SMC2 explained

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 SMC2 gene.^{[1] [2]} 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.^[3] Several studies have demonstrated the necessity of SMC2 for cell division and proliferation.^{[4] [5]}

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. 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.^[6]

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.

Interactions

SMC2 has been shown to interact with DNMT3B.^[7]

Clinical significance

Cornelia de Lange Syndrome

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.^[8] 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.^[9] 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. 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^[10] 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.

Further reading

• Ham MF, Takakuwa T, Rahadiani N, Tresnasari K, Nakajima H, Aozasa K . Condensin mutations and abnormal chromosomal structures in pyothorax-associated lymphoma . Cancer Science . 98 . 7 . 1041–7 . Jul 2007 . 17488335 . 10.1111/j.1349-7006.2007.00500.x . 25888221 . 11158810 .
• 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 . Large-scale mapping of human protein-protein interactions by mass spectrometry . Molecular Systems Biology . 3 . 1 . 89 . 2007 . 17353931 . 1847948 . 10.1038/msb4100134 .
• Andersen JS, Lam YW, Leung AK, Ong SE, Lyon CE, Lamond AI, Mann M . Nucleolar proteome dynamics . Nature . 433 . 7021 . 77–83 . Jan 2005 . 15635413 . 10.1038/nature03207 . 2005Natur.433...77A . 4344740 .
• Geiman TM, Sankpal UT, Robertson AK, Chen Y, Mazumdar M, Heale JT, Schmiesing JA, Kim W, Yokomori K, Zhao Y, Robertson KD . Isolation and characterization of a novel DNA methyltransferase complex linking DNMT3B with components of the mitotic chromosome condensation machinery . Nucleic Acids Research . 32 . 9 . 2716–29 . 2004 . 15148359 . 419596 . 10.1093/nar/gkh589 .
• Przewloka MR, Pardington PE, Yannone SM, Chen DJ, Cary RB . In vitro and in vivo interactions of DNA ligase IV with a subunit of the condensin complex . Molecular Biology of the Cell . 14 . 2 . 685–97 . Feb 2003 . 12589063 . 150001 . 10.1091/mbc.E01-11-0117 .
• Kimura K, Cuvier O, Hirano T . Chromosome condensation by a human condensin complex in Xenopus egg extracts . The Journal of Biological Chemistry . 276 . 8 . 5417–20 . Feb 2001 . 11136719 . 10.1074/jbc.C000873200 . free .
• Schmiesing JA, Gregson HC, Zhou S, Yokomori K . A human condensin complex containing hCAP-C-hCAP-E and CNAP1, a homolog of Xenopus XCAP-D2, colocalizes with phosphorylated histone H3 during the early stage of mitotic chromosome condensation . Molecular and Cellular Biology . 20 . 18 . 6996–7006 . Sep 2000 . 10958694 . 88774 . 10.1128/MCB.20.18.6996-7006.2000 .

External links

• PDBe-KB provides an overview of all the structure information available in the PDB for Human Structural maintenance of chromosomes protein 2
• PDBe-KB provides an overview of all the structure information available in the PDB for Mouse Structural maintenance of chromosomes protein 2

Notes and References

1. Schmiesing JA, Ball AR, Gregson HC, Alderton JM, Zhou S, Yokomori K . Identification of two distinct human SMC protein complexes involved in mitotic chromosome dynamics . Proceedings of the National Academy of Sciences of the United States of America . 95 . 22 . 12906–11 . Oct 1998 . 9789013 . 23650 . 10.1073/pnas.95.22.12906 . 1998PNAS...9512906S . free .
2. Web site: Entrez Gene: SMC2 structural maintenance of chromosomes 2.
3. Eeftens . Jorine M. . Katan . Allard J. . Kschonsak . Marc . Hassler . Markus . de Wilde . Liza . Dief . Essam M. . Haering . Christian H. . Dekker . Cees . 2016-03-01 . Condensin Smc2-Smc4 Dimers Are Flexible and Dynamic . Cell Reports . English . 14 . 8 . 1813–1818 . 10.1016/j.celrep.2016.01.063 . 2211-1247 . 4785793 . 26904946.
4. Li . Xixi . Song . Guili . Zhao . Yasong . Ren . Jing . Li . Qing . Cui . Zongbin . September 2021 . Functions of SMC2 in the Development of Zebrafish Liver . Biomedicines . en . 9 . 9 . 1240 . 10.3390/biomedicines9091240 . 2227-9059 . 8465584 . 34572426 . free .
5. Dávalos . Verónica . Súarez-López . Lucía . Castaño . Julio . Messent . Anthea . Abasolo . Ibane . Fernandez . Yolanda . Guerra-Moreno . Angel . Espín . Eloy . Armengol . Manel . Musulen . Eva . Ariza . Aurelio . Sayós . Joan . Arango . Diego . Schwartz . Simó . 2012-12-21 . Human SMC2 Protein, a Core Subunit of Human Condensin Complex, Is a Novel Transcriptional Target of the WNT Signaling Pathway and a New Therapeutic Target * . Journal of Biological Chemistry . English . 287 . 52 . 43472–43481 . 10.1074/jbc.M112.428466 . 0021-9258 . 3527934 . 23095742 . free .
6. Losada . Ana . Hirano . Tatsuya . 2005-06-01 . Dynamic molecular linkers of the genome: the first decade of SMC proteins . Genes & Development . en . 19 . 11 . 1269–1287 . 10.1101/gad.1320505 . 15937217 . 0890-9369. free .
7. Geiman TM, Sankpal UT, Robertson AK, Chen Y, Mazumdar M, Heale JT, Schmiesing JA, Kim W, Yokomori K, Zhao Y, Robertson KD . Isolation and characterization of a novel DNA methyltransferase complex linking DNMT3B with components of the mitotic chromosome condensation machinery . Nucleic Acids Research . 32 . 9 . 2716–29 . 2004 . 15148359 . 419596 . 10.1093/nar/gkh589 .
8. Web site: 2023-04-10 . Cornelia de Lange syndrome - About the Disease - Genetic and Rare Diseases Information Center . rarediseases.info.nih.gov..
9. Cao . Ruixue . Pu . Tian . Fang . Shaohai . Long . Fei . Xie . Jing . Xu . Yuejuan . Chen . Sun . Sun . Kun . Xu . Rang . 2015 . Patients Carrying 9q31.1-q32 Deletion Share Common Features with Cornelia de Lange Syndrome . Cellular Physiology and Biochemistry . english . 35 . 1 . 270–280 . 10.1159/000369694 . 1015-8987 . 25591769. 41785465 . free .
10. Montero . Sara . Seras-Franzoso . Joaquin . Andrade . Fernanda . Martinez-Trucharte . Francesc . Vilar-Hernández . Mireia . Quesada . Manuel . Xandri . Helena . Arango . Diego . Abasolo . Ibane . Rafael . Diana . Schwartz . Simo . 2020-02-21 . Intracellular Delivery of Anti-SMC2 Antibodies against Cancer Stem Cells . Pharmaceutics . en . 12 . 2 . 185 . 10.3390/pharmaceutics12020185 . free . 1999-4923 . 7076674 . 32098204.