Human Gene KLK8 (uc002pur.1) Description and Page Index
  Description: Homo sapiens kallikrein-related peptidase 8 (KLK8), transcript variant 1, mRNA.
RefSeq Summary (NM_007196): Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. This gene is one of the fifteen kallikrein subfamily members located in tandem in a gene cluster on chromosome 19. The encoded protein may be involved in proteolytic cascade in the skin and may serve as a biomarker for ovarian cancer. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013].
Transcript (Including UTRs)
   Position: hg19 chr19:51,499,264-51,504,965 Size: 5,702 Total Exon Count: 6 Strand: -
Coding Region
   Position: hg19 chr19:51,499,315-51,504,423 Size: 5,109 Coding Exon Count: 5 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr19:51,499,264-51,504,965)mRNA (may differ from genome)Protein (260 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCETreefam

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Kallikrein-8; Short=hK8; EC=; AltName: Full=Neuropsin; Short=NP; AltName: Full=Ovasin; AltName: Full=Serine protease 19; AltName: Full=Serine protease TADG-14; AltName: Full=Tumor-associated differentially expressed gene 14 protein; Flags: Precursor;
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.
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: Inhibited by a range of serine protease inhibitors including antipain, aprotinin, leupeptin, benzamidine and soybean trypsin inhibitor.
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.07 mM for Pro-Phe-Arg-MCA; KM=0.07 mM for Z-Val-Val-Arg-MCA; KM=0.07 mM for Boc-Val-Pro-Arg-MCA; KM=0.10 mM for Boc-Leu-Lys-Arg-MCA; KM=0.10 mM for Boc-Val-Leu-Lys-MCA; KM=0.07 mM for Boc-Phe-Ser-Arg-MCA; Vmax=7.1 umol/min/mg enzyme toward Pro-Phe-Arg-MCA; Vmax=5.4 umol/min/mg enzyme toward Z-Val-Val-Arg-MCA; Vmax=3.9 umol/min/mg enzyme toward Boc-Val-Pro-Arg-MCA; Vmax=2.6 umol/min/mg enzyme toward Boc-Leu-Lys-Arg-MCA; Vmax=1.9 umol/min/mg enzyme toward Boc-Val-Leu-Lys-MCA; Vmax=1.6 umol/min/mg enzyme toward Boc-Phe-Ser-Arg-MCA; pH dependence: Optimum pH is 8.5. Active from pH 7-10;
SUBUNIT: Interacts with SPINK9.
SUBCELLULAR LOCATION: Secreted. Cytoplasm. Note=Shows a cytoplasmic distribution in the keratinocytes.
TISSUE SPECIFICITY: Isoform 1 is predominantly expressed in the pancreas. Isoform 2 is expressed in adult brain and hippocampus. Isoform 1 and isoform 2 are found in fetal brain and placenta. Detected in salivary gland, uterus, thymus, breast, testis and kidney but not in spleen, liver, lung or normal ovarian tissue. Displays an 11.5-fold increase in Alzheimer disease hippocampus compared to controls and is overexpressed in some ovarian carcinomas. Expressed at low levels in normal skin while high levels are found in psoriasis vulgaris, seborrheic keratosis, lichen planus and squamous cell carcinoma skin samples. Expressed in the keratinocytes.
MISCELLANEOUS: Expressed at high levels in serum, ascites fluid and tumor cytosol of advanced stage ovarian cancer patients and may serve as a marker of ovarian cancer.
SIMILARITY: Belongs to the peptidase S1 family. Kallikrein subfamily.
SIMILARITY: Contains 1 peptidase S1 domain.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): KLK8
CDC HuGE Published Literature: KLK8

-  MalaCards Disease Associations
  MalaCards Gene Search: KLK8
Diseases sorted by gene-association score: spinal cord injury (9), polyradiculopathy (8), splenic sequestration (7), ovarian cancer, somatic (3)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 34.47 RPKM in Skin - Sun Exposed (Lower leg)
Total median expression: 113.57 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -68.41186-0.368 Picture PostScript Text
3' UTR -5.0051-0.098 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR009003 - Pept_cys/ser_Trypsin-like
IPR018114 - Peptidase_S1/S6_AS
IPR001254 - Peptidase_S1_S6
IPR001314 - Peptidase_S1A

Pfam Domains:
PF00089 - Trypsin
PF13365 - Trypsin-like peptidase domain

SCOP Domains:
50494 - Trypsin-like serine proteases

ModBase Predicted Comparative 3D Structure on O60259
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 Protein Sequence    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004252 serine-type endopeptidase activity
GO:0005515 protein binding
GO:0008233 peptidase activity
GO:0008236 serine-type peptidase activity
GO:0016787 hydrolase activity

Biological Process:
GO:0006508 proteolysis
GO:0007613 memory
GO:0008219 cell death
GO:0009611 response to wounding
GO:0031642 negative regulation of myelination
GO:0043616 keratinocyte proliferation
GO:0048681 negative regulation of axon regeneration
GO:0048812 neuron projection morphogenesis
GO:0050807 regulation of synapse organization
GO:0050808 synapse organization

