ID:DKC1_HUMAN DESCRIPTION: RecName: Full=H/ACA ribonucleoprotein complex subunit 4; EC=5.4.99.-; AltName: Full=CBF5 homolog; AltName: Full=Dyskerin; AltName: Full=Nopp140-associated protein of 57 kDa; AltName: Full=Nucleolar protein NAP57; AltName: Full=Nucleolar protein family A member 4; AltName: Full=snoRNP protein DKC1; FUNCTION: Isoform 1: Required for ribosome biogenesis and telomere maintenance. Probable catalytic subunit of H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA. This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1. Each rRNA can contain up to 100 pseudouridine ('psi') residues, which may serve to stabilize the conformation of rRNAs. Also required for correct processing or intranuclear trafficking of TERC, the RNA component of the telomerase reverse transcriptase (TERT) holoenzyme. FUNCTION: Isoform 3: Promotes cell to cell and cell to substratum adhesion, increases the cell proliferation rate and leads to cytokeratin hyper-expression (when overexpressed in HeLa cells). CATALYTIC ACTIVITY: RNA uridine = RNA pseudouridine. SUBUNIT: Part of the H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which contains NHP2/NOLA2, GAR1/NOLA1, NOP10/NOLA3, and DKC1/NOLA4, which is presumed to be the catalytic subunit. The complex contains a stable core formed by binding of one or two NOP10-DKC1 heterodimers to NHP2; GAR1 subsequently binds to this core via DKC1. The complex binds a box H/ACA small nucleolar RNA (snoRNA), which may target the specific site of modification within the RNA substrate. During assembly, the complex contains NAF1 instead of GAR1/NOLA1. The complex also interacts with TERC, which contains a 3'-terminal domain related to the box H/ACA snoRNAs. Specific interactions with snoRNAs or TERC are mediated by GAR1 and NHP2. Associates with NOLC1/NOPP140. H/ACA snoRNPs interact with the SMN complex, consisting of SMN1 or SMN2, GEMIN2/SIP1, DDX20/GEMIN3, and GEMIN4. This is mediated by interaction between GAR1 and SMN1 or SMN2. The SMN complex may be required for correct assembly of the H/ACA snoRNP complex. Component of the telomerase holoenzyme complex at least composed of TERT, DKC1, WRAP53/TCAB1, NOP10, NHP2, GAR1, TEP1, EST1A, POT1 and a telomerase RNA template component (TERC). Interacts with SHQ1; this interaction may lead to the stabilization of DKC1, from the time of its synthesis until its association with NOP10, NHP2, and NAF1 at the nascent H/ACA RNA. INTERACTION: Q9Y265:RUVBL1; NbExp=5; IntAct=EBI-713091, EBI-353675; SUBCELLULAR LOCATION: Isoform 1: Nucleus, nucleolus. Nucleus, Cajal body. Note=Also localized to Cajal bodies (coiled bodies). SUBCELLULAR LOCATION: Isoform 3: Cytoplasm. TISSUE SPECIFICITY: Ubiquitously expressed. DISEASE: Defects in DKC1 are a cause of dyskeratosis congenita X- linked recessive (XDKC) [MIM:305000]. XDKC is a rare, progressive bone marrow failure syndrome characterized by the triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. DISEASE: Defects in DKC1 are the cause of Hoyeraal-Hreidarsson syndrome (HHS) [MIM:300240]. HHS is a multisystem disorder affecting males and is characterized by aplastic anemia, immunodeficiency, microcephaly, cerebellar hypoplasia, and growth retardation. SIMILARITY: Belongs to the pseudouridine synthase TruB family. SIMILARITY: Contains 1 PUA domain. WEB RESOURCE: Name=DKC1base; Note=DKC1 mutation db; URL="http://bioinf.uta.fi/DKC1base/"; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/DKC1ID157.html"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/DKC1";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O60832
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Protein O60832 (Reactome details) participates in the following event(s):
R-HSA-164616 Biogenesis And Assembly Of The Telomerase RNP R-HSA-163096 Recruitment of Telomerase RNP to the Telomeric Chromosome End R-HSA-163120 Disassociation of Telomerase RNP and the Chromosome End R-HSA-163099 Alignment Of The RNA Template On The Telomeric Chromosome End R-HSA-164617 Elongation of Extended Telomeric Chromosome End R-HSA-164620 Translocation Of Telomerase RNP And Alignment Of RNA Template (TERC) To Extended Single Stranded Telomeric Chromosome-End R-HSA-163090 Elongation Of The Telomeric Chromosome End R-HSA-6790905 Box H/ACA snoRNP transforms uridine to pseudouridine in pre-rRNA R-HSA-171319 Telomere Extension By Telomerase R-HSA-180786 Extension of Telomeres R-HSA-6790901 rRNA modification in the nucleus and cytosol R-HSA-157579 Telomere Maintenance R-HSA-8868773 rRNA processing in the nucleus and cytosol R-HSA-73886 Chromosome Maintenance R-HSA-72312 rRNA processing R-HSA-1640170 Cell Cycle R-HSA-8953854 Metabolism of RNA
GeneReviews article(s) related to gene DKC1: dkc (Dyskeratosis Congenita and Related Telomere Biology Disorders) pf (Pulmonary Fibrosis Predisposition Overview)
Gene Model Information
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
