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KLK8 (kallikrein-related peptidase 8)

Written2012-07Yves Courty
Centre d'Etude des Pathologies Respiratoires, INSERM U1100 - EA6305, Faculte de Medecine, 10 bvd Tonnelle, 37032 Tours cedex, France

(Note : for Links provided by Atlas : click)


HGNC (Hugo) KLK8
HGNC Alias symbHNP
HGNC Previous namePRSS19
HGNC Previous namekallikrein 8 (neuropsin/ovasin)
LocusID (NCBI) 11202
Atlas_Id 41088
Location 19q13.41  [Link to chromosome band 19q13]
Location_base_pair Starts at 50996008 and ends at 51001702 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping KLK8.png]
Local_order Telomere to centromere.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
Note This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Kallikreins are a subgroup of serine proteases having diverse physiological functions.


  The KLK8 gene comprises 8 exons (dark color, classic numerals) and 7 introns. Shown here are the 6 alternative transcripts predicted to encode protein variants (only the coding exons are depicted). Yellow boxes: non coding sequences; blue and green boxes: coding sequences. Sequences coding for identical amino acids are indicated in green whereas blue designates sequences generating distinct amino acids.
Description The KLK8 gene is approximately 7.8 Kb in length, consisting of 8 exons (5 of them are coding exons) and 7 introns.
Transcription Human KLK8 was originally cloned (Yoshida et al., 1998) as the human ortholog of the mouse brain protease neuropsin (Chen et al., 1995). Using Northern blot and RT-PCR analyses, it has been shown that KLK8 is expressed mainly in breast, cervix, esophagus, skin, ovary, testis, salivary glands and vagina. Adrenal, brain, colon, heart, kidney, lung, muscle and prostate also express KLK8 mRNA at medium to low levels. The transcription start site of KLK8 appears tissue-specific (Lu et al., 2009). Eight alternatively spliced variants have been identified for the KLK8 gene. These variants differ in the number and length of the 5' untranslated exons and/or coding exons. The splice variants are predicted to encode 6 protein isoforms. Type 1 and Type 2 transcripts differ in their coding exon 2 sequence. Type 2 includes extra 45 amino acids at the N-terminus of the coding exon 2. Thus, Type 1 and Type 2 KLK8 mRNA variants produce 2 zymogens that differ only in their propeptide sequences. Type 2 variant is absent in nonhuman primates, and is thus a human-specific splice form (Li et al., 2004; Lu et al., 2007). Type 1 mRNA is predominantly expressed in the pancreas and Type 2 mRNA in adult brain and hippocampus. Type 2 KLK8 is also abundantly expressed in fetal brain, placenta and in human embryonic stem cells, suggesting a potential role in embryogenesis (Mitsui et al., 1999; Lu et al., 2009). The Type 3 mRNA variant includes coding exons 1, 4, and 5 and encodes a truncated form of the KLK8 protein (Magklara et al., 2001). Type 4 variant lacks coding exons 2, 3, 4. It encodes a putative protein of 32 amino acid residues that contains the KLK8 signal peptide and another peptide that is not related to KLK8 (Magklara et al., 2001). Type 3 and Type 4 mRNAs are abundant in many normal tissues (brain, pancreas, skin) and are overproduced in ovarian and lung cancers (Magklara et al., 2001; Planque et al., 2010). Coding exon 2 is missing in Type 5 mRNA whereas Type 6 mRNA lacks coding exon 3. For these both variants, the alternative splicing creates a stop codon that prematurely terminates translation. Type 5 and Type 6 mRNAs were detected in lung cancer cell lines and tissues (Sher et al., 2006; Planque et al., 2010).
Pseudogene None identified.


  Schematic structure of the KLK8 Type1 protein. The amino acid numbering for the residues of the catalytic triad (His70, Asp120, Ser212) are relative to the full-length protein starting from Met1.
