Q9NX24 (NHP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
H/ACA ribonucleoprotein complex subunit 2

Alternative name(s):
Nucleolar protein family A member 2
snoRNP protein NHP2

Gene names

Name:	NHP2
Synonyms:	NOLA2
ORF Names:	HSPC286

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	153 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Required for ribosome biogenesis and telomere maintenance. Part of the 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. May also be required for correct processing or intranuclear trafficking of TERC, the RNA component of the telomerase reverse transcriptase (TERT) holoenzyme. Ref.10
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). Ref.1 Ref.11
Subcellular location	Nucleus › nucleolus. Nucleus › Cajal body. Note: Also localized to Cajal bodies (coiled bodies). Ref.1 Ref.8 Ref.9
Tissue specificity	Expressed in brain, colon, heart, kidney, ovary, pancreas, placenta, prostate, skeletal muscle, small intestine, spleen, testis and thymus. Also expressed at lower levels in the liver. Ref.2
Developmental stage	Transcript peaks at G1/S transition. Ref.2
Involvement in disease	Dyskeratosis congenita, autosomal recessive, 2 (DKCB2) [MIM:613987]: A rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15
Sequence similarities	Belongs to the ribosomal protein L7Ae family.
Sequence caution	The sequence AAF28964.1 differs from that shown. Reason: Frameshift at positions 37, 119 and 120.

Ontologies

Keywords
Biological process	Ribosome biogenesis rRNA processing
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation Dyskeratosis congenita
Ligand	RNA-binding
Molecular function	Ribonucleoprotein
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	rRNA pseudouridine synthesis Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	Cajal body Inferred from electronic annotation. Source: UniProtKB-SubCell nucleolus Inferred from electronic annotation. Source: UniProtKB-SubCell small nucleolar ribonucleoprotein complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	snoRNA binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 153	153	H/ACA ribonucleoprotein complex subunit 2		PRO_0000136763
Amino acid modifications
	Modified residue	19	1	Phosphoserine Ref.13
	Cross-link	5		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.12
Natural variations
	Natural variant	118	1	A → T. Ref.15 Corresponds to variant rs139588879 [ dbSNP | Ensembl ].		VAR_065870
	Natural variant	126	1	V → M in DKCB2. Ref.15 Corresponds to variant rs121908090 [ dbSNP | Ensembl ].		VAR_065871
	Natural variant	139	1	Y → H in DKCB2. Ref.15 Corresponds to variant rs121908089 [ dbSNP | Ensembl ].		VAR_065872

