Gene/Proteome Database (LMPD)
LMPD ID
LMP005684
Gene ID
Species
Mus musculus (Mouse)
Gene Name
jumonji domain containing 6
Gene Symbol
Synonyms
5730436I23Rik; D11Ertd195e; PSR; PtdSerR; Ptdsr; mKIAA0585
Alternate Names
bifunctional arginine demethylase and lysyl-hydroxylase JMJD6; lysyl-hydroxylase JMJD6; phosphatidylserine receptor; jmjC domain-containing protein 6; histone arginine demethylase JMJD6; peptide-lysine 5-dioxygenase JMJD6; jumonji domain-containing protein 6; apoptotic cell clearance receptor PtdSerR
Chromosome
11
Map Location
11 E2|11 81.49 cM
EC Number
1.14.11.-
Summary
This gene encodes a nuclear protein with a JmjC domain. JmjC domain-containing proteins are predicted to function as protein hydroxylases or histone demethylases. This protein functions in differentiation of multiple tissues during development, and in anti-inflammatory cytokine signaling. It was first identified as a putative phosphatidylserine receptor involved in phagocytosis of apoptotic cells; however, subsequent studies have indicated that this protein does not directly function in the clearance of apoptotic cells, and questioned whether it is a true phosphatidylserine receptor. [provided by RefSeq, Jul 2008]
Orthologs
Proteins
| bifunctional arginine demethylase and lysyl-hydroxylase JMJD6 | |
|---|---|
| Refseq ID | NP_203971 |
| Protein GI | 125988379 |
| UniProt ID | Q9ERI5 |
| mRNA ID | NM_033398 |
| Length | 403 |
| RefSeq Status | REVIEWED |
| MNHKSKKRIREAKRSARPELKDSLDWTRHNYYESYPLNPAAVPDNVERADALQLSVKEFVERYERPYKPVVLLNAQEGWSAQEKWTLERLKRKYRNQKFKCGEDNDGYSVKMKMKYYIEYMESTRDDSPLYIFDSSYGEHPKRRKLLEDYKVPKFFTDDLFQYAGEKRRPPYRWFVMGPPRSGTGIHIDPLGTSAWNALVQGHKRWCLFPTNTPRELIKVTREEGGNQQDEAITWFNVIYPRTQLPTWPPEFKPLEILQKPGETVFVPGGWWHVVLNLDTTIAITQNFASSTNFPVVWHKTVRGRPKLSRKWYRILKQEHPELAVLADAVDLQESTGIASDSSSDSSSSSSSSSSDSDSECESGSEGDGTTHRRKKRRTCSMVGNGDTTSQDDCVSKERSSSR | |
Gene Information
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0005730 | ISS:UniProtKB | C | nucleolus |
| GO:0005654 | ISS:UniProtKB | C | nucleoplasm |
| GO:0005634 | IDA:UniProtKB | C | nucleus |
| GO:0005886 | IDA:MGI | C | plasma membrane |
| GO:0033746 | ISS:UniProtKB | F | histone demethylase activity (H3-R2 specific) |
| GO:0033749 | ISS:UniProtKB | F | histone demethylase activity (H4-R3 specific) |
| GO:0005506 | IEA:Ensembl | F | iron ion binding |
| GO:0070815 | ISS:UniProtKB | F | peptidyl-lysine 5-dioxygenase activity |
| GO:0004872 | IDA:MGI | F | receptor activity |
| GO:0003727 | ISS:UniProtKB | F | single-stranded RNA binding |
| GO:0008380 | IEA:UniProtKB-KW | P | RNA splicing |
| GO:0033077 | IMP:MGI | P | T cell differentiation in thymus |
| GO:0043277 | IMP:MGI | P | apoptotic cell clearance |
| GO:0001568 | IMP:MGI | P | blood vessel development |
| GO:0007166 | IDA:MGI | P | cell surface receptor signaling pathway |
| GO:0048821 | IMP:MGI | P | erythrocyte development |
| GO:0007507 | IMP:MGI | P | heart development |
| GO:0001822 | IMP:MGI | P | kidney development |
| GO:0030324 | IMP:MGI | P | lung development |
| GO:0006397 | IEA:UniProtKB-KW | P | mRNA processing |
| GO:0042116 | IMP:MGI | P | macrophage activation |
| GO:0018395 | ISS:UniProtKB | P | peptidyl-lysine hydroxylation to 5-hydroxy-L-lysine |
| GO:0043654 | IDA:MGI | P | recognition of apoptotic cell |
| GO:0048024 | IMP:UniProtKB | P | regulation of mRNA splicing, via spliceosome |
| GO:0006355 | IEA:UniProtKB-KW | P | regulation of transcription, DNA-templated |
| GO:0060041 | IMP:MGI | P | retina development in camera-type eye |
| GO:0002040 | IMP:UniProtKB | P | sprouting angiogenesis |
| GO:0006351 | IEA:UniProtKB-KW | P | transcription, DNA-templated |
Domain Information
InterPro Annotations
| Accession | Description |
|---|---|
| IPR003347 | JmjC domain |
