UniProtKB - Q92876 (KLK6_HUMAN)
Protein
Kallikrein-6
Gene
KLK6
Organism
Homo sapiens (Human)
Status
Functioni
Serine protease which exhibits a preference for Arg over Lys in the substrate P1 position and for Ser or Pro in the P2 position. Shows activity against amyloid precursor protein, myelin basic protein, gelatin, casein and extracellular matrix proteins such as fibronectin, laminin, vitronectin and collagen. Degrades alpha-synuclein and prevents its polymerization, indicating that it may be involved in the pathogenesis of Parkinson disease and other synucleinopathies. May be involved in regulation of axon outgrowth following spinal cord injury. Tumor cells treated with a neutralizing KLK6 antibody migrate less than control cells, suggesting a role in invasion and metastasis.6 Publications
Activity regulationi
Inhibited by a range of serine protease inhibitors including soybean trypsin inhibitor, benzamidine and serpins. Activated by a range of glycosaminoglycans including chondroitin sulfate, dermatan sulfate, heparan sulfate and heparin.2 Publications
Kineticsi
- KM=1562 µM for Tosyl-Gly-Pro-Arg-AMC2 Publications
- KM=777 µM for Tosyl-Gly-Pro-Lys-AMC2 Publications
- KM=0.410 mM for Phe-Ser-Arg-AMC2 Publications
- KM=0.455 mM for Gly-Gly-Arg-AMC2 Publications
- KM=0.335 mM for Asp-Pro-Arg-AMC2 Publications
- KM=0.758 mM for Gln-Gly-Arg-AMC2 Publications
- KM=0.625 mM for Pro-Phe-Arg-AMC2 Publications
- KM=0.271 mM for Val-Pro-Arg-AMC2 Publications
- KM=1.72 mM for Val-Leu-Lys-AMC2 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 62 | Charge relay system1 Publication | 1 | |
Active sitei | 106 | Charge relay system1 Publication | 1 | |
Active sitei | 197 | Charge relay system1 Publication | 1 |
GO - Molecular functioni
- serine-type endopeptidase activity Source: UniProtKB
GO - Biological processi
- amyloid precursor protein metabolic process Source: UniProtKB
- central nervous system development Source: UniProtKB
- collagen catabolic process Source: UniProtKB
- hormone metabolic process Source: UniProtKB
- myelination Source: UniProtKB
- positive regulation of G protein-coupled receptor signaling pathway Source: UniProtKB
- protein autoprocessing Source: UniProtKB
- regulation of cell differentiation Source: UniProtKB
- regulation of neuron projection development Source: Ensembl
- response to wounding Source: UniProtKB
- tissue regeneration Source: UniProtKB
Keywordsi
Molecular function | Hydrolase, Protease, Serine protease |
Enzyme and pathway databases
BRENDAi | 3.4.21.104, 2681 3.4.21.34, 2681 3.4.21.B10, 2681 |
PathwayCommonsi | Q92876 |
SABIO-RKi | Q92876 |
Protein family/group databases
MEROPSi | S01.236 |
Names & Taxonomyi
Protein namesi | Recommended name: Kallikrein-6 (EC:3.4.21.-)Alternative name(s): Neurosin Protease M SP59 Serine protease 18 Serine protease 9 Zyme |
Gene namesi | Name:KLK6 Synonyms:PRSS18, PRSS9 |
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:6367, KLK6 |
MIMi | 602652, gene |
neXtProti | NX_Q92876 |
VEuPathDBi | HostDB:ENSG00000167755.13 |
Subcellular locationi
Mitochondrion
Endoplasmic reticulum
Extracellular region or secreted
Nucleus
Other locations
Note: In brain, detected in the nucleus of glial cells and in the nucleus and cytoplasm of neurons. Detected in the mitochondrial and microsomal fractions of HEK-293 cells and released into the cytoplasm following cell stress.
