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Q9H6W3 (NO66_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 96. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Bifunctional lysine-specific demethylase and histidyl-hydroxylase NO66

EC=1.14.11.-
EC=1.14.11.27
Alternative name(s):
60S ribosomal protein L8 histidine hydroxylase
Histone lysine demethylase NO66
Myc-associated protein with JmjC domain
Nucleolar protein 66
Short name=hsNO66
Ribosomal oxygenase NO66
Short name=ROX
Gene names
Name:NO66
Synonyms:C14orf169, MAPJD
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length641 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Oxygenase that can act as both a histone lysine demethylase and a ribosomal histidine hydroxylase. Specifically demethylates 'Lys-4' (H3K4me) and 'Lys-36' (H3K36me) of histone H3, thereby playing a central role in histone code. Preferentially demethylates trimethylated H3 'Lys-4' (H3K4me3) and monomethylated H3 'Lys-4' (H3K4me1) residues, while it has weaker activity for dimethylated H3 'Lys-36' (H3K36me2). Also catalyzes the hydroxylation of 60S ribosomal protein L8 on 'His-216'. Acts as a regulator of osteoblast differentiation via its interaction with SP7/OSX by demethylating H3K4me and H3K36me, thereby inhibiting SP7/OSX-mediated promoter activation By similarity. May also play a role in ribosome biogenesis and in the replication or remodeling of certain heterochromatic region. Participates in MYC-induced transcriptional activation. Ref.1 Ref.5 Ref.9

Catalytic activity

Protein N6,N(6)-dimethyl-L-lysine + 2-oxoglutarate + O2 = protein N(6)-methyl-L-lysine + succinate + formaldehyde + CO2. Ref.9

Protein N(6)-methyl-L-lysine + 2-oxoglutarate + O2 = protein L-lysine + succinate + formaldehyde + CO2. Ref.9

L-histidine-[60S ribosomal protein L8] + 2-oxoglutarate + O2 = (3S)-3-hydroxy-L-histidine-[60S ribosomal protein L8] + succinate + CO2. Ref.9

Cofactor

Binds 1 Fe2+ ion per subunit By similarity.

Subunit structure

Interacts with SP7/OSX; the interaction is direct By similarity. Interacts with MYC. Interacts with PHF19; leading to its recruitment to H3K36me3 sites. Ref.5 Ref.8

Subcellular location

Nucleusnucleolus. Nucleusnucleoplasm. Note: Granular part of nucleoli. Nucleoplasm, nucleoplasmic foci, some of them associated with nucleoli. Ref.1 Ref.5

Tissue specificity

Widely expressed. Overexpressed in lung carcinomas. Ref.1 Ref.5

Sequence similarities

Belongs to the MINA53/NO66 family. NO66 subfamily.

Contains 1 JmjC domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandIron
Metal-binding
   Molecular functionChromatin regulator
Dioxygenase
Oxidoreductase
Repressor
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processhistone H3-K36 demethylation

Inferred from sequence or structural similarity. Source: UniProtKB

histone H3-K4 demethylation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of osteoblast differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentnucleolus

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionhistone demethylase activity (H3-K36 specific)

Inferred from sequence or structural similarity. Source: UniProtKB

histone demethylase activity (H3-K4 specific)

Inferred from sequence or structural similarity. Source: UniProtKB

iron ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sp7Q8VI676EBI-2513645,EBI-7608836From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9H6W3-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9H6W3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-212: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 641641Bifunctional lysine-specific demethylase and histidyl-hydroxylase NO66
PRO_0000264613

Regions

Domain294 – 439146JmjC

Sites

Metal binding3401Iron; catalytic By similarity
Metal binding3421Iron; catalytic By similarity
Metal binding4051Iron; catalytic By similarity

Amino acid modifications

Modified residue11N-acetylmethionine Ref.10
Modified residue1091Phosphoserine Ref.6 Ref.7

