Full text data of JMJD6
JMJD6
(KIAA0585, PTDSR)
[Confidence: low (only semi-automatic identification from reviews)]
Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6; 1.14.11.- (Histone arginine demethylase JMJD6; JmjC domain-containing protein 6; Jumonji domain-containing protein 6; Lysyl-hydroxylase JMJD6; Peptide-lysine 5-dioxygenase JMJD6; Phosphatidylserine receptor; Protein PTDSR)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6; 1.14.11.- (Histone arginine demethylase JMJD6; JmjC domain-containing protein 6; Jumonji domain-containing protein 6; Lysyl-hydroxylase JMJD6; Peptide-lysine 5-dioxygenase JMJD6; Phosphatidylserine receptor; Protein PTDSR)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q6NYC1
ID JMJD6_HUMAN Reviewed; 403 AA.
AC Q6NYC1; B3KMN8; B4DGX1; Q86VY0; Q8IUM5; Q9Y4E2;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 05-JUL-2004, sequence version 1.
DT 22-JAN-2014, entry version 97.
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; Synonyms=KIAA0585, PTDSR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Stomach cancer;
RA Izawa M., Takahashi M.;
RT "Identification of an alternative form of phosphatidylserine
RT receptor.";
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX.
RT The complete sequences of 100 new cDNA clones from brain which can
RT code for large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Brain, and Embryo;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP SUBCELLULAR LOCATION, AND NUCLEAR LOCALIZATION SIGNALS.
RX PubMed=14729065; DOI=10.1016/j.yexcr.2003.09.023;
RA Cui P., Qin B., Liu N., Pan G., Pei D.;
RT "Nuclear localization of the phosphatidylserine receptor protein via
RT multiple nuclear localization signals.";
RL Exp. Cell Res. 293:154-163(2004).
RN [8]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=15072554; DOI=10.1677/jme.0.0320497;
RA Cao W.M., Murao K., Imachi H., Hiramine C., Abe H., Yu X., Dobashi H.,
RA Wong N.C.W., Takahara J., Ishida T.;
RT "Phosphatidylserine receptor cooperates with high-density lipoprotein
RT receptor in recognition of apoptotic cells by thymic nurse cells.";
RL J. Mol. Endocrinol. 32:497-505(2004).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=15622002;
RA Koeninger J., Balaz P., Wagner M., Shi X., Cima I., Zimmermann A.,
RA di Sebastiano P., Buechler M.W., Friess H.;
RT "Phosphatidylserine receptor in chronic pancreatitis: evidence for a
RT macrophage independent role.";
RL Ann. Surg. 241:144-151(2005).
RN [10]
RP FUNCTION AS HISTONE DEMETHYLASE, AND MUTAGENESIS OF HIS-187; ASP-189
RP AND HIS-273.
RX PubMed=17947579; DOI=10.1126/science.1145801;
RA Chang B., Chen Y., Zhao Y., Bruick R.K.;
RT "JMJD6 is a histone arginine demethylase.";
RL Science 318:444-447(2007).
RN [11]
RP FUNCTION AS LYSYL-HYDROXYLASE, COFACTOR, INTERACTION WITH LUC7L2;
RP LUC7L3 AND U2AF2, AND MUTAGENESIS OF HIS-187 AND ASP-189.
RX PubMed=19574390; DOI=10.1126/science.1175865;
RA Webby C.J., Wolf A., Gromak N., Dreger M., Kramer H., Kessler B.,
RA Nielsen M.L., Schmitz C., Butler D.S., Yates J.R. III, Delahunty C.M.,
RA Hahn P., Lengeling A., Mann M., Proudfoot N.J., Schofield C.J.,
RA Boettger A.;
RT "Jmjd6 catalyses lysyl-hydroxylation of U2AF65, a protein associated
RT with RNA splicing.";
RL Science 325:90-93(2009).
RN [12]
RP SUBCELLULAR LOCATION, RNA-BINDING, AND FUNCTION.
RX PubMed=21060799; DOI=10.1371/journal.pone.0013769;
RA Hahn P., Wegener I., Burrells A., Bose J., Wolf A., Erck C.,
RA Butler D., Schofield C.J., Bottger A., Lengeling A.;
RT "Analysis of Jmjd6 cellular localization and testing for its
RT involvement in histone demethylation.";
RL PLoS ONE 5:E13769-E13769(2010).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP INTERACTION WITH BRD4.
