JMJD6_BOVIN
ID JMJD6_BOVIN Reviewed; 403 AA.
AC Q58DS6;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 99.
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;
GN Name=JMJD6 {ECO:0000250|UniProtKB:Q6NYC1};
GN Synonyms=PTDSR {ECO:0000312|EMBL:AAX46368.1};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1] {ECO:0000312|EMBL:AAX46368.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
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. On distal enhancers, so called
CC anti-pause enhancers, demethylates both histone H4R3me2 and the methyl
CC cap of 7SKsnRNA leading to the dismissal of the 7SKsnRNA:HEXIM1
CC inhibitor complex. After removal of repressive marks, the complex
CC BRD4:JMJD6 attract and retain the P-TEFb complex on chromatin, leading
CC to its activation, promoter-proximal polymerase II pause release, and
CC transcriptional activation. Demethylates other arginine methylated-
CC proteins such as ESR1. Has no histone lysine demethylase activity (By
CC similarity). Required for differentiation of multiple organs during
CC embryogenesis. Acts as a key regulator of hematopoietic
CC differentiation: required for angiogenic sprouting by regulating the
CC pre-mRNA splicing activity of U2AF2/U2AF65 (By similarity). Seems to be
CC necessary for the regulation of macrophage cytokine responses (By
CC 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,
CC ECO:0000250|UniProtKB:Q6NYC1};
CC -!- SUBUNIT: Homooligomerizes; requires lysyl-hydroxylase activity.
CC Interacts with LUC7L2, LUC7L3 and U2AF2/U2AF65 (By similarity).
CC Interacts with LIAT1 (By similarity). Interacts with CDK9 and CCNT1;
CC the interaction is direct with CDK9 and associates the P-TEFb complex
CC when active. Interacts (via JmjC and N-terminal domains) with BRD4 (via
CC NET domain); the interaction is stronger in presence of ssRNA and
CC recruits JMJD6 on distal enhancers (By similarity).
CC {ECO:0000250|UniProtKB:Q6NYC1, ECO:0000250|UniProtKB:Q9ERI5}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
CC {ECO:0000250|UniProtKB:Q6NYC1}. Nucleus, nucleolus
CC {ECO:0000250|UniProtKB:Q6NYC1}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q6NYC1}. Note=Mainly found throughout the
CC nucleoplasm outside of regions containing heterochromatic DNA, with
CC some localization in nucleolus. During mitosis, excluded from the
CC nucleus and reappears in the telophase of the cell cycle.
CC {ECO:0000250|UniProtKB:Q6NYC1}.
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 -!- SIMILARITY: Belongs to the JMJD6 family. {ECO:0000305}.
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DR EMBL; BT021521; AAX46368.1; -; mRNA.
DR RefSeq; NP_001029492.2; NM_001034320.2.
DR AlphaFoldDB; Q58DS6; -.
DR SMR; Q58DS6; -.
DR STRING; 9913.ENSBTAP00000025492; -.
DR PaxDb; Q58DS6; -.
DR PRIDE; Q58DS6; -.
DR GeneID; 508343; -.
DR KEGG; bta:508343; -.
DR CTD; 23210; -.
DR eggNOG; KOG2130; Eukaryota.
DR HOGENOM; CLU_016785_8_0_1; -.
DR InParanoid; Q58DS6; -.
DR OrthoDB; 609279at2759; -.
DR TreeFam; TF314988; -.
DR Proteomes; UP000009136; Unplaced.
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:0035515; F:oxidative RNA demethylase activity; ISS:UniProtKB.
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:0140537; F:transcription regulator activator activity; 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:0035513; P:oxidative RNA demethylation; ISS:UniProtKB.
DR GO; GO:0018395; P:peptidyl-lysine hydroxylation to 5-hydroxy-L-lysine; ISS:UniProtKB.
DR GO; GO:0006909; P:phagocytosis; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
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 Chromatin regulator; Cytoplasm; Developmental protein; Differentiation;
KW Dioxygenase; Iron; Metal-binding; mRNA processing; mRNA splicing; Nucleus;
KW Oxidoreductase; Reference proteome; RNA-binding; Transcription;
KW Transcription regulation.
FT CHAIN 1..403
FT /note="Bifunctional arginine demethylase and lysyl-
FT hydroxylase JMJD6"
FT /id="PRO_0000312839"
FT DOMAIN 141..305
FT /note="JmjC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT REGION 336..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 336..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"
SQ SEQUENCE 403 AA; 46527 MW; 74BC887C072B3A59 CRC64;
MNHKSKKRIR EAKRSARPEL KDSLDWTRHN YFESFPLNPA AVADNVERAD ALQLSVEEFV
ERYERPYKPV VLLNAQEGWS AQEKWTLERL KRKYRNQKFK CGEDNDGYSV KMKMKYYIEY
MESTRDDSPL YIFDSSYGEH PKRRKLLEDY KVPKFFTDDL FQYAGEKRRP PYRWFVMGPP
RSGTGIHIDP LGTSAWNALV QGHKRWCLFP TSTPRELIKV TREEGGNQQD EAITWFNIIY
PRTQLPTWPP EFKPLEILQK PGETVFVPGG WWHVVLNLDT TIAITQNFAS STNFPVVWHK
TVRGRPKLSR KWYRILKQEH PELAVLADSV DLQESTGIAS DSSSDSSSSS SSSSSDSDSE
CESGSEGEGT MHRRKKRRTC GMVGNGDTTS QDDCVSKERS SSR