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB-KW
Extracellular region or secreted
- extracellular region Source: UniProtKB
- extracellular space Source: UniProtKB
Mitochondrion
- mitochondrion Source: UniProtKB-SubCell
Nucleus
- nucleolus Source: UniProtKB-SubCell
Other locations
- cytoplasm Source: UniProtKB
- secretory granule Source: GO_Central
Keywords - Cellular componenti
Cytoplasm, Endoplasmic reticulum, Microsome, Mitochondrion, Nucleus, SecretedPathology & Biotechi
Organism-specific databases
DisGeNETi | 5653 |
OpenTargetsi | ENSG00000167755 |
PharmGKBi | PA30156 |
Miscellaneous databases
Pharosi | Q92876, Tchem |
Chemistry databases
ChEMBLi | CHEMBL4448 |
DrugBanki | DB03127, Benzamidine |
GuidetoPHARMACOLOGYi | 2376 |
Genetic variation databases
BioMutai | KLK6 |
DMDMi | 3914480 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 16 | Sequence analysisAdd BLAST | 16 | |
PropeptideiPRO_0000027940 | 17 – 21 | Activation peptideSequence analysis | 5 | |
ChainiPRO_0000027941 | 22 – 244 | Kallikrein-6Add BLAST | 223 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 28 ↔ 157 | |||
Disulfide bondi | 47 ↔ 63 | |||
Disulfide bondi | 131 ↔ 231 | |||
Glycosylationi | 134 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 138 ↔ 203 | |||
Disulfide bondi | 168 ↔ 182 | |||
Disulfide bondi | 193 ↔ 218 |
Post-translational modificationi
Inactivated by autolytic cleavage after Arg-80.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 80 – 81 | Cleavage; by autolysis | 2 |
Keywords - PTMi
Autocatalytic cleavage, Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, ZymogenProteomic databases
EPDi | Q92876 |
jPOSTi | Q92876 |
MassIVEi | Q92876 |
MaxQBi | Q92876 |
PaxDbi | Q92876 |
PeptideAtlasi | Q92876 |
PRIDEi | Q92876 |
ProteomicsDBi | 75559 [Q92876-1] 75560 [Q92876-2] 75561 [Q92876-3] |
PTM databases
GlyGeni | Q92876, 1 site, 15 N-linked glycans (1 site) |
PhosphoSitePlusi | Q92876 |
Expressioni
Tissue specificityi
In fluids, highest levels found in milk of lactating women followed by cerebrospinal fluid, nipple aspirate fluid and breast cyst fluid. Also found in serum, seminal plasma and some amniotic fluids and breast tumor cytosolic extracts. Not detected in urine. At the tissue level, highest concentrations found in glandular tissues such as salivary glands followed by lung, colon, fallopian tube, placenta, breast, pituitary and kidney. Not detected in skin, spleen, bone, thyroid, heart, ureter, liver, muscle, endometrium, testis, pancreas, seminal vesicle, ovary, adrenals and prostate. In brain, detected in gray matter neurons (at protein level). Colocalizes with pathological inclusions such as Lewy bodies and glial cytoplasmic inclusions. Overexpressed in primary breast tumors but not expressed in metastatic tumors.5 Publications
Inductioni
By spinal cord injury. This effect is particularly prominent in macrophages, microglia and reactive astrocytes.1 Publication
Gene expression databases
Bgeei | ENSG00000167755, Expressed in C1 segment of cervical spinal cord and 154 other tissues |
ExpressionAtlasi | Q92876, baseline and differential |
Genevisiblei | Q92876, HS |
Organism-specific databases
HPAi | ENSG00000167755, Tissue enhanced (brain, esophagus) |
Interactioni
Binary interactionsi
Q92876
Protein-protein interaction databases
BioGRIDi | 111634, 12 interactors |
IntActi | Q92876, 169 interactors |
MINTi | Q92876 |
STRINGi | 9606.ENSP00000366047 |
Chemistry databases
BindingDBi | Q92876 |
Miscellaneous databases
RNActi | Q92876, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q92876 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q92876 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 22 – 242 | Peptidase S1PROSITE-ProRule annotationAdd BLAST | 221 |
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG3627, Eukaryota |
GeneTreei | ENSGT00990000203560 |
