Structural maintenance of chromosomes protein 4 (SMC-4) also known as chromosome-associated polypeptide C (CAP-C) or XCAP-C homolog is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''SMC4''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. SMC-4 is a core subunit of

condensin Condensins are large protein complexes that play a central role in chromosome condensation and segregation during mitosis and meiosis (Figure 1). Their subunits were originally identified as major components of mitotic chromosomes assembled in ' ...

I and II, large protein complexes involved in high order chromosome organization, including condensation and segregation. SMC-4 protein is commonly associated with the SMC-2 protein, another protein complex within the SMC protein family. SMC-4 dimerizes with SMC-2, creating the flexible and dynamic structure of the condensin holocomplex. An over-expression of the SMC-4 protein is shown to impact

carcinogenesis Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cell (biology), cells are malignant transformation, transformed into cancer cells. The process is characterized by changes at the cellular, G ...

Structure and interactions

The primary 5 domain structure of SMC proteins is highly conserved among species. The basic structure of SMC proteins are characterized by a non-helical hinge group, separated by two anti-parallel α-helical

coiled-coil A coiled coil is a structural motif in proteins in which two to seven alpha-helices are coiled together like the strands of a rope. ( Dimers and trimers are the most common types.) They have been found in roughly 5-10% of proteins and have a v ...

domains, along with two Amino-terminal globular domains containing ATP hydrolytic sites, or nucleotide-binding motifs located at the

C-terminus The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein Proteins are large biomolecules and macromolecules that comp ...

and

N-terminus The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

called the Walker A and Walker B motifs. In

eukaryote The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...

dimerization In chemistry, dimerization is the process of joining two identical or similar molecular entities by bonds. The resulting bonds can be either strong or weak. Many symmetrical chemical species are described as dimers, even when the monomer is u ...

is mediated by the self-folding of the non-helical hinge group on the SMC protein. Dimerization occurs at the non-helical hinge group of SMC-4, which then associates with the non-helical hinge group of SMC-2, creating a V-shaped

heterodimeric In biochemistry, a protein dimer is a macromolecular complex or multimer formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ...

structure. the holocomplex of condensin contains the SMC-4 and SMC-2 heterodimer subunits, along with 3 other non-SMC subunits, CAP-D2, CAP-G, and CAP-H. In the condensin holocomplex, a protein subunit called kleisin joins the C-terminus and N-terminus

ATPase ATPases (, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, ATP hydrolase, adenosine triphosphatase) are a class of enzymes that catalyze the decomposition of ATP into ADP and a free phosphate ion or ...

end domains of both SMC-4 and SMC-2 proteins. when the condensin holocomplex is bound with ATP at these end domains, the condensin will assume a "closed" conformation state. SMC-4 is a dynamic and flexible protein, allowing different domain components to occasionally interact with others. This is speculated to be involved in the mechanical ability of the complex when associated with chromosomes. In budding yeast, these interactions may result in open "O" appearances, or collapsed B-shaped states as a result of its dynamic ability.

Clinical significance

The SMC-4 protein is associated with abnormal cell and tumor growth, and involved with migration and invasion. In general, the presence of over-expressed SMC-4 proteins is thought to be correlated with

. It is found that an over-expression or down-regulation of the SMC-4 protein alters TGFβ/Smad signaling pathways in glioma cells. SMC-4-transduced glioma cells showed activation of the TGFβ/Smad signaling pathway which was not present in SMC-4 silenced glioma cells. This pathway was shown to be correlated with an "aggressive" behavioral phenotype in glioma cells. An over-expression of SMC-4 can induce a higher rate of proliferation, and ultimately increased invasive capability. A down-regulation of SMC-4 reduced this quality. The SMC-4 protein is involved with normal lung development however, adenocarcinoma lung tissue shows an over-expression of SMC-4. additionally, SMC-4 may act as independent prognostic factor for

and lung adenocarcinoma. Studies suggest that over-expression of the SMC-4 protein in human liver tissue may be correlated with progression of

hepatocellular carcinoma Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide. HCC most common ...

References

External links

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PDBe-KB
provides an overview of all the structure information available in the PDB for Human Structural maintenance of chromosomes protein 4 (SMC4)
PDBe-KB
provides an overview of all the structure information available in the PDB for Mouse Structural maintenance of chromosomes protein 4 (SMC4) {{Nucleus

Structure and interactions

Clinical significance

References

Further reading

External links