Human Gene DKC1 (ENST00000369550.10) from GENCODE V44
  Description: Homo sapiens dyskerin pseudouridine synthase 1 (DKC1), transcript variant 6, non-coding RNA. (from RefSeq NR_110023)
RefSeq Summary (NM_001363): This gene functions in two distinct complexes. It plays an active role in telomerase stabilization and maintenance, as well as recognition of snoRNAs containing H/ACA sequences which provides stability during biogenesis and assembly into H/ACA small nucleolar RNA ribonucleoproteins (snoRNPs). This gene is highly conserved and widely expressed, and may play additional roles in nucleo-cytoplasmic shuttling, DNA damage response, and cell adhesion. Mutations have been associated with X-linked dyskeratosis congenita. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014].
Gencode Transcript: ENST00000369550.10
Gencode Gene: ENSG00000130826.19
Transcript (Including UTRs)
   Position: hg38 chrX:154,762,864-154,777,689 Size: 14,826 Total Exon Count: 15 Strand: +
Coding Region
   Position: hg38 chrX:154,762,966-154,776,867 Size: 13,902 Coding Exon Count: 15 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chrX:154,762,864-154,777,689)mRNA (may differ from genome)Protein (514 aa)
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-  Comments and Description Text from UniProtKB
  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";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: DKC1
Diseases sorted by gene-association score: dyskeratosis congenita, x-linked* (1242), dyskeratosis congenita* (860), dkc1-related dyskeratosis congenita* (100), leukoplakia (28), incontinentia pigmenti (20), aplastic anemia (15), cerebellar hypoplasia (14), pancytopenia (13), congenital intrauterine infection-like syndrome (13), revesz syndrome (13), torch syndrome (10), dyskeratosis congenita autosomal dominant (9), adermatoglyphia (7), pseudo-torch syndrome 1 (7), fusariosis (7), reticulate acropigmentation of kitamura (6), dowling-degos disease (4), fanconi anemia, complementation group a (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • D016604 Aflatoxin B1
  • D013749 Tetrachlorodibenzodioxin
  • D001564 Benzo(a)pyrene
  • C029497 2,3-bis(3'-hydroxybenzyl)butyrolactone
  • C016403 2,4-dinitrotoluene
  • C532162 2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine
  • C019499 2-nitrofluorene
  • C016583 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
  • C035207 4-amino-2,6-dinitrotoluene
  • D015123 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
          more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 43.28 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 653.19 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -42.90102-0.421 Picture PostScript Text
3' UTR -204.40822-0.249 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR012960 - Dyskerin-like
IPR002501 - PsdUridine_synth
IPR020103 - PsdUridine_synth_cat_dom
IPR002478 - PUA
IPR015947 - PUA-like_domain
IPR004802 - tRNA_PsdUridine_synth_B_fam
IPR004521 - Uncharacterised_CHP00451

Pfam Domains:
PF08068 - DKCLD (NUC011) domain
PF01472 - PUA domain
PF01509 - TruB family pseudouridylate synthase (N terminal domain)

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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
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Protein SequenceProtein SequenceProtein SequenceProtein SequenceProtein SequenceProtein Sequence
AlignmentAlignmentAlignmentAlignmentAlignmentAlignment

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003720 telomerase activity
GO:0003723 RNA binding
GO:0005515 protein binding
GO:0009982 pseudouridine synthase activity
GO:0016853 isomerase activity
GO:0034513 box H/ACA snoRNA binding
GO:0070034 telomerase RNA binding

Biological Process:
GO:0000495 box H/ACA snoRNA 3'-end processing
GO:0001522 pseudouridine synthesis
GO:0006364 rRNA processing
GO:0006396 RNA processing
GO:0007004 telomere maintenance via telomerase
GO:0008283 cell proliferation
GO:0009451 RNA modification
GO:0031118 rRNA pseudouridine synthesis
GO:0031120 snRNA pseudouridine synthesis
GO:0032212 positive regulation of telomere maintenance via telomerase
GO:0033979 box H/ACA snoRNA metabolic process
GO:0042254 ribosome biogenesis
GO:0051973 positive regulation of telomerase activity
GO:0090666 scaRNA localization to Cajal body
GO:0090669 telomerase RNA stabilization
GO:1904851 positive regulation of establishment of protein localization to telomere
GO:1904871 positive regulation of protein localization to Cajal body
GO:1904872 regulation of telomerase RNA localization to Cajal body
GO:1904874 positive regulation of telomerase RNA localization to Cajal body
GO:1990481 mRNA pseudouridine synthesis