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005737 cytoplasm
GO:0097180 serine protease inhibitor complex

-  Descriptions from all associated GenBank mRNAs
  DQ267419 - Homo sapiens kallikrein 9 and kallikrein 8 bicistronic mRNA, partial sequence, alternatively spliced.
KX519466 - Homo sapiens kallikrein-8 isoform 6 (KLK8) mRNA, complete cds, alternatively spliced.
KX519467 - Homo sapiens kallikrein-8 isoform 7 (KLK8) mRNA, complete cds, alternatively spliced.
KX519468 - Homo sapiens kallikrein-8 isoform 8 (KLK8) mRNA, complete cds, alternatively spliced.
KX519469 - Homo sapiens kallikrein-8 isoform 9 (KLK8) mRNA, complete cds, alternatively spliced.
KX519470 - Homo sapiens kallikrein-8 isoform 10 (KLK8) mRNA, complete cds, alternatively spliced.
KX519471 - Homo sapiens kallikrein-8 isoform 11 (KLK8) mRNA, complete cds, alternatively spliced.
KX519472 - Homo sapiens kallikrein-8 isoform 12 (KLK8) mRNA, complete cds, alternatively spliced.
KX519473 - Homo sapiens kallikrein-8 isoform 13 (KLK8) mRNA, complete cds, alternatively spliced.
KY549322 - Homo sapiens kallikrein-related peptidase 8 transcript variant 15 (KLK8) mRNA, complete cds, alternatively spliced.
AB009849 - Homo sapiens mRNA for neuropsin, complete cds.
AY359036 - Homo sapiens clone DNA48336 KLK8 (UNQ283) mRNA, complete cds.
AB008927 - Homo sapiens mRNA for neuropsin type2, complete cds.
AB008390 - Homo sapiens mRNA for neuropsin type1, complete cds.
AF055982 - Homo sapiens serine protease TADG14 mRNA, complete cds.
AF095742 - Homo sapiens serine protease ovasin mRNA, complete cds.
BC040887 - Homo sapiens kallikrein-related peptidase 8, mRNA (cDNA clone MGC:50513 IMAGE:5742016), complete cds.
DQ267420 - Homo sapiens kallikrein 9 and kallikrein 8 bicistronic mRNA, partial sequence, alternatively spliced.
JD447616 - Sequence 428640 from Patent EP1572962.
HQ448625 - Synthetic construct Homo sapiens clone IMAGE:100072064; CCSB011344_02 kallikrein-related peptidase 8 (KLK8) gene, encodes complete protein.
KJ898376 - Synthetic construct Homo sapiens clone ccsbBroadEn_07770 KLK8 gene, encodes complete protein.
JD426258 - Sequence 407282 from Patent EP1572962.
JD384157 - Sequence 365181 from Patent EP1572962.
JD540862 - Sequence 521886 from Patent EP1572962.
CU691932 - Synthetic construct Homo sapiens gateway clone IMAGE:100021277 5' read KLK8 mRNA.
EU350538 - Homo sapiens KLK8 protein type 1 (KLK8) mRNA, partial cds, alternatively spliced.
EU350539 - Homo sapiens KLK8 protein type 2 (KLK8) mRNA, partial cds, alternatively spliced.
AY566267 - Homo sapiens kallikrein 9 and kallikrein 8 bicistronic mRNA, partial sequence.
JD530545 - Sequence 511569 from Patent EP1572962.
JD178208 - Sequence 159232 from Patent EP1572962.
JD339490 - Sequence 320514 from Patent EP1572962.
JD340042 - Sequence 321066 from Patent EP1572962.
JD373147 - Sequence 354171 from Patent EP1572962.
JD535723 - Sequence 516747 from Patent EP1572962.
JD229593 - Sequence 210617 from Patent EP1572962.
JD417942 - Sequence 398966 from Patent EP1572962.
JD102705 - Sequence 83729 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein O60259 (Reactome details) participates in the following event(s):

R-HSA-8850831 KLK5 cleaves and activates KLK8
R-HSA-6809371 Formation of the cornified envelope
R-HSA-6805567 Keratinization
R-HSA-1266738 Developmental Biology

-  Other Names for This Gene
  Alternate Gene Symbols: KLK8_HUMAN, NM_007196, NP_009127, NRPN, O60259, PRSS19, Q5V9X1, Q5V9X2, Q8IW69, Q9HCB3, Q9NR68, Q9NR69, Q9UIL9, Q9UQ47, TADG14, UNQ283/PRO322
UCSC ID: uc002pur.1
RefSeq Accession: NM_007196
Protein: O60259 (aka KLK8_HUMAN)
CCDS: CCDS12813.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_007196.2
exon count: 6CDS single in 3' UTR: no RNA size: 1013
ORF size: 783CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 1766.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.