Q9H6W3 (NO66_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	641 AA.
Sequence status	Complete.
Protein existence	Evidence 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	Nucleus › nucleolus. Nucleus › nucleoplasm. 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 process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Iron Metal-binding
Molecular function	Chromatin regulator Dioxygenase Oxidoreductase Repressor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of osteoblast differentiation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from sequence or structural similarity. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleolus 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_function	histone 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 single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 641

641

Bifunctional lysine-specific demethylase and histidyl-hydroxylase NO66

PRO_0000264613

Regions

Domain

294 – 439

146

JmjC

Sites

Metal binding

340

1

Iron; catalytic By similarity

Metal binding

342

1

Iron; catalytic By similarity

Metal binding

405

1

Iron; catalytic By similarity

Amino acid modifications

Modified residue

109

1

Phosphoserine Ref.6 Ref.7

Natural variations

Alternative sequence

1 – 212

212

Missing in isoform 2.

VSP_038663

Natural variant

17

1

K → R. Ref.1 Ref.2 Ref.4
Corresponds to variant rs10144469 [ dbSNP | Ensembl ].

VAR_062422

Natural variant

218

1

F → S.
Corresponds to variant rs758109 [ dbSNP | Ensembl ].

VAR_057819

Natural variant

239

1

Q → H.
Corresponds to variant rs34970526 [ dbSNP | Ensembl ].

VAR_060191

Natural variant

364

1

V → A. Ref.1 Ref.2 Ref.4
Corresponds to variant rs3813563 [ dbSNP | Ensembl ].

VAR_062423

Experimental info

Sequence conflict

392

1

E → G in BAG61814. Ref.2

Secondary structure

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641

Helix Strand Turn

Details...

Helix

184 – 192

9

Helix

198 – 210

13

Helix

215 – 221

7

Turn

222 – 225

4

Beta strand

228 – 230

3

Turn

235 – 240

6

Helix

244 – 253

10

Turn

259 – 261

3

Beta strand

262 – 266

5

Beta strand

271 – 274

4

Beta strand

278 – 280

3

Helix

283 – 291

9

Beta strand

295 – 299

5

Helix

301 – 304

4

Helix

306 – 319

14

Beta strand

324 – 330

7

Beta strand

332 – 334

3

Beta strand

343 – 353

11

Beta strand

355 – 360

6

Helix

365 – 367

3

Helix

379 – 381

3

Beta strand

386 – 391

6

Beta strand

396 – 399

4

Beta strand

404 – 410

7

Beta strand

415 – 422

8

Helix

428 – 446

19

Helix

448 – 451

4

Helix

458 – 460

3

Helix

464 – 466

3

Helix

472 – 487

16

Helix

488 – 491

4

Helix

494 – 508

15

Helix

516 – 520

5

Helix

523 – 525

3

Beta strand

529 – 531

3

Beta strand

534 – 537

4

Beta strand

547 – 552

6

Beta strand

555 – 561

7

Beta strand

564 – 570

7

Beta strand

584 – 587

4

Helix

589 – 591

3

Helix

592 – 601

10

Helix

608 – 610

3

Helix

616 – 628

13

Beta strand

632 – 636

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 19, 2010. Version 2. Checksum: E66A4342B1D1BFF2	FASTA	641	71,086
	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
	Isoform 2 [UniParc]. Checksum: F07631F3A3F8CDB7	FASTA	429	48,687
	10 20 30 40 50 60 MPPDHFYRRL WEREAVLVRR QDHTYYQGLF STADLDSMLR NEEVQFGQHL DAARYINGRR 70 80 90 100 110 120 ETLNPPGRAL PAAAWSLYQA GCSLRLLCPQ AFSTTVWQFL AVLQEQFGSM AGSNVYLTPP 130 140 150 160 170 180 NSQGFAPHYD DIEAFVLQLE GRKLWRVYRP RVPTEELALT SSPNFSQDDL GEPVLQTVLE 190 200 210 220 230 240 PGDLLYFPRG FIHQAECQDG VHSLHLTLST YQRNTWGDFL EAILPLAVQA AMEENVEFRR 250 260 270 280 290 300 GLPRDFMDYM GAQHSDSKDP RRTAFMEKVR VLVARLGHFA PVDAVADQRA KDFIHDSLPP 310 320 330 340 350 360 VLTDRERALS VYGLPIRWEA GEPVNVGAQL TTETEVHMLQ DGIARLVGEG GHLFLYYTVE 370 380 390 400 410 420 NSRVYHLEEP KCLEIYPQQA DAMELLLGSY PEFVRVGDLP CDSVEDQLSL ATTLYDKGLL LTKMPLALN

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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. , 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.
+	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.

IPI

IPI00002879.
IPI00954824.

RefSeq

NP_078920.2. NM_024644.3.

UniGene

Hs.509916.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4DIQ	X-ray	2.40	A/B	167-641	[»]
4E4H	X-ray	2.28	A/B/C/D	183-641	[»]

ProteinModelPortal

Q9H6W3.

SMR

Q9H6W3. Positions 181-641.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9H6W3. 2 interactions.

PTM databases

PhosphoSite

Q9H6W3.

Polymorphism databases

DMDM

284018103.

Proteomic databases

PeptideAtlas

Q9H6W3.

PRIDE

Q9H6W3.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

79697.

KEGG

hsa:79697.

UCSC

uc001xok.1. human.

Organism-specific databases

CTD

79697.

GeneCards

GC14P073958.

H-InvDB

HIX0011794.

HGNC

HGNC:20968. C14orf169.

MIM

611919. gene.

neXtProt

NX_Q9H6W3.

PharmGKB

PA134919088.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

HBG060021.

Gene expression databases

CleanEx

HS_C14orf169.

Genevestigator

Q9H6W3.

Family and domain databases

InterPro

IPR003347. JmjC_dom.
IPR013109. NO66/MINA.
[Graphical view]

PANTHER

PTHR13096. PTHR13096. 1 hit.

Pfam

PF08007. Cupin_4. 1 hit.
[Graphical view]

SMART

SM00558. JmjC. 1 hit.
[Graphical view]

PROSITE

PS51184. JMJC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

79697.

NextBio

68992.

SOURCE

Search...

Entry information

Entry name

NO66_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 86 of the entry and version 2 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.