Description The canonical KLK8 protein encoded by Type 1 mRNA has a secretion signal (pre-) peptide (28 amino acids), followed by an activation (pro-) peptide (4 amino acids) and the mature chain (228 amino acids) with 1 potential N-linked glycosylation site. The catalytic triad of His73, Asp120, Ser212 (relative to Met = 1) is conserved and is essential for proteolytic activity. After synthesis as a KLK8 precursor, the signal peptide is then cleaved and pro-KLK8 (zymogen) is subsequently secreted from the cell. Upon activation, the propeptide is removed to generate the mature active enzyme. Type 2 KLK8 has an insert of 45 amino acids between Ala23 and Gly24 at the C-terminus of the leader sequence of canonical KLK8. Therefore, this isoform has larger signal peptide and propeptide and has been produced intact as recombinant protein (Lu et al., 2009). Beside the canonical KLK8 protein, only the predicted peptide encoded by KLK8 Type 4 mRNA has been yet detected in vivo. This form was identified by mass spectrometry in bronchoalveolar lavage fluid (Oumeraci et al., 2011).
Expression KLK8 protein has been detected in a wide range of tissues at low (10 to 100 ng/g, adrenal, cervix, heart, kidney, liver, ovary, salivary gland, vagina) to high (1 µg to 10 µg/g, breast, esophagus, skin, tensil) levels (Shaw and Diamandis, 2007). KLK8 has also been detected in body fluid, such as milk, amniotic fluid, cerebrospinal fluid, seminal plasma, serum, saliva and sweat (Kishi et al., 2003; Shaw and Diamandis, 2007; Eissa et al., 2011). Age at the first full term pregnancy (FFTP) influences secretion of KLK8 protein in breast milk. Indeed in a recent study, a significant increase in KLK8 expression was observed from the onset of lactation to breast weaning depending on FFTP age (<26 or >26) (Qin et al., 2012).
Localisation KLK8 is a secreted protein and is localized intracellularly to the cytoplasm. In epidermis, KLK8 is localized within the trans-Golgi network, lamellar granules and intercellular spaces between the stratum granulosum and stratum corneum (Ishida-Yamamoto et al., 2004). Diffuse cytoplasmic staining was observed for KLK8 in the secretory segment in eccrine sweat glands and in the intradermal sensory nerve (Komatsu et al., 2005). KLK8 is present in relatively high levels in ductal cells, as well as in non-ductal cells, of normal salivary gland tissues and benign and malignant salivary gland tumors (Darling et al., 2008). In brain, KLK8 is expressed in the cell body of oligodendrocytes (He et al., 2001).
Function KLK8 is a serine protease which exhibits trypsin-like activity with strong preference for Arg over Lys in the P1 position (Kishi et al., 2006; Eissa et al., 2011). KLK8 activity is inhibited by general serine protease inhibitors such as a2-antiplasmin, protein C inhibitor and PI-6 (Proteinase inhibitor 6) (Scott et al., 2007). Several potential substrates have been identified for KLK8 in human or mouse including extracellular matrix components (Single-chain tPA, fibronectin, gelatin, collagen type IV, fibrinogen) (Rajapakse et al., 2005), cell adhesion molecules (L1cam) and membranous receptors (EphB2, PAR2) (Matsumoto-Miyai et al., 2003; Nakamura et al., 2006; Attwood et al., 2011; Ramachandran et al., 2012), antimicrobial peptides (LL-37) and zymogens of kallikrein-related peptidases (proKLK1 and proKLK11) (Eissa et al., 2011). The physiological functions of KLK8 are not fully understood. Accumulating evidence has suggested pivotal roles for KLK8 in development, maturation and cognitive functions. KLK8 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 (Komai et al., 2000; Oka et al., 2002; Nakamura et al., 2006; Terayama et al., 2007; Horii et al., 2008; Yoshida, 2010; Ishikawa et al., 2011; Shiosaka and Ishikawa, 2011). KLK8 has also been involved in skin desquamation and wound healing and in keratinocyte proliferation (Inoue et al., 1998; Kirihara et al., 2003; Kishibe et al., 2007; Yoshida, 2010; Eissa et al., 2011; Kishibe et al., 2012). It has been shown that KLK8 is differentially expressed in a number of malignancies, including ovarian, cervical, head and neck, breast and salivary gland cancers (Kishi et al., 2003; Cane et al., 2004; Borgono et al., 2006; Darling et al., 2008; Liu et al., 2008; Kountourakis et al., 2009), but the mechanisms of its involvement in these cancer have yet to be determined. In lung cancer, KLK8 suppress tumor cell invasiveness in vitro and in vivo (Sher et al., 2006).
