UniProtKB - O60259 (KLK8_HUMAN)
Kallikrein-8
KLK8
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.
1 PublicationMiscellaneous
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.1 Publication EC:3.4.21.118
Activity regulationi
Kineticsi
- KM=0.07 mM for Pro-Phe-Arg-MCA1 Publication
- KM=0.07 mM for Z-Val-Val-Arg-MCA1 Publication
- KM=0.07 mM for Boc-Val-Pro-Arg-MCA1 Publication
- KM=0.10 mM for Boc-Leu-Lys-Arg-MCA1 Publication
- KM=0.10 mM for Boc-Val-Leu-Lys-MCA1 Publication
- KM=0.07 mM for Boc-Phe-Ser-Arg-MCA1 Publication
- Vmax=7.1 µmol/min/mg enzyme toward Pro-Phe-Arg-MCA1 Publication
- Vmax=5.4 µmol/min/mg enzyme toward Z-Val-Val-Arg-MCA1 Publication
- Vmax=3.9 µmol/min/mg enzyme toward Boc-Val-Pro-Arg-MCA1 Publication
- Vmax=2.6 µmol/min/mg enzyme toward Boc-Leu-Lys-Arg-MCA1 Publication
- Vmax=1.9 µmol/min/mg enzyme toward Boc-Val-Leu-Lys-MCA1 Publication
- Vmax=1.6 µmol/min/mg enzyme toward Boc-Phe-Ser-Arg-MCA1 Publication
pH dependencei
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 73 | Charge relay systemBy similarity | 1 | |
Active sitei | 120 | Charge relay systemBy similarity | 1 | |
Active sitei | 212 | Charge relay systemBy similarity | 1 |
GO - Molecular functioni
- serine-type endopeptidase activity Source: UniProtKB
GO - Biological processi
- cell death Source: UniProtKB
- keratinocyte proliferation Source: UniProtKB
- memory Source: UniProtKB
- negative regulation of axon regeneration Source: UniProtKB
- negative regulation of myelination Source: UniProtKB
- neuron projection morphogenesis Source: UniProtKB
- regulation of synapse organization Source: UniProtKB
- response to wounding Source: UniProtKB
- synapse organization Source: Ensembl
Keywordsi
Molecular function | Hydrolase, Protease, Serine protease |
Enzyme and pathway databases
BRENDAi | 3.4.21.118, 2681 |
PathwayCommonsi | O60259 |
Reactomei | R-HSA-6809371, Formation of the cornified envelope |
SignaLinki | O60259 |
Protein family/group databases
MEROPSi | S01.244 |
Names & Taxonomyi
Protein namesi | Recommended name: Kallikrein-8 (EC:3.4.21.118)Short name: hK8 Alternative name(s): Neuropsin Short name: NP Ovasin Serine protease 19 Serine protease TADG-14 Tumor-associated differentially expressed gene 14 protein |
Gene namesi | Name:KLK8 Synonyms:NRPN, PRSS19, TADG14 ORF Names:UNQ283/PRO322 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:6369, KLK8 |
MIMi | 605644, gene |
neXtProti | NX_O60259 |
VEuPathDBi | HostDB:ENSG00000129455 |
Subcellular locationi
Extracellular region or secreted
- extracellular region Source: Reactome
- extracellular space Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
- secretory granule Source: GO_Central
- serine protease inhibitor complex Source: BHF-UCL
Keywords - Cellular componenti
Cytoplasm, SecretedPathology & Biotechi
Organism-specific databases
DisGeNETi | 11202 |
OpenTargetsi | ENSG00000129455 |
PharmGKBi | PA30158 |
Miscellaneous databases
Pharosi | O60259, Tchem |
Chemistry databases
ChEMBLi | CHEMBL4812 |
