{{Short description|Protein-coding gene in the species Homo sapiens}} {{Infobox_gene}} '''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]].<ref name="pmid9417923">{{cite journal | vauthors = Cabello OA, Baldini A, Bhat M, Bellen H, Belmont JW | title = Localization of BRRN1, the human homologue of Drosophila barr, to 2q11.2 | journal = Genomics | volume = 46 | issue = 2 | pages = 311–313 | date = December 1997 | pmid = 9417923 | doi = 10.1006/geno.1997.5021 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: NCAPH non-SMC condensin I complex, subunit H| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=23397}}</ref> 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.<ref name="Cui_2019" />
== 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 [[chromosome]]s.<ref name="Cui_2019">{{cite journal | vauthors = Cui F, Hu J, Xu Z, Tan J, Tang H | title = Overexpression of NCAPH is upregulated and predicts a poor prognosis in prostate cancer | journal = Oncology Letters | volume = 17 | issue = 6 | pages = 5768–5776 | date = June 2019 | pmid = 31186803 | pmc = 6507296 | doi = 10.3892/ol.2019.10260 }}</ref> CAP-H is associated with [[mitosis|mitotic]] chromosomes, except during the early phase of chromosome condensation. During interphase, the protein has a distinct punctate [[nucleolar]] localization.<ref name="entrez"/>
== Structure and interactions == [[File:Condensin-Schema.svg|alt=Condensin protein complex.|left|thumb|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 [[Eukaryote|eukaryotes]], NCAPH associates with [[NCAPG]], [[NCAPD2]], and the N and C termini of the [[SMC4|SMC-4]] and [[SMC2|SMC-2]] proteins. NCAPH creates a bridge between the head groups of the SMC proteins and functions as a kleisin protein.<ref name="Cui_2019" /><ref name="Palecek_2015">{{cite journal | vauthors = Palecek JJ, Gruber S | title = Kite Proteins: a Superfamily of SMC/Kleisin Partners Conserved Across Bacteria, Archaea, and Eukaryotes | journal = Structure | volume = 23 | issue = 12 | pages = 2183–2190 | date = December 2015 | pmid = 26585514 | doi = 10.1016/j.str.2015.10.004 | doi-access = free }}</ref><ref name="Hara_2019">{{cite journal | vauthors = Hara K, Kinoshita K, Migita T, Murakami K, Shimizu K, Takeuchi K, Hirano T, Hashimoto H | display-authors = 6 | title = Structural basis of HEAT-kleisin interactions in the human condensin I subcomplex | journal = EMBO Reports | volume = 20 | issue = 5 | date = May 2019 | article-number = e47183 | pmid = 30858338 | pmc = 6501013 | doi = 10.15252/embr.201847183 }}</ref>
The interaction between NCAPH and the globular [[ATPase]] head binding sites of the [[C-terminus|C terminus]] and [[N-terminus|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 [[Helix bundle|helical bundle]].<ref name="Palecek_2015" /> 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.<ref name="Hara_2019" /><ref>{{cite journal | vauthors = Palecek JJ, Gruber S | title = Kite Proteins: a Superfamily of SMC/Kleisin Partners Conserved Across Bacteria, Archaea, and Eukaryotes | journal = Structure | volume = 23 | issue = 12 | pages = 2183–2190 | date = December 2015 | pmid = 26585514 | doi = 10.1016/j.str.2015.10.004 | doi-access = free }}</ref>
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.<ref name="Hara_2019" />
== Clinical significance == NCAPH may be used as a prognostic indicator of [[carcinogenesis]] in humans, as the abnormal [[Over expression|over-expression]] of NCAPH is observed in many cancer types.<ref name="Yin_2017">{{cite journal | vauthors = 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 | display-authors = 6 | title = NCAPH plays important roles in human colon cancer | journal = Cell Death & Disease | volume = 8 | issue = 3 | pages = e2680 | date = March 2017 | pmid = 28300828 | pmc = 5386579 | doi = 10.1038/cddis.2017.88 }}</ref>
