Reviewed, UniProtKB/Swiss-Prot Q6NYC1 (JMJD6_HUMAN)

Names and origin

Protein names

Recommended name:
    Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6
    EC=1.14.11.-
Alternative name(s):
    Histone arginine demethylase JMJD6
    Peptide-lysine 5-dioxygenase JMJD6
    Lysyl-hydroxylase JMJD6
    JmjC domain-containing protein 6
    Jumonji domain-containing protein 6
    Phosphatidylserine receptor
      Short name=Protein PTDSR

Gene names

Name:	JMJD6
Synonyms:	KIAA0585, PTDSR

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	403 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Dioxygenase that can both act as a histone arginine demethylase and a lysyl-hydroxylase. Arginine demethylase which demethylates histone H3 at 'Arg-2' (H3R2me) and histone H4 at 'Arg-3' (H4R3me), thereby playing a central role in histone code. Also acts as a lysyl-hydroxylase that catalyzes 5-hydroxylation on specific lysine residues of target proteins such as U2AF2/U2AF65 and LUC7L2. Acts as a regulator of RNA splicing by mediating 5-hydroxylation of U2AF2/U2AF65, affecting the pre-mRNA splicing activity of U2AF2/U2AF65. Required for differentiation of multiple organs during embryogenesis. Probably acts as a key regulator of hematopoietic differentiation. Seems to be necessary for the regulation of macrophage cytokine responses. Ref.10 Ref.12
Cofactor	Binds 1 Fe2+ ion per subunit. Ref.12
Subunit structure	Interacts with CROP, LUC7L2 and U2AF2/U2AF65. Ref.12
Subcellular location	Nucleus. Ref.7
Tissue specificity	Highly expressed in the heart, skeletal muscle and kidney. Expressed at moderate or low level in brain, placenta, lung, liver, pancreas, spleen, thymus, prostate, testis and ovary. Up-regulated in many patients with chronic pancreatitis. Expressed in nursing thymic epithelial cells. Ref.2 Ref.8 Ref.9
Induction	Up-regulated upon cytokine treatment, but not upon TNF-alpha treatment. Ref.8
Domain	The nuclear localization signal motifs are necessary and sufficient to target it into the nucleus.
Sequence similarities	Belongs to the JMJD6 family. Contains 1 JmjC domain.
Caution	Was initially thought to constitute the phosphatidylserine receptor, a receptor that mediates recognition of phosphatidylserine, a specific marker only present at the surface of apoptotic cells. Phosphatidylserine receptor probably participates in apoptotic cell phagocytosis. This protein was identified using phage display expressing mAb 217, an antibody that specifically recognizes phosphatidylserine receptor. However, its nuclear localization and the fact that mAb 217 antibody still recognizes the phosphatidylserine receptor in mice lacking JMJD6, strongly suggest that it does not constitute the receptor for phosphatidylserine and is not involved in apoptotic cell removal.

Ontologies

Keywords
Biological process	Differentiation Transcription Transcription regulation mRNA processing mRNA splicing
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	Iron Metal-binding
Molecular function	Chromatin regulator Developmental protein Dioxygenase Oxidoreductase
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	RNA splicing Inferred from electronic annotation. Source: UniProtKB-KW histone H3-R2 demethylation Ref.10 Inferred from direct assay. Source: UniProtKB histone H4-R3 demethylation Ref.10 Inferred from direct assay. Source: UniProtKB mRNA processing Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW peptidyl-lysine hydroxylation to 5-hydroxy-L-lysine Ref.12 Inferred from direct assay. Source: UniProtKB regulation of nuclear mRNA splicing, via spliceosome Ref.12 Inferred from mutant phenotype. Source: UniProtKB regulation of transcription Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Ref.7 Inferred from direct assay. Source: UniProtKB
Molecular function	histone demethylase activity (H3-R2 specific) Ref.10 Inferred from direct assay. Source: UniProtKB histone demethylase activity (H4-R3 specific) Ref.10 Inferred from direct assay. Source: UniProtKB identical protein binding Inferred from direct assay. Source: UniProtKB iron ion binding Inferred from electronic annotation. Source: UniProtKB-KW oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Inferred from electronic annotation. Source: UniProtKB-KW peptidyl-lysine 5-dioxygenase activity Ref.12 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q6NYC1-1)

Also known as: Alpha;

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: Q6NYC1-2)

Also known as: Beta;

The sequence of this isoform differs from the canonical sequence as follows:
     361-402: Missing.
     403-403: R → RIRDTCGGRAHP

Isoform 3 (identifier: Q6NYC1-3)

The sequence of this isoform differs from the canonical sequence as follows:
     403-403: R → RIRDTCGGRAHP