RX PubMed=21555454; DOI=10.1128/MCB.01341-10;
RA Rahman S., Sowa M.E., Ottinger M., Smith J.A., Shi Y., Harper J.W.,
RA Howley P.M.;
RT "The Brd4 extraterminal domain confers transcription activation
RT independent of pTEFb by recruiting multiple proteins, including
RT NSD3.";
RL Mol. Cell. Biol. 31:2641-2652(2011).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 1-335 IN COMPLEX WITH NICKEL
RP IONS, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF
RP TYR-131; LYS-204; GLU-231; THR-285 AND ASN-287.
RX PubMed=20684070; DOI=10.1016/j.jmb.2010.05.054;
RA Mantri M., Krojer T., Bagg E.A., Webby C.J., Butler D.S., Kochan G.,
RA Kavanagh K.L., Oppermann U., McDonough M.A., Schofield C.J.;
RT "Crystal structure of the 2-oxoglutarate- and Fe(II)-dependent lysyl
RT hydroxylase JMJD6.";
RL J. Mol. Biol. 401:211-222(2010).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 1-334 IN COMPLEX WITH IRON
RP IONS AND 2-OXOGLUTARATE, POSSIBLE FUNCTION, AND RNA-BINDING.
RX PubMed=20679243; DOI=10.1073/pnas.1008832107;
RA Hong X., Zang J., White J., Wang C., Pan C.H., Zhao R., Murphy R.C.,
RA Dai S., Henson P., Kappler J.W., Hagman J., Zhang G.;
RT "Interaction of JMJD6 with single-stranded RNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:14568-14572(2010).
CC -!- FUNCTION: Dioxygenase that can both act as a histone arginine
CC demethylase and a lysyl-hydroxylase. Acts as a lysyl-hydroxylase
CC that catalyzes 5-hydroxylation on specific lysine residues of
CC target proteins such as U2AF2/U2AF65 and LUC7L2. Acts as a
CC regulator of RNA splicing by mediating 5-hydroxylation of
CC U2AF2/U2AF65, affecting the pre-mRNA splicing activity of
CC U2AF2/U2AF65. In addition to peptidyl-lysine 5-dioxygenase
CC activity, may act as a RNA hydroxylase, as suggested by its
CC ability to bind single strand RNA. Also acts as an arginine
CC demethylase which demethylates histone H3 at 'Arg-2' (H3R2me) and
CC histone H4 at 'Arg-3' (H4R3me), thereby playing a role in histone
CC code. However, histone arginine demethylation may not constitute
CC the primary activity in vivo. Has no histone lysine demethylase
CC activity. Required for differentiation of multiple organs during
CC embryogenesis. Acts as a key regulator of hematopoietic
CC differentiation: required for angiogenic sprouting by regulating
CC the pre-mRNA splicing activity of U2AF2/U2AF65. Seems to be
CC necessary for the regulation of macrophage cytokine responses.
CC -!- COFACTOR: Binds 1 Fe(2+) ion per subunit.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=39 uM for 2-oxoglutarate;
CC -!- SUBUNIT: Interacts with LUC7L2, LUC7L3 and U2AF2/U2AF65. Interacts
CC with BRD4.
CC -!- INTERACTION:
CC Q8NAV1:PRPF38A; NbExp=2; IntAct=EBI-8464037, EBI-715374;
CC Q01081:U2AF1; NbExp=2; IntAct=EBI-8464037, EBI-632461;
CC Q9NP64:ZCCHC17; NbExp=2; IntAct=EBI-8464037, EBI-746345;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm. Nucleus, nucleolus.
CC Note=Mainly found throughout the nucleoplasm outside of regions
CC containing heterochromatic DNA, with some localization in
CC nucleolus. During mitosis, excluded from the nucleus and reappears
CC in the telophase of the cell cycle.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Alpha;
CC IsoId=Q6NYC1-1; Sequence=Displayed;
CC Name=2; Synonyms=Beta;
CC IsoId=Q6NYC1-2; Sequence=VSP_014022, VSP_014023;
CC Name=3;
CC IsoId=Q6NYC1-3; Sequence=VSP_014023;
CC -!- TISSUE SPECIFICITY: Highly expressed in the heart, skeletal muscle
CC and kidney. Expressed at moderate or low level in brain, placenta,
CC lung, liver, pancreas, spleen, thymus, prostate, testis and ovary.
