SMARCD2

What is SMARCD2 protein?

SMARCD2 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 2) gene is a protein coding gene which situated on the long arm of chromosome 17 at locus 17q23. The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose members display helicase and ATPase activities and which are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI and has sequence similarity to the yeast Swp73 protein. The SMARCD2 protein is consisted of 531 amino acids and its molecular mass is approximately 58.9 kDa.

What is the function of SMARCD2 protein?

The SMARCD2 protein, also known as SNF2L or BAF60b, is a subunit of the ATP-dependent SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin-remodeling complexes. These complexes play a crucial role in various cellular processes through their ability to remodel chromatin structure, which affects gene expression. SMARCD2-containing SWI/SNF complexes use the energy from ATP hydrolysis to alter chromatin structure, which allows or inhibits the access of transcription factors to DNA, thereby regulating gene expression. SMARCD2 is essential for the development of granulocytes, which include neutrophils and eosinophils. SMARCD2 is necessary for the recruitment of the CEBPɛ transcription factor to the promoter of neutrophilic secondary granule genes, which is critical for granulocyte differentiation.

Fig1. Activation of SMARCD2 and its functions under physiological or pathological conditions. (Shuyi Ji, 2017)

SMARCD2 Related Signaling Pathway

SMARCD2, also known as SNF2L or BAF60b, is a subunit of the SWI/SNF chromatin remodeling complex, which plays a role in various cellular processes by altering chromatin structure and influencing gene expression. Although not directly mentioned in the search results, the JAK/STAT pathway, which is involved in cytokine signaling and immune cell differentiation, could potentially intersect with SMARCD2 function, given the role of the SWI/SNF complex in immune cell development. The SWI/SNF complex, including SMARCD2, may also interact with signal transduction pathways that transmit extracellular signals to the nucleus, leading to changes in gene expression.

SMARCD2 Related Diseases

Mutations in the SMARCD2 gene are associated with Specific Granule Deficiency 2, a rare genetic disorder characterized by the lack of secondary granules in neutrophils, leading to recurrent infections. SMARCD2 has been implicated in various cancers, where it may play a role in tumor progression or serve as a potential therapeutic target. Loss-of-function mutations in both CEBPE and SMARCD2 identified in patients with SGD disrupt the interaction with SWI/SNF complexes and secondary granule gene expression, providing a molecular basis for the disease.

Bioapplications of SMARCD2

SMARCD2's interaction with various proteins could be studied in a proteomics context to understand its network within the cell and its influence on cellular pathways. As mentioned in the search results, the targeting of SMARCD2 or related proteins for degradation using protein degradation techniques like PROTACs could be a strategy in cancer treatment. SMARCD2 could be a target for small molecule drugs or other therapeutics that modulate its activity, with potential applications in treating diseases where its function is impaired.

Case Study 1: Maximilian Witzel, 2017

The researchers identify SMARCD2 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily D, member 2), also known as BAF60b (BRG1/Brahma-associated factor 60b), as a critical regulator of myeloid differentiation in humans, mice, and zebrafish. Studying patients from three unrelated pedigrees characterized by neutropenia, specific granule deficiency, myelodysplasia with excess of blast cells, and various developmental aberrations, they identified three homozygous loss-of-function mutations in SMARCD2. Using mice and zebrafish as model systems, they showed that SMARCD2 controls early steps in the differentiation of myeloid-erythroid progenitor cells. In vitro, SMARCD2 interacts with the transcription factor CEBPɛ and controls expression of neutrophil proteins stored in specific granules. Defective expression of SMARCD2 leads to transcriptional and chromatin changes in acute myeloid leukemia (AML) human promyelocytic cells.

Fig1. Immunoblot showing absence of SMARCD2 protein expression (molecular weight, 58.9 kDa; arrowhead).

Fig2. Enumeration of neutrophils in smarcd2wt/wt versus smarcd21/1 zebrafish.

Case Study 2: Pierre Priam, 2017

Recent studies suggest that individual subunits of chromatin-remodeling complexes produce biologically specific meaning in different cell types through combinatorial assembly. Here the researchers show that granulocyte development requires SMARCD2, a subunit of ATP-dependent SWI/SNF (BAF) chromatin-remodeling complexes. Smarcd2-deficient mice fail to generate functionally mature neutrophils and eosinophils, a phenotype reminiscent of neutrophil-specific granule deficiency (SGD) in humans, for which loss-of-function mutations in CEBPE (encoding CEBPɛ) have been reported. SMARCD2-containing SWI/SNF complexes are necessary for CEBPɛ transcription factor recruitment to the promoter of neutrophilic secondary granule genes and for granulocyte differentiation. The homologous SMARCD1 protein (63% identical at the amino acid level) cannot replace the role of SMARCD2 in granulocyte development. They find that SMARCD2 functional specificity is conferred by its divergent coiled-coil 1 and SWIB domains. Strikingly, both CEBPE and SMARCD2 loss-of-function mutations identified in patients with SGD abolish the interaction with SWI/SNF and thereby secondary granule gene expression, thus providing a molecular basis for this disease.

Fig3. SMARCD2 can rescue the granulocyte differentiation defect of Smarcd2-deficient E14.5 fetal liver cells.

Fig4. SMARCD2 interacts with CEBPɛ in NIH/3T3 cells.

SMARCD2 has several biochemical functions, for example, . Some of the functions are cooperated with other proteins, some of the functions could acted by SMARCD2 itself. We selected most functions SMARCD2 had, and list some proteins which have the same functions with SMARCD2. You can find most of the proteins on our site.

SMARCD2 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 SMARCD2 here. Most of them are supplied by our site. Hope this information will be useful for your research of SMARCD2.