Homology The human KLK8 protein sequence shares 40-70% homology with other members of the human tissue kallikreins, and 70% identity with that of the mouse orthologue.


Note Genomewide DNA linkage analysis identified a susceptibility locus for intracranial aneurysm (IA) on chromosome 19q13 in the Finnish population. Two SNPs located in the intronic region of KLK8 were found significantly associated with IA (Weinsheimer et al., 2007). A significant allelic association between several KLK8 SNPs and bipolar disorder has recently been reported (Izumi et al., 2008).
No germinal or somatic mutations are identified to be associated with cancer so far.

Implicated in

Entity Carcinomas
Note Several carcinomas (ovarian, cervical, oral, salivary glands and lung cancers) show high expression of the KLK8 gene. Depending on the cancer type, KLK8 acts as tumor promoting or tumor suppressing factor.
Entity Ovarian cancer
Disease Expression of KLK8 was not detected on the surface epithelium of normal ovaries by immunohistochemistry. In contrast, KLK8 protein was detected in ovarian carcinomas with a significantly higher detection rate of KLK8 expression in early stage disease compared to advanced stage disease (Shigemasa et al., 2004). Other analyses using sandwich-type immunoassays found KLK8 protein in cancer tissue extracts, serum and ascites fluid of ovarian cancer patients (Kishi et al., 2003; Shigemasa et al., 2004; Borgono et al., 2006).
Prognosis It had been proposed that KLK8 is an independent marker of favorable prognosis in ovarian cancer at both the mRNA and protein levels. For example, KLK8 mRNA levels were found associated with longer disease-free survival (PFS) (Magklara et al., 2001; Shigemasa et al., 2004). The tissue concentration of KLK8 was also described as an independent marker of favorable prognosis in ovarian cancer. Patients with KLK8-positive tumors had a significantly longer PFS and overall survival than KLK8-negative patients (Borgono et al., 2006). Higher ascites fluid KLK8 concentration was also associated with better ovarian cancer PFS (Kishi et al., 2003). Using another approach, Kountourakis et al. showed significant correlations between tumour mask KLK8 protein expression levels and clinicopathological variables, including grade, residual disease and clinical response to chemotherapy. There was also a significant correlation between KLK8 tumour mask expression and five years progression-free survival (Kountourakis et al., 2009).
Entity Non-small cell lung cancer
Disease In non-small cell lung cancer (NSCLC), KLK8 appears to suppress tumor cell invasiveness by degrading fibronectin, thereby suppressing integrin signaling, and also retards cancer cell motility by inhibiting actin polymerization. In a mouse model, KLK8 suppresses tumor growth and invasion in vivo (Sher et al., 2006). Compared with sera from normal subjects, sera of patients with NSCLC had lower levels of KLK8. Using a KLK8 ELISA on 51 patients with NSCLC and 50 normal controls, it was shown that KLK8 may have utility as a lung cancer biomarker when used in conjunction with KLK4, KLK10, KLK11, KLK12, KLK13, and KLK14 (Planque et al., 2008).
Prognosis In patients with non-small cell lung cancer, the time to postoperative recurrence was longer for early-stage patients with high KLK8 gene expression than for patients with low KLK8 gene expression (Sher et al., 2006). Another study has revealed that the Type 4 KLK8 alternative splice variant, alone or in combination with other KLK mRNAs, may be a new independent marker of unfavorable prognosis in lung cancer (Planque et al., 2010).