CC Up-regulated in many patients with chronic pancreatitis. Expressed
CC in nursing thymic epithelial cells.
CC -!- INDUCTION: Up-regulated upon cytokine treatment, but not upon TNF
CC treatment.
CC -!- DOMAIN: The nuclear localization signal motifs are necessary and
CC sufficient to target it into the nucleus.
CC -!- SIMILARITY: Belongs to the JMJD6 family.
CC -!- SIMILARITY: Contains 1 JmjC domain.
CC -!- CAUTION: Was initially thought to constitute the
CC phosphatidylserine receptor, a receptor that mediates recognition
CC of phosphatidylserine, a specific marker only present at the
CC surface of apoptotic cells. Phosphatidylserine receptor probably
CC participates in apoptotic cell phagocytosis. This protein was
CC identified using phage display expressing mAb 217, an antibody
CC that specifically recognizes phosphatidylserine receptor. However,
CC its nuclear localization and the fact that mAb 217 antibody still
CC recognizes the phosphatidylserine receptor in mice lacking JMJD6,
CC strongly suggest that it does not constitute the receptor for
CC phosphatidylserine and is not involved in apoptotic cell removal.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH47003.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=BAA25511.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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DR EMBL; AB073711; BAC16755.1; -; mRNA.
DR EMBL; AB011157; BAA25511.1; ALT_INIT; mRNA.
DR EMBL; AK021780; BAG51050.1; -; mRNA.
DR EMBL; AK294816; BAG57932.1; -; mRNA.
DR EMBL; AC005837; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471099; EAW89434.1; -; Genomic_DNA.
DR EMBL; BC047003; AAH47003.1; ALT_INIT; mRNA.
DR EMBL; BC066654; AAH66654.1; -; mRNA.
DR RefSeq; NP_001074930.1; NM_001081461.1.
DR RefSeq; NP_055982.2; NM_015167.2.
DR UniGene; Hs.514505; -.
DR PDB; 3K2O; X-ray; 1.75 A; A/B=1-335.
DR PDB; 3LD8; X-ray; 2.70 A; A=1-334.
DR PDB; 3LDB; X-ray; 2.70 A; A=1-334.
DR PDBsum; 3K2O; -.
DR PDBsum; 3LD8; -.
DR PDBsum; 3LDB; -.
DR ProteinModelPortal; Q6NYC1; -.
DR SMR; Q6NYC1; 1-335.
DR IntAct; Q6NYC1; 26.
DR MINT; MINT-3086431; -.
DR STRING; 9606.ENSP00000394085; -.
DR PhosphoSite; Q6NYC1; -.
DR DMDM; 67461014; -.
DR PaxDb; Q6NYC1; -.
DR PRIDE; Q6NYC1; -.
DR Ensembl; ENST00000397625; ENSP00000380750; ENSG00000070495.
DR Ensembl; ENST00000445478; ENSP00000394085; ENSG00000070495.
DR GeneID; 23210; -.
DR KEGG; hsa:23210; -.
DR UCSC; uc002jso.3; human.
DR CTD; 23210; -.
DR GeneCards; GC17M074708; -.
DR HGNC; HGNC:19355; JMJD6.
DR HPA; CAB004548; -.
DR MIM; 604914; gene.
DR neXtProt; NX_Q6NYC1; -.
DR PharmGKB; PA162392513; -.
DR eggNOG; NOG124833; -.
DR HOGENOM; HOG000265824; -.
DR HOVERGEN; HBG054774; -.
DR InParanoid; Q6NYC1; -.
DR KO; K11323; -.
DR EvolutionaryTrace; Q6NYC1; -.
DR GeneWiki; JMJD6; -.
DR GenomeRNAi; 23210; -.
DR NextBio; 44753; -.
DR PRO; PR:Q6NYC1; -.
DR ArrayExpress; Q6NYC1; -.
DR Bgee; Q6NYC1; -.
DR CleanEx; HS_JMJD6; -.
DR Genevestigator; Q6NYC1; -.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0033746; F:histone demethylase activity (H3-R2 specific); IDA:UniProtKB.
DR GO; GO:0033749; F:histone demethylase activity (H4-R3 specific); IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:BHF-UCL.
DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB.
DR GO; GO:0070815; F:peptidyl-lysine 5-dioxygenase activity; IDA:UniProtKB.
