Q61955 (KLK8_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	260 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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

Ontologies

Keywords
Cellular component	Cytoplasm Secreted
Domain	Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell death Inferred from mutant phenotype Ref.24. Source: UniProtKB keratinocyte proliferation Inferred from mutant phenotype Ref.23. Source: UniProtKB memory Inferred from mutant phenotype Ref.21. Source: UniProtKB negative regulation of axon regeneration Inferred from mutant phenotype Ref.24. Source: UniProtKB negative regulation of myelination Inferred from mutant phenotype Ref.24. Source: UniProtKB neuron projection morphogenesis Inferred from direct assay Ref.17. Source: UniProtKB proteolysis Inferred from electronic annotation. Source: UniProtKB-KW regulation of synapse organization Inferred from mutant phenotype Ref.15. Source: UniProtKB response to wounding Inferred from direct assay Ref.12Ref.11Ref.16. Source: UniProtKB synapse organization Inferred from mutant phenotype Ref.20. Source: MGI
Cellular_component	cytoplasm Inferred from direct assay Ref.22. Source: UniProtKB extracellular space Inferred from direct assay Ref.4. Source: UniProtKB
Molecular_function	serine-type endopeptidase activity Inferred from direct assay Ref.19Ref.4. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 28

28

Potential

Propeptide

29 – 32

4

PRO_0000027948

Chain

33 – 260

228

Kallikrein-8

PRO_0000027949

Regions

Domain

33 – 257

225

Peptidase S1

Sites

Active site

73

1

Charge relay system By similarity

Active site

120

1

Charge relay system By similarity

Active site

212

1

Charge relay system By similarity

Amino acid modifications

Glycosylation

110

1

N-linked (GlcNAc...) Potential

Disulfide bond

39 ↔ 173

Disulfide bond

58 ↔ 74

Disulfide bond

145 ↔ 246

Disulfide bond

152 ↔ 218

Disulfide bond

184 ↔ 198

Disulfide bond

208 ↔ 233

Secondary structure

1

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260

Helix Strand Turn

Details...

Beta strand

47 – 52

6

Beta strand

55 – 64

10

Beta strand

67 – 70

4

Helix

72 – 74

3

Beta strand

80 – 84

5

Beta strand

96 – 98

3

Beta strand

100 – 105

6

Beta strand

122 – 128

7

Beta strand

133 – 136

4

Beta strand

151 – 158

8

Beta strand

160 – 164

5

Beta strand

172 – 178

7

Helix

181 – 187

7

Turn

189 – 191

3

Beta strand

196 – 200

5

Beta strand

215 – 218

4

Beta strand

221 – 228

8

Beta strand

231 – 233

3

Beta strand

240 – 244

5

Helix

245 – 256

12

Sequences

	Sequence		Length	Mass (Da)
	Q61955 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: BE5F6F6BE37CD60E	FASTA	260	28,524
	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

References

	« Hide 'large scale' referencesShow '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.

IPI

IPI00127511.

PIR

I56559.

RefSeq

NP_032966.1. NM_008940.2.

UniGene

Mm.458023.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1NPM	X-ray	2.10	A/B	33-257	[»]

ProteinModelPortal

Q61955.

SMR

Q61955. Positions 33-257.

ModBase

Search...

Protein-protein interaction databases

STRING

10090.ENSMUSP00000082588.

Protein family/group databases

MEROPS

S01.244.

PTM databases

PhosphoSite

Q61955.

Proteomic databases

PaxDb

Q61955.

PRIDE

Q61955.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000085461; ENSMUSP00000082588; ENSMUSG00000064023.

GeneID

259277.

KEGG

mmu:259277.

UCSC

uc009gns.1. mouse.

Organism-specific databases

CTD

11202.

MGI

MGI:1343327. Klk8.

Phylogenomic databases

eggNOG

COG5640.

GeneTree

ENSGT00690000101721.

HOGENOM

HOG000251820.

HOVERGEN

HBG013304.

InParanoid

Q61955.

KO

K08650.

OMA

TKLYAEN.

OrthoDB

EOG4XKV7F.

Enzyme and pathway databases

BRENDA

3.4.21.118. 3474.

Gene expression databases

Bgee

Q61955.

CleanEx

MM_KLK8.

Genevestigator

Q61955.

GermOnline

ENSMUSG00000064023. Mus musculus.

Family and domain databases

InterPro

IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]

Pfam

PF00089. Trypsin. 1 hit.
[Graphical view]

PRINTS

PR00722. CHYMOTRYPSIN.

SMART

SM00020. Tryp_SPc. 1 hit.
[Graphical view]

SUPFAM

SSF50494. Pept_Ser_Cys. 1 hit.

PROSITE

PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q61955.

NextBio

392031.

SOURCE

Search...

Entry information

Entry name

KLK8_MOUSE

Accession

Primary (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 3, 2013
This is version 112 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program