Entity Breast cancer
Disease KLK8 is downregulated in breast cancer tissues and cell lines (Yousef et al., 2004). On the other hand, KLK8, along with several other kallikrein genes, could be primarily up-regulated by 17b-estradiol and, to a lesser degree, by other steroid hormones in hormone receptor-positive breast cancer cell lines MCF-7 and T-47D, suggesting a coordinated kallikrein expression as part of a complex regulatory mechanism that controls the expression of these genes and also their downstream physiological function (Paliouras and Diamandis, 2007).
Entity Cervical cancer
Disease At the mRNA level, KLK8 was found to be highly expressed in 82% primary cervical cancer cell lines and in 87% established cervical cancer cell lines. In addition, immunohistochemistry staining of paraffin-embedded cervical cancer specimens showed KLK8 expression in tumor cells and its absence on normal cervical epithelial cells (Cane et al., 2004).
Entity Bladder cancer
Disease Reverse transcription-polymerase chain reaction analysis of 42 primary bladder tumor samples revealed an higher expression level of KLK8 mRNA in invasive tumors than in superficial tumors (Shinoda et al., 2007).
Entity Salivary gland cancers
Disease The KLK8 immunoreactivity was determined in normal salivary gland tissue and in malignant salivary gland tumors. In general, all the tumors showed a relatively high overall staining for both ductal and non-ductal cells, particularly mucoepidermoid carcinomas and adenocarcinoma NOS (Darling et al., 2008).
Entity Oral squamous cell carcinoma
Disease Comparison of oral squamous carcinoma (OSC) cell lines with either overexpression or silencing of uPAR revealed that the more aggressive phenotype is associated with a co-overexpression of KLK5, KLK7, KLK8 and KLK10. Furthermore, immunohistochemical analysis demonstrated strong reactivity for KLKs 5, 7, 8 and 10 in both orthotopic murine tumors and human OSC tissues. These results suggest that KLK8 along with other KLKs is involved in malignant progression of oral squamous cell carcinoma (Pettus et al., 2009).
Entity Skin diseases
Note KLK8 involvement in normal skin barrier formation and inflammatory skin disease pathology has recently become apparent. Work done in Klk8/neuropsin-null mice suggested that Klk8/neuropsin is involved in skin barrier homeostasis, whereby healing of chemically wounded or UV-irradiated mouse skin is largely impaired in its absence (Kitayoshi et al., 1999; Kirihara et al., 2003; Kishibe et al., 2012). Additionally, the dramatic increase of KLK8 mRNA in hyperkeratotic skin of psoriasis vulgaris, seborrheic keratosis, lichen planus, and squamous cell carcinoma patients, compared with normal and basal cell carcinoma skin, suggested that human KLK8 is involved in keratinocyte differentiation and skin barrier formation (Kuwae et al., 2002; Shingaki et al., 2010; Shingaki et al., 2012). KLK8 protein overexpression was also detected in psoriasis, atopic dermatitis, and peeling skin syndrome skin tissues (Komatsu et al., 2006; Komatsu et al., 2007a; Komatsu et al., 2007b). KLK8 together with KLK5, KLK6, KLK7, KLK10 and KLK12 was upregulated in normal human keratinocytes following SP1 silencing. Moreover, thymic stromal lymphopoietin (TSLP), an epithelial-derived T(H)2-promoting cytokine, was induced in Sp1-silenced keratinocytes because of elevated KLK activity. This observation suggests that KLKs may contribute to T(H)2 immune responses in the skin by inducing TSLP (Bin et al., 2011).