DR GO; GO:0004872; F:receptor activity; IEA:Ensembl.
DR GO; GO:0003727; F:single-stranded RNA binding; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:Ensembl.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0048821; P:erythrocyte development; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR GO; GO:0030324; P:lung development; IEA:Ensembl.
DR GO; GO:0042116; P:macrophage activation; IEA:Ensembl.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0018395; P:peptidyl-lysine hydroxylation to 5-hydroxy-L-lysine; IDA:UniProtKB.
DR GO; GO:0043654; P:recognition of apoptotic cell; IEA:Ensembl.
DR GO; GO:0048024; P:regulation of mRNA splicing, via spliceosome; IMP:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0060041; P:retina development in camera-type eye; IEA:Ensembl.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR GO; GO:0002040; P:sprouting angiogenesis; ISS:UniProtKB.
DR GO; GO:0033077; P:T cell differentiation in thymus; IEA:Ensembl.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR InterPro; IPR003347; JmjC_dom.
DR Pfam; PF02373; JmjC; 1.
DR SMART; SM00558; JmjC; 1.
DR PROSITE; PS51184; JMJC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromatin regulator;
KW Complete proteome; Developmental protein; Differentiation;
KW Dioxygenase; Iron; Metal-binding; mRNA processing; mRNA splicing;
KW Nucleus; Oxidoreductase; Reference proteome; RNA-binding;
KW Transcription; Transcription regulation.
FT CHAIN 1 403 Bifunctional arginine demethylase and
FT lysyl-hydroxylase JMJD6.
FT /FTId=PRO_0000129369.
FT DOMAIN 141 305 JmjC.
FT MOTIF 6 10 Nuclear localization signal 1.
FT MOTIF 91 95 Nuclear localization signal 2.
FT MOTIF 141 145 Nuclear localization signal 3.
FT MOTIF 167 170 Nuclear localization signal 4.
FT MOTIF 373 378 Nuclear localization signal 5.
FT COMPBIAS 340 365 Ser-rich.
FT METAL 187 187 Iron; catalytic.
FT METAL 189 189 Iron; catalytic.
FT METAL 273 273 Iron; catalytic.
FT BINDING 184 184 Substrate (By similarity).
FT BINDING 197 197 2-oxoglutarate.
FT BINDING 204 204 Substrate (By similarity).
FT BINDING 285 285 2-oxoglutarate.
FT VAR_SEQ 361 402 Missing (in isoform 2).
FT /FTId=VSP_014022.
FT VAR_SEQ 403 403 R -> RIRDTCGGRAHP (in isoform 2 and
FT isoform 3).
FT /FTId=VSP_014023.
FT MUTAGEN 131 131 Y->F: Abolishes 2-oxoglutarate-binding
FT and enzyme activity.
FT MUTAGEN 187 187 H->A: Loss of catalytic activity; when
FT associated with A-189 and A-273.
FT MUTAGEN 189 189 D->A: Loss of catalytic activity; when
FT associated with A-187 and A-273.
FT MUTAGEN 204 204 K->A: Impairs enzyme activity without
FT affecting 2-oxoglutarate-binding.
FT MUTAGEN 231 231 E->A: Impairs both hydroxylation activity
FT and 2-oxoglutarate turnover assays.
FT MUTAGEN 273 273 H->A: Loss of catalytic activity; when
FT associated with A-187 and A-189.
FT MUTAGEN 285 285 T->A: Impairs enzyme activity and 2-
FT oxoglutarate-binding.
FT MUTAGEN 287 287 N->A: Impairs enzyme activity.
FT CONFLICT 136 136 S -> G (in Ref. 3; BAG51050).