Studies show that, in prostate cancer,<ref name="Cui_2019_2">{{cite journal | vauthors = Cui F, Hu J, Xu Z, Tan J, Tang H | title = Overexpression of NCAPH is upregulated and predicts a poor prognosis in prostate cancer | journal = Oncology Letters | volume = 17 | issue = 6 | pages = 5768–5776 | date = June 2019 | pmid = 31186803 | pmc = 6507296 | doi = 10.3892/ol.2019.10260 }}</ref> nasopharyngeal carcinoma,<ref>{{cite journal | vauthors = Xu L, Jiang Y, Zheng J, Xie G, Li J, Shi L, Fan S | title = Aberrant expression of β-catenin and E-cadherin is correlated with poor prognosis of nasopharyngeal cancer | journal = Human Pathology | volume = 44 | issue = 7 | pages = 1357–1364 | date = July 2013 | pmid = 23375645 | doi = 10.1016/j.humpath.2012.10.025 }}</ref> hepatocellular carcinoma,<ref>{{cite journal | vauthors = Sun C, Huang S, Wang H, Xie R, Zhang L, Zhou Q, He X, Ju W | display-authors = 6 | title = Non-SMC condensin I complex subunit H enhances proliferation, migration, and invasion of hepatocellular carcinoma | journal = Molecular Carcinogenesis | volume = 58 | issue = 12 | pages = 2266–2275 | date = December 2019 | pmid = 31523845 | pmc = 6899668 | doi = 10.1002/mc.23114 }}</ref> and breast cancers,<ref>{{cite journal | vauthors = Lu H, Shi C, Wang S, Yang C, Wan X, Luo Y, Tian L, Li L | display-authors = 6 | title = Identification of NCAPH as a biomarker for prognosis of breast cancer | journal = Molecular Biology Reports | volume = 47 | issue = 10 | pages = 7831–7842 | date = October 2020 | pmid = 33009967 | doi = 10.1007/s11033-020-05859-9 | s2cid = 222157669 }}</ref> NCAPH is commonly over-expressed, and may be used as a biomarker for various cancer types and a viable [[Prognosis|prognostic]] factor for identification and potential drug targeting.<ref name="Cui_2019_2" />
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.<ref name="Yin_2017" /><ref name="Xiong_2020">{{cite journal | vauthors = Xiong Q, Fan S, Duan L, Liu B, Jiang X, Chen X, Xiong C, Tao Q, Wang J, Zhang H, Chen C, Duan Y | display-authors = 6 | title = NCAPH is negatively associated with Mcl‑1 in non‑small cell lung cancer | journal = Molecular Medicine Reports | volume = 22 | issue = 4 | pages = 2916–2924 | date = October 2020 | pmid = 32945371 | pmc = 7453632 | doi = 10.3892/mmr.2020.11359 }}</ref> 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.<ref name="Xiong_2020" />
== References == {{reflist}}
== Further reading == {{refbegin | 2}} * {{cite journal | vauthors = Nomura N, Nagase T, Miyajima N, Sazuka T, Tanaka A, Sato S, Seki N, Kawarabayasi Y, Ishikawa K, Tabata S | display-authors = 6 | title = 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 | journal = DNA Research | volume = 1 | issue = 5 | pages = 223–229 | year = 1995 | pmid = 7584044 | doi = 10.1093/dnares/1.5.223 | doi-access = free }} * {{cite journal | vauthors = Hirano T, Kobayashi R, Hirano M | title = Condensins, chromosome condensation protein complexes containing XCAP-C, XCAP-E and a Xenopus homolog of the Drosophila Barren protein | journal = Cell | volume = 89 | issue = 4 | pages = 511–521 | date = May 1997 | pmid = 9160743 | doi = 10.1016/S0092-8674(00)80233-0 | s2cid = 15061740 | doi-access = free }} * {{cite journal | vauthors = Kimura K, Cuvier O, Hirano T | title = Chromosome condensation by a human condensin complex in Xenopus egg extracts | journal = The Journal of Biological Chemistry | volume = 276 | issue = 8 | pages = 5417–5420 | date = February 2001 | pmid = 11136719 | doi = 10.1074/jbc.C000873200 | doi-access = free }} * {{cite journal | vauthors = Cabello OA, Eliseeva E, He WG, Youssoufian H, Plon SE, Brinkley BR, Belmont JW | title = Cell cycle-dependent expression and nucleolar localization of hCAP-H | journal = Molecular Biology of the Cell | volume = 12 | issue = 11 | pages = 3527–3537 | date = November 2001 | pmid = 11694586 | pmc = 60273 | doi = 10.1091/mbc.12.11.3527 }} * {{cite journal | vauthors = Heale JT, Ball AR, Schmiesing JA, Kim JS, Kong X, Zhou S, Hudson DF, Earnshaw WC, Yokomori K | display-authors = 6 | title = Condensin I interacts with the PARP-1-XRCC1 complex and functions in DNA single-strand break repair | journal = Molecular Cell | volume = 21 | issue = 6 | pages = 837–848 | date = March 2006 | pmid = 16543152 | pmc = 7115950 | doi = 10.1016/j.molcel.2006.01.036 }} * {{cite journal | vauthors = Nousiainen M, Silljé HH, Sauer G, Nigg EA, Körner R | title = Phosphoproteome analysis of the human mitotic spindle | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 14 | pages = 5391–5396 | date = April 2006 | pmid = 16565220 | pmc = 1459365 | doi = 10.1073/pnas.0507066103 | doi-access = free | bibcode = 2006PNAS..103.5391N }} * {{cite journal | vauthors = Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP | title = A probability-based approach for high-throughput protein phosphorylation analysis and site localization | journal = Nature Biotechnology | volume = 24 | issue = 10 | pages = 1285–1292 | date = October 2006 | pmid = 16964243 | doi = 10.1038/nbt1240 | s2cid = 14294292 }} {{refend}}
{{gene-2-stub}} {{Nucleus}}
[[Category:Human proteins]] [[Category:Genes mutated in mice]]