NCAPH explained

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.^{[1] [2]} 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.

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.^[3] 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.^[2]

Structure and interactions

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.^{[4] [5]}

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. 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.^[6]

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.

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.^[7]

Studies show that, in prostate cancer,^[8] nasopharyngeal carcinoma,^[9] hepatocellular carcinoma,^[10] and breast cancers,^[11] 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.

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.^[12]  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.

Further reading

• Nomura N, Nagase T, Miyajima N, Sazuka T, Tanaka A, Sato S, Seki N, Kawarabayasi Y, Ishikawa K, Tabata S . 6 . Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1 . DNA Research . 1 . 5 . 223–229 . 1995 . 7584044 . 10.1093/dnares/1.5.223 . free .
• Hirano T, Kobayashi R, Hirano M . Condensins, chromosome condensation protein complexes containing XCAP-C, XCAP-E and a Xenopus homolog of the Drosophila Barren protein . Cell . 89 . 4 . 511–521 . May 1997 . 9160743 . 10.1016/S0092-8674(00)80233-0 . 15061740 . free .
• Kimura K, Cuvier O, Hirano T . Chromosome condensation by a human condensin complex in Xenopus egg extracts . The Journal of Biological Chemistry . 276 . 8 . 5417–5420 . February 2001 . 11136719 . 10.1074/jbc.C000873200 . free .
• Cabello OA, Eliseeva E, He WG, Youssoufian H, Plon SE, Brinkley BR, Belmont JW . Cell cycle-dependent expression and nucleolar localization of hCAP-H . Molecular Biology of the Cell . 12 . 11 . 3527–3537 . November 2001 . 11694586 . 60273 . 10.1091/mbc.12.11.3527 .
• Heale JT, Ball AR, Schmiesing JA, Kim JS, Kong X, Zhou S, Hudson DF, Earnshaw WC, Yokomori K . 6 . Condensin I interacts with the PARP-1-XRCC1 complex and functions in DNA single-strand break repair . Molecular Cell . 21 . 6 . 837–848 . March 2006 . 16543152 . 7115950 . 10.1016/j.molcel.2006.01.036 .
• Nousiainen M, Silljé HH, Sauer G, Nigg EA, Körner R . Phosphoproteome analysis of the human mitotic spindle . Proceedings of the National Academy of Sciences of the United States of America . 103 . 14 . 5391–5396 . April 2006 . 16565220 . 1459365 . 10.1073/pnas.0507066103 . free . 2006PNAS..103.5391N .
• Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP . A probability-based approach for high-throughput protein phosphorylation analysis and site localization . Nature Biotechnology . 24 . 10 . 1285–1292 . October 2006 . 16964243 . 10.1038/nbt1240 . 14294292 .

Notes and References

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