strandi122 – 1287
Beta strandi133 – 1364
Beta strandi151 – 1588
Beta strandi160 – 1645
Beta strandi172 – 1787
Helixi181 – 1877
Turni189 – 1913
Beta strandi196 – 2005
Beta strandi215 – 2184
Beta strandi221 – 2288
Beta strandi231 – 2333
Beta strandi240 – 2445
Helixi245 – 25612

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1NPMX-ray2.10A/B33-257[»]
ProteinModelPortaliQ61955.
SMRiQ61955. Positions 33-257.

Miscellaneous databases

EvolutionaryTraceiQ61955.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini33 – 257225Peptidase S1
Add
BLAST

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiCOG5640.
GeneTreeiENSGT00750000117409.
HOGENOMiHOG000251820.
HOVERGENiHBG013304.
InParanoidiQ61955.
KOiK08650.
OMAiTKLYAEN.
OrthoDBiEOG75B84T.
PhylomeDBiQ61955.
TreeFamiTF331065.

Family and domain databases

InterProiIPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[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

MGRPPPCAIQ PWILLLLFMG AWAGLTRAQG SKILEGRECI PHSQPWQAAL    50
FQGERLICGG VLVGDRWVLT AAHCKKQKYS VRLGDHSLQS RDQPEQEIQV 100
AQSIQHPCYN NSNPEDHSHD IMLIRLQNSA NLGDKVKPVQ LANLCPKVGQ 150
KCIISGWGTV TSPQENFPNT LNCAEVKIYS QNKCERAYPG KITEGMVCAG 200
SSNGADTCQG DSGGPLVCDG MLQGITSWGS DPCGKPEKPG VYTKICRYTT 250
WIKKTMDNRD 260
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:
EMBL
GenBank
DDBJ
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_032966.1. NM_008940.2.
XP_006540971.1. XM_006540908.1.
UniGeneiMm.458023.

Genome annotation databases

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

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
D30785 mRNA. Translation: BAA06451.1 .
AB032202 Genomic DNA. Translation: BAA92435.1 .
BC055895 mRNA. Translation: AAH55895.1 .
AB074296 mRNA. Translation: BAB92021.1 .
CCDSi CCDS21182.1.
PIRi I56559.
RefSeqi NP_032966.1. NM_008940.2.
XP_006540971.1. XM_006540908.1.
UniGenei Mm.458023.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1NPM X-ray 2.10 A/B 33-257 [» ]
ProteinModelPortali Q61955.
SMRi Q61955. Positions 33-257.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 234416. 1 interaction.
STRINGi 10090.ENSMUSP00000082588.

Protein family/group databases

MEROPSi S01.244.

PTM databases

PhosphoSitei Q61955.

Proteomic databases

PaxDbi Q61955.
PRIDEi Q61955.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000085461 ; ENSMUSP00000082588 ; ENSMUSG00000064023 .
GeneIDi 259277.
KEGGi mmu:259277.
UCSCi uc009gns.1. mouse.

Organism-specific databases

CTDi 11202.
MGIi MGI:1343327. Klk8.

Phylogenomic databases

eggNOGi COG5640.
GeneTreei ENSGT00750000117409.
HOGENOMi HOG000251820.
HOVERGENi HBG013304.
InParanoidi Q61955.
KOi K08650.
OMAi TKLYAEN.
OrthoDBi EOG75B84T.
PhylomeDBi Q61955.
TreeFami TF331065.

Enzyme and pathway databases

BRENDAi 3.4.21.118. 3474.

Miscellaneous databases

EvolutionaryTracei Q61955.
NextBioi 392031.
PROi Q61955.
SOURCEi Search...

Gene expression databases

Bgeei Q61955.
CleanExi MM_KLK8.
Genevestigatori Q61955.

Family and domain databases

InterProi IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view ]
Pfami PF00089. Trypsin. 1 hit.
[Graphical view ]
PRINTSi PR00722. CHYMOTRYPSIN.
SMARTi SM00020. Tryp_SPc. 1 hit.
[Graphical view ]
SUPFAMi SSF50494. SSF50494. 1 hit.
PROSITEi PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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. 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.

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: July 9, 2014
This is version 122 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

External Data

Dasty 3

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