HOGENOMi | CLU_006842_1_1_1 |
InParanoidi | Q92876 |
OMAi | HTSCHIL |
PhylomeDBi | Q92876 |
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 (3+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
Isoform 1 (identifier: Q92876-1) [UniParc]FASTAAdd to basket
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
MKKLMVVLSL IAAAWAEEQN KLVHGGPCDK TSHPYQAALY TSGHLLCGGV
60 70 80 90 100
LIHPLWVLTA AHCKKPNLQV FLGKHNLRQR ESSQEQSSVV RAVIHPDYDA
110 120 130 140 150
ASHDQDIMLL RLARPAKLSE LIQPLPLERD CSANTTSCHI LGWGKTADGD
160 170 180 190 200
FPDTIQCAYI HLVSREECEH AYPGQITQNM LCAGDEKYGK DSCQGDSGGP
210 220 230 240
LVCGDHLRGL VSWGNIPCGS KEKPGVYTNV CRYTNWIQKT IQAK
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketM0QYA5 | M0QYA5_HUMAN | Kallikrein-6 | KLK6 | 69 | Annotation score: |
Mass spectrometryi
Molecular mass is 25866 Da. Determined by MALDI. 1 Publication
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_061776 | 78 | R → W. Corresponds to variant dbSNP:rs61469141EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_034403 | 1 – 107 | Missing in isoform 2. 1 PublicationAdd BLAST | 107 | |
Alternative sequenceiVSP_034404 | 14 – 40 | AWAEE…QAALY → GIFRSSWGSITFGKGRVPRS RVLLSGL in isoform 3. 1 PublicationAdd BLAST | 27 | |
Alternative sequenceiVSP_034405 | 41 – 244 | Missing in isoform 3. 1 PublicationAdd BLAST | 204 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U62801 mRNA Translation: AAB07113.1 D78203 mRNA Translation: BAA11306.1 AF013988 mRNA Translation: AAB66483.1 AF149289 Genomic DNA Translation: AAD51475.1 AF243527 Genomic DNA Translation: AAG33359.1 AY318867 mRNA Translation: AAP82446.1 AY318868 mRNA No translation available. AY318869 mRNA Translation: AAP82448.1 AY318870 mRNA No translation available. DQ223012 mRNA Translation: ABB04464.1 AK314897 mRNA Translation: BAG37411.1 BT006852 mRNA Translation: AAP35498.1 AC011483 Genomic DNA No translation available. CH471135 Genomic DNA Translation: EAW71953.1 CH471135 Genomic DNA Translation: EAW71954.1 BC015525 mRNA Translation: AAH15525.1 |
CCDSi | CCDS12811.1 [Q92876-1] CCDS42599.1 [Q92876-2] |
RefSeqi | NP_001012982.1, NM_001012964.2 [Q92876-1] NP_001012983.1, NM_001012965.2 [Q92876-2] NP_001306877.1, NM_001319948.1 [Q92876-2] NP_001306878.1, NM_001319949.1 [Q92876-2] NP_002765.1, NM_002774.3 [Q92876-1] |
Genome annotation databases
Ensembli | ENST00000310157; ENSP00000309148; ENSG00000167755 [Q92876-1] ENST00000376851; ENSP00000366047; ENSG00000167755 [Q92876-1] ENST00000391808; ENSP00000375684; ENSG00000167755 [Q92876-2] ENST00000594641; ENSP00000470482; ENSG00000167755 [Q92876-1] ENST00000597379; ENSP00000469630; ENSG00000167755 [Q92876-3] ENST00000599881; ENSP00000471948; ENSG00000167755 [Q92876-3] |
GeneIDi | 5653 |
KEGGi | hsa:5653 |
UCSCi | uc002pui.4, human [Q92876-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U62801 mRNA Translation: AAB07113.1 D78203 mRNA Translation: BAA11306.1 AF013988 mRNA Translation: AAB66483.1 AF149289 Genomic DNA Translation: AAD51475.1 AF243527 Genomic DNA Translation: AAG33359.1 AY318867 mRNA Translation: AAP82446.1 AY318868 mRNA No translation available. AY318869 mRNA Translation: AAP82448.1 AY318870 mRNA No translation available. DQ223012 mRNA Translation: ABB04464.1 AK314897 mRNA Translation: BAG37411.1 BT006852 mRNA Translation: AAP35498.1 AC011483 Genomic DNA No translation available. CH471135 Genomic DNA Translation: EAW71953.1 CH471135 Genomic DNA Translation: EAW71954.1 BC015525 mRNA Translation: AAH15525.1 |
CCDSi | CCDS12811.1 [Q92876-1] CCDS42599.1 [Q92876-2] |
RefSeqi | NP_001012982.1, NM_001012964.2 [Q92876-1] NP_001012983.1, NM_001012965.2 [Q92876-2] NP_001306877.1, NM_001319948.1 [Q92876-2] NP_001306878.1, NM_001319949.1 [Q92876-2] NP_002765.1, NM_002774.3 [Q92876-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1GVL | X-ray | 1.80 | A | 21-243 | [»] | |