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 403	403	Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6		PRO_0000129369
Regions
	Domain	141 – 305	165	JmjC
	Motif	6 – 10	5	Nuclear localization signal 1 Ref.7
	Motif	91 – 95	5	Nuclear localization signal 2 Ref.7
	Motif	141 – 145	5	Nuclear localization signal 3 Ref.7
	Motif	167 – 170	4	Nuclear localization signal 4 Ref.7
	Motif	373 – 378	6	Nuclear localization signal 5 Ref.7
	Compositional bias	340 – 365	26	Ser-rich
Sites
	Metal binding	187	1	Iron; catalytic Probable
	Metal binding	189	1	Iron; catalytic Probable
	Metal binding	273	1	Iron; catalytic Probable
	Binding site	184	1	Substrate By similarity
	Binding site	204	1	Substrate By similarity
Natural variations
	Alternative sequence	361 – 402	42	Missing in isoform 2.		VSP_014022
	Alternative sequence	403	1	R → RIRDTCGGRAHP in isoform 2 and isoform 3.		VSP_014023
Experimental info
	Mutagenesis	187	1	H → A: Loss of catalytic activity; when associated with A-189 and A-273. Ref.10 Ref.12
	Mutagenesis	189	1	D → A: Loss of catalytic activity; when associated with A-187 and A-273. Ref.10 Ref.12
	Mutagenesis	273	1	H → A: Loss of catalytic activity; when associated with A-187 and A-189. Ref.10
	Sequence conflict	136	1	S → G in BAG51050. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Alpha) [UniParc]. Last modified July 5, 2004. Version 1. Checksum: 9C9AADA98B24B035	FASTA	403	46,462
	10 20 30 40 50 60 MNHKSKKRIR EAKRSARPEL KDSLDWTRHN YYESFSLSPA AVADNVERAD ALQLSVEEFV 70 80 90 100 110 120 ERYERPYKPV VLLNAQEGWS AQEKWTLERL KRKYRNQKFK CGEDNDGYSV KMKMKYYIEY 130 140 150 160 170 180 MESTRDDSPL YIFDSSYGEH PKRRKLLEDY KVPKFFTDDL FQYAGEKRRP PYRWFVMGPP 190 200 210 220 230 240 RSGTGIHIDP LGTSAWNALV QGHKRWCLFP TSTPRELIKV TRDEGGNQQD EAITWFNVIY 250 260 270 280 290 300 PRTQLPTWPP EFKPLEILQK PGETVFVPGG WWHVVLNLDT TIAITQNFAS STNFPVVWHK 310 320 330 340 350 360 TVRGRPKLSR KWYRILKQEH PELAVLADSV DLQESTGIAS DSSSDSSSSS SSSSSDSDSE 370 380 390 400 CESGSEGDGT VHRRKKRRTC SMVGNGDTTS QDDCVSKERS SSR
	Isoform 2 (Beta). Checksum: 14154B874F1983DF	FASTA	372	43,109
	10 20 30 40 50 60 MNHKSKKRIR EAKRSARPEL KDSLDWTRHN YYESFSLSPA AVADNVERAD ALQLSVEEFV 70 80 90 100 110 120 ERYERPYKPV VLLNAQEGWS AQEKWTLERL KRKYRNQKFK CGEDNDGYSV KMKMKYYIEY 130 140 150 160 170 180 MESTRDDSPL YIFDSSYGEH PKRRKLLEDY KVPKFFTDDL FQYAGEKRRP PYRWFVMGPP 190 200 210 220 230 240 RSGTGIHIDP LGTSAWNALV QGHKRWCLFP TSTPRELIKV TRDEGGNQQD EAITWFNVIY 250 260 270 280 290 300 PRTQLPTWPP EFKPLEILQK PGETVFVPGG WWHVVLNLDT TIAITQNFAS STNFPVVWHK 310 320 330 340 350 360 TVRGRPKLSR KWYRILKQEH PELAVLADSV DLQESTGIAS DSSSDSSSSS SSSSSDSDSE 370 RIRDTCGGRA HP
	Isoform 3. Checksum: CD586580857C6C46	FASTA	414	47,626
	10 20 30 40 50 60 MNHKSKKRIR EAKRSARPEL KDSLDWTRHN YYESFSLSPA AVADNVERAD ALQLSVEEFV 70 80 90 100 110 120 ERYERPYKPV VLLNAQEGWS AQEKWTLERL KRKYRNQKFK CGEDNDGYSV KMKMKYYIEY 130 140 150 160 170 180 MESTRDDSPL YIFDSSYGEH PKRRKLLEDY KVPKFFTDDL FQYAGEKRRP PYRWFVMGPP 190 200 210 220 230 240 RSGTGIHIDP LGTSAWNALV QGHKRWCLFP TSTPRELIKV TRDEGGNQQD EAITWFNVIY 250 260 270 280 290 300 PRTQLPTWPP EFKPLEILQK PGETVFVPGG WWHVVLNLDT TIAITQNFAS STNFPVVWHK 310 320 330 340 350 360 TVRGRPKLSR KWYRILKQEH PELAVLADSV DLQESTGIAS DSSSDSSSSS SSSSSDSDSE 370 380 390 400 410 CESGSEGDGT VHRRKKRRTC SMVGNGDTTS QDDCVSKERS SSRIRDTCGG RAHP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of an alternative form of phosphatidylserine receptor." Izawa M., Takahashi M. Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Stomach cancer.
[2]	"Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:31-39(1998) [PubMed: 9628581] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), TISSUE SPECIFICITY. Tissue: Brain.
[3]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). Tissue: Brain and Embryo.
[4]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed: 16625196] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Skin and Uterus.
[7]	"Nuclear localization of the phosphatidylserine receptor protein via multiple nuclear localization signals." Cui P., Qin B., Liu N., Pan G., Pei D. Exp. Cell Res. 293:154-163(2004) [PubMed: 14729065] [Abstract] Cited for: SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNALS.
[8]	"Phosphatidylserine receptor cooperates with high-density lipoprotein receptor in recognition of apoptotic cells by thymic nurse cells." Cao W.M., Murao K., Imachi H., Hiramine C., Abe H., Yu X., Dobashi H., Wong N.C.W., Takahara J., Ishida T. J. Mol. Endocrinol. 32:497-505(2004) [PubMed: 15072554] [Abstract] Cited for: TISSUE SPECIFICITY, INDUCTION.
[9]	"Phosphatidylserine receptor in chronic pancreatitis: evidence for a macrophage independent role." Koeninger J., Balaz P., Wagner M., Shi X., Cima I., Zimmermann A., di Sebastiano P., Buechler M.W., Friess H. Ann. Surg. 241:144-151(2005) [PubMed: 15622002] [Abstract] Cited for: TISSUE SPECIFICITY.
[10]	"JMJD6 is a histone arginine demethylase." Chang B., Chen Y., Zhao Y., Bruick R.K. Science 318:444-447(2007) [PubMed: 17947579] [Abstract] Cited for: FUNCTION AS HISTONE DEMETHYLASE, MUTAGENESIS OF HIS-187; ASP-189 AND HIS-273.
[11]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[12]	"Jmjd6 catalyses lysyl-hydroxylation of U2AF65, a protein associated with RNA splicing." Webby C.J., Wolf A., Gromak N., Dreger M., Kramer H., Kessler B., Nielsen M.L., Schmitz C., Butler D.S., Yates J.R. III, Delahunty C.M., Hahn P., Lengeling A., Mann M., Proudfoot N.J., Schofield C.J., Boettger A. Science 325:90-93(2009) [PubMed: 19574390] [Abstract] Cited for: FUNCTION AS LYSYL-HYDROXYLASE, COFACTOR, INTERACTION WITH CROP; LUC7L2 AND U2AF2, MUTAGENESIS OF HIS-187 AND ASP-189.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB073711 mRNA. Translation: BAC16755.1. AB011157 mRNA. Translation: BAA25511.1. Different initiation. AK021780 mRNA. Translation: BAG51050.1. AK294816 mRNA. Translation: BAG57932.1. AC005837 Genomic DNA. No translation available. CH471099 Genomic DNA. Translation: EAW89434.1. BC047003 mRNA. Translation: AAH47003.1. Different initiation. BC066654 mRNA. Translation: AAH66654.1.
IPI	IPI00375496. IPI00550958. IPI00604598.
RefSeq	NP_001074930.1. NP_055982.2.
UniGene	Hs.514505
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q6NYC1.
PTM databases
PhosphoSite	Q6NYC1.
Proteomic databases
PRIDE	Q6NYC1.
Genome annotation databases
Ensembl	ENST00000303996; ENSP00000302916; ENSG00000070495; Homo sapiens. [Genome view] ENST00000344991; ENSP00000345857; ENSG00000070495; Homo sapiens. [Genome view] ENST00000397625; ENSP00000380750; ENSG00000070495; Homo sapiens. [Genome view] ENST00000445478; ENSP00000394085; ENSG00000070495; Homo sapiens. [Genome view]
GeneID	23210.
KEGG	hsa:23210.
UCSC	uc002jsn.1. human. uc002jso.1. human.
Organism-specific databases
CTD	23210.
GeneCards	GC17M072221.
H-InvDB	HIX0014203.
HGNC	HGNC:19355. JMJD6.
HPA	CAB004548.
MIM	604914. gene.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q6NYC1.
OMA	MHRRKKR.
Gene expression databases
ArrayExpress	Q6NYC1.
Bgee	Q6NYC1.
CleanEx	HS_JMJD6.
Genevestigator	Q6NYC1.
GermOnline	ENSG00000070495. Homo sapiens.
Family and domain databases
InterPro	IPR013129. TF_JmjC. IPR003347. TF_JmjC_AAH. [Graphical view]
Pfam	PF02373. JmjC. 1 hit. [Graphical view]
SMART	SM00558. JmjC. 1 hit. [Graphical view]
PROSITE	PS51184. JMJC. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	44753.
SOURCE	Search...

Entry information

Entry name

JMJD6_HUMAN

Accession

Primary (citable) accession number: Q6NYC1
Secondary accession number(s): B3KMN8 , B4DGX1, Q86VY0, Q8IUM5, Q9Y4E2

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 7, 2005
Last sequence update:	July 5, 2004
Last modified:	November 3, 2009
This is version 56 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.