Entity Brain diseases
Note Under non-pathological conditions, KLK8 protein is localized mainly to the neurons of the cerebral cortex and hippocampus. Immunohistochemistry for KLK8 also demonstrated signals in cerebellum (The Human Protein Atlas). A variety of transcriptional controls through both physiological and nonphysiological activity, such as long-term potentiation, chemically induced plasticity, kindling epileptogenesis, and experimental encephalitis, have been shown to positively regulate Klk8 gene expression in mice (Momota et al., 1998; Komai et al., 2000; He et al., 2001; Ishikawa et al., 2011). Increased anxiety like response was also observed in Klk8/neuropsin-deficient mice (Horii et al., 2008). Recently, Attwood et al. (Attwood et al., 2011) have shown that Klk8/neuropsin is involved in stress-related plasticity in the amygdala by the cleavage of EphB2 during stress and the reduction of EphB2-NMDA binding. So currently, accumulating evidence supports pivotal roles of Klk8 in the early phase of synaptic plasticity, late associativity, and behavioral memory (Shiosaka and Ishikawa, 2011). Further studies are required to determine if KLK8 is involved in human brain diseases, however an overexpression of KLK8 has yet been observed in Alzheimer's disease hippocampus (Shimizu-Okabe et al., 2001).


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PMID 21508957
Inhibition of transcription factor specificity protein 1 alters the gene expression profile of keratinocytes leading to upregulation of kallikrein-related peptidases and thymic stromal lymphopoietin.
Bin L, Kim BE, Hall CF, Leach SM, Leung DY.
J Invest Dermatol. 2011 Nov;131(11):2213-22. doi: 10.1038/jid.2011.202. Epub 2011 Jul 14.
PMID 21753780
Human kallikrein 8 protein is a favorable prognostic marker in ovarian cancer.
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Clin Cancer Res. 2006 Mar 1;12(5):1487-93.
PMID 16533772
The novel serine protease tumor-associated differentially expressed gene-14 (KLK8/Neuropsin/Ovasin) is highly overexpressed in cervical cancer.
Cane S, Bignotti E, Bellone S, Palmieri M, De las Casas L, Roman JJ, Pecorelli S, Cannon MJ, O'brien T, Santin AD.
Am J Obstet Gynecol. 2004 Jan;190(1):60-6.
PMID 14749636
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J Neurosci. 1995 Jul;15(7 Pt 2):5088-97.
PMID 7623137
Human kallikrein 8 expression in salivary gland tumors.
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Head Neck Pathol. 2008 Sep;2(3):169-74. Epub 2008 Jul 3.
PMID 20614312
Kallikrein-related peptidase-8 (KLK8) is an active serine protease in human epidermis and sweat and is involved in a skin barrier proteolytic cascade.
Eissa A, Amodeo V, Smith CR, Diamandis EP.
J Biol Chem. 2011 Jan 7;286(1):687-706. Epub 2010 Oct 12.
PMID 20940292
Expression of neuropsin in oligodendrocytes after injury to the CNS.
He XP, Shiosaka S, Yoshida S.
Neurosci Res. 2001 Apr;39(4):455-62.
PMID 11274744
Increased anxiety-like behavior in neuropsin (kallikrein-related peptidase 8) gene-deficient mice.
Horii Y, Yamasaki N, Miyakawa T, Shiosaka S.
Behav Neurosci. 2008 Jun;122(3):498-504.
PMID 18513120
Expression of neuropsin in the keratinizing epithelial tissue-immunohistochemical analysis of wild-type and nude mice.
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J Invest Dermatol. 1998 Jun;110(6):923-31.
PMID 9620300
Epidermal lamellar granules transport different cargoes as distinct aggregates.
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J Invest Dermatol. 2004 May;122(5):1137-44.
PMID 15140216
Diversity of neuropsin (KLK8)-dependent synaptic associativity in the hippocampal pyramidal neuron.
Ishikawa Y, Tamura H, Shiosaka S.
J Physiol. 2011 Jul 15;589(Pt 14):3559-73. Epub 2011 Jun 6.
PMID 21646406
Genetic variations of human neuropsin gene and psychiatric disorders: polymorphism screening and possible association with bipolar disorder and cognitive functions.
