KLK6 Protein

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KLK6 Protein

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KLK6 Protein

title: KLK6 Protein
<div class="infobox infobox-protein"> [@blaber2002]
<table> [@diamandis2004]
<tr><th>Protein Name</th><td>Kallikrein 6 (Protease M)</td></tr> [@zarghi2018]
<tr><th>Gene</th><td>[KLK6](/genes/klk6)</td></tr> [@okada2010]
<tr><th>UniProt ID</th><td>[Q92815](https://www.uniprot.org/uniprot/Q92815)</td></tr> [@mitsui2019]
<tr><th>PDB Structure</</th><td>1L2E, 2PMN</td></tr>
<tr><th>Molecular Weight</th><td>251 aa (27 kDa)</td></tr>
<tr><th>Subcellular Localization</th><td>Secreted, extracellular</td></tr>
<tr><th>Protein Family</th><td>Trypsin-like serine protease family, Kallikreins</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

KLK6 Protein (Kallikrein 6)

Overview

Klk6 Protein plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.

Introduction

Kallikrein 6 (KLK6), also known as protease M or neurosin, is a member of the kallikrein family of serine proteases. It is expressed in various tissues including the brain, spinal cord, and peripheral nervous system. KLK6 has been implicated in neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, and multiple system atrophy (MSA), where it plays roles in protein processing, neuroinflammation, and [alpha-synuclein](/mechanisms/alpha-synuclein) metabolism.

Structure

...

KLK6 Protein

title: KLK6 Protein
<div class="infobox infobox-protein"> [@blaber2002]
<table> [@diamandis2004]
<tr><th>Protein Name</th><td>Kallikrein 6 (Protease M)</td></tr> [@zarghi2018]
<tr><th>Gene</th><td>[KLK6](/genes/klk6)</td></tr> [@okada2010]
<tr><th>UniProt ID</th><td>[Q92815](https://www.uniprot.org/uniprot/Q92815)</td></tr> [@mitsui2019]
<tr><th>PDB Structure</</th><td>1L2E, 2PMN</td></tr>
<tr><th>Molecular Weight</th><td>251 aa (27 kDa)</td></tr>
<tr><th>Subcellular Localization</th><td>Secreted, extracellular</td></tr>
<tr><th>Protein Family</th><td>Trypsin-like serine protease family, Kallikreins</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

KLK6 Protein (Kallikrein 6)

Overview

Klk6 Protein plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.

Introduction

Kallikrein 6 (KLK6), also known as protease M or neurosin, is a member of the kallikrein family of serine proteases. It is expressed in various tissues including the brain, spinal cord, and peripheral nervous system. KLK6 has been implicated in neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, and multiple system atrophy (MSA), where it plays roles in protein processing, neuroinflammation, and [alpha-synuclein](/mechanisms/alpha-synuclein) metabolism.

Structure

KLK6 has the characteristic structure of trypsin-like serine proteases:

Signal peptide (aa 1-17): Directs secretion
Propeptide (aa 18-25): Activation peptide removed by cleavage
Catalytic domain (aa 26-251): Serine protease active site
Active site residues: His57, Asp102, Ser195 (chymotrypsin numbering)

Structural Features

Catalytic triad: His-Asp-Ser protease mechanism
Disulfide bonds: 6 conserved cysteine residues
Glycosylation sites: N-linked carbohydrates

Normal Function

Proteolytic Activity

KLK6 is a broad-spectrum protease:

Extracellular matrix remodeling: Degrades ECM components
Cytokine processing: Activates/inactivates signaling molecules
Protein turnover: Cleaves misfolded proteins

Brain Expression

[Neurons](/entities/neurons): Moderate expression in cortical neurons
[Astrocytes](/entities/astrocytes): Higher expression in reactive astrocytes
[Microglia](/entities/microglia): Induced expression in activated [microglia](/cell-types/microglia-neuroinflammation)
Oligodendrocytes: Present in myelin sheaths

Physiological Roles

Myelin maintenance: Regulates myelin protein turnover
Synaptic plasticity: Modulates synaptic proteins
Neuroprotection: Cleaves toxic protein aggregates
Wound healing: Involved in tissue repair

Role in Disease

Parkinson's Disease (PD)

KLK6 is critically involved in PD pathogenesis:

[Alpha-synuclein](/proteins/alpha-synuclein) cleavage: KLK6 can cleave α-synuclein, affecting aggregation
Dysregulated expression: Altered levels in PD brains
Enzyme activity changes: Correlation with disease severity
Protective vs. pathogenic: Dual role in aggregation and clearance

Multiple System Atrophy (MSA)

Elevated expression: KLK6 increased in MSA brain tissue
Oligodendrocyte involvement: Role in glial cytoplasmic inclusions
Disease specificity: Potential biomarker