Natural variations

Alternative sequence1 – 212212Missing in isoform 2.
VSP_038663
Natural variant171K → R. Ref.1 Ref.2 Ref.4
Corresponds to variant rs10144469 [ dbSNP | Ensembl ].
VAR_062422
Natural variant2181F → S.
Corresponds to variant rs758109 [ dbSNP | Ensembl ].
VAR_057819
Natural variant2391Q → H.
Corresponds to variant rs34970526 [ dbSNP | Ensembl ].
VAR_060191
Natural variant3641V → A. Ref.1 Ref.2 Ref.4
Corresponds to variant rs3813563 [ dbSNP | Ensembl ].
VAR_062423

Experimental info

Sequence conflict3921E → G in BAG61814. Ref.2

Secondary structure

....................................................................................... 641
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 19, 2010. Version 2.
Checksum: E66A4342B1D1BFF2

FASTA64171,086
        10         20         30         40         50         60 
MDGLQASAGP LRRGRPKRRR KPQPHSGSVL ALPLRSRKIR KQLRSVVSRM AALRTQTLPS 

        70         80         90        100        110        120 
ENSEESRVES TADDLGDALP GGAAVAAVPD AARREPYGHL GPAELLEASP AARSLQTPSA 

       130        140        150        160        170        180 
RLVPASAPPA RLVEVPAAPV RVVETSALLC TAQHLAAVQS SGAPATASGP QVDNTGGEPA 

       190        200        210        220        230        240 
WDSPLRRVLA ELNRIPSSRR RAARLFEWLI APMPPDHFYR RLWEREAVLV RRQDHTYYQG 

       250        260        270        280        290        300 
LFSTADLDSM LRNEEVQFGQ HLDAARYING RRETLNPPGR ALPAAAWSLY QAGCSLRLLC 

       310        320        330        340        350        360 
PQAFSTTVWQ FLAVLQEQFG SMAGSNVYLT PPNSQGFAPH YDDIEAFVLQ LEGRKLWRVY 

       370        380        390        400        410        420 
RPRVPTEELA LTSSPNFSQD DLGEPVLQTV LEPGDLLYFP RGFIHQAECQ DGVHSLHLTL 

       430        440        450        460        470        480 
STYQRNTWGD FLEAILPLAV QAAMEENVEF RRGLPRDFMD YMGAQHSDSK DPRRTAFMEK 

       490        500        510        520        530        540 
VRVLVARLGH FAPVDAVADQ RAKDFIHDSL PPVLTDRERA LSVYGLPIRW EAGEPVNVGA 

       550        560        570        580        590        600 
QLTTETEVHM LQDGIARLVG EGGHLFLYYT VENSRVYHLE EPKCLEIYPQ QADAMELLLG 

       610        620        630        640 
SYPEFVRVGD LPCDSVEDQL SLATTLYDKG LLLTKMPLAL N 

« Hide

Isoform 2 [UniParc].

Checksum: F07631F3A3F8CDB7
Show »

