GZMK

What is GZMK Protein?

Granzyme K (GZMK) is a protein made by immune cells like natural killer (NK) and cytotoxic T cells. It belongs to the serine protease family, important for the immune system's fight against infections and cancer. GZMK enters target cells to trigger cell death, helping clear out infected or cancerous cells. Higher levels of GZMK are linked to improved outcomes in certain cancers. It’s more common in cells with immune experience, indicating a more mature response. Scientists are studying GZMK to grasp its role in immunity and its potential in cancer therapy, aiming to harness the body's natural defenses.

What is the Function of GZMK Protein?

Granzyme K (GZMK) helps the immune system destroy harmful cells like infected or cancerous ones. Made by cells like NK and cytotoxic T cells, GZMK enters these problematic cells and triggers processes that lead to their death, aiding in clearing threats from the body. It’s also linked to better results in some cancers, which makes it a focus in cancer research aiming to use the immune system as a treatment tool. Its distinct function among other granzymes indicates a special role in fine-tuning immune responses and dealing with diseases.

GZMK Related Signaling Pathway

Granzyme K (GZMK) is crucial in immune pathways that target viruses and cancer cells. Released by NK and cytotoxic T cells, GZMK enters target cells to trigger apoptosis, helping eliminate harmful cells safely. It's also part of wider immune signaling that activates other immune cells and promotes inflammation, directing defense efforts to needed areas. Exploring GZMK-related pathways is enhancing understanding, offering insights for therapies to boost natural immune responses against cancer and other diseases.

GZMK Related Diseases

Granzyme K (GZMK) has been linked to various diseases, especially those involving immune system dysfunctions, such as certain autoimmune diseases and some types of cancer. This enzyme, which belongs to the granzyme family and is housed in cytotoxic cells like T-cells and natural killer (NK) cells, plays a pivotal role in initiating apoptosis in target cells. Dysregulation of GZMK has been observed in conditions like rheumatoid arthritis, where the immune system mistakenly attacks joint tissues. In cancers, particularly hematological malignancies, aberrant expression of granzyme K can influence tumor cell proliferation and resistance to therapies. Research has also indicated its potential involvement in chronic inflammatory diseases and viral infections. As a key player in immune response, understanding GZMK's mechanism can aid in developing targeted therapies and improve our grasp on immune regulation, making it a topic of significant interest in immunology and oncology research circles.

Bioapplications of GZMK

Granzyme K (GZMK) is really catching the attention of researchers who see its cool bioapplications, especially in cancer therapy. Think about it: GZMK helps kill off bad cells like viruses and cancer cells naturally. This ability is being looked at for designing drugs that can aim right at cancer cells and avoid harming the healthy ones—kinda like precision strikes. These smart therapies could lessen the side effects common with chemotherapy by being more selective. Also, because GZMK influences how the immune system reacts, it's being explored for new ways to treat autoimmune diseases, where a balance in immune attack is super important. By digging deeper into what GZMK does and how it does it, scientists hope to open new paths in treatment, making it a hot topic in the biotech world.

Case Study 1: Richardson KC. et al. Front Immunol. 2024

Psoriasis causes itchy, red, and scaly patches on the skin. It's tied to the IL-23/IL-17 pathway, and blocking this pathway can help manage the disease. An enzyme called Granzyme K (GzmK) from immune cells is found in higher levels in psoriasis-affected skin. In psoriasis mouse models, removing GzmK eased symptoms, causing less skin redness and fewer plaques. Studies show GzmK prompts inflammation and boosts skin cell growth, making psoriasis worse.

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  Fig1. Western blot immunodetection of GzmK.
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  Fig2. IL-23 gene expression analyzed by RT-PCR in THP-1 macrophages ± GzmK exposure.

Case Study 2: Duquette D. et al. J Immunol. 2023

NK and CD8 T cells attack infected or tumor cells using molecules like granzyme K (GzmK), which is promising for cancer prognosis. Found in certain lymphocytes, GzmK levels rise with immune experience, absent in newborns. These cells, linked to memory, decrease in GzmK when TCR-triggered, as GzmB rises. GzmK+ cells, less in IFN-γ than GzmB+ cells, might be memory-like. They're in the liver, fat, and found in colorectal cancer tumors, producing IFN-γ without IL-17a.

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  Fig3. Percent of memory subsets TN, TCM, TE, and TEMRA in adult human CD8 non-MAIT cells by GzmK/GzmB quadrant subset.
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  Fig4. Summary graphs show percent of GzmK+ and GzmB+ cells in CD45+ lymphocytes.

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  Fig1. Mechanism for GZMK action on experimental RA-SFs. (Liting Xu, 2024)
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  Fig2. Mechanism of GzmK in impaired thermal injury repair. (Christopher T Turner, 2019)

GZMK has several biochemical functions, for example, serine-type endopeptidase activity,serine-type peptidase activity. Some of the functions are cooperated with other proteins, some of the functions could acted by GZMK itself. We selected most functions GZMK had, and list some proteins which have the same functions with GZMK. You can find most of the proteins on our site.

Function	Related Protein
serine-type endopeptidase activity	PRSS37,RHBDL3,MMP8,C1rb,ST14B,MCPT2,PROCA,KLK12,KLK1B16,TMPRSS5
serine-type peptidase activity	PRTN3,FURINB,DPP6B,KLK1B22,MCPT9,CFD,RBP3,DPP7,SEC11C,TPP1

GZMK has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with GZMK here. Most of them are supplied by our site. Hope this information will be useful for your research of GZMK.

LIG4;PNKP