FT HELIX 3 16
FT HELIX 23 27
FT HELIX 31 34
FT HELIX 39 41
FT STRAND 48 50
FT HELIX 51 53
FT HELIX 56 62
FT TURN 63 67
FT STRAND 70 74
FT TURN 75 78
FT HELIX 81 84
FT HELIX 87 93
FT STRAND 98 103
FT STRAND 109 113
FT HELIX 114 123
FT STRAND 132 135
FT HELIX 137 139
FT HELIX 143 149
FT HELIX 154 156
FT HELIX 160 164
FT TURN 166 168
FT STRAND 173 178
FT STRAND 183 187
FT HELIX 190 192
FT STRAND 194 202
FT STRAND 204 209
FT HELIX 215 218
FT HELIX 222 225
FT HELIX 226 228
FT HELIX 232 238
FT HELIX 240 244
FT HELIX 250 252
FT STRAND 255 259
FT STRAND 264 267
FT STRAND 272 279
FT STRAND 281 288
FT TURN 291 293
FT HELIX 294 304
FT HELIX 306 319
FT HELIX 321 333
SQ SEQUENCE 403 AA; 46462 MW; 9C9AADA98B24B035 CRC64;
MNHKSKKRIR EAKRSARPEL KDSLDWTRHN YYESFSLSPA AVADNVERAD ALQLSVEEFV
ERYERPYKPV VLLNAQEGWS AQEKWTLERL KRKYRNQKFK CGEDNDGYSV KMKMKYYIEY
MESTRDDSPL YIFDSSYGEH PKRRKLLEDY KVPKFFTDDL FQYAGEKRRP PYRWFVMGPP
RSGTGIHIDP LGTSAWNALV QGHKRWCLFP TSTPRELIKV TRDEGGNQQD EAITWFNVIY
PRTQLPTWPP EFKPLEILQK PGETVFVPGG WWHVVLNLDT TIAITQNFAS STNFPVVWHK
TVRGRPKLSR KWYRILKQEH PELAVLADSV DLQESTGIAS DSSSDSSSSS SSSSSDSDSE
CESGSEGDGT VHRRKKRRTC SMVGNGDTTS QDDCVSKERS SSR
//
ID JMJD6_HUMAN Reviewed; 403 AA.
AC Q6NYC1; B3KMN8; B4DGX1; Q86VY0; Q8IUM5; Q9Y4E2;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 05-JUL-2004, sequence version 1.
DT 22-JAN-2014, entry version 97.
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; Synonyms=KIAA0585, PTDSR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Stomach cancer;
RA Izawa M., Takahashi M.;
RT "Identification of an alternative form of phosphatidylserine
RT receptor.";
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX.
RT The complete sequences of 100 new cDNA clones from brain which can
RT code for large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Brain, and Embryo;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP SUBCELLULAR LOCATION, AND NUCLEAR LOCALIZATION SIGNALS.
RX PubMed=14729065; DOI=10.1016/j.yexcr.2003.09.023;
RA Cui P., Qin B., Liu N., Pan G., Pei D.;
RT "Nuclear localization of the phosphatidylserine receptor protein via
RT multiple nuclear localization signals.";
RL Exp. Cell Res. 293:154-163(2004).
RN [8]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=15072554; DOI=10.1677/jme.0.0320497;
RA Cao W.M., Murao K., Imachi H., Hiramine C., Abe H., Yu X., Dobashi H.,
RA Wong N.C.W., Takahara J., Ishida T.;
RT "Phosphatidylserine receptor cooperates with high-density lipoprotein
RT receptor in recognition of apoptotic cells by thymic nurse cells.";
RL J. Mol. Endocrinol. 32:497-505(2004).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=15622002;
RA Koeninger J., Balaz P., Wagner M., Shi X., Cima I., Zimmermann A.,
RA di Sebastiano P., Buechler M.W., Friess H.;
RT "Phosphatidylserine receptor in chronic pancreatitis: evidence for a
RT macrophage independent role.";
RL Ann. Surg. 241:144-151(2005).
RN [10]
RP FUNCTION AS HISTONE DEMETHYLASE, AND MUTAGENESIS OF HIS-187; ASP-189
RP AND HIS-273.
RX PubMed=17947579; DOI=10.1126/science.1145801;
RA Chang B., Chen Y., Zhao Y., Bruick R.K.;
RT "JMJD6 is a histone arginine demethylase.";
RL Science 318:444-447(2007).
RN [11]
RP FUNCTION AS LYSYL-HYDROXYLASE, COFACTOR, INTERACTION WITH LUC7L2;
RP LUC7L3 AND U2AF2, AND MUTAGENESIS OF HIS-187 AND ASP-189.
RX PubMed=19574390; DOI=10.1126/science.1175865;
RA Webby C.J., Wolf A., Gromak N., Dreger M., Kramer H., Kessler B.,
RA Nielsen M.L., Schmitz C., Butler D.S., Yates J.R. III, Delahunty C.M.,
RA Hahn P., Lengeling A., Mann M., Proudfoot N.J., Schofield C.J.,
RA Boettger A.;
RT "Jmjd6 catalyses lysyl-hydroxylation of U2AF65, a protein associated
RT with RNA splicing.";
RL Science 325:90-93(2009).
