NCAPH

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]

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)[1] Band 2q11.2 Start 96,335,766 bp[1] End 96,377,091 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 F1 Start 126,945,729 bp[2] End 126,975,874 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) 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 BioGPS 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 Species Human Mouse 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 Mb Chr 2: 126.95 – 126.98 Mb PubMed search [3] [4]
Wikidata
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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.

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]