SMC4

SMC4
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	4U4P
Identifiers
Aliases	SMC4 , CAP-C, CAPC, SMC-4, SMC4L1, hCAP-C, structural maintenance of chromosomes 4
External IDs	OMIM: 605575 MGI: 1917349 HomoloGene: 4015 GeneCards: SMC4
Gene location (Human)
Chr.	Chromosome 3 (human)
End	160,434,954 bp
Gene location (Mouse)
Chr.	Chromosome 3 (mouse)
End	68,941,956 bp
RNA expression pattern
	Top expressed in
	ganglionic eminence; ; spongy bone; ; bone marrow cells; ; Achilles tendon; ; right coronary artery; ; appendix; ; rectum; ; secondary oocyte; ; cavity of mouth; ; visceral pleura;
	Top expressed in
	spermatocyte; ; thymus; ; maxillary prominence; ; dermis; ; hand; ; ureter; ; atrium; ; abdominal wall; ; primitive streak; ; seminiferous tubule;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	protein heterodimerization activity ; nucleotide binding ; protein binding ; ATP binding ; single-stranded DNA binding ;
Cellular component	chromosome ; nucleus ; condensin complex ; nucleoplasm ; cytoplasm ; cytosol ; nuclear speck ;
Biological process	mitotic sister chromatid segregation ; meiotic chromosome segregation ; cell division ; cell cycle ; kinetochore organization ; mitotic chromosome condensation ; meiotic chromosome condensation ; chromosome condensation ; chromosome organization ;
	Sources:Amigo / QuickGO
Orthologs
	10051
	70099
	ENSG00000113810
	ENSMUSG00000034349
	Q9NTJ3
	Q8CG47
	NM_001002799 ; NM_001002800 ; NM_001288753 ; NM_005496
	NM_133786 ; NM_001356976
	NP_001002800 ; NP_001275682 ; NP_005487
	NP_598547 ; NP_001343905
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated January 09, 2024

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.^[5]^[6]^[7] SMC-4 is a core subunit of condensin I and II, large protein complexes involved in high order chromosome organization,^[8] including condensation and segregation.^[9] 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.^[8] An over-expression of the SMC-4 protein is shown to impact carcinogenesis.^[10]^[11]^[9]

Structure and interactions

Structure of a condensin protein holocomplex, displaying the SMC-4/SMC-2 heterodimer, and additional subunits. Kleisin is also depicted (blue). Condensin-Schema.svg — Structure of a condensin protein holocomplex, displaying the SMC-4/SMC-2 heterodimer, and additional subunits. Kleisin is also depicted (blue).

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 domains, along with two Amino-terminal globular domains containing ATP hydrolytic sites, or nucleotide-binding motifs located at the C-terminus and N-terminus called the Walker A and Walker B motifs.^[12]

In eukaryotes, dimerization 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 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.^[9]

In the condensin holocomplex, a protein subunit called kleisin joins the C-terminus and N-terminus ATPase 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.^[8] 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.^[8] In budding yeast, these interactions may result in open "O" appearances, or collapsed B-shaped states as a result of its dynamic ability.^[13]

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 carcinogenesis.^[10]

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.^[10]

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 carcinogenesis and lung adenocarcinoma.^[9]

Studies suggest that over-expression of the SMC-4 protein in human liver tissue may be correlated with progression of hepatocellular carcinoma.^[11]

Related Research Articles

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

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.

SMAD4, also called SMAD family member 4, Mothers against decapentaplegic homolog 4, or DPC4 is a highly conserved protein present in all metazoans. It belongs to the SMAD family of transcription factor proteins, which act as mediators of TGF-β signal transduction. The TGFβ family of cytokines regulates critical processes during the lifecycle of metazoans, with important roles during embryo development, tissue homeostasis, regeneration, and immune regulation.

Aurora kinase B is a protein that functions in the attachment of the mitotic spindle to the centromere.

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.

Regulator of chromosome condensation 1, also known as RCC1, Ran guanine nucleotide exchange factor and RanGEF, is the name for a human gene and protein.

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

Macrophage-capping protein (CAPG) also known as actin regulatory protein CAP-G is a protein that in humans is encoded by the CAPG gene.

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.

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

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.

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. Abnormal expression of NCAPH may be linked to various types of carcinogenesis as a prognostic indicator.

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.

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

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. 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. Several studies have demonstrated the necessity of SMC2 for cell division and proliferation.

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.

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. SMC1B protein appears to participate with other cohesins REC8, STAG3 and SMC3 in sister-chromatid cohesion throughout the whole meiotic process in human oocytes.

Xenopus egg extract is a lysate that is prepared by crushing the eggs of the African clawed frog Xenopus laevis. It offers a powerful cell-free system for studying various cell biological processes, including cell cycle progression, nuclear transport, DNA replication and chromosome segregation. It is also called Xenopus egg cell-free system or Xenopus egg cell-free extract.

