JMJD6_DANRE
ID JMJD6_DANRE Reviewed; 403 AA.
AC Q6PFM0; Q8JI07; Q8JI08;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 2.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6;
DE EC=1.14.11.-;
DE AltName: Full=Histone arginine demethylase JMJD6;
DE AltName: Full=JmjC domain-containing protein 6;
DE AltName: Full=Jumonji domain-containing protein 6;
DE AltName: Full=Lysyl-hydroxylase JMJD6;
DE AltName: Full=Peptide-lysine 5-dioxygenase JMJD6;
DE AltName: Full=Phosphatidylserine receptor;
DE Short=Protein PTDSR;
DE Short=zfpsr;
GN Name=jmjd6; Synonyms=psr, ptdsr; ORFNames=zgc:66264;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RC TISSUE=Embryo;
RX PubMed=15469976; DOI=10.1242/dev.01409;
RA Hong J.-R., Lin G.-H., Lin C.J.-F., Wang W.-P., Lee C.-C., Lin T.-L.,
RA Wu J.-L.;
RT "Phosphatidylserine receptor is required for the engulfment of dead
RT apoptotic cells and for normal embryonic development in zebrafish.";
RL Development 131:5417-5427(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=SJD;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Dioxygenase that can both act as a arginine demethylase and a
CC lysyl-hydroxylase. Acts as a lysyl-hydroxylase that catalyzes 5-
CC hydroxylation on specific lysine residues of target proteins such as
CC u2af2/u2af65 and LUC7L2. Regulates RNA splicing by mediating 5-
CC hydroxylation of u2af2/u2af65, affecting the pre-mRNA splicing activity
CC of u2af2/u2af65. Hydroxylates its own N-terminus, which is required for
CC homooligomerization. In addition to peptidyl-lysine 5-dioxygenase
CC activity, may act as an RNA hydroxylase, as suggested by its ability to
CC bind single strand RNA. Also acts as an arginine demethylase which
CC preferentially demethylates asymmetric dimethylation. Demethylates
CC histone H3 at 'Arg-2' (H3R2me) and histone H4 at 'Arg-3' (H4R3me),
CC including mono-, symmetric di- and asymmetric dimethylated forms,
CC thereby playing a role in histone code. However, histone arginine
CC demethylation may not constitute the primary activity in vivo. In
CC collaboration with brd4, interacts with the positive transcription
CC elongation factor b (P-TEFb) complex in its active form to regulate
CC polymerase II promoter-proximal pause release for transcriptional
CC activation of a large cohort of genes. Demethylates other arginine
CC methylated-proteins such as esr1. Has no histone lysine demethylase
CC activity (By similarity). Required for differentiation of multiple
CC organs during embryogenesis. Acts as a key regulator of hematopoietic
CC differentiation (By similarity). {ECO:0000250|UniProtKB:Q6NYC1,
CC ECO:0000250|UniProtKB:Q9ERI5}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + L-lysyl-[protein] + O2 = (5S)-5-hydroxy-L-
CC lysyl-[protein] + CO2 + succinate; Xref=Rhea:RHEA:58360, Rhea:RHEA-
CC COMP:9752, Rhea:RHEA-COMP:15144, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:141843;
CC Evidence={ECO:0000250|UniProtKB:Q6NYC1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 2-oxoglutarate + N(omega),N(omega)'-dimethyl-L-arginyl-
CC [protein] + 2 O2 = 2 CO2 + 2 formaldehyde + L-arginyl-[protein] + 2
CC succinate; Xref=Rhea:RHEA:58348, Rhea:RHEA-COMP:10532, Rhea:RHEA-
CC COMP:11992, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:16842, ChEBI:CHEBI:29965, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:88221; Evidence={ECO:0000250|UniProtKB:Q6NYC1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + N(omega),N(omega)'-dimethyl-L-arginyl-
CC [protein] + O2 = CO2 + formaldehyde + N(omega)-methyl-L-arginyl-
CC [protein] + succinate; Xref=Rhea:RHEA:58472, Rhea:RHEA-COMP:11990,
CC Rhea:RHEA-COMP:11992, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:16842, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:65280, ChEBI:CHEBI:88221;
CC Evidence={ECO:0000250|UniProtKB:Q6NYC1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + a 5'-end methyltriphosphate-guanosine-
CC ribonucleotide-snRNA + O2 = a 5'-end triphospho-guanosine-
CC ribonucleotide-snRNA + CO2 + formaldehyde + H(+) + succinate;
CC Xref=Rhea:RHEA:58784, Rhea:RHEA-COMP:15220, Rhea:RHEA-COMP:15221,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:16842, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:138278, ChEBI:CHEBI:142789;
CC Evidence={ECO:0000250|UniProtKB:Q6NYC1};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000250|UniProtKB:Q6NYC1};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250|UniProtKB:Q6NYC1};
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
CC {ECO:0000250|UniProtKB:Q6NYC1}. Nucleus, nucleolus
CC {ECO:0000250|UniProtKB:Q6NYC1}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q6NYC1}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Long.;
CC Name=1;
CC IsoId=Q6PFM0-1; Sequence=Displayed;
CC Name=2; Synonyms=Short;
CC IsoId=Q6PFM0-2; Sequence=VSP_014026, VSP_014027;
CC -!- TISSUE SPECIFICITY: After the somite segmentation period, it is
CC apparent throughout the embryo and the hatching gland. At the larval (3
CC dpf) stage, it is detected in the heart and kidney.