1L2E | X-ray | 1.75 | A | 22-244 | [»] | |
1LO6 | X-ray | 1.56 | A | 22-244 | [»] | |
3VFE | X-ray | 1.88 | A | 22-244 | [»] | |
4D8N | X-ray | 1.68 | A | 22-244 | [»] | |
5NX1 | X-ray | 1.85 | A | 22-244 | [»] | |
5NX3 | X-ray | 2.30 | A | 22-244 | [»] | |
6QFF | X-ray | 1.64 | A/B | 22-243 | [»] | |
6QFG | X-ray | 1.68 | A/B | 22-244 | [»] | |
6QFH | X-ray | 1.65 | A/B | 22-243 | [»] | |
6QH9 | X-ray | 2.27 | A/B | 22-244 | [»] | |
6QHA | X-ray | 1.82 | A/B | 22-244 | [»] | |
6QHB | X-ray | 1.84 | A/B | 22-244 | [»] | |
6QHC | X-ray | 1.87 | A/B | 22-244 | [»] | |
6SKB | X-ray | 1.84 | A/B/C | 12-244 | [»] | |
6SKC | X-ray | 2.18 | A/B | 22-244 | [»] | |
6SKD | X-ray | 2.26 | A/B | 22-244 | [»] | |
SMRi | Q92876 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 111634, 12 interactors |
IntActi | Q92876, 169 interactors |
MINTi | Q92876 |
STRINGi | 9606.ENSP00000366047 |
Chemistry databases
BindingDBi | Q92876 |
ChEMBLi | CHEMBL4448 |
DrugBanki | DB03127, Benzamidine |
GuidetoPHARMACOLOGYi | 2376 |
Protein family/group databases
MEROPSi | S01.236 |
PTM databases
GlyGeni | Q92876, 1 site, 15 N-linked glycans (1 site) |
PhosphoSitePlusi | Q92876 |
Genetic variation databases
BioMutai | KLK6 |
DMDMi | 3914480 |
Proteomic databases
EPDi | Q92876 |
jPOSTi | Q92876 |
MassIVEi | Q92876 |
MaxQBi | Q92876 |
PaxDbi | Q92876 |
PeptideAtlasi | Q92876 |
PRIDEi | Q92876 |
ProteomicsDBi | 75559 [Q92876-1] 75560 [Q92876-2] 75561 [Q92876-3] |
Protocols and materials databases
Antibodypediai | 32402, 345 antibodies |
DNASUi | 5653 |
Genome annotation databases
Ensembli | ENST00000310157; ENSP00000309148; ENSG00000167755 [Q92876-1] ENST00000376851; ENSP00000366047; ENSG00000167755 [Q92876-1] ENST00000391808; ENSP00000375684; ENSG00000167755 [Q92876-2] ENST00000594641; ENSP00000470482; ENSG00000167755 [Q92876-1] ENST00000597379; ENSP00000469630; ENSG00000167755 [Q92876-3] ENST00000599881; ENSP00000471948; ENSG00000167755 [Q92876-3] |
GeneIDi | 5653 |
KEGGi | hsa:5653 |
UCSCi | uc002pui.4, human [Q92876-1] |
Organism-specific databases
CTDi | 5653 |
DisGeNETi | 5653 |
GeneCardsi | KLK6 |
HGNCi | HGNC:6367, KLK6 |
HPAi | ENSG00000167755, Tissue enhanced (brain, esophagus) |
MIMi | 602652, gene |
neXtProti | NX_Q92876 |
OpenTargetsi | ENSG00000167755 |
PharmGKBi | PA30156 |
VEuPathDBi | HostDB:ENSG00000167755.13 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3627, Eukaryota |
GeneTreei | ENSGT00990000203560 |
HOGENOMi | CLU_006842_1_1_1 |
InParanoidi | Q92876 |
OMAi | HTSCHIL |
PhylomeDBi | Q92876 |
TreeFami | TF331065 |
Enzyme and pathway databases
BRENDAi | 3.4.21.104, 2681 3.4.21.34, 2681 3.4.21.B10, 2681 |
PathwayCommonsi | Q92876 |
SABIO-RKi | Q92876 |
Miscellaneous databases
BioGRID-ORCSi | 5653, 9 hits in 880 CRISPR screens |
ChiTaRSi | KLK6, human |
EvolutionaryTracei | Q92876 |
GeneWikii | KLK6 |
GenomeRNAii | 5653 |
Pharosi | Q92876, Tchem |
PROi | PR:Q92876 |
RNActi | Q92876, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000167755, Expressed in C1 segment of cervical spinal cord and 154 other tissues |
ExpressionAtlasi | Q92876, baseline and differential |
Genevisiblei | Q92876, 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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | KLK6_HUMAN | |
Accessioni | Q92876Primary (citable) accession number: Q92876 Secondary accession number(s): A6NJA1, A8MW09, Q6H301 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 15, 1998 |
Last sequence update: | February 1, 1997 | |
Last modified: | February 10, 2021 | |
This is version 182 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, Direct protein sequencing, Reference proteomeDocuments
- 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 - 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 - Peptidase families
Classification of peptidase families and list of entries