Alzheimer's Disease

Amyloid processing: Effects on [Aβ](/proteins/amyloid-beta) metabolism
[Tau](/proteins/tau) pathology: Interaction with tau protein
Neuroinflammation: Cytokine activation

Amyotrophic Lateral Sclerosis (ALS)

Motor neuron expression: Present in affected neurons
Proteolytic activity: Altered in disease
Potential biomarker: CSF levels as indicator

Enzyme Activity

Substrate Specificity

KLK6 prefers cleavage after:

Arginine (R)
Lysine (K)
Phenylalanine (F) to lesser extent

Key Substrates

| Substrate | Cleavage Effect |
|-----------|-----------------|
| α-Synuclein | Aggregation modulation |
| Myelin basic protein | Processing |
| Collagen | ECM degradation |
| Cytokines | Activation |

Therapeutic Implications

Drug Development

Inhibitors: KLK6-specific protease inhibitors
Activity modulators: Enhance beneficial cleavage
Biomarker potential: CSF/serum levels

Clinical Applications

Diagnostic markers: KLK6 in CSF
Disease progression: Correlation with severity
Treatment monitoring: Response indicators

Expression Patterns

Regional Distribution

Substantia nigra: Dopaminergic neurons
[Cortex](/brain-regions/cortex): Pyramidal neurons
Spinal cord: Motor neurons
Peripheral nerves: Sensory neurons

Cellular Localization

Neuronal soma and processes
Astrocytic processes
Microglial lysosomes
Oligodendrocyte cytoplasm

Animal Models

Knockout Studies

Klk6-deficient mice show subtle neurological phenotypes
Altered response to neurotoxic insults
Changes in protein aggregation models

Key Publications

[Bernett MJ, et al. (2004) KLK6 structure and function. J Biol Chem.](https://doi.org/10.1074/jbc.M403292200)

[Scarisbrick IA, et al. (2002) Kallikrein 6 in neurodegeneration. J Neurosci Res.](https://doi.org/10.1002/jnr.10340)

[Iwata A, et al. (2003) KLK6 and alpha-synuclein. J Biol Chem.](https://doi.org/10.1074/jbc.M306660200)

External Links

[UniProt Q92815](https://www.uniprot.org/uniprot/Q92815)
[RCSB PDB 1L2E](https://www.rcsb.org/structure/1L2E)
[NCBI Gene KLK6](https://www.ncbi.nlm.nih.gov/gene/5653)
[Allen Brain Atlas](https://human.brain-map.org/microarray/search/show?search_term=KLK6)

Overview

Klk6 Protein plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.

Background

The study of Klk6 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

References

[Bernett MJ, et al, (2004) (2004)](https://pubmed.ncbi.nlm.nih.gov/15123658/)

[Scarisbrick IA, et al, (2002) (2002)](https://pubmed.ncbi.nlm.nih.gov/12359135/)

[Iwata A, et al, (2003) (2003)](https://pubmed.ncbi.nlm.nih.gov/14527906/)

[Blaber M, et al, (2002) (2002)](https://pubmed.ncbi.nlm.nih.gov/12416974/)

[Diamandis EP, et al, (2004) (2004)](https://pubmed.ncbi.nlm.nih.gov/15046855/)

[Zarghi A, et al, (2018) (2018)](https://pubmed.ncbi.nlm.nih.gov/29530366/)

[Okada A, et al, (2010) (2010)](https://pubmed.ncbi.nlm.nih.gov/20063271/)

[Mitsui S, et al, (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/31178832/)

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Related Entities

KLK6PROTEIN

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slug	proteins-klk6-protein
kg_node_id	KLK6PROTEIN
entity_type	protein
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-8dbf26324efc
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'proteins-klk6-protein'}
_schema_version	1

📊 Evidence Profile

Evidence Balance

+0%

Certainty

45%

Debates

0

Incoming

9

Outgoing

10

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

KLK6 Protein

KLK6 Protein

KLK6 Protein (Kallikrein 6)

Overview

Introduction

Structure

KLK6 Protein

KLK6 Protein (Kallikrein 6)

Overview

Introduction

Structure

Structural Features

Normal Function

Proteolytic Activity

Brain Expression

Physiological Roles

Role in Disease

Parkinson's Disease (PD)

Multiple System Atrophy (MSA)

Alzheimer's Disease

Amyotrophic Lateral Sclerosis (ALS)

Enzyme Activity

Substrate Specificity

Key Substrates

Therapeutic Implications

Drug Development

Clinical Applications

Expression Patterns

Regional Distribution

Cellular Localization

Animal Models

Knockout Studies

Key Publications

See Also

External Links

Overview

Background

References

💬 Discussion