SMARCD3

What is SMARCD3 Protein?

SMARCD3, also referred to as BAF60C, is a protein encoded by the SMARCD3 gene in humans. This protein is part of the SWI/SNF family known for its role in chromatin remodeling—a critical process in gene expression regulation. These proteins, including SMARCD3, possess helicase and ATPase activities, allowing them to change the structure of chromatin to control which genes are turned on or off. SMARCD3 helps form the SNF/SWI complex, sharing similarities in sequence with the yeast protein Swp73. Interestingly, there are several transcript variants of SMARCD3, each of which can be switched in or out of the complex to guide its remodeling role to specific chromatin sites. This versatility affects gene activity, influencing cell development, behavior, and even its role in diseases. Additionally, SMARCD3 works alongside TBX15 to spur the development of glycolytic fast-twitch muscles via the activation of the Akt/PKB signaling pathway, underlining its diverse functions in biological processes.

What is the Function of SMARCD3 Protein?

SMARCD3, sometimes called BAF60C, has a pretty important job in our cells. It’s a part of the SWI/SNF family, which is all about managing chromatin—the material that makes up chromosomes. Basically, chromatin structure affects whether specific genes are active or not. SMARCD3 plays a vital role by helping to shuffle around nucleosomes, which are the spools that DNA winds around. By doing this, it can change how accessible parts of the DNA are to be read and expressed as proteins. This action is powered by ATP, a kind of energy currency in cells. SMARCD3 shares traits with the yeast protein Swp73 and can exist in multiple forms thanks to different splicing options. These forms allow it to tailor its effects, impacting cell growth, differentiation, and their role in diseases. It's also involved in muscle development through a pathway known as Akt/PKB. Essentially, SMARCD3 is like a switch operator, flipping genetic switches to make sure everything’s running smoothly.

SMARCD3 Related Signaling Pathway

SMARCD3, also known as BAF60C, connects with the Akt/PKB signaling pathway, which is crucial for things like cell growth and survival. In this pathway, SMARCD3 helps activate signals that are important for developing fast-twitch muscle fibers, the kind needed for quick and intense movements. Think about when you sprint or lift heavy weights—these are the muscles that kick in. SMARCD3 essentially acts like a conductor, ensuring the right signals are sent out to encourage muscle growth and adaptation. By interacting with other proteins, it helps cells know when to grow or change, which is essential for muscles to become stronger and more efficient. It's like the body's way of sending a memo to beef up muscles when they're needed most.

SMARCD3 Related Diseases

If SMARCD3, also known as BAF60C, isn't working right, it can cause a few health issues. Because it's involved in gene regulation and muscle development, problems with SMARCD3 can lead to muscle disorders. It has a hand in telling muscle cells how to grow and what type of muscle fiber to become, so any hiccups can mess with muscle function. Moreover, since SMARCD3 is part of the machinery that controls which genes are active or silent, issues here might contribute to certain types of cancer or developmental problems. When SMARCD3 can't do its job properly, the balance of growth and differentiation gets disturbed, which can lead to cells not forming tissues correctly or growing too much, thus causing health complications.

Bioapplications of SMARCD3

SMARCD3, or BAF60C, offers some exciting bioapplications because of its role in gene regulation and muscle development. In the world of muscle research, it's pretty valuable for understanding how muscles grow and repair, helping scientists develop treatments for muscle-wasting disorders. By figuring out how SMARCD3 influences muscle cell differentiation and growth, researchers can craft strategies to boost muscle regeneration in conditions like muscular dystrophy. Additionally, because it’s involved in chromatin remodeling, SMARCD3 is a target for cancer research. It helps in studying how changes in gene expression contribute to cancer progression, which could lead to new therapies by targeting the pathways SMARCD3 is part of. Essentially, this protein serves as a gateway for potentially controlling or correcting cellular developments that go awry, making it a key player in both therapeutic and regenerative medicine fields.

Case Study 1: Jordan NV. et al. Mol Cell Biol. 2013

Researchers identified a gene signature tied to EMT in stem and breast cancer cells. RNA interference revealed 10 genes helping revert certain breast cancer cells to an epithelial state. Smarcd3/Baf60c, when knocked down, strongly promoted this shift. In contrast, adding it to normal mammary cells triggered EMT, mirroring changes in tough breast cancer types and increasing Wnt5a expression. Blocking Wnt5a reversed this EMT, showing Smarcd3/Baf60c influences EMT through WNT signaling activation.

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  Fig1. Expression of Smarcd3/Baf60c in HMECs at levels comparable to those in EpCAM- SUM149 cells.
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  Fig2. Elevated gene expression of mesenchymal markers N-cadherin, vimentin, and Smarcd3/Baf60c in Snail-, Slug-, and D3-HMECs measured by qRT-PCR.

Case Study 2: Wang Y. et al. Mol Cell. 2013

Fatty acid and triglyceride production increase after eating and with insulin. This requires activating enzymes like fatty acid synthase. BAF60c plays a crucial role here, helping turn on fat-related genes in the liver. Insulin triggers BAF60c's phosphorylation by PKCζ/λ, moving it to the nucleus to interact with modified USF-1, forming the lipoBAF complex. This complex changes chromatin to boost lipogenic genes, raising fat production and triglyceride levels in response to food and insulin.

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  Fig3. GST-USF-1 fusion protein was used for pull-down of BAF60c using glutathione beads.
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  Fig4. In vitro translated wild type or S247A mutant BAF60c were in vitro phosphorylated before immunoblotting.

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  Fig1. Summary of SMARCD3 interaction network. (Ming Jiang, 2020)
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  Fig2. Insulin signaling pathway for posttranslational modifications of BAF60c and USF-1 in chromatin remodeling and activation of lipogenic genes. (Yuhui Wang, 2013)

SMARCD3 has several biochemical functions, for example, chromatin binding,ligand-dependent nuclear receptor binding,ligand-dependent nuclear receptor transcription coactivator activity. Some of the functions are cooperated with other proteins, some of the functions could acted by SMARCD3 itself. We selected most functions SMARCD3 had, and list some proteins which have the same functions with SMARCD3. You can find most of the proteins on our site.

Function	Related Protein
ligand-dependent nuclear receptor transcription coactivator activity	LRP2BP,PSMC3IP,RBM14,HELZ2,DCAF6,CCDC62,ZCCHC18,PRKCBB,WDR77,MED14
ligand-dependent nuclear receptor binding	MED1,ISL1,NCOR1,UBA3,C1D,BAZ2A,JUND,NCOA2,NCOA1,ARID1A
chromatin binding	ORC1L,SMARCE1,SIX1,SIN3B,OST4,TAF2,MEN1,SSBP1,JUB,DNMT3B
receptor binding	PKD2,HLA-A,TIGIT,ECI2,CSK,ARPP19,AGXT,NPPC,NXPH3,SERPINE2
nuclear hormone receptor binding	CRY1,HIF1A,NCOR1,TCF7L2,NRIP1,CRX,NCOA1,NCOA2,TACC2,CTNNB1
transcription factor binding	MYOCD,ARHGEF2,MED25,PIM1,TRIB2,TFDP2,HEY2,TNFRSF10A,FIGLA,NKX3-1
protein binding	NMRK1,DDX31,AVPI1,TRIP6,BET1,EMG1,HIRIP3,UBE2Z,SNCG,C19orf47

SMARCD3 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 SMARCD3 here. Most of them are supplied by our site. Hope this information will be useful for your research of SMARCD3.

Myod1;Smarca4;Akirin2