Sequences

	Sequence		Length	Mass (Da)
	Q9NX24 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 7658FDFF88AF3178	FASTA	153	17,201
	10 20 30 40 50 60 MTKIKADPDG PEAQAEACSG ERTYQELLVN QNPIAQPLAS RRLTRKLYKC IKKAVKQKQI 70 80 90 100 110 120 RRGVKEVQKF VNKGEKGIMV LAGDTLPIEV YCHLPVMCED RNLPYVYIPS KTDLGAAAGS 130 140 150 KRPTCVIMVK PHEEYQEAYD ECLEEVQSLP LPL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human H/ACA small nucleolar RNPs and telomerase share evolutionarily conserved proteins NHP2 and NOP10." Pogacic V., Dragon F., Filipowicz W. Mol. Cell. Biol. 20:9028-9040(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH GAR1; SMALL NUCLEOLAR RNAS AND TERC, SUBCELLULAR LOCATION.
[2]	"Expression of the human homologue of the small nucleolar RNA-binding protein NHP2 gene during monocytic differentiation of U937 cells." Kang H.S., Jung H.M., Jun D., Huh T.L., Kim Y.H. Biochim. Biophys. Acta 1575:31-39(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[3]	"Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells." Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X. , Gu J., Chen S.-J., Chen Z. Genome Res. 10:1546-1560(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Umbilical cord blood.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Muscle and Placenta.
[8]	"Directed proteomic analysis of the human nucleolus." Andersen J.S., Lyon C.E., Fox A.H., Leung A.K.L., Lam Y.W., Steen H., Mann M., Lamond A.I. Curr. Biol. 12:1-11(2002) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION.
[9]	"Functional proteomic analysis of human nucleolus." Scherl A., Coute Y., Deon C., Calle A., Kindbeiter K., Sanchez J.-C., Greco A., Hochstrasser D.F., Diaz J.-J. Mol. Biol. Cell 13:4100-4109(2002) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[10]	"Architecture and assembly of mammalian H/ACA small nucleolar and telomerase ribonucleoproteins." Wang C., Meier U.T. EMBO J. 23:1857-1867(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CHARACTERIZATION OF THE H/ACA SNORNP COMPLEX.
[11]	"A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis." Venteicher A.S., Abreu E.B., Meng Z., McCann K.E., Terns R.M., Veenstra T.D., Terns M.P., Artandi S.E. Science 323:644-648(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE TELOMERASE HOLOENZYME COMPLEX.
[12]	"A proteomic screen for nucleolar SUMO targets shows SUMOylation modulates the function of Nop5/Nop58." Westman B.J., Verheggen C., Hutten S., Lam Y.W., Bertrand E., Lamond A.I. Mol. Cell 39:618-631(2010) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION AT LYS-5.
[13]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]	"Mutations in the telomerase component NHP2 cause the premature ageing syndrome dyskeratosis congenita." Vulliamy T., Beswick R., Kirwan M., Marrone A., Digweed M., Walne A., Dokal I. Proc. Natl. Acad. Sci. U.S.A. 105:8073-8078(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS DKCB2 MET-126 AND HIS-139, VARIANT THR-118.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ293309 mRNA. Translation: CAC08452.1. AF401219 mRNA. Translation: AAL02175.1. AF161404 mRNA. Translation: AAF28964.1. Frameshift. AK000486 mRNA. Translation: BAA91198.1. CR457238 mRNA. Translation: CAG33519.1. AC136632 Genomic DNA. No translation available. BC000009 mRNA. Translation: AAH00009.1. BC006387 mRNA. Translation: AAH06387.1.
IPI	IPI00041325.
RefSeq	NP_001030005.1. NM_001034833.1. NP_060308.1. NM_017838.3.
UniGene	Hs.728908.
3D structure databases
ProteinModelPortal	Q9NX24.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NX24. 6 interactions.
STRING	9606.ENSP00000274606.
PTM databases
PhosphoSite	Q9NX24.
Polymorphism databases
DMDM	68565945.
2D gel databases
SWISS-2DPAGE	Q9NX24.
Proteomic databases
PaxDb	Q9NX24.
PeptideAtlas	Q9NX24.
PRIDE	Q9NX24.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000274606; ENSP00000274606; ENSG00000145912.
GeneID	55651.
KEGG	hsa:55651.
UCSC	uc003mir.2. human.
Organism-specific databases
CTD	55651.
GeneCards	GC05M177510.
HGNC	HGNC:14377. NHP2.
HPA	HPA044171.
MIM	606470. gene. 613987. phenotype.
neXtProt	NX_Q9NX24.
Orphanet	1775. Dyskeratosis congenita.
PharmGKB	PA164723898.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1358.
HOGENOM	HOG000055227.
HOVERGEN	HBG000328.
InParanoid	Q9NX24.
KO	K11129.
OMA	HLPAVCE.
OrthoDB	EOG4W3SP7.
PhylomeDB	Q9NX24.
Gene expression databases
ArrayExpress	Q9NX24.
Bgee	Q9NX24.
CleanEx	HS_NHP2.
Genevestigator	Q9NX24.
GermOnline	ENSG00000145912. Homo sapiens.
Family and domain databases
InterPro	IPR002415. H/ACA_rnp_Nhp2_euk. IPR004038. Ribosomal_L7Ae/L30e/S12e/Gad45. IPR018492. Ribosomal_L7Ae/L8/Nhp2. [Graphical view]
Pfam	PF01248. Ribosomal_L7Ae. 1 hit. [Graphical view]
PRINTS	PR00881. L7ARS6FAMILY. PR00883. NUCLEARHMG.
PROSITE	PS01082. RIBOSOMAL_L7AE. False negative. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	NHP2. human.
GenomeRNAi	55651.
NextBio	60350.
SOURCE	Search...

Entry information

Entry name

NHP2_HUMAN

Accession

Primary (citable) accession number: Q9NX24
Secondary accession number(s): A6NKY8, Q9P095

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 5, 2005
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 114 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.