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NCAPH

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NCAPH
Identifiers
AliasesNCAPH, BRRN1, CAP-H, non-SMC condensin I complex subunit H, MCPH23, CAPH
External IDsOMIM: 602332; MGI: 2444777; HomoloGene: 133986; GeneCards: NCAPH; OMA:NCAPH - orthologs
Orthologs
SpeciesHumanMouse
Entrez

23397

215387

Ensembl

ENSG00000121152

ENSMUSG00000034906

UniProt

Q15003

Q8C156

RefSeq (mRNA)

NM_001281710
NM_001281711
NM_001281712
NM_015341

NM_144818

RefSeq (protein)

NP_001268639
NP_001268640
NP_001268641
NP_056156

NP_659067

Location (UCSC)Chr 2: 96.34 – 96.38 MbChr 2: 126.95 – 126.98 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

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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

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Condensin protein complex.
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

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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]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000121152 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000034906 – 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. ^ 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.
  6. ^ a b "Entrez Gene: NCAPH non-SMC condensin I complex, subunit H".
  7. ^ a b c 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.
  8. ^ a b 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.
  9. ^ a b c 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.
  10. ^ 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.
  11. ^ a b 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.
  12. ^ a b 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.
  13. ^ 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.
  14. ^ 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.
  15. ^ 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.
  16. ^ a b 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.

Further reading

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