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 NCAPHgene.[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 interphasechromatin 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.
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]
^"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. PMID9417923.
^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. PMID23375645.
^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. PMID33009967. S2CID222157669.
Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP (October 2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nature Biotechnology. 24 (10): 1285–1292. doi:10.1038/nbt1240. PMID16964243. S2CID14294292.
