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MGP000836

UniProt Annotations

Entry Information
Gene Namedyskeratosis congenita 1, dyskerin
Protein EntryDKC1_HUMAN
UniProt IDO60832
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=O60832-1; Sequence=Displayed; Name=3; IsoId=O60832-2; Sequence=VSP_042422;
Catalytic ActivityRNA uridine = RNA pseudouridine.
DiseaseDyskeratosis congenita, X-linked (DKCX) [MIM:305000]: 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. {ECO:0000269|PubMed:10364516, ECO:0000269|PubMed:15304085, ECO:0000269|PubMed:17417794, ECO:0000269|PubMed:18802941, ECO:0000269|PubMed:19734544, ECO:0000269|PubMed:19879169, ECO:0000269|PubMed:9590285}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseHoyeraal-Hreidarsson syndrome (HHS) [MIM:305000]: A clinically severe variant of dyskeratosis congenita that is characterized by multisystem involvement, early onset in utero, and often results in death in childhood. Affected individuals show intrauterine growth retardation, microcephaly, cerebellar hypoplasia, delayed development, and bone marrow failure resulting in immunodeficiency. {ECO:0000269|PubMed:10583221, ECO:0000269|PubMed:12437656, ECO:0000269|PubMed:19734544, ECO:0000269|PubMed:24914498}. Note=The disease is caused by mutations affecting the gene represented in this entry.
FunctionIsoform 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.
FunctionIsoform 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).
InteractionQ6NT76:HMBOX1; NbExp=2; IntAct=EBI-713091, EBI-2549423; Q96HR8:NAF1; NbExp=6; IntAct=EBI-713091, EBI-2515597; Q9Y265:RUVBL1; NbExp=8; IntAct=EBI-713091, EBI-353675;
SimilarityBelongs to the pseudouridine synthase TruB family. {ECO:0000305}.
SimilarityContains 1 PUA domain. {ECO:0000255|PROSITE- ProRule:PRU00161}.
Subcellular LocationIsoform 1: Nucleus, nucleolus. Nucleus, Cajal body. Note=Also localized to Cajal bodies (coiled bodies).
Subcellular LocationIsoform 3: Cytoplasm.
SubunitPart 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. {ECO:0000269|PubMed:11074001, ECO:0000269|PubMed:16601202, ECO:0000269|PubMed:16618814, ECO:0000269|PubMed:19179534, ECO:0000269|PubMed:19383767, ECO:0000269|PubMed:19734544}.
Tissue SpecificityUbiquitously expressed. {ECO:0000269|PubMed:10903840}.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/DKC1ID157.html";
Web ResourceName=DKC1base; Note=DKC1 mutation db; URL="http://structure.bmc.lu.se/idbase/DKC1base/";
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