SMC2

Last updated
SMC2
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases SMC2 , CAP-E, CAPE, SMC-2, SMC2L1, structural maintenance of chromosomes 2
External IDs OMIM: 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

Contents

NP_001288341
NP_032043

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

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]

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). Condensin-Schema.svg
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.

Related Research Articles

<span class="mw-page-title-main">Condensin</span>

Condensins are large protein complexes that play a central role in chromosome assembly and segregation during mitosis and meiosis. Their subunits were originally identified as major components of mitotic chromosomes assembled in Xenopus egg extracts.

SMC complexes represent a large family of ATPases that participate in many aspects of higher-order chromosome organization and dynamics. SMC stands for Structural Maintenance of Chromosomes.

<span class="mw-page-title-main">Cohesin</span> Protein complex that regulates the separation of sister chromatids during cell division

Cohesin is a protein complex that mediates sister chromatid cohesion, homologous recombination, and DNA looping. Cohesin is formed of SMC3, SMC1, SCC1 and SCC3. Cohesin holds sister chromatids together after DNA replication until anaphase when removal of cohesin leads to separation of sister chromatids. The complex forms a ring-like structure and it is believed that sister chromatids are held together by entrapment inside the cohesin ring. Cohesin is a member of the SMC family of protein complexes which includes Condensin, MukBEF and SMC-ScpAB.

<span class="mw-page-title-main">SMC1A</span> Protein-coding gene in humans

Structural maintenance of chromosomes protein 1A (SMC1A) is a protein that in humans is encoded by the SMC1A gene. SMC1A is a subunit of the cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. In somatic cells, cohesin is formed of SMC1A, SMC3, RAD21 and either SA1 or SA2 whereas in meiosis, cohesin is formed of SMC3, SMC1B, REC8 and SA3.

<span class="mw-page-title-main">DNMT3B</span> Protein-coding gene in the species Homo sapiens

DNA (cytosine-5)-methyltransferase 3 beta, is an enzyme that in humans in encoded by the DNMT3B gene. Mutation in this gene are associated with immunodeficiency, centromere instability and facial anomalies syndrome.

<span class="mw-page-title-main">SMARCA5</span> Protein-coding gene in the species Homo sapiens

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 is a protein that in humans is encoded by the SMARCA5 gene.

<span class="mw-page-title-main">SMC3</span> Protein-coding gene in humans

Structural maintenance of chromosomes protein 3 (SMC3) is a protein that in humans is encoded by the SMC3 gene. SMC3 is a subunit of the Cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. Cohesin is formed of SMC3, SMC1, RAD21 and either SA1 or SA2. In humans, SMC3 is present in all cohesin complexes whereas there are multiple paralogs for the other subunits.

<span class="mw-page-title-main">KIF4A</span> Protein-coding gene in the species Homo sapiens

Kinesin family member 4A is a protein that in humans is encoded by the KIF4A gene.

<span class="mw-page-title-main">AKAP8</span> Protein-coding gene in the species Homo sapiens

A-kinase anchor protein 8 is an enzyme that, in humans, is encoded by the AKAP8 gene.

<span class="mw-page-title-main">WAPAL</span> Protein-coding gene in the species Homo sapiens

Wings apart-like protein homolog (WAPL) is a protein that in humans is encoded by the WAPAL gene. WAPL is a key regulator of the Cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. Cohesin is formed of SMC3, SMC1, RAD21 and either SA1 or SA2. Cohesin has a ring-like arrangement and it is thought that it associates with the chromosome by entrapping it whether as a loop of DNA, a single strand or a pair of sister chromosomes. WAPL forms a complex with PDS5A or PDS5B and releases cohesin from DNA by opening the interface between SMC3 and RAD21.

<span class="mw-page-title-main">SMC4</span> Protein-coding gene in the species Homo sapiens

Structural maintenance of chromosomes protein 4 (SMC-4) also known as chromosome-associated polypeptide C (CAP-C) or XCAP-C homolog is a protein that in humans is encoded by the SMC4 gene. SMC-4 is a core subunit of condensin 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.

<span class="mw-page-title-main">SMC6</span> Protein-coding gene in the species Homo sapiens

Structural maintenance of chromosomes protein 6 is a protein that in humans is encoded by the SMC6 gene.

<span class="mw-page-title-main">NCAPD2</span> Protein-coding gene in the species Homo sapiens

Condensin complex subunit 1 also known as chromosome-associated protein D2 (CAP-D2) or non-SMC condensin I complex subunit D2 (NCAPD2) or XCAP-D2 homolog is a protein that in humans is encoded by the NCAPD2 gene. CAP-D2 is a subunit of condensin I, a large protein complex involved in chromosome condensation.

<span class="mw-page-title-main">SMC5</span> Protein-coding gene in the species Homo sapiens

Structural maintenance of chromosomes protein 5 is a protein encoded by the SMC5 gene in human.

<span class="mw-page-title-main">NCAPD3</span> Protein-coding gene in the species Homo sapiens

Condensin-2 complex subunit D3 (CAP-D3) also known as non-SMC condensin II complex subunit D3 (NCAPD3) is a protein that, in humans, is encoded by the NCAPD3 gene. CAP-D3 is a subunit of condensin II, a large protein complex involved in chromosome condensation.

<span class="mw-page-title-main">NCAPH</span> Protein-coding gene in the species Homo sapiens

Condensin complex subunit 2 also known as chromosome-associated protein H (CAP-H) or non-SMC condensin I complex subunit H (NCAPH) is a protein that in humans is encoded by the NCAPH gene. CAP-H is a subunit of condensin I, a large protein complex involved in chromosome condensation

<span class="mw-page-title-main">NCAPG</span> Protein-coding gene in the species Homo sapiens

Condensin complex subunit 3 also known as condensin subunit CAP-G (CAP-G) or non-SMC condensin I complex subunit G (NCAPG) is a protein that in humans is encoded by the NCAPG gene. CAP-G is a subunit of condensin I, a large protein complex involved in chromosome condensation.

<span class="mw-page-title-main">NCAPG2</span> Protein-coding gene in the species Homo sapiens

Condensin-2 complex subunit G2 (CAP-G2) also known as chromosome-associated protein G2 (CAP-G2) or leucine zipper protein 5 (LUZP5) is a protein that in humans is encoded by the NCAPG2 gene. CAP-G2 is a subunit of condensin II, a large protein complex involved in chromosome condensation. It interacts with PLK1 through its C-terminal region during mitosis

<span class="mw-page-title-main">NCAPH2</span> Protein-coding gene in the species Homo sapiens

Condensin-2 complex subunit H2, also known as chromosome-associated protein H2 (CAP-H2) or non-SMC condensin II complex subunit H2 (NCAPH2), is a protein that in humans is encoded by the NCAPH2 gene. CAP-H2 is a subunit of condensin II, a large protein complex involved in chromosome condensation.

<span class="mw-page-title-main">SMC1B</span> Protein-coding gene in the species Homo sapiens

Structural maintenance of chromosomes protein 1B (SMC-1B) is a protein that in humans is encoded by the SMC1B gene. SMC proteins engage in chromosome organization and can be broken into 3 groups based on function which are cohesins, condensins, and DNA repair.SMC-1B belongs to a family of proteins required for chromatid cohesion and DNA recombination during meiosis and mitosis. SMC1ß protein appears to participate with other cohesins REC8, STAG3 and SMC3 in sister-chromatid cohesion throughout the whole meiotic process in human oocytes.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000136824 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 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. 1 2 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. 1 2 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.

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