FASTA42948,687

References

« Hide 'large scale' references
[1]"NO66, a highly conserved dual location protein in the nucleolus and in a special type of synchronously replicating chromatin."
Eilbracht J., Reichenzeller M., Hergt M., Schnoelzer M., Heid H., Stoehr M., Franke W.W., Schmidt-Zachmann M.S.
Mol. Biol. Cell 15:1816-1832(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANTS ARG-17 AND ALA-364.
[2]"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. expand/collapse author list , 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] (ISOFORMS 1 AND 2), VARIANTS ARG-17 AND ALA-364.
[3]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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] (ISOFORM 1), VARIANTS ARG-17 AND ALA-364.
Tissue: Lymph and Mammary gland.
[5]"Identification of Myc-associated protein with JmjC domain as a novel therapeutic target oncogene for lung cancer."
Suzuki C., Takahashi K., Hayama S., Ishikawa N., Kato T., Ito T., Tsuchiya E., Nakamura Y., Daigo Y.
Mol. Cancer Ther. 6:542-551(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MYC, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[6]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-109, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-109, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[8]"Polycomb PHF19 binds H3K36me3 and recruits PRC2 and demethylase NO66 to embryonic stem cell genes during differentiation."
Brien G.L., Gambero G., O'Connell D.J., Jerman E., Turner S.A., Egan C.M., Dunne E.J., Jurgens M.C., Wynne K., Piao L., Lohan A.J., Ferguson N., Shi X., Sinha K.M., Loftus B.J., Cagney G., Bracken A.P.
Nat. Struct. Mol. Biol. 19:1273-1281(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PHF19.
[9]"Oxygenase-catalyzed ribosome hydroxylation occurs in prokaryotes and humans."
Ge W., Wolf A., Feng T., Ho C.H., Sekirnik R., Zayer A., Granatino N., Cockman M.E., Loenarz C., Loik N.D., Hardy A.P., Claridge T.D., Hamed R.B., Chowdhury R., Gong L., Robinson C.V., Trudgian D.C., Jiang M. expand/collapse author list , Mackeen M.M., McCullagh J.S., Gordiyenko Y., Thalhammer A., Yamamoto A., Yang M., Liu-Yi P., Zhang Z., Schmidt-Zachmann M., Kessler B.M., Ratcliffe P.J., Preston G.M., Coleman M.L., Schofield C.J.
Nat. Chem. Biol. 8:960-962(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS RPL8 HYDROXYLASE, CATALYTIC ACTIVITY.
[10]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY390535 mRNA. Translation: AAR27292.1.
AK025455 mRNA. Translation: BAB15138.1.
AK299994 mRNA. Translation: BAG61814.1.
AC005280 Genomic DNA. No translation available.
BC011350 mRNA. Translation: AAH11350.1.
BC071954 mRNA. Translation: AAH71954.1.
RefSeqNP_078920.2. NM_024644.4.
UniGeneHs.509916.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4DIQX-ray2.40A/B167-641[»]
4E4HX-ray2.28A/B/C/D183-641[»]
ProteinModelPortalQ9H6W3.
SMRQ9H6W3. Positions 183-638.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122818. 4 interactions.
IntActQ9H6W3. 3 interactions.
MINTMINT-5009834.

PTM databases

PhosphoSiteQ9H6W3.

Polymorphism databases

DMDM284018103.

Proteomic databases

PeptideAtlasQ9H6W3.
PRIDEQ9H6W3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID79697.
KEGGhsa:79697.
UCSCuc001xok.1. human. [Q9H6W3-1]

Organism-specific databases

CTD79697.
GeneCardsGC14P073958.
H-InvDBHIX0011794.
HGNCHGNC:20968. C14orf169.
MIM611919. gene.
neXtProtNX_Q9H6W3.
PharmGKBPA134919088.
GenAtlasSearch...

Phylogenomic databases

HOVERGENHBG060021.
KOK16914.
PhylomeDBQ9H6W3.

Gene expression databases

CleanExHS_C14orf169.
GenevestigatorQ9H6W3.

Family and domain databases

InterProIPR003347. JmjC_dom.
IPR013109. NO66/MINA.
[Graphical view]
PANTHERPTHR13096:SF0. PTHR13096:SF0. 1 hit.
PfamPF08007. Cupin_4. 1 hit.
[Graphical view]
SMARTSM00558. JmjC. 1 hit.
[Graphical view]
PROSITEPS51184. JMJC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi79697.
NextBio68992.
PROQ9H6W3.
SOURCESearch...

Entry information

Entry nameNO66_HUMAN
AccessionPrimary (citable) accession number: Q9H6W3
Secondary accession number(s): B4DT02
Entry history
Integrated into UniProtKB/Swiss-Prot: December 12, 2006
Last sequence update: January 19, 2010
Last modified: April 16, 2014
This is version 96 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM