Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6

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

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Protein attributes

Sequence length	403 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

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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 LUC7L2, LUC7L3 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.

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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	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	RNA splicing Inferred from electronic annotation. Source: UniProtKB-KW cellular transcription 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 cellular transcription Inferred from electronic annotation. Source: UniProtKB-KW regulation of nuclear mRNA splicing, via spliceosome Ref.12 Inferred from mutant phenotype. Source: UniProtKB
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...

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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

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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

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Sequences

Sequence		Length	Mass (Da)
Isoform 1 (Alpha) [UniParc]. Last modified July 5, 2004. Version 1. Checksum: 9C9AADA98B24B035 Show »	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 « Hide
Isoform 2 (Beta). Checksum: 14154B874F1983DF Show »	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 « Hide
Isoform 3. Checksum: CD586580857C6C46 Show »	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 « Hide

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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. 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. 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. 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 LUC7L2; LUC7L3 AND U2AF2, MUTAGENESIS OF HIS-187 AND ASP-189.
[13]	"Structure of an oxygenase." Structural genomics consortium (SGC) Submitted (NOV-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 1-335 IN COMPLEX WITH NICKEL IONS.
+	Additional computationally mapped references.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3K2O	X-ray	1.75	A/B	1-335	[»]

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]
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

eggNOG

prNOG09054.

HOGENOM

HBG315636.

HOVERGEN

HBG054774.

InParanoid

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...

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Entry information

Entry name

JMJD6_HUMAN

Accession

Primary (citable) accession number: Q6NYC1
Secondary accession number(s): B3KMN8

Q9Y4E2

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 7, 2005
Last sequence update:	July 5, 2004
Last modified:	March 2, 2010
This is version 61 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.

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Relevant documents

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families