Cellular Component:
GO:0001650 fibrillar center
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005697 telomerase holoenzyme complex
GO:0005730 nucleolus
GO:0005737 cytoplasm
GO:0015030 Cajal body
GO:0031429 box H/ACA snoRNP complex
GO:0072589 box H/ACA scaRNP complex
GO:0090661 box H/ACA telomerase RNP complex


-  Descriptions from all associated GenBank mRNAs
  LF211549 - JP 2014500723-A/19052: Polycomb-Associated Non-Coding RNAs.
MA447126 - JP 2018138019-A/19052: Polycomb-Associated Non-Coding RNAs.
LF385329 - JP 2014500723-A/192832: Polycomb-Associated Non-Coding RNAs.
MA620906 - JP 2018138019-A/192832: Polycomb-Associated Non-Coding RNAs.
BC009928 - Homo sapiens dyskeratosis congenita 1, dyskerin, mRNA (cDNA clone MGC:4843 IMAGE:3604732), complete cds.
AK307672 - Homo sapiens cDNA, FLJ97620.
AK225077 - Homo sapiens mRNA for dyskerin variant, clone: CAS04510.
U59151 - Human Cbf5p homolog (CBF5) mRNA, complete cds.
AF067008 - Homo sapiens dyskerin (DKC1) mRNA, complete cds.
JD423285 - Sequence 404309 from Patent EP1572962.
JD500309 - Sequence 481333 from Patent EP1572962.
JF279874 - Homo sapiens dyskeratosis congenita 1 isoform 3 (DKC1) mRNA, complete cds, alternatively spliced.
KC954523 - Homo sapiens dyskeratosis congenita 1 isoform 4 mRNA, complete cds, alternatively spliced.
KC954524 - Homo sapiens dyskeratosis congenita 1 isoform 5 mRNA, complete cds, alternatively spliced.
KC954525 - Homo sapiens dyskeratosis congenita 1 isoform 6 mRNA, complete cds, alternatively spliced.
BC002547 - Homo sapiens dyskeratosis congenita 1, dyskerin, mRNA (cDNA clone IMAGE:3138436), **** WARNING: chimeric clone ****.
JD172757 - Sequence 153781 from Patent EP1572962.
BC010015 - Homo sapiens dyskeratosis congenita 1, dyskerin, mRNA (cDNA clone MGC:15313 IMAGE:4303933), complete cds.
KJ905728 - Synthetic construct Homo sapiens clone ccsbBroadEn_15398 DKC1 gene, encodes complete protein.
KJ891052 - Synthetic construct Homo sapiens clone ccsbBroadEn_00446 DKC1 gene, encodes complete protein.
KR710385 - Synthetic construct Homo sapiens clone CCSBHm_00012094 DKC1 (DKC1) mRNA, encodes complete protein.
KR710386 - Synthetic construct Homo sapiens clone CCSBHm_00012107 DKC1 (DKC1) mRNA, encodes complete protein.
KR710387 - Synthetic construct Homo sapiens clone CCSBHm_00012123 DKC1 (DKC1) mRNA, encodes complete protein.
CU679575 - Synthetic construct Homo sapiens gateway clone IMAGE:100023211 5' read DKC1 mRNA.
AB587489 - Synthetic construct DNA, clone: pF1KB8679, Homo sapiens DKC1 gene for dyskeratosis congenita 1, dyskerin, without stop codon, in Flexi system.
AM392631 - Synthetic construct Homo sapiens clone IMAGE:100002065 for hypothetical protein (DKC1 gene).
AM392823 - Synthetic construct Homo sapiens clone IMAGE:100002068 for hypothetical protein (DKC1 gene).
DQ895984 - Synthetic construct Homo sapiens clone IMAGE:100010444; FLH189237.01L; RZPDo839D0164D dyskeratosis congenita 1, dyskerin (DKC1) gene, encodes complete protein.
DQ892737 - Synthetic construct clone IMAGE:100005367; FLH189241.01X; RZPDo839D0174D dyskeratosis congenita 1, dyskerin (DKC1) gene, encodes complete protein.
LF380953 - JP 2014500723-A/188456: Polycomb-Associated Non-Coding RNAs.
MA616530 - JP 2018138019-A/188456: Polycomb-Associated Non-Coding RNAs.
LF380954 - JP 2014500723-A/188457: Polycomb-Associated Non-Coding RNAs.
MA616531 - JP 2018138019-A/188457: Polycomb-Associated Non-Coding RNAs.
LF380955 - JP 2014500723-A/188458: Polycomb-Associated Non-Coding RNAs.
MA616532 - JP 2018138019-A/188458: Polycomb-Associated Non-Coding RNAs.
LF380956 - JP 2014500723-A/188459: Polycomb-Associated Non-Coding RNAs.
MA616533 - JP 2018138019-A/188459: Polycomb-Associated Non-Coding RNAs.
LF380957 - JP 2014500723-A/188460: Polycomb-Associated Non-Coding RNAs.
MA616534 - JP 2018138019-A/188460: Polycomb-Associated Non-Coding RNAs.
LF380959 - JP 2014500723-A/188462: Polycomb-Associated Non-Coding RNAs.
MA616536 - JP 2018138019-A/188462: Polycomb-Associated Non-Coding RNAs.
LF380963 - JP 2014500723-A/188466: Polycomb-Associated Non-Coding RNAs.
MA616540 - JP 2018138019-A/188466: Polycomb-Associated Non-Coding RNAs.
LF380965 - JP 2014500723-A/188468: Polycomb-Associated Non-Coding RNAs.
MA616542 - JP 2018138019-A/188468: Polycomb-Associated Non-Coding RNAs.
LF380966 - JP 2014500723-A/188469: Polycomb-Associated Non-Coding RNAs.
MA616543 - JP 2018138019-A/188469: Polycomb-Associated Non-Coding RNAs.
LF380967 - JP 2014500723-A/188470: Polycomb-Associated Non-Coding RNAs.
MA616544 - JP 2018138019-A/188470: Polycomb-Associated Non-Coding RNAs.
JD551984 - Sequence 533008 from Patent EP1572962.
JD263525 - Sequence 244549 from Patent EP1572962.
JD474454 - Sequence 455478 from Patent EP1572962.
JD181544 - Sequence 162568 from Patent EP1572962.
JD236581 - Sequence 217605 from Patent EP1572962.
LF380968 - JP 2014500723-A/188471: Polycomb-Associated Non-Coding RNAs.
MA616545 - JP 2018138019-A/188471: Polycomb-Associated Non-Coding RNAs.
JD331284 - Sequence 312308 from Patent EP1572962.
JD501374 - Sequence 482398 from Patent EP1572962.
JD386336 - Sequence 367360 from Patent EP1572962.
JD167355 - Sequence 148379 from Patent EP1572962.
JD231032 - Sequence 212056 from Patent EP1572962.
JD173867 - Sequence 154891 from Patent EP1572962.
LF380969 - JP 2014500723-A/188472: Polycomb-Associated Non-Coding RNAs.
MA616546 - JP 2018138019-A/188472: Polycomb-Associated Non-Coding RNAs.
JD523954 - Sequence 504978 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

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

-  Other Names for This Gene
  Alternate Gene Symbols: DKC1_HUMAN, ENST00000369550.1, ENST00000369550.2, ENST00000369550.3, ENST00000369550.4, ENST00000369550.5, ENST00000369550.6, ENST00000369550.7, ENST00000369550.8, ENST00000369550.9, F5BSB3, NOLA4, NR_110023, O43845, O60832, Q96G67, Q9Y505, uc004fmm.1, uc004fmm.2, uc004fmm.3, uc004fmm.4, uc004fmm.5, uc004fmm.6
UCSC ID: ENST00000369550.10
RefSeq Accession: NM_001363
Protein: O60832 (aka DKC1_HUMAN)
CCDS: CCDS14761.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene DKC1:
dkc (Dyskeratosis Congenita and Related Telomere Biology Disorders)
pf (Pulmonary Fibrosis Predisposition Overview)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.