CC {ECO:0000269|PubMed:15469976}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryos from the one-cell
CC developmental stage to the 3 days post-fertilization (dpf) larval
CC stage. {ECO:0000269|PubMed:15469976}.
CC -!- DOMAIN: The nuclear localization signal motifs are necessary and
CC sufficient to target it into the nucleus.
CC {ECO:0000250|UniProtKB:Q6NYC1}.
CC -!- PTM: Hydroxylates its own N-terminus; hydroxylation is required for
CC homooligomerization. {ECO:0000250|UniProtKB:Q6NYC1}.
CC -!- DISRUPTION PHENOTYPE: Fishes display an accumulation of a large number
CC of dead apoptotic cells in whole early embryo. These cells interfere
CC with embryonic cell migration. In addition, normal development of the
CC somite, brain, heart and notochord are sequentially disrupted up to 24
CC hours post-fertilization. {ECO:0000269|PubMed:15469976}.
CC -!- SIMILARITY: Belongs to the JMJD6 family. {ECO:0000305}.
CC -!- CAUTION: Was initially thought to constitute the phosphatidylserine
CC receptor, a receptor that mediates recognition of phosphatidylserine, a
CC specific marker only present at the surface of apoptotic cells, and
CC participates in apoptotic cell phagocytosis. However, some results
CC strongly suggest that it does not constitute the receptor for
CC phosphatidylserine and is not involved in apoptotic cell removal.
CC {ECO:0000305}.
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DR EMBL; AF401484; AAM90671.1; -; mRNA.
DR EMBL; AF401485; AAM90672.1; -; mRNA.
DR EMBL; BC057498; AAH57498.1; -; mRNA.
DR RefSeq; NP_739567.3; NM_170761.3. [Q6PFM0-1]
DR AlphaFoldDB; Q6PFM0; -.
DR SMR; Q6PFM0; -.
DR STRING; 7955.ENSDARP00000107901; -.
DR PaxDb; Q6PFM0; -.
DR PRIDE; Q6PFM0; -.
DR Ensembl; ENSDART00000157822; ENSDARP00000139813; ENSDARG00000102896. [Q6PFM0-1]
DR GeneID; 266962; -.
DR KEGG; dre:266962; -.
DR CTD; 23210; -.
DR ZFIN; ZDB-GENE-040426-17; jmjd6.
DR eggNOG; KOG2130; Eukaryota.
DR GeneTree; ENSGT00940000156867; -.
DR HOGENOM; CLU_016785_8_0_1; -.
DR InParanoid; Q6PFM0; -.
DR OMA; DLFKYCG; -.
DR OrthoDB; 609279at2759; -.
DR PhylomeDB; Q6PFM0; -.
DR TreeFam; TF314988; -.
DR Reactome; R-DRE-3214842; HDMs demethylate histones.
DR PRO; PR:Q6PFM0; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 3.
DR Bgee; ENSDARG00000102896; Expressed in early embryo and 27 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032451; F:demethylase activity; ISS:UniProtKB.
