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Protein

Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6

Gene

Jmjd6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Dioxygenase that can both act as a histone arginine demethylase and a lysyl-hydroxylase. 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. In addition to peptidyl-lysine 5-dioxygenase activity, may act as an RNA hydroxylase, as suggested by its ability to bind single strand RNA. Also acts as an arginine demethylase which demethylates histone H3 at 'Arg-2' (H3R2me) and histone H4 at 'Arg-3' (H4R3me), thereby playing a role in histone code. However, histone arginine demethylation may not constitute the primary activity in vivo. Has no histone lysine demethylase activity. Required for differentiation of multiple organs during embryogenesis. Acts as a key regulator of hematopoietic differentiation: required for angiogenic sprouting by regulating the pre-mRNA splicing activity of U2AF2/U2AF65. Seems to be necessary for the regulation of macrophage cytokine responses (By similarity).By similarity2 Publications

Cofactori

Fe2+By similarityNote: Binds 1 Fe2+ ion per subunit.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei184 – 1841SubstrateBy similarity
Metal bindingi187 – 1871Iron; catalyticPROSITE-ProRule annotation
Metal bindingi189 – 1891Iron; catalyticPROSITE-ProRule annotation
Binding sitei197 – 19712-oxoglutarateBy similarity
Binding sitei204 – 2041SubstrateBy similarity
Metal bindingi273 – 2731Iron; catalyticPROSITE-ProRule annotation
Binding sitei285 – 28512-oxoglutarateBy similarity

GO - Molecular functioni

  • histone demethylase activity (H3-R2 specific) Source: UniProtKB
  • histone demethylase activity (H4-R3 specific) Source: UniProtKB
  • identical protein binding Source: MGI
  • iron ion binding Source: MGI
  • peptidyl-lysine 5-dioxygenase activity Source: UniProtKB
  • protein homodimerization activity Source: MGI
  • receptor activity Source: MGI
  • RNA binding Source: MGI
  • single-stranded RNA binding Source: UniProtKB

GO - Biological processi

  • apoptotic cell clearance Source: MGI
  • blood vessel development Source: MGI
  • cell surface receptor signaling pathway Source: MGI
  • erythrocyte development Source: MGI
  • heart development Source: MGI
  • histone H3-R2 demethylation Source: MGI
  • histone H4-R3 demethylation Source: MGI
  • kidney development Source: MGI
  • lung development Source: MGI
  • macrophage activation Source: MGI
  • mRNA processing Source: UniProtKB-KW
  • peptidyl-lysine hydroxylation to 5-hydroxy-L-lysine Source: UniProtKB
  • recognition of apoptotic cell Source: MGI
  • regulation of mRNA splicing, via spliceosome Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB-KW
  • retina development in camera-type eye Source: MGI
  • RNA splicing Source: UniProtKB-KW
  • sprouting angiogenesis Source: UniProtKB
  • T cell differentiation in thymus Source: MGI
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Developmental protein, Dioxygenase, Oxidoreductase

Keywords - Biological processi

Differentiation, mRNA processing, mRNA splicing, Transcription, Transcription regulation

Keywords - Ligandi

Iron, Metal-binding, RNA-binding

Enzyme and pathway databases

ReactomeiR-MMU-3214842. HDMs demethylate histones.

Names & Taxonomyi

Protein namesi
Recommended name:
Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6 (EC:1.14.11.-)
Alternative name(s):
Histone arginine demethylase JMJD6
JmjC domain-containing protein 6
Jumonji domain-containing protein 6
Lysyl-hydroxylase JMJD6
Peptide-lysine 5-dioxygenase JMJD6
Phosphatidylserine receptor
Short name:
Protein PTDSR
Gene namesi
Name:Jmjd6
Synonyms:Kiaa0585, Ptdsr
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1858910. Jmjd6.

