Q9ESX5 (DKC1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
H/ACA ribonucleoprotein complex subunit 4
EC=5.4.99.-

Alternative name(s):
Dyskerin
Nopp140-associated protein of 57 kDa
Nucleolar protein NAP57
Nucleolar protein family A member 4
snoRNP protein DKC1

Gene names

Name:

Dkc1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	509 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.4 Ref.5
Catalytic activity	RNA uridine = RNA pseudouridine.
Subunit structure	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) By similarity. 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 By similarity.
Subcellular location	Nucleus › nucleolus. Nucleus › Cajal body. Note: Also localized to Cajal bodies (coiled bodies).
Tissue specificity	Ubiquitously expressed, with elevated levels in Purkinje cells, the olfactory bulb, and Leydig cells of the testis. Ref.1
Developmental stage	Expressed throughout development, particularly in developing epithelial tissues. Ref.1
Sequence similarities	Belongs to the pseudouridine synthase TruB family. Contains 1 PUA domain.

Ontologies

Keywords
Biological process	Ribosome biogenesis rRNA processing
Cellular component	Nucleus
Ligand	RNA-binding
Molecular function	Isomerase Ribonucleoprotein
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	rRNA modification Inferred from sequence alignment PubMed 10679015. Source: MGI
Cellular_component	Cajal body Inferred from electronic annotation. Source: UniProtKB-SubCell nucleolus Traceable author statement Ref.1. Source: MGI telomerase holoenzyme complex Inferred from electronic annotation. Source: Compara
Molecular_function	RNA binding Traceable author statement Ref.1. Source: MGI pseudouridine synthase activity Inferred from electronic annotation. Source: InterPro pseudouridylate synthase activity Traceable author statement Ref.1. Source: MGI snoRNP binding Inferred from sequence or structural similarity PubMed 10679015. Source: MGI telomerase activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 509	508	H/ACA ribonucleoprotein complex subunit 4		PRO_0000121984
Regions
	Domain	297 – 372	76	PUA
	Region	2 – 21	20	Nucleolar localization By similarity
	Region	446 – 509	64	Nuclear and nucleolar localization By similarity
	Compositional bias	11 – 17	7	Poly-Lys
Sites
	Active site	125	1	Nucleophile By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylalanine By similarity
	Modified residue	451	1	Phosphoserine Ref.8 Ref.9 Ref.10 Ref.12
	Modified residue	453	1	Phosphoserine Ref.8 Ref.9 Ref.10 Ref.12
	Modified residue	455	1	Phosphoserine Ref.8 Ref.12
	Modified residue	458	1	Phosphothreonine Ref.10
	Modified residue	481	1	Phosphoserine Ref.7 Ref.9
	Modified residue	508	1	Phosphoserine Ref.6 Ref.11 Ref.12
Experimental info
	Mutagenesis	353	1	A → V: Destabilization of TERC, impaired telomerase function, and reduced rRNA pseudouridylation and pre-rRNA processing. Ref.5
	Mutagenesis	402	1	G → E: Reduced rRNA pseudouridylation and pre-rRNA processing. Ref.5
	Sequence conflict	234 – 241	8	GLLLGVGG → CFVLGSGC in CAC04528. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9ESX5 [UniParc]. Last modified July 27, 2011. Version 4. Checksum: 17C50FDF48912A14	FASTA	509	57,402
	10 20 30 40 50 60 MADAEVITFP KKHKKKKDRK PLQEDDVAEI QHAEEFLIKP ESKVAQLDTS QWPLLLKNFD 70 80 90 100 110 120 KLNVRTAHYT PLPCGSNPLK REIGDYIRTG FINLDKPSNP SSHEVVAWIR RILRVEKTGH 130 140 150 160 170 180 SGTLDPKVTG CLIVCIERAT RLVKSQQSAG KEYVGIVRLH NAIEGGTQLS RALETLTGAL 190 200 210 220 230 240 FQRPPLIAAV KRQLRVRTIY ESKMIEYDPE RRLGIFWVSC EAGTYIRTLC VHLGLLLGVG 250 260 270 280 290 300 GQMQELRRVR SGVMSEKDHM VTMHDVLDAQ WLYDNHKDES YLRRVVYPLE KLLTSHKRLV 310 320 330 340 350 360 MKDSAVNAIC YGAKIMLPGL LRYEDGIEVN QEIVVITTKG EAICMAIALM TTAVISTCDH 370 380 390 400 410 420 GIVAKIKRVI MERDTYPRKW GLGPKASQKK MMIKQGLLDK HGKPTDNTPA TWKQDYIDYS 430 440 450 460 470 480 DSGKNTLVTE AVQAPQLAAE AVNVIKRKRD SESESDETPT VPQLKEKKKK KDKKPKTVLE 490 500 SGGETGDGDN DTTKKKKKKK VKVVEEMSE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Gene structure and expression of the mouse dyskeratosis congenita gene, dkc1." Heiss N.S., Baechner D., Salowsky R., Kolb A., Kioschis P., Poustka A. Genomics 67:153-163(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. Strain: 129/Ola.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Colon.
[3]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[4]	"Dyskeratosis congenita and cancer in mice deficient in ribosomal RNA modification." Ruggero D., Grisendi S., Piazza F., Rego E., Mari F., Rao P.H., Cordon-Cardo C., Pandolfi P.P. Science 299:259-262(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[5]	"Mouse dyskerin mutations affect accumulation of telomerase RNA and small nucleolar RNA, telomerase activity, and ribosomal RNA processing." Mochizuki Y., He J., Kulkarni S., Bessler M., Mason P.J. Proc. Natl. Acad. Sci. U.S.A. 101:10756-10761(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ALA-353 AND GLY-402.
[6]	"Comprehensive identification of phosphorylation sites in postsynaptic density preparations." Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L. Mol. Cell. Proteomics 5:914-922(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-508, MASS SPECTROMETRY. Tissue: Brain.
[7]	"Protein phosphorylation and expression profiling by Yin-yang multidimensional liquid chromatography (Yin-yang MDLC) mass spectrometry." Dai J., Jin W.-H., Sheng Q.-H., Shieh C.-H., Wu J.-R., Zeng R. J. Proteome Res. 6:250-262(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, MASS SPECTROMETRY. Tissue: Liver.
[8]	"A differential phosphoproteomic analysis of retinoic acid-treated P19 cells." Smith J.C., Duchesne M.A., Tozzi P., Ethier M., Figeys D. J. Proteome Res. 6:3174-3186(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-451; SER-453 AND SER-455, MASS SPECTROMETRY. Tissue: Teratocarcinoma.
[9]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-451; SER-453 AND SER-481, MASS SPECTROMETRY. Tissue: Liver.
[10]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-451; SER-453 AND THR-458, MASS SPECTROMETRY. Tissue: Melanoma.
[11]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-508, MASS SPECTROMETRY. Tissue: Macrophage.
[12]	"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry." Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J. Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-451; SER-453; SER-455 AND SER-508, MASS SPECTROMETRY. Tissue: Embryonic fibroblast.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ250973 , AJ250972, AJ250974, AJ250975, AJ250976, AJ250978, AJ250980, AJ250981, AJ250979, AJ250977 Genomic DNA. Translation: CAC04528.1. AK136418 mRNA. Translation: BAE22970.1. AL808110 Genomic DNA. Translation: CAM26485.1.
IPI	IPI00113635.
RefSeq	NP_001025478.1. NM_001030307.2.
UniGene	Mm.291062.
3D structure databases
ProteinModelPortal	Q9ESX5.
SMR	Q9ESX5. Positions 48-408.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-1854010.
PTM databases
PhosphoSite	Q9ESX5.
Proteomic databases
PaxDb	Q9ESX5.
PRIDE	Q9ESX5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000033776; ENSMUSP00000033776; ENSMUSG00000031403.
GeneID	245474.
KEGG	mmu:245474.
UCSC	uc009tpo.2. mouse.
Organism-specific databases
CTD	1736.
MGI	MGI:1861727. Dkc1.
Phylogenomic databases
eggNOG	COG0130.
GeneTree	ENSGT00510000047092.
HOGENOM	HOG000231224.
HOVERGEN	HBG081442.
InParanoid	Q3UWE5.
KO	K11131.
Gene expression databases
ArrayExpress	Q9ESX5.
Bgee	Q9ESX5.
Genevestigator	Q9ESX5.
GermOnline	ENSMUSG00000031403. Mus musculus.
Family and domain databases
Gene3D	2.30.130.10. 1 hit.
InterPro	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. [Graphical view]
PANTHER	PTHR23127. PTHR23127. 1 hit.
Pfam	PF08068. DKCLD. 1 hit. PF01472. PUA. 1 hit. PF01509. TruB_N. 1 hit. [Graphical view]
SMART	SM00359. PUA. 1 hit. [Graphical view]
SUPFAM	SSF55120. PsdUridine_synth_cat_dom. 1 hit. SSF88697. PUA-like. 1 hit.
TIGRFAMs	TIGR00425. CBF5. 1 hit. TIGR00451. unchar_dom_2. 1 hit.
PROSITE	PS50890. PUA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	386727.
SOURCE	Search...

Entry information

Entry name

DKC1_MOUSE

Accession

Primary (citable) accession number: Q9ESX5
Secondary accession number(s): Q3UWE5

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2004
Last sequence update:	July 27, 2011
Last modified:	May 29, 2013
This is version 100 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program