DR GO; GO:0032452; F:histone demethylase activity; ISS:UniProtKB.
DR GO; GO:0033746; F:histone H3-methyl-arginine-2 demethylase activity; ISS:UniProtKB.
DR GO; GO:0033749; F:histone H3-methyl-arginine-3 demethylase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0106140; F:P-TEFb complex binding; IBA:GO_Central.
DR GO; GO:0070815; F:peptidyl-lysine 5-dioxygenase activity; ISS:UniProtKB.
DR GO; GO:0003727; F:single-stranded RNA binding; ISS:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0070079; P:histone H4-R3 demethylation; ISS:UniProtKB.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0018395; P:peptidyl-lysine hydroxylation to 5-hydroxy-L-lysine; ISS:UniProtKB.
DR GO; GO:0006909; P:phagocytosis; IMP:ZFIN.
DR GO; GO:0006482; P:protein demethylation; ISS:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; ISS:UniProtKB.
DR GO; GO:0048024; P:regulation of mRNA splicing, via spliceosome; ISS:UniProtKB.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR GO; GO:0002040; P:sprouting angiogenesis; ISS:UniProtKB.
DR InterPro; IPR003347; JmjC_dom.
DR Pfam; PF02373; JmjC; 1.
DR SMART; SM00558; JmjC; 1.
DR PROSITE; PS51184; JMJC; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Chromatin regulator; Cytoplasm;
KW Developmental protein; Differentiation; Dioxygenase; Iron; Metal-binding;
KW mRNA processing; mRNA splicing; Nucleus; Oxidoreductase;
KW Reference proteome; RNA-binding; Transcription; Transcription regulation.
FT CHAIN 1..403
FT /note="Bifunctional arginine demethylase and lysyl-
FT hydroxylase JMJD6"
FT /id="PRO_0000129374"
FT DOMAIN 141..305
FT /note="JmjC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 335..403
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 6..10
FT /note="Nuclear localization signal 1"
FT /evidence="ECO:0000250|UniProtKB:Q6NYC1"
FT MOTIF 91..95
FT /note="Nuclear localization signal 2"
FT /evidence="ECO:0000250|UniProtKB:Q6NYC1"
FT MOTIF 141..145
FT /note="Nuclear localization signal 3"
FT /evidence="ECO:0000250|UniProtKB:Q6NYC1"
FT MOTIF 167..170
FT /note="Nuclear localization signal 4"
FT /evidence="ECO:0000250|UniProtKB:Q6NYC1"
FT MOTIF 373..378
FT /note="Nuclear localization signal 5"
FT /evidence="ECO:0000250|UniProtKB:Q6NYC1"
FT COMPBIAS 335..360
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 184
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 187
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT BINDING 189
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT BINDING 197
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6NYC1"
FT BINDING 204
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 273
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT BINDING 285
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6NYC1"
FT VAR_SEQ 214..226
FT /note="PRELIKVTRDEGG -> HTRFIIFNKLVCE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15469976"
FT /id="VSP_014026"
FT VAR_SEQ 227..403
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15469976"
FT /id="VSP_014027"
FT CONFLICT 385
FT /note="N -> S (in Ref. 2; AAH57498)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 403 AA; 46687 MW; 9E0F7E1C8AFE0194 CRC64;
MNHKSKKRIK EAKRSARPEL KDSSDWTKHE YCKSFDLSHR SVKDNVERAD VQRLSPEEFI
QRFEKPYKPV VLLNVEDSWP AREKWTLERL KRKYRNQKFK CGEDNDGYSV KMKMKYYVEY
LESTHDDSPL YIFDSSFGEH AKRRKLLEDY QVPLFFRDDL FQFAGEKRRP PYRWFVMGPA
RSGTGIHIDP LGTSAWNALV QGHKRWCLFP THTPRELIKV TRDEGGNQQD EAITWFNVIY
PRTQQSTWPD EFRPLEILQR PGETVFVPGG WWHVVLNLDT TIAVTQNFAS TTNFPIVWHK
TVRGRPKLSR KWYRILKQER PDIAAIADKV DLQESTGIAS DSSSDSSSSS SSSSSDSDSE
ADSGSEGDAM THRRKKRRTG GMMGNGDITS QDDCASKERS SSR