GuidetoPHARMACOLOGYi | 2378 |
Genetic variation databases
BioMutai | KLK8 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 28 | Sequence analysisAdd BLAST | 28 | |
PropeptideiPRO_0000027946 | 29 – 32 | By similarity | 4 | |
ChainiPRO_0000027947 | 33 – 260 | Kallikrein-8Add BLAST | 228 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 39 ↔ 173 | PROSITE-ProRule annotation | ||
Disulfide bondi | 58 ↔ 74 | PROSITE-ProRule annotation | ||
Glycosylationi | 110 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 145 ↔ 246 | PROSITE-ProRule annotation | ||
Disulfide bondi | 152 ↔ 218 | PROSITE-ProRule annotation | ||
Disulfide bondi | 184 ↔ 198 | PROSITE-ProRule annotation | ||
Disulfide bondi | 208 ↔ 233 | PROSITE-ProRule annotation |
Keywords - PTMi
Disulfide bond, Glycoprotein, ZymogenProteomic databases
EPDi | O60259 |
MassIVEi | O60259 |
PeptideAtlasi | O60259 |
PRIDEi | O60259 |
ProteomicsDBi | 49286 [O60259-1] 49287 [O60259-2] 49288 [O60259-3] |
PTM databases
GlyGeni | O60259, 1 site |
PhosphoSitePlusi | O60259 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000129455, Expressed in zone of skin and 122 other tissues |
ExpressionAtlasi | O60259, baseline and differential |
Genevisiblei | O60259, HS |
Organism-specific databases
HPAi | ENSG00000129455, Group enriched (esophagus, skin, vagina) |
Interactioni
Subunit structurei
Interacts with SPINK9.
1 PublicationBinary interactionsi
O60259
Protein-protein interaction databases
BioGRIDi | 116371, 44 interactors |
IntActi | O60259, 20 interactors |
Chemistry databases
BindingDBi | O60259 |
Miscellaneous databases
RNActi | O60259, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | O60259 |
SMRi | O60259 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 33 – 257 | Peptidase S1PROSITE-ProRule annotationAdd BLAST | 225 |
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
GeneTreei | ENSGT01020000230389 |
HOGENOMi | CLU_006842_1_1_1 |
InParanoidi | O60259 |
OMAi | GQECKPH |
OrthoDBi | 1314811at2759 |
PhylomeDBi | O60259 |
TreeFami | TF331065 |
Family and domain databases
CDDi | cd00190, Tryp_SPc, 1 hit |
Gene3Di | 2.40.10.10, 2 hits |
InterProi | View protein in InterPro IPR009003, Peptidase_S1_PA IPR043504, Peptidase_S1_PA_chymotrypsin IPR001314, Peptidase_S1A IPR001254, Trypsin_dom IPR018114, TRYPSIN_HIS IPR033116, TRYPSIN_SER |
Pfami | View protein in Pfam PF00089, Trypsin, 1 hit |
PRINTSi | PR00722, CHYMOTRYPSIN |
SMARTi | View protein in SMART SM00020, Tryp_SPc, 1 hit |
SUPFAMi | SSF50494, SSF50494, 1 hit |
PROSITEi | View protein in PROSITE PS50240, TRYPSIN_DOM, 1 hit PS00134, TRYPSIN_HIS, 1 hit PS00135, TRYPSIN_SER, 1 hit |
s (4+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MGRPRPRAAK TWMFLLLLGG AWAGHSRAQE DKVLGGHECQ PHSQPWQAAL
60 70 80 90 100
FQGQQLLCGG VLVGGNWVLT AAHCKKPKYT VRLGDHSLQN KDGPEQEIPV
110 120 130 140 150
VQSIPHPCYN SSDVEDHNHD LMLLQLRDQA SLGSKVKPIS LADHCTQPGQ
160 170 180 190 200
KCTVSGWGTV TSPRENFPDT LNCAEVKIFP QKKCEDAYPG QITDGMVCAG
210 220 230 240 250
SSKGADTCQG DSGGPLVCDG ALQGITSWGS DPCGRSDKPG VYTNICRYLD
