What is the Difference Between H-ras K-ras and N-ras

The key difference between H-ras K-ras and N-ras is the position of the respective gene responsible for the protein. The gene for H-ras is located in chromosome 11 while K-ras is located in chromosome 12, and N-ras is located in chromosome 1.

RAS proteins are a group of proteins that aid in the activation of cell signaling transduction mechanisms that are responsible for cell cycle activation. RAS proteins can activate the signal cascade that finally activates transcription to aid in cell cycle progression. Thus, H-ras, K-ras, and N-ras act as GTPases.

CONTENTS

1. Overview and Key Difference
2. What is H-ras
3. What is K-ras
4. What is N-ras
5. Similarities – H-ras K-ras and N-ras
6. H-ras vs K-ras vs N-ras in Tabular Form
7. Summary – H-ras vs K-ras vs N-ras

What is H-ras?

H-ras, derived from Harvey Rat sarcoma virus, is an enzyme also known as the transforming protein P21. HRAS gene codes this protein. This gene is located in the p arm of the 11^th chromosome. The H-ras protein is involved in activating the MAP – K pathway upon binding to GTP. Therefore, it is also known as GTPase H-ras. The main function of H-ras is to regulate cell division. The activity is H-ras is in response to growth factor stimulation. The activation of H-ras creates a signal cascade mechanism that promotes cell proliferation. The binding of H-ras protein takes place at the cell membrane. Following this binding, the signal transduction pathway is activated.

Mutations in the HRAS gene can lead to the onset of cancers as it acts as a proto-oncogene. Therefore, following mutations, normal cells are converted to cancerous cells. HRAS mutations are commonly observed in the bladder, thyroid, salivary duct carcinoma, epithelial-myoepithelial carcinoma, and kidney cancers.

What is K-ras?

K-ras, derived from the Kirsten rat sarcoma virus, is a protein that can act as a GTPase to mediate cell signal mechanisms to activate the RAS/MAPK pathway. This protein belongs to the p21 group of proteins. It mainly helps in signaling for cell proliferation, differentiation, and maturation of specialized cells.

K-ras protein acts as a nuclear signal. The K-ras gene undergoes alternative splicing to produce two gene products – K-ras4A and K-ras4B.  K-ras plays an important role in activating signal transduction mechanisms in glucose regulation as well. Mutations in the K-ras gene can also lead to cancers such as lung cancers and colorectal cancers as it acts as a proto-oncogene.

What is N-ras?

N-ras, derived from the neuroblastoma cells, is also a type of protein that belongs to the GTPase group of proteins. N-ras also helps in activating the signal transduction mechanism and the signal cascade belonging to the activation of the RASK pathway. Thus, the main function is to aid the normal cell cycle control.

The N-ras gene that is responsible for encoding the protein specifies two transcripts through alternate splicing. The main difference is based on the C terminal amino acids of the two products. N-ras is also a proto-oncogene and, therefore upon mutations, may lead to the onset of cancers of the melanoma type.

What are the Similarities Between H-ras K-ras and N-ras?

• H-ras K-ras and N-ras are proteins of the RAS group of proteins.
• They are GTPase proteins.
• Moreover, all three genes can act as proto-oncogenes to facilitate the onset of cancer.
• All three proteins activate the signal transduction mechanisms through the activation of signal cascades.
• They help the activation of the MAPK pathway.
• All three proteins regulate the cell cycle, proliferation, differentiation, and maturation of cells.
• Mutations in all three proteins can be diagnosed through genomics, transcriptomics, or proteomics studies.

What is the Difference Between H-ras K-ras and N-ras?

While all three proteins H-ras, K-ras, and N-ras, belong to the same group of RAS proteins, the key difference between H-ras K-ras and N-ras is in the position of the gene. The gene for H-ras is located in chromosome 11 while K-ras is located in chromosome 12, and N-ras is located in chromosome 1. Another difference between H-ras K-ras and N-ras is that K-ras and N-ras primarily show alternate variant forms due to alternate splicing while H -ras does not show any.

The below infographic presents the differences between H-ras K-ras and N-ras in tabular form for side by side comparison.

Summary – H-ras vs K-ras vs N-ras

The diversity of RAS family proteins increases the importance of studying these proteins under varying conditions. The key difference between H-ras K-ras and N-ras is based on their respective gene locations. The genes of H-ras, K-ras, and N-ras are located in the chromosomes 11, 12, and 1, respectively. Thus, H-ras is derived from Harvey rat sarcoma virus, K-ras is derived from Kirsten rat sarcoma virus, and N-ras is derived from neuroblastoma cells in humans. However, all three proteins perform the same function in acting as a GTPase protein in activating cell signaling pathways. However, due to the diversity of the ras proteins, following the mutations, they give rise to different cancer mechanisms. So, this summarizes the difference between H-ras K-ras and N-ras.

Reference:

1. Castellano, Esther, and Eugenio Santos. “Functional Specificity of RAS Isoforms: So Similar but so Different.” Genes & Cancer, SAGE Publications, Mar. 2011.

Image Courtesy:

1. “Hras surface colored by conservation” By ElaineMeng – Own work (CC BY-SA 3.0) via Commons Wikimedia
2. “KRAS2008” By Healthvalue2Tony Marcel, MD – Own work (CC BY 3.0) via Commons Wikimedia
3. “Protein NRAS PDB 121p” By Emw – Own work (CC BY-SA 3.0) via Commons Wikimedia