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PMID 18354391
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. 2003 Oct;149(4):700-6.
PMID 14616360
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PMID 16800733
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PMID 12507964
Kallikrein-related peptidase 8-dependent skin wound healing is associated with upregulation of kallikrein-related peptidase 6 and PAR2.
Kishibe M, Bando Y, Tanaka T, Ishida-Yamamoto A, Iizuka H, Yoshida S.
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PMID 22358061
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PMID 10421059
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PMID 10762375
Aberrant human tissue kallikrein levels in the stratum corneum and serum of patients with psoriasis: dependence on phenotype, severity and therapy.
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Br J Dermatol. 2007b May;156(5):875-83.
PMID 17459012
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Thromb Haemost. 2009 Mar;101(3):541-6.
PMID 19277417
Epidermal expression of serine protease, neuropsin (KLK8) in normal and pathological skin samples.
Kuwae K, Matsumoto-Miyai K, Yoshida S, Sadayama T, Yoshikawa K, Hosokawa K, Shiosaka S.
Mol Pathol. 2002 Aug;55(4):235-41.
PMID 12147714
Recent origin of a hominoid-specific splice form of neuropsin, a gene involved in learning and memory.
Li Y, Qian YP, Yu XJ, Wang YQ, Dong DG, Sun W, Ma RM, Su B.
Mol Biol Evol. 2004 Nov;21(11):2111-5. Epub 2004 Jul 28.
PMID 15282331
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J Pathol. 2008 Mar;214(4):489-97.
PMID 18213732
Functional characterization of the human-specific (type II) form of kallikrein 8, a gene involved in learning and memory.
Lu ZX, Huang Q, Su B.
Cell Res. 2009 Feb;19(2):259-67.
PMID 19125171
A human-specific mutation leads to the origin of a novel splice form of neuropsin (KLK8), a gene involved in learning and memory.
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PMID 17487847
The human KLK8 (neuropsin/ovasin) gene: identification of two novel splice variants and its prognostic value in ovarian cancer.
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PMID 11309326
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Matsumoto-Miyai K, Ninomiya A, Yamasaki H, Tamura H, Nakamura Y, Shiosaka S.
J Neurosci. 2003 Aug 27;23(21):7727-36.
PMID 12944500
A novel isoform of a kallikrein-like protease, TLSP/hippostasin, (PRSS20), is expressed in the human brain and prostate.
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PMID 10872828
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Eur J Neurosci. 1998 Feb;10(2):760-4.
PMID 9749739
Role of neuropsin in formation and maturation of Schaffer-collateral L1cam-immunoreactive synaptic boutons.
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PMID 16537644
Extracellular serine protease neuropsin (KLK8) modulates neurite outgrowth and fasciculation of mouse hippocampal neurons in culture.
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PMID 11880192
Bronchoalveolar lavage fluid of lung cancer patients: mapping the uncharted waters using proteomics technology.
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PMID 21334092
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PMID 16897430
Multiple kallikrein (KLK 5, 7, 8, and 10) expression in squamous cell carcinoma of the oral cavity.
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PMID 19085836
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PMID 20360129
A multiparametric serum kallikrein panel for diagnosis of non-small cell lung carcinoma.
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PMID 18316555
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PMID 22436421
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PMID 16337200
Proteinase-activated receptors (PARs): differential signalling by kallikrein-related peptidases KLK8 and KLK14.
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PMID 22505524
SerpinB6 is an inhibitor of kallikrein-8 in keratinocytes.
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PMID 17761692
Distribution of 15 human kallikreins in tissues and biological fluids.
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PMID 17573418
Human kallikrein 8 protease confers a favorable clinical outcome in non-small cell lung cancer by suppressing tumor cell invasiveness.
Sher YP, Chou CC, Chou RH, Wu HM, Wayne Chang WS, Chen CH, Yang PC, Wu CW, Yu CL, Peck K.
Cancer Res. 2006 Dec 15;66(24):11763-70.