260
WIKKIIGSKG
The sequence of this isoform differs from the canonical sequence as follows:
23-23: A → AACGSLDLLTKLYAENLPCVHLNPQWPSQPSHCPRGWRSNPLPPAA
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketM0R231 | M0R231_HUMAN | Kallikrein-8 | KLK8 | 97 | Annotation score: | ||
A0A0A0MQY9 | A0A0A0MQY9_HUMAN | Kallikrein-8 | KLK8 | 139 | Annotation score: | ||
M0R390 | M0R390_HUMAN | Kallikrein-8 | KLK8 | 54 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 195 | G → V in AAH40887 (PubMed:15489334).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_051855 | 154 | V → I. Corresponds to variant dbSNP:rs16988799Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_005401 | 23 | A → AACGSLDLLTKLYAENLPCV HLNPQWPSQPSHCPRGWRSN PLPPAA in isoform 2. 1 Publication | 1 | |
Alternative sequenceiVSP_030350 | 24 – 164 | Missing in isoform 3. 1 PublicationAdd BLAST | 141 | |
Alternative sequenceiVSP_030351 | 25 – 32 | HSRAQEDK → RFWRPPGV in isoform 4. Curated | 8 | |
Alternative sequenceiVSP_030352 | 33 – 260 | Missing in isoform 4. CuratedAdd BLAST | 228 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB009849 mRNA Translation: BAA28673.1 AB012761 Genomic DNA Translation: BAA28676.1 AF055982 mRNA Translation: AAD56050.1 AB008390 mRNA Translation: BAA82665.1 AB008927 mRNA Translation: BAA82666.1 AB010780 Genomic DNA Translation: BAA88684.1 AF243527 Genomic DNA Translation: AAG33361.1 AF251125 Genomic DNA Translation: AAF79144.1 AF251125 Genomic DNA Translation: AAF79145.1 AF095742 mRNA Translation: AAD25979.1 AF095743 Genomic DNA Translation: AAD29574.1 DQ267420 mRNA Translation: ABB83339.1 AY359036 mRNA Translation: AAQ89395.1 AC011473 Genomic DNA Translation: AAG23254.1 AC011483 Genomic DNA No translation available. CH471135 Genomic DNA Translation: EAW71962.1 BC040887 mRNA Translation: AAH40887.1 AY563055 Genomic DNA Translation: AAT76913.1 AY563055 Genomic DNA Translation: AAT76914.1 AY563056 Genomic DNA Translation: AAT76915.1 AY563056 Genomic DNA Translation: AAT76916.1 AY563057 Genomic DNA Translation: AAT76917.1 AY563057 Genomic DNA Translation: AAT76918.1 AY563058 Genomic DNA Translation: AAT76919.1 AY563058 Genomic DNA Translation: AAT76920.1 AY563059 Genomic DNA Translation: AAT76921.1 AY563059 Genomic DNA Translation: AAT76922.1 AY563060 Genomic DNA Translation: AAT76923.1 AY563060 Genomic DNA Translation: AAT76924.1 AY563061 Genomic DNA Translation: AAT76925.1 AY563061 Genomic DNA Translation: AAT76926.1 AY563062 Genomic DNA Translation: AAT76927.1 AY563062 Genomic DNA Translation: AAT76928.1 AY563063 Genomic DNA Translation: AAT76929.1 AY563063 Genomic DNA Translation: AAT76930.1 AY563064 Genomic DNA Translation: AAT76931.1 AY563064 Genomic DNA Translation: AAT76932.1 AY563065 Genomic DNA Translation: AAT76933.1 AY563065 Genomic DNA Translation: AAT76934.1 AY563066 Genomic DNA Translation: AAT76935.1 AY563066 Genomic DNA Translation: AAT76936.1 AY563067 Genomic DNA Translation: AAT76937.1 AY563067 Genomic DNA Translation: AAT76938.1 |