Subcellular locationi

  • Nucleusnucleoplasm 1 Publication
  • Nucleusnucleolus By similarity

  • Note: Mainly found throughout the nucleoplasm outside of regions containing heterochromatic DNA, with some localization in nucleolus. During mitosis, excluded from the nucleus and reappears in the telophase of the cell cycle (By similarity).By similarity

GO - Cellular componenti

  • cytosol Source: MGI
  • intracellular ribonucleoprotein complex Source: MGI
  • nucleolus Source: UniProtKB
  • nucleoplasm Source: UniProtKB
  • nucleus Source: UniProtKB
  • plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice display perinatal lethality, growth retardation, severe anemia and a delay in terminal differentiation of the kidney, intestine, liver and lungs during embryogenesis. Moreover, eye development can be severely disturbed, ranging from defects in retinal differentiation to complete unilateral or bilateral absence of eyes. According to PubMed:14645847, mice are defective in removing apoptotic cells, especially in the lung and brain, in which dead cells accumulate, causing abnormal development and leading to neonatal lethality. According to PubMed:14715629, mice lacking Jmjd6 display a reduced number of macrophages and apoptotic cells in fetal liver. In contrast, according to PubMed:15345036, mice show a normal engulfment of apoptotic cells. The contradictory results concerning apoptosis and macrophage function may be explained by the fact that the protein plays a key role in hematopoietic differentiation.3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 403403Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6PRO_0000129370Add
BLAST

Proteomic databases

MaxQBiQ9ERI5.
PaxDbiQ9ERI5.
PRIDEiQ9ERI5.

PTM databases

iPTMnetiQ9ERI5.
PhosphoSiteiQ9ERI5.

Expressioni

Tissue specificityi

Widely expressed. Expressed in brain, eye, spinal chord, thymus, lung, liver, kidney and intestine.2 Publications

Developmental stagei

Expressed early in development. Expressed from embryonic stem cells and throughout embryogenesis.2 Publications

Gene expression databases

BgeeiENSMUSG00000056962.
CleanExiMM_JMJD6.
ExpressionAtlasiQ9ERI5. baseline and differential.
GenevisibleiQ9ERI5. MM.

Interactioni

Subunit structurei

Interacts with LUC7L2 and LUC7L3. Interacts with BRD4 (By similarity). Interacts with U2AF2/U2AF65. Interacts with LIAT1.By similarity2 Publications

GO - Molecular functioni

  • identical protein binding Source: MGI
  • protein homodimerization activity Source: MGI

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000047570.

Structurei

3D structure databases

ProteinModelPortaliQ9ERI5.
SMRiQ9ERI5. Positions 1-335.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini141 – 305165JmjCPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi6 – 105Nuclear localization signal 1By similarity
Motifi91 – 955Nuclear localization signal 2By similarity
Motifi141 – 1455Nuclear localization signal 3By similarity
Motifi167 – 1704Nuclear localization signal 4By similarity
Motifi373 – 3786Nuclear localization signal 5By similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi340 – 36526Ser-richAdd
BLAST

Domaini

The nuclear localization signal motifs are necessary and sufficient to target it into the nucleus.By similarity

Sequence similaritiesi

Belongs to the JMJD6 family.Curated
Contains 1 JmjC domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2130. Eukaryota.
ENOG410XQCR. LUCA.
GeneTreeiENSGT00530000063579.
HOGENOMiHOG000265824.
HOVERGENiHBG054774.
InParanoidiQ9ERI5.
KOiK11323.
OrthoDBiEOG091G0AJ6.
PhylomeDBiQ9ERI5.
TreeFamiTF314988.

Family and domain databases

InterProiIPR003347. JmjC_dom.
[Graphical view]
PfamiPF02373. JmjC. 1 hit.
[Graphical view]
SMARTiSM00558. JmjC. 1 hit.
[Graphical view]
PROSITEiPS51184. JMJC. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9ERI5-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MNHKSKKRIR EAKRSARPEL KDSLDWTRHN YYESYPLNPA AVPDNVERAD
60 70 80 90 100
ALQLSVKEFV ERYERPYKPV VLLNAQEGWS AQEKWTLERL KRKYRNQKFK
110 120 130 140 150
CGEDNDGYSV KMKMKYYIEY MESTRDDSPL YIFDSSYGEH PKRRKLLEDY
160 170 180 190 200
KVPKFFTDDL FQYAGEKRRP PYRWFVMGPP RSGTGIHIDP LGTSAWNALV
210 220 230 240 250
QGHKRWCLFP TNTPRELIKV TREEGGNQQD EAITWFNVIY PRTQLPTWPP
260 270 280 290 300
EFKPLEILQK PGETVFVPGG WWHVVLNLDT TIAITQNFAS STNFPVVWHK
310 320 330 340 350
TVRGRPKLSR KWYRILKQEH PELAVLADAV DLQESTGIAS DSSSDSSSSS
360 370 380 390 400
SSSSSDSDSE CESGSEGDGT THRRKKRRTC SMVGNGDTTS QDDCVSKERS

SSR
Length:403
Mass (Da):46,567
Last modified:December 4, 2007 - v2
Checksum:iD440E880B2F1BB37
GO
Isoform 2 (identifier: Q9ERI5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     270-298: GWWHVVLNLDTTIAITQNFASSTNFPVVW → IDELEETIPVRPSSDWSGLVLYCHFGVES
     299-403: Missing.