PMID 17178872
Human kallikrein 8 (hK8/TADG-14) expression is associated with an early clinical stage and favorable prognosis in ovarian cancer.
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Oncol Rep. 2004 Jun;11(6):1153-9.
PMID 15138549
Expression of the kallikrein gene family in normal and Alzheimer's disease brain.
Shimizu-Okabe C, Yousef GM, Diamandis EP, Yoshida S, Shiosaka S, Fahnestock M.
Neuroreport. 2001 Aug 28;12(12):2747-51.
PMID 11522960
NGF-p75 and neuropsin/KLK8 pathways stimulate each other to cause hyperkeratosis and acanthosis in inflamed skin.
Shingaki K, Taniguchi M, Kanazawa S, Matsuzaki S, Maeda T, Miyata S, Kubo T, Torii K, Shiosaka S, Tohyama M.
J Dermatol Sci. 2012 Jul;67(1):71-3. Epub 2012 Mar 30.
PMID 22520925
Association of KLK5 overexpression with invasiveness of urinary bladder carcinoma cells.
Shinoda Y, Kozaki K, Imoto I, Obara W, Tsuda H, Mizutani Y, Shuin T, Fujioka T, Miki T, Inazawa J.
Cancer Sci. 2007 Jul;98(7):1078-86. Epub 2007 Apr 24.
PMID 17459052
Neuropsin--a possible modulator of synaptic plasticity.
Shiosaka S, Ishikawa Y.
J Chem Neuroanat. 2011 Sep;42(1):24-9. Epub 2011 Jun 6.
PMID 21679765
Neuropsin promotes oligodendrocyte death, demyelination and axonal degeneration after spinal cord injury.
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Neuroscience. 2007 Aug 10;148(1):175-87. Epub 2007 Jul 12.
PMID 17629414
Association of kallikrein gene polymorphisms with intracranial aneurysms.
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This paper should be referenced as such :
Courty, Y
KLK8 (kallikrein-related peptidase 8)
Atlas Genet Cytogenet Oncol Haematol. 2013;17(1):21-27.
Free journal version : [ pdf ]   [ DOI ]

External links


HGNC (Hugo)KLK8   6369
Atlas Explorer : (Salamanque)KLK8
Entrez_Gene (NCBI)KLK8    kallikrein related peptidase 8
AliasesHNP; NP; NRPN; PRSS19; 
GeneCards (Weizmann)KLK8
Ensembl hg19 (Hinxton)ENSG00000129455 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000129455 [Gene_View]  ENSG00000129455 [Sequence]  chr19:50996008-51001702 [Contig_View]  KLK8 [Vega]
ICGC DataPortalENSG00000129455
TCGA cBioPortalKLK8
AceView (NCBI)KLK8
Genatlas (Paris)KLK8
SOURCE (Princeton)KLK8
Genetics Home Reference (NIH)KLK8
Genomic and cartography
GoldenPath hg38 (UCSC)KLK8  -     chr19:50996008-51001702 -  19q13.41   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)KLK8  -     19q13.41   [Description]    (hg19-Feb_2009)
GoldenPathKLK8 - 19q13.41 [CytoView hg19]  KLK8 - 19q13.41 [CytoView hg38]
Genome Data Viewer NCBIKLK8 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AA320217 AA587273 AB008390 AB008927 AB009849
RefSeq transcript (Entrez)NM_001281431 NM_007196 NM_144505 NM_144506 NM_144507
Consensus coding sequences : CCDS (NCBI)KLK8
Gene ExpressionKLK8 [ NCBI-GEO ]   KLK8 [ EBI - ARRAY_EXPRESS ]   KLK8 [ SEEK ]   KLK8 [ MEM ]
Gene Expression Viewer (FireBrowse)KLK8 [ Firebrowse - Broad ]
GenevisibleExpression of KLK8 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)11202
GTEX Portal (Tissue expression)KLK8
Human Protein AtlasENSG00000129455-KLK8 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO60259   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO60259  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO60259
Catalytic activity : Enzyme3.4.21.118 [ Enzyme-Expasy ] [ IntEnz-EBI ] [ BRENDA ] [ KEGG ]   [ MEROPS ]