CCDSi | CCDS12813.1 [O60259-1] CCDS12814.1 [O60259-3] CCDS12815.1 [O60259-4] CCDS42600.1 [O60259-2] |
RefSeqi | NP_001268360.1, NM_001281431.1 NP_009127.1, NM_007196.3 [O60259-1] NP_653088.1, NM_144505.2 [O60259-2] NP_653089.1, NM_144506.2 [O60259-3] NP_653090.1, NM_144507.2 [O60259-4] |
Genome annotation databases
Ensembli | ENST00000320838.9; ENSP00000325072.5; ENSG00000129455.15 [O60259-4] ENST00000347619.8; ENSP00000341555.3; ENSG00000129455.15 [O60259-3] ENST00000391806.6; ENSP00000375682.1; ENSG00000129455.15 [O60259-2] ENST00000593490.1; ENSP00000469278.1; ENSG00000129455.15 [O60259-4] ENST00000600767.5; ENSP00000472016.1; ENSG00000129455.15 |
GeneIDi | 11202 |
KEGGi | hsa:11202 |
UCSCi | uc002puq.2, human [O60259-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB009849 mRNA Translation: BAA28673.1 AB012761 Genomic DNA Translation: BAA28676.1 AF055982 mRNA Translation: AAD56050.1 AB008390 mRNA Translation: BAA82665.1 AB008927 mRNA Translation: BAA82666.1 AB010780 Genomic DNA Translation: BAA88684.1 AF243527 Genomic DNA Translation: AAG33361.1 AF251125 Genomic DNA Translation: AAF79144.1 AF251125 Genomic DNA Translation: AAF79145.1 AF095742 mRNA Translation: AAD25979.1 AF095743 Genomic DNA Translation: AAD29574.1 DQ267420 mRNA Translation: ABB83339.1 AY359036 mRNA Translation: AAQ89395.1 AC011473 Genomic DNA Translation: AAG23254.1 AC011483 Genomic DNA No translation available. CH471135 Genomic DNA Translation: EAW71962.1 BC040887 mRNA Translation: AAH40887.1 AY563055 Genomic DNA Translation: AAT76913.1 AY563055 Genomic DNA Translation: AAT76914.1 AY563056 Genomic DNA Translation: AAT76915.1 AY563056 Genomic DNA Translation: AAT76916.1 AY563057 Genomic DNA Translation: AAT76917.1 AY563057 Genomic DNA Translation: AAT76918.1 AY563058 Genomic DNA Translation: AAT76919.1 AY563058 Genomic DNA Translation: AAT76920.1 AY563059 Genomic DNA Translation: AAT76921.1 AY563059 Genomic DNA Translation: AAT76922.1 AY563060 Genomic DNA Translation: AAT76923.1 AY563060 Genomic DNA Translation: AAT76924.1 AY563061 Genomic DNA Translation: AAT76925.1 AY563061 Genomic DNA Translation: AAT76926.1 AY563062 Genomic DNA Translation: AAT76927.1 AY563062 Genomic DNA Translation: AAT76928.1 AY563063 Genomic DNA Translation: AAT76929.1 AY563063 Genomic DNA Translation: AAT76930.1 AY563064 Genomic DNA Translation: AAT76931.1 AY563064 Genomic DNA Translation: AAT76932.1 AY563065 Genomic DNA Translation: AAT76933.1 AY563065 Genomic DNA Translation: AAT76934.1 AY563066 Genomic DNA Translation: AAT76935.1 AY563066 Genomic DNA Translation: AAT76936.1 AY563067 Genomic DNA Translation: AAT76937.1 AY563067 Genomic DNA Translation: AAT76938.1 |
CCDSi | CCDS12813.1 [O60259-1] CCDS12814.1 [O60259-3] CCDS12815.1 [O60259-4] CCDS42600.1 [O60259-2] |
RefSeqi | NP_001268360.1, NM_001281431.1 NP_009127.1, NM_007196.3 [O60259-1] NP_653088.1, NM_144505.2 [O60259-2] NP_653089.1, NM_144506.2 [O60259-3] NP_653090.1, NM_144507.2 [O60259-4] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5MS3 | X-ray | 2.30 | A | 33-260 | [»] | |