In biology, the chromosome scaffold is the backbone that supports the structure of the chromosomes. It is composed of a group of non-histone proteins that are essential in the structure and maintenance of eukaryotic chromosomes throughout the cell cycle. These scaffold proteins are responsible for the condensation of chromatin during mitosis.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000113810 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000034349 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Entrez Gene: SMC4 structural maintenance of chromosomes 4".
↑ Nishiwaki T, Daigo Y, Kawasoe T, Nagasawa Y, Ishiguro H, Fujita M, et al. (Jun 1999). "Isolation and characterization of a human cDNA homologous to the Xenopus laevis XCAP-C gene belonging to the structural maintenance of chromosomes (SMC) family". Journal of Human Genetics. 44 (3): 197–202. doi: 10.1007/s100380050142 . PMID 10319587.
↑ Schmiesing JA, Ball AR, Gregson HC, Alderton JM, Zhou S, Yokomori K (October 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): 12906–12911. Bibcode:1998PNAS...9512906S. doi: 10.1073/pnas.95.22.12906 . PMC 23650 . PMID 9789013.
1 2 3 4 Eeftens JM, Katan AJ, Kschonsak M, Hassler M, de Wilde L, Dief EM, et al. (March 2016). "Condensin Smc2-Smc4 Dimers Are Flexible and Dynamic". Cell Reports. 14 (8): 1813–1818. doi:10.1016/j.celrep.2016.01.063. PMC 4785793 . PMID 26904946.
1 2 3 4 Zhang C, Kuang M, Li M, Feng L, Zhang K, Cheng S (September 2016). "SMC4, which is essentially involved in lung development, is associated with lung adenocarcinoma progression". Scientific Reports. 6 (1): 34508. Bibcode:2016NatSR...634508Z. doi:10.1038/srep34508. PMC 5043270 . PMID 27687868.
1 2 3 Jiang L, Zhou J, Zhong D, Zhou Y, Zhang W, Wu W, et al. (March 2017). "Overexpression of SMC4 activates TGFβ/Smad signaling and promotes aggressive phenotype in glioma cells". Oncogenesis. 6 (3): e301. doi:10.1038/oncsis.2017.8. PMC 5533949 . PMID 28287612.
1 2 Zhou B, Chen H, Wei D, Kuang Y, Zhao X, Li G, et al. (June 2014). "A novel miR-219-SMC4-JAK2/Stat3 regulatory pathway in human hepatocellular carcinoma". Journal of Experimental & Clinical Cancer Research. 33 (1): 55. doi: 10.1186/1756-9966-33-55 . PMC 4096530 . PMID 24980149.
↑ Hirano T (February 2002). "The ABCs of SMC proteins: two-armed ATPases for chromosome condensation, cohesion, and repair". Genes & Development. 16 (4): 399–414. doi: 10.1101/gad.955102 . PMID 11850403. S2CID 45664625.
↑ Ryu JK, Katan AJ, van der Sluis EO, Wisse T, de Groot R, Haering CH, Dekker C (December 2020). "The condensin holocomplex cycles dynamically between open and collapsed states". Nature Structural & Molecular Biology. 27 (12): 1134–1141. doi:10.1038/s41594-020-0508-3. PMID 32989304. S2CID 222146992.

External links

SMC4 human gene location in the UCSC Genome Browser .
SMC4 human gene details in the UCSC Genome Browser .
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)

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000113810 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000034349 - 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.

[entrez-5] "Entrez Gene: SMC4 structural maintenance of chromosomes 4".

[pmid10319587-6] Nishiwaki T, Daigo Y, Kawasoe T, Nagasawa Y, Ishiguro H, Fujita M, et al. (Jun 1999). "Isolation and characterization of a human cDNA homologous to the Xenopus laevis XCAP-C gene belonging to the structural maintenance of chromosomes (SMC) family". Journal of Human Genetics. 44 (3): 197–202. doi: 10.1007/s100380050142 . PMID 10319587.

[pmid9789013-7] Schmiesing JA, Ball AR, Gregson HC, Alderton JM, Zhou S, Yokomori K (October 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): 12906–12911. Bibcode:1998PNAS...9512906S. doi: 10.1073/pnas.95.22.12906 . PMC 23650 . PMID 9789013.

[:12-8] 1 2 3 4 Eeftens JM, Katan AJ, Kschonsak M, Hassler M, de Wilde L, Dief EM, et al. (March 2016). "Condensin Smc2-Smc4 Dimers Are Flexible and Dynamic". Cell Reports. 14 (8): 1813–1818. doi:10.1016/j.celrep.2016.01.063. PMC 4785793 . PMID 26904946.

[:03-9] 1 2 3 4 Zhang C, Kuang M, Li M, Feng L, Zhang K, Cheng S (September 2016). "SMC4, which is essentially involved in lung development, is associated with lung adenocarcinoma progression". Scientific Reports. 6 (1): 34508. Bibcode:2016NatSR...634508Z. doi:10.1038/srep34508. PMC 5043270 . PMID 27687868.

[:22-10] 1 2 3 Jiang L, Zhou J, Zhong D, Zhou Y, Zhang W, Wu W, et al. (March 2017). "Overexpression of SMC4 activates TGFβ/Smad signaling and promotes aggressive phenotype in glioma cells". Oncogenesis. 6 (3): e301. doi:10.1038/oncsis.2017.8. PMC 5533949 . PMID 28287612.

[Zhou_55-11] 1 2 Zhou B, Chen H, Wei D, Kuang Y, Zhao X, Li G, et al. (June 2014). "A novel miR-219-SMC4-JAK2/Stat3 regulatory pathway in human hepatocellular carcinoma". Journal of Experimental & Clinical Cancer Research. 33 (1): 55. doi: 10.1186/1756-9966-33-55 . PMC 4096530 . PMID 24980149.

[12] Hirano T (February 2002). "The ABCs of SMC proteins: two-armed ATPases for chromosome condensation, cohesion, and repair". Genes & Development. 16 (4): 399–414. doi: 10.1101/gad.955102 . PMID 11850403. S2CID 45664625.

[13] Ryu JK, Katan AJ, van der Sluis EO, Wisse T, de Groot R, Haering CH, Dekker C (December 2020). "The condensin holocomplex cycles dynamically between open and collapsed states". Nature Structural & Molecular Biology. 27 (12): 1134–1141. doi:10.1038/s41594-020-0508-3. PMID 32989304. S2CID 222146992.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]