NCAPH

NCAPH
Identifiers
Aliases	NCAPH , BRRN1, CAP-H, non-SMC condensin I complex subunit H, MCPH23, CAPH
External IDs	OMIM: 602332; MGI: 2444777; HomoloGene: 133986; GeneCards: NCAPH; OMA:NCAPH - orthologs
Gene location (Human)
Chr.	Chromosome 2 (human)
End	96,377,091 bp
Gene location (Mouse)
Chr.	Chromosome 2 (mouse)
End	126,975,874 bp
RNA expression pattern
	Top expressed in
	ventricular zone; ; ganglionic eminence; ; gonad; ; left testis; ; right testis; ; testicle; ; secondary oocyte; ; sperm; ; mucosa of transverse colon; ; rectum;
	Top expressed in
	otic placode; ; tail of embryo; ; saccule; ; genital tubercle; ; otic vesicle; ; fetal liver hematopoietic progenitor cell; ; vas deferens; ; condyle; ; fossa; ; medial ganglionic eminence;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	protein binding ; chromatin binding ; DNA topoisomerase binding ; DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activator activity ;
Cellular component	cytoplasm ; membrane ; chromosome ; condensin complex ; nucleus ; cytosol ;
Biological process	cell division ; cell cycle ; chromosome condensation ; mitotic chromosome condensation ; meiotic chromosome condensation ; meiotic chromosome segregation ; positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity ; female meiotic nuclear division ; female meiosis chromosome separation ;
	Sources:Amigo / QuickGO
Orthologs
	23397
	215387
	ENSG00000121152
	ENSMUSG00000034906
	Q15003
	Q8C156
	NM_001281710 ; NM_001281711 ; NM_001281712 ; NM_015341
	NM_144818
	NP_001268639 ; NP_001268640 ; NP_001268641 ; NP_056156
	NP_659067
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated November 28, 2024

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.^[5]^[6] 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.^[7]

Function

CAP-H is a member of the barr protein family and a regulatory subunit of the condensin complex. This complex is required for the conversion of interphase chromatin into condensed chromosomes.^[7] CAP-H is associated with mitotic chromosomes, except during the early phase of chromosome condensation. During interphase, the protein has a distinct punctate nucleolar localization.^[6]

Structure and interactions

NCAPH, or CAP-H Joining the terminal ends of the SMC-2 and SMC-4 heterodimer to create the condensin holocomplex. Condensin-Schema.svg — NCAPH, or CAP-H Joining the terminal ends of the SMC-2 and SMC-4 heterodimer to create the condensin holocomplex.

As one of the main subunits in the highly conserved SMC condensin I complex in eukaryotes, NCAPH associates with NCAPG, NCAPD2, and the N and C termini of the SMC-4 and SMC-2 proteins. NCAPH creates a bridge between the head groups of the SMC proteins and functions as a kleisin protein.^[7]^[8]^[9]

The interaction between NCAPH and the globular ATPase head binding sites of the C terminus and N terminus of the SMC heterodimer allows condensin to have dynamic properties. The C terminus end of NCAPH assumes a winged-helix conformation, which then associates with either head group of the SMC protein. At the opposite end of the kleisin protein, the N terminus associates with proximal coiled coil of the other SMC protein, and creates a helical bundle.^[8] This attribute enables the condensin complex to have open and closed conformations in order to associate with chromatin and aid in proper folding of DNA in the condensation process.^[9]^[10]

Studies suggest that the sub-complex formed between NCAPH and NCAPG is critical for interactions with single-stranded DNA and double-stranded DNA to assist mitotic chromosome assembly in eukaryotes.^[9]

Clinical significance

NCAPH may be used as a prognostic indicator of carcinogenesis in humans, as the abnormal over-expression of NCAPH is observed in many cancer types.^[11]

Studies show that, in prostate cancer,^[12] nasopharyngeal carcinoma,^[13] hepatocellular carcinoma,^[14] and breast cancers,^[15] NCAPH is commonly over-expressed, and may be used as a biomarker for various cancer types and a viable prognostic factor for identification and potential drug targeting.^[12]

In colon cancer, NCAPH is shown to be higher expressed in cancerous cells compared to non-cancerous epithelial cells. supplementally, when NCAPH is depleted, studies show a decrease in colon cancer cell proliferation.^[11]^[16] Studies show that high expression of NCAPH in colon cancer and non-small cell lung cancer patients had an increased survival rate than those with a lower expression of NCAPH.^[16]

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.

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

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.

G2/mitotic-specific cyclin-B1 is a protein that in humans is encoded by the CCNB1 gene.