UniProt Annotations
Entry Information
Comments
| Comment Type | Description |
|---|---|
| Alternative Products | Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q9ERI5-1; Sequence=Displayed; Name=2; IsoId=Q9ERI5-2; Sequence=VSP_014024, VSP_014025; Note=No experimental confirmation available.; |
| 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. {ECO:0000305}. |
| Cofactor | Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000250}; Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250}; |
| Developmental Stage | Expressed early in development. Expressed from embryonic stem cells and throughout embryogenesis. {ECO:0000269|PubMed:14645847, ECO:0000269|PubMed:15345036}. |
| Disruption Phenotype | 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. {ECO:0000269|PubMed:14645847, ECO:0000269|PubMed:14715629, ECO:0000269|PubMed:15345036}. |
| Domain | The nuclear localization signal motifs are necessary and sufficient to target it into the nucleus. {ECO:0000250}. |
| Function | 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). {ECO:0000250}. |
| Sequence Caution | Sequence=BAC65599.1; Type=Erroneous initiation; Evidence={ECO:0000305}; |
| Similarity | Belongs to the JMJD6 family. {ECO:0000305}. |
| Similarity | Contains 1 JmjC domain. {ECO:0000255|PROSITE- ProRule:PRU00538}. |
| Subcellular Location | Nucleus, nucleoplasm {ECO:0000269|PubMed:14729065}. Nucleus, nucleolus {ECO:0000250}. 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). {ECO:0000250}. |
| Subunit | Interacts with LUC7L2 and LUC7L3. Interacts with BRD4 (By similarity). Interacts with U2AF2/U2AF65. {ECO:0000250, ECO:0000269|PubMed:21300889}. |
| Tissue Specificity | Widely expressed. Expressed in brain, eye, spinal chord, thymus, lung, liver, kidney and intestine. {ECO:0000269|PubMed:14645847, ECO:0000269|PubMed:15345036}. |
Identical and Related Proteins
Unique RefSeq proteins for LMP005684 (as displayed in Record Overview)
| Protein GI | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| 125988379 | RefSeq | NP_203971 | 403 | bifunctional arginine demethylase and lysyl-hydroxylase JMJD6 |
Identical Sequences to LMP005684 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:125988379 | GenBank | EDL34598.1 | 403 | phosphatidylserine receptor, isoform CRA_c [Mus musculus] |
| GI:125988379 | SwissProt | Q9ERI5.2 | 403 | RecName: Full=Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6; AltName: Full=Histone arginine demethylase JMJD6; AltName: Full=JmjC domain-containing protein 6; AltName: Full=Jumonji domain-containing protein 6; AltName: Full=Lysyl-hydroxylase JMJD6; AltName: Full=Peptide-lysine 5-dioxygenase JMJD6; AltName: Full=Phosphatidylserine receptor; Short=Protein PTDSR [Mus musculus] |
Related Sequences to LMP005684 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:125988379 | GenBank | AAG27719.1 | 403 | apoptotic cell clearance receptor PtdSerR [Mus musculus] |
| GI:125988379 | GenBank | AAH56629.1 | 403 | Jumonji domain containing 6 [Mus musculus] |
| GI:125988379 | GenBank | AAR65242.1 | 403 | Sequence 5 from patent US 6630313 |
| GI:125988379 | GenBank | EDM06699.1 | 403 | rCG35128, isoform CRA_d [Rattus norvegicus] |
| GI:125988379 | RefSeq | NP_001012143.2 | 403 | bifunctional arginine demethylase and lysyl-hydroxylase JMJD6 [Rattus norvegicus] |
| GI:125988379 | SwissProt | Q6AYK2.2 | 403 | RecName: Full=Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6; AltName: Full=Histone arginine demethylase JMJD6; AltName: Full=JmjC domain-containing protein 6; AltName: Full=Jumonji domain-containing protein 6; AltName: Full=Lysyl-hydroxylase JMJD6; AltName: Full=Peptide-lysine 5-dioxygenase JMJD6; AltName: Full=Phosphatidylserine receptor; Short=Protein PTDSR [Rattus norvegicus] |