Domaine pattern : Prosite (Expaxy)TRYPSIN_DOM (PS50240)    TRYPSIN_HIS (PS00134)    TRYPSIN_SER (PS00135)   
Domains : Interpro (EBI)Peptidase_S1_PA    Peptidase_S1_PA_chymotrypsin    Peptidase_S1A    Trypsin_dom    TRYPSIN_HIS    TRYPSIN_SER   
Domain families : Pfam (Sanger)Trypsin (PF00089)   
Domain families : Pfam (NCBI)pfam00089   
Domain families : Smart (EMBL)Tryp_SPc (SM00020)  
Conserved Domain (NCBI)KLK8
PDB (RSDB)5MS3    5MS4   
PDB Europe5MS3    5MS4   
PDB (PDBSum)5MS3    5MS4   
PDB (IMB)5MS3    5MS4   
Structural Biology KnowledgeBase5MS3    5MS4   
SCOP (Structural Classification of Proteins)5MS3    5MS4   
CATH (Classification of proteins structures)5MS3    5MS4   
AlphaFold pdb e-kbO60259   
Human Protein Atlas [tissue]ENSG00000129455-KLK8 [tissue]
Protein Interaction databases
IntAct (EBI)O60259
Ontologies - Pathways
Ontology : AmiGOserine-type endopeptidase activity  protein binding  extracellular region  extracellular space  cytoplasm  proteolysis  memory  memory  cell death  response to wounding  secretory granule  negative regulation of myelination  keratinocyte proliferation  negative regulation of axon regeneration  neuron projection morphogenesis  neuron projection morphogenesis  regulation of synapse organization  synapse organization  serine protease inhibitor complex  
Ontology : EGO-EBIserine-type endopeptidase activity  protein binding  extracellular region  extracellular space  cytoplasm  proteolysis  memory  memory  cell death  response to wounding  secretory granule  negative regulation of myelination  keratinocyte proliferation  negative regulation of axon regeneration  neuron projection morphogenesis  neuron projection morphogenesis  regulation of synapse organization  synapse organization  serine protease inhibitor complex  
REACTOMEO60259 [protein]
REACTOME PathwaysR-HSA-6809371 [pathway]   
NDEx NetworkKLK8
Atlas of Cancer Signalling NetworkKLK8
Wikipedia pathwaysKLK8
Orthology - Evolution
GeneTree (enSembl)ENSG00000129455
Phylogenetic Trees/Animal Genes : TreeFamKLK8
Homologs : HomoloGeneKLK8
Homology/Alignments : Family Browser (UCSC)KLK8
Gene fusions - Rearrangements
Fusion : FusionHubKLK7--KLK8    KLK8--ZER1    KLK9--KLK8   
Fusion : QuiverKLK8
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerKLK8 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)KLK8
Exome Variant ServerKLK8
GNOMAD BrowserENSG00000129455
Varsome BrowserKLK8
ACMGKLK8 variants
Genomic Variants (DGV)KLK8 [DGVbeta]
DECIPHERKLK8 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisKLK8 
ICGC Data PortalKLK8 
TCGA Data PortalKLK8 
Broad Tumor PortalKLK8
OASIS PortalKLK8 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICKLK8  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DKLK8
Mutations and Diseases : HGMDKLK8
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)KLK8
DoCM (Curated mutations)KLK8
CIViC (Clinical Interpretations of Variants in Cancer)KLK8
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry KLK8
NextProtO60259 [Medical]
Target ValidationKLK8
Huge Navigator KLK8 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDKLK8
Pharm GKB GenePA30158
Clinical trialKLK8
DataMed IndexKLK8
PubMed53 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu Jan 20 14:10:22 CET 2022

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