5MS4 | X-ray | 2.10 | A/B/C/D | 33-260 | [»] | |
AlphaFoldDBi | O60259 | |||||
SMRi | O60259 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 116371, 44 interactors |
IntActi | O60259, 20 interactors |
Chemistry databases
BindingDBi | O60259 |
ChEMBLi | CHEMBL4812 |
GuidetoPHARMACOLOGYi | 2378 |
Protein family/group databases
MEROPSi | S01.244 |
PTM databases
GlyGeni | O60259, 1 site |
PhosphoSitePlusi | O60259 |
Genetic variation databases
BioMutai | KLK8 |
Proteomic databases
EPDi | O60259 |
MassIVEi | O60259 |
PeptideAtlasi | O60259 |
PRIDEi | O60259 |
ProteomicsDBi | 49286 [O60259-1] 49287 [O60259-2] 49288 [O60259-3] |
Protocols and materials databases
Antibodypediai | 32417, 1191 antibodies from 32 providers |
DNASUi | 11202 |
Genome annotation databases
Organism-specific databases
CTDi | 11202 |
DisGeNETi | 11202 |
GeneCardsi | KLK8 |
HGNCi | HGNC:6369, KLK8 |
HPAi | ENSG00000129455, Group enriched (esophagus, skin, vagina) |
MIMi | 605644, gene |
neXtProti | NX_O60259 |
OpenTargetsi | ENSG00000129455 |
PharmGKBi | PA30158 |
VEuPathDBi | HostDB:ENSG00000129455 |
GenAtlasi | Search... |
Phylogenomic databases
GeneTreei | ENSGT01020000230389 |
HOGENOMi | CLU_006842_1_1_1 |
InParanoidi | O60259 |
OMAi | GQECKPH |
OrthoDBi | 1314811at2759 |
PhylomeDBi | O60259 |
TreeFami | TF331065 |
Enzyme and pathway databases
BRENDAi | 3.4.21.118, 2681 |
PathwayCommonsi | O60259 |
Reactomei | R-HSA-6809371, Formation of the cornified envelope |
SignaLinki | O60259 |
Miscellaneous databases
BioGRID-ORCSi | 11202, 10 hits in 1066 CRISPR screens |
GeneWikii | KLK8 |
GenomeRNAii | 11202 |
Pharosi | O60259, Tchem |
PROi | PR:O60259 |
RNActi | O60259, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000129455, Expressed in zone of skin and 122 other tissues |
ExpressionAtlasi | O60259, baseline and differential |
Genevisiblei | O60259, HS |
Family and domain databases
CDDi | cd00190, Tryp_SPc, 1 hit |
Gene3Di | 2.40.10.10, 2 hits |
InterProi | View protein in InterPro IPR009003, Peptidase_S1_PA IPR043504, Peptidase_S1_PA_chymotrypsin IPR001314, Peptidase_S1A IPR001254, Trypsin_dom IPR018114, TRYPSIN_HIS IPR033116, TRYPSIN_SER |
Pfami | View protein in Pfam PF00089, Trypsin, 1 hit |
PRINTSi | PR00722, CHYMOTRYPSIN |
SMARTi | View protein in SMART SM00020, Tryp_SPc, 1 hit |
SUPFAMi | SSF50494, SSF50494, 1 hit |
PROSITEi | View protein in PROSITE PS50240, TRYPSIN_DOM, 1 hit PS00134, TRYPSIN_HIS, 1 hit PS00135, TRYPSIN_SER, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | KLK8_HUMAN | |
Accessioni | O60259Primary (citable) accession number: O60259 Secondary accession number(s): Q5V9X1 Q9UQ47 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1999 |
Last sequence update: | August 1, 1998 | |
Last modified: | May 25, 2022 | |
This is version 186 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Peptidase families
Classification of peptidase families and list of entries - Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families