Note: No experimental confirmation available.
Show »
Length:298
Mass (Da):35,177
Checksum:i121EB0B5CF938554
GO

Sequence cautioni

The sequence BAC65599 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti43 – 431P → S in AAG27719 (PubMed:10811223).Curated
Sequence conflicti43 – 431P → S in AAH56629 (PubMed:15489334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei270 – 29829GWWHV…FPVVW → IDELEETIPVRPSSDWSGLV LYCHFGVES in isoform 2. 1 PublicationVSP_014024Add
BLAST
Alternative sequencei299 – 403105Missing in isoform 2. 1 PublicationVSP_014025Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF304118 mRNA. Translation: AAG27719.1.
AK122317 mRNA. Translation: BAC65599.1. Different initiation.
AL645542 Genomic DNA. Translation: CAP19369.1.
BC056629 mRNA. Translation: AAH56629.1.
CCDSiCCDS25678.1. [Q9ERI5-1]
RefSeqiNP_203971.2. NM_033398.2. [Q9ERI5-1]
UniGeneiMm.481684.

Genome annotation databases

EnsembliENSMUST00000047616; ENSMUSP00000047570; ENSMUSG00000056962. [Q9ERI5-1]
GeneIDi107817.
KEGGimmu:107817.
UCSCiuc007mmi.1. mouse. [Q9ERI5-1]
uc007mmj.1. mouse. [Q9ERI5-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF304118 mRNA. Translation: AAG27719.1.
AK122317 mRNA. Translation: BAC65599.1. Different initiation.
AL645542 Genomic DNA. Translation: CAP19369.1.
BC056629 mRNA. Translation: AAH56629.1.
CCDSiCCDS25678.1. [Q9ERI5-1]
RefSeqiNP_203971.2. NM_033398.2. [Q9ERI5-1]
UniGeneiMm.481684.

3D structure databases

ProteinModelPortaliQ9ERI5.
SMRiQ9ERI5. Positions 1-335.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000047570.

PTM databases

iPTMnetiQ9ERI5.
PhosphoSiteiQ9ERI5.

Proteomic databases

MaxQBiQ9ERI5.
PaxDbiQ9ERI5.
PRIDEiQ9ERI5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000047616; ENSMUSP00000047570; ENSMUSG00000056962. [Q9ERI5-1]
GeneIDi107817.
KEGGimmu:107817.
UCSCiuc007mmi.1. mouse. [Q9ERI5-1]
uc007mmj.1. mouse. [Q9ERI5-2]

Organism-specific databases

CTDi23210.
MGIiMGI:1858910. Jmjd6.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG2130. Eukaryota.
ENOG410XQCR. LUCA.
GeneTreeiENSGT00530000063579.
HOGENOMiHOG000265824.
HOVERGENiHBG054774.
InParanoidiQ9ERI5.
KOiK11323.
OrthoDBiEOG091G0AJ6.
PhylomeDBiQ9ERI5.
TreeFamiTF314988.

Enzyme and pathway databases

ReactomeiR-MMU-3214842. HDMs demethylate histones.

Miscellaneous databases

ChiTaRSiJmjd6. mouse.
PROiQ9ERI5.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000056962.
CleanExiMM_JMJD6.
ExpressionAtlasiQ9ERI5. baseline and differential.
GenevisibleiQ9ERI5. MM.

Family and domain databases

InterProiIPR003347. JmjC_dom.
[Graphical view]
PfamiPF02373. JmjC. 1 hit.
[Graphical view]
SMARTiSM00558. JmjC. 1 hit.
[Graphical view]
PROSITEiPS51184. JMJC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiJMJD6_MOUSE
AccessioniPrimary (citable) accession number: Q9ERI5
Secondary accession number(s): A2AA26, A8Y5I2, Q80TX1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 7, 2005
Last sequence update: December 4, 2007
Last modified: September 7, 2016
This is version 119 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.