Structural maintenance of chromosomes protein 2 (SMC-2), also known as chromosome-associated protein E (CAP-E), is a protein that in humans is encoded by the SMC2gene.[5][6] SMC2 is part of the SMC protein family and is a core subunit of condensin I and II, large protein complexes involved in chromosome condensation, overall organization.[7] Several studies have demonstrated the necessity of SMC2 for cell division and proliferation.[8][9]
Structure
As one of the 6 Eukaryotic SMC proteins, SMC2 forms a heterodimer with SMC4 via their hinge domains. The heterodimer formed functions as a flexible and dynamic holocomplex core, which complexes with variant other non-SMC regulatory proteins to form condensin.[7] In condensin I, SMC2 complexes with CAP-H, CAP-D2, and CAP-G. In condensin II, SMC2 complexes with CAP-H2, CAP-D3, and CAP-G2. Subunits CAP-H and CAP-H2 are categorized as kleisin proteins, similar to Scc1 which is found in cohesin, while CAP-D2, CAP-G, CAP-D3, and CAP-G2 contain structural HEAT repeats.[10]
Structure of a condensin protein holocomplex, displaying the SMC-2/SMC-4 heterodimer, and additional subunits. Kleisin is also depicted (blue).
Function
SMC2 works in the condensin complex as transcriptional regulation by compacting replicated DNA prior to mitotic division via supercoiling of the DNA. SMC2 also functions in resolving Sister chromatids prior to Anaphase.[9]
Mutations in the SMC2 gene have been associated with a variety of human diseases, including Cornelia de Lange syndrome (CdLS), which is characterized by developmental abnormalities, cognitive impairment, and a range of physical abnormalities.[12] A study showed a deletion of a portion of the long arm of chromosome 9 (9q31.1-q32) causes symptoms similar to those found in patients with CdLS.[13] This deletion overlaps the gene encoding SMC2. Many mutations in a variety of different genes have been linked to CdLS, however around 30% of cases have not been linked to one of the known genes.[13] More research is being done to discover other causes for this syndrome.
Cancer
Other studies have suggested that alterations in SMC2 protein expression may be involved in the development and progression of cancer. Overexpression of SMC2 has been found to lead to tumorigenesis and malignancy. Now, some research studies are exploring inhibition of SMC2[14] as a potential therapeutic target for the treatment of cancer as the inhibition of SMC2 expression or activity can lead to the induction of cell death in cancer cells.
Ham MF, Takakuwa T, Rahadiani N, Tresnasari K, Nakajima H, Aozasa K (Jul 2007). "Condensin mutations and abnormal chromosomal structures in pyothorax-associated lymphoma". Cancer Science. 98 (7): 1041–7. doi:10.1111/j.1349-7006.2007.00500.x. PMID17488335. S2CID25888221.
Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC1847948. PMID17353931.
