SMC2

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.[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]

SMC2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSMC2, CAP-E, CAPE, SMC-2, SMC2L1, structural maintenance of chromosomes 2
External IDsOMIM: 605576 MGI: 106067 HomoloGene: 4705 GeneCards: SMC2
Orthologs
SpeciesHumanMouse
Entrez

10592

14211

Ensembl

ENSG00000136824

ENSMUSG00000028312

UniProt

O95347
Q05D74

Q8CG48

RefSeq (mRNA)

NM_001042550
NM_001042551
NM_001265602
NM_006444

NM_001301412
NM_008017

RefSeq (protein)

NP_001036015
NP_001036016
NP_001252531
NP_006435
NP_006435.2

NP_001288341
NP_032043

Location (UCSC)Chr 9: 104.09 – 104.14 MbChr 4: 52.44 – 52.49 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

Interactions

SMC2 has been shown to interact with DNMT3B.[11]

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.[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.

References
  1. GRCh38: Ensembl release 89: ENSG00000136824 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000028312 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Schmiesing JA, Ball AR, Gregson HC, Alderton JM, Zhou S, Yokomori K (Oct 1998). "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. Bibcode:1998PNAS...9512906S. doi:10.1073/pnas.95.22.12906. PMC 23650. PMID 9789013.
  6. "Entrez Gene: SMC2 structural maintenance of chromosomes 2".
  7. 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. 14 (8): 1813–1818. doi:10.1016/j.celrep.2016.01.063. ISSN 2211-1247. PMC 4785793. PMID 26904946.
  8. Li, Xixi; Song, Guili; Zhao, Yasong; Ren, Jing; Li, Qing; Cui, Zongbin (September 2021). "Functions of SMC2 in the Development of Zebrafish Liver". Biomedicines. 9 (9): 1240. doi:10.3390/biomedicines9091240. ISSN 2227-9059. PMC 8465584. PMID 34572426.
  9. 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. 287 (52): 43472–43481. doi:10.1074/jbc.M112.428466. ISSN 0021-9258. PMC 3527934. PMID 23095742.
  10. Losada, Ana; Hirano, Tatsuya (2005-06-01). "Dynamic molecular linkers of the genome: the first decade of SMC proteins". Genes & Development. 19 (11): 1269–1287. doi:10.1101/gad.1320505. ISSN 0890-9369. PMID 15937217.
  11. Geiman TM, Sankpal UT, Robertson AK, Chen Y, Mazumdar M, Heale JT, Schmiesing JA, Kim W, Yokomori K, Zhao Y, Robertson KD (2004). "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. doi:10.1093/nar/gkh589. PMC 419596. PMID 15148359.
  12. "Cornelia de Lange syndrome - About the Disease - Genetic and Rare Diseases Information Center". rarediseases.info.nih.gov. 2023-04-10.
  13. 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. 35 (1): 270–280. doi:10.1159/000369694. ISSN 1015-8987. PMID 25591769. S2CID 41785465.
  14. 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. 12 (2): 185. doi:10.3390/pharmaceutics12020185. ISSN 1999-4923. PMC 7076674. PMID 32098204.

Further reading
  • 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


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