HBB

What is HBB Protein?

The HBB protein, also called hemoglobin subunit beta, is an essential part of hemoglobin, which carries oxygen in our blood. It's made by the HBB gene found on chromosome 11. This protein works with alpha globin to form hemoglobin A, the main type of hemoglobin in adults. HBB is crucial for transporting oxygen and influencing blood characteristics like clotting and pressure. Mutations in the HBB gene can lead to genetic disorders like sickle cell disease and beta thalassemia, but they may also provide some resistance to malaria. This dual role highlights HBB's complex impact on health and evolution.

What is the Function of HBB Protein?

The HBB protein plays a key role in hemoglobin, which is essential for transporting oxygen in our bloodstream. Hemoglobin consists of two alpha and two beta chains, and the HBB protein specifically helps capture oxygen in the lungs and deliver it throughout the body. It also assists in sending carbon dioxide back to the lungs for exhaling. Besides these functions, HBB is involved in the metabolism of glutathione and can serve as an indicator of anemia. Mutations in the HBB gene may lead to conditions like sickle cell disease or beta-thalassemia, which disrupt how hemoglobin works and can result in anemia. This protein is mostly found in red blood cells and could also indicate certain cancers, such as kidney renal clear cell carcinoma. We can identify HBB in blood samples through mass spectrometry, confirming its presence in plasma and serum.

HBB Related Signaling Pathway

The HBB protein plays a critical role in hemoglobin, the molecule responsible for carrying oxygen throughout the bloodstream. It captures oxygen in the lungs and delivers it to tissues, while also helping to expel carbon dioxide. Beyond this, HBB helps manage oxidative stress and acts as a marker for diseases such as anemia. When the HBB gene has mutations, it can result in blood-related disorders like sickle cell disease and beta-thalassemia. Primarily located in red blood cells, HBB is also associated with certain cancers. It can be detected in blood samples, underscoring its importance in both physiological functions and disease states.

HBB Related Diseases

HBB is associated with several health conditions, mainly blood disorders. Sickle cell disease is one of the most commonly known, where abnormal HBB leads to distorted red blood cells, causing pain and potential organ damage. Another important condition related to HBB is beta-thalassemia. This occurs when there isn't enough HBB produced, leading to anemia. Additionally, changes in the HBB gene can cause hemolytic anemia and other associated issues. While these conditions mainly affect how the blood works, they can also influence a person's overall health, demonstrating how crucial HBB is for maintaining good health.

Bioapplications of HBB

Another noteworthy condition associated with HBB is beta-thalassemia, which arises when HBB production is low, leading to anemia. Additionally, mutations in the HBB gene can cause hemolytic anemia and various related complications. While these disorders mainly affect blood functionality, they can also have a broader impact on overall health, emphasizing the crucial role that HBB plays in sustaining well-being.

Case Study 1: Xu X. et al. Technol Cancer Res Treat. 2024

Recent studies highlight that hemoglobin beta (HBB) is crucial in both blood disorders and cancers. In lung cancer, researchers assessed HBB's clinical and diagnostic significance. They found that HBB levels were lower in cancer tissues and pre-surgery plasma but higher post-surgery. HBB levels correlated with gender and cancer stages across 66 cases. Using ROC curves, HBB was confirmed to be a strong diagnostic marker for lung cancer, especially when combined with carcinoembryonic antigen (CEA). Altering HBB expression also impacted lung cancer cell growth via the ERK1/2 pathway.

• 
  Fig1. Comparison of plasma HBB levels between pre- and postoperative samples.
• 
  Fig2. Western blot demonstrated that the HBB level was significantly increased.

Case Study 2: Liu Y. et al. Sci China Life Sci. 2024

Chemoresistance is a big hurdle in cancer treatment, often caused by reactive oxygen species (ROS) and certain gene expressions. Researchers found that lncRNA16 plays a role in reducing ROS and affecting chemoresistance. In non-small cell lung cancer (NSCLC) patients, higher serum lncRNA16 was linked to poorer responses to platinum-based chemotherapy. This research showed that lncRNA16 boosts hemoglobin subunit beta (HBB) and NDUFAF5 levels, blocking autophagy and stopping ROS production by bringing HBB and NDUFAF5 together in mitochondria. Preclinical mouse tests suggest targeting lncRNA16 may restore chemo sensitivity and slow tumor growth, without significant toxicity.

• 
  Fig3. Western blot was performed to detect the effects of the combination of lncRNA16 knockdown with autophagy inhibition on HBB protein levels
• 
  Fig4. Co-IP was performed to investigate the effects of RNase treatment on the binding of HBB with NDUFAF5.

• 
  Fig1. Schematic diagram of lncRNA16 promoting chemoresistance and chemotherapeutic sensibilization exerted by lncRNA16 intervention via Nano silncRNA16. (Yanfang Liu, 2024)
• 
  Fig2. Pathways associated with erythrocytosis. (Jernej Gašperšič, 2021)

HBB has several biochemical functions, for example, contributes_to haptoglobin binding,heme binding,hemoglobin binding. Some of the functions are cooperated with other proteins, some of the functions could acted by HBB itself. We selected most functions HBB had, and list some proteins which have the same functions with HBB. You can find most of the proteins on our site.

Function	Related Protein
contributes_to peroxidase activity	HBA2,HBA-A2,HBA1
contributes_to haptoglobin binding	HBA1,HBA2,HBA-A2
oxygen transporter activity	CYGB,CYGB1,NGB,HBAA,HBBE3,HBB-BH1,HBE1,IPCEF1,HBG2,HBB-Y
iron ion binding	CYP2P8,CYP2C54,OGFOD1,CYP2K22,HBB-BH1,CYP19A1A,NFU1,CYP8B1,Scd1,MFI2
protein binding	DHX32,KLRB1B,RARS,BNIP3,DERL1,DDX18,ABLIM1,WLS,SMPDL3A,RAB11FIP2
oxygen binding	CYP2W1,CYP26A1,CYP3A4,CYP2D9,CYP2P10,CYP2R1,CYP2X7,CYP2K17,CYP2AA8,CYP2C39
hemoglobin binding	LRP2,CUBN,HP,HPR,AHSP
heme binding	CYP2J2,CYP3A25,CYP3A4,HBD,CYP11B2,CYP11A1,CYP3A43,CYP4A12A,DUOX2,CYP2C18

HBB 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 HBB here. Most of them are supplied by our site. Hope this information will be useful for your research of HBB.

HBA1