Double-strand-break repair protein rad21 homolog is a protein that in humans is encoded by the RAD21 gene. RAD21, an essential gene, encodes a DNA double-strand break (DSB) repair protein that is evolutionarily conserved in all eukaryotes from budding yeast to humans. RAD21 protein is a structural component of the highly conserved cohesin complex consisting of RAD21, SMC1A, SMC3, and SCC3 [ STAG1 (SA1) and STAG2 (SA2) in multicellular organisms] proteins, involved in sister chromatid cohesion.

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.

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

Protein CIP2A also known as cancerous inhibitor of PP2A (CIP2A) is a protein that in humans is encoded by the KIAA1524 gene.

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.

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.

Loop extrusion is a major mechanism of Nuclear organization. It is a dynamic process in which structural maintenance of chromosomes (SMC) protein complexes progressively grow loops of DNA or chromatin. In this process, SMC complexes, such as condensin or cohesin, bind to DNA/chromatin, use ATP-driven motor activity to reel in DNA, and as a result, extrude the collected DNA as a loop.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000121152 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000034906 – 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.
↑ Cabello OA, Baldini A, Bhat M, Bellen H, Belmont JW (December 1997). "Localization of BRRN1, the human homologue of Drosophila barr, to 2q11.2". Genomics. 46 (2): 311–313. doi:10.1006/geno.1997.5021. PMID 9417923.
1 2 "Entrez Gene: NCAPH non-SMC condensin I complex, subunit H".
1 2 3 Cui F, Hu J, Xu Z, Tan J, Tang H (June 2019). "Overexpression of NCAPH is upregulated and predicts a poor prognosis in prostate cancer". Oncology Letters. 17 (6): 5768–5776. doi:10.3892/ol.2019.10260. PMC 6507296 . PMID 31186803.
1 2 Palecek JJ, Gruber S (December 2015). "Kite Proteins: a Superfamily of SMC/Kleisin Partners Conserved Across Bacteria, Archaea, and Eukaryotes". Structure. 23 (12): 2183–2190. doi: 10.1016/j.str.2015.10.004 . PMID 26585514.
1 2 3 Hara K, Kinoshita K, Migita T, Murakami K, Shimizu K, Takeuchi K, et al. (May 2019). "Structural basis of HEAT-kleisin interactions in the human condensin I subcomplex". EMBO Reports. 20 (5). doi:10.15252/embr.201847183. PMC 6501013 . PMID 30858338.
↑ Palecek JJ, Gruber S (December 2015). "Kite Proteins: a Superfamily of SMC/Kleisin Partners Conserved Across Bacteria, Archaea, and Eukaryotes". Structure. 23 (12): 2183–2190. doi: 10.1016/j.str.2015.10.004 . PMID 26585514.
1 2 Yin L, Jiang LP, Shen QS, Xiong QX, Zhuo X, Zhang LL, et al. (March 2017). "NCAPH plays important roles in human colon cancer". Cell Death & Disease. 8 (3): e2680. doi:10.1038/cddis.2017.88. PMC 5386579 . PMID 28300828.
1 2 Cui F, Hu J, Xu Z, Tan J, Tang H (June 2019). "Overexpression of NCAPH is upregulated and predicts a poor prognosis in prostate cancer". Oncology Letters. 17 (6): 5768–5776. doi:10.3892/ol.2019.10260. PMC 6507296 . PMID 31186803.
↑ Xu L, Jiang Y, Zheng J, Xie G, Li J, Shi L, Fan S (July 2013). "Aberrant expression of β-catenin and E-cadherin is correlated with poor prognosis of nasopharyngeal cancer". Human Pathology. 44 (7): 1357–1364. doi:10.1016/j.humpath.2012.10.025. PMID 23375645.
↑ Sun C, Huang S, Wang H, Xie R, Zhang L, Zhou Q, et al. (December 2019). "Non-SMC condensin I complex subunit H enhances proliferation, migration, and invasion of hepatocellular carcinoma". Molecular Carcinogenesis. 58 (12): 2266–2275. doi:10.1002/mc.23114. PMC 6899668 . PMID 31523845.
↑ Lu H, Shi C, Wang S, Yang C, Wan X, Luo Y, et al. (October 2020). "Identification of NCAPH as a biomarker for prognosis of breast cancer". Molecular Biology Reports. 47 (10): 7831–7842. doi:10.1007/s11033-020-05859-9. PMID 33009967. S2CID 222157669.
1 2 Xiong Q, Fan S, Duan L, Liu B, Jiang X, Chen X, et al. (October 2020). "NCAPH is negatively associated with Mcl‑1 in non‑small cell lung cancer". Molecular Medicine Reports. 22 (4): 2916–2924. doi:10.3892/mmr.2020.11359. PMC 7453632 . PMID 32945371.