RN [12]
RP SUBCELLULAR LOCATION, RNA-BINDING, AND FUNCTION.
RX PubMed=21060799; DOI=10.1371/journal.pone.0013769;
RA Hahn P., Wegener I., Burrells A., Bose J., Wolf A., Erck C.,
RA Butler D., Schofield C.J., Bottger A., Lengeling A.;
RT "Analysis of Jmjd6 cellular localization and testing for its
RT involvement in histone demethylation.";
RL PLoS ONE 5:E13769-E13769(2010).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP INTERACTION WITH BRD4.
RX PubMed=21555454; DOI=10.1128/MCB.01341-10;
RA Rahman S., Sowa M.E., Ottinger M., Smith J.A., Shi Y., Harper J.W.,
RA Howley P.M.;
RT "The Brd4 extraterminal domain confers transcription activation
RT independent of pTEFb by recruiting multiple proteins, including
RT NSD3.";
RL Mol. Cell. Biol. 31:2641-2652(2011).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 1-335 IN COMPLEX WITH NICKEL
RP IONS, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF
RP TYR-131; LYS-204; GLU-231; THR-285 AND ASN-287.
RX PubMed=20684070; DOI=10.1016/j.jmb.2010.05.054;
RA Mantri M., Krojer T., Bagg E.A., Webby C.J., Butler D.S., Kochan G.,
RA Kavanagh K.L., Oppermann U., McDonough M.A., Schofield C.J.;
RT "Crystal structure of the 2-oxoglutarate- and Fe(II)-dependent lysyl
RT hydroxylase JMJD6.";
RL J. Mol. Biol. 401:211-222(2010).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 1-334 IN COMPLEX WITH IRON
RP IONS AND 2-OXOGLUTARATE, POSSIBLE FUNCTION, AND RNA-BINDING.
RX PubMed=20679243; DOI=10.1073/pnas.1008832107;
RA Hong X., Zang J., White J., Wang C., Pan C.H., Zhao R., Murphy R.C.,
RA Dai S., Henson P., Kappler J.W., Hagman J., Zhang G.;
RT "Interaction of JMJD6 with single-stranded RNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:14568-14572(2010).
CC -!- FUNCTION: Dioxygenase that can both act as a histone arginine
CC demethylase and a lysyl-hydroxylase. Acts as a lysyl-hydroxylase
CC that catalyzes 5-hydroxylation on specific lysine residues of
CC target proteins such as U2AF2/U2AF65 and LUC7L2. Acts as a
CC regulator of RNA splicing by mediating 5-hydroxylation of
CC U2AF2/U2AF65, affecting the pre-mRNA splicing activity of
CC U2AF2/U2AF65. In addition to peptidyl-lysine 5-dioxygenase
CC activity, may act as a RNA hydroxylase, as suggested by its
CC ability to bind single strand RNA. Also acts as an arginine
CC demethylase which demethylates histone H3 at 'Arg-2' (H3R2me) and
CC histone H4 at 'Arg-3' (H4R3me), thereby playing a role in histone
CC code. However, histone arginine demethylation may not constitute
CC the primary activity in vivo. Has no histone lysine demethylase
CC activity. Required for differentiation of multiple organs during
CC embryogenesis. Acts as a key regulator of hematopoietic
CC differentiation: required for angiogenic sprouting by regulating
CC the pre-mRNA splicing activity of U2AF2/U2AF65. Seems to be
CC necessary for the regulation of macrophage cytokine responses.
CC -!- COFACTOR: Binds 1 Fe(2+) ion per subunit.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=39 uM for 2-oxoglutarate;
CC -!- SUBUNIT: Interacts with LUC7L2, LUC7L3 and U2AF2/U2AF65. Interacts
CC with BRD4.
CC -!- INTERACTION:
CC Q8NAV1:PRPF38A; NbExp=2; IntAct=EBI-8464037, EBI-715374;
CC Q01081:U2AF1; NbExp=2; IntAct=EBI-8464037, EBI-632461;
CC Q9NP64:ZCCHC17; NbExp=2; IntAct=EBI-8464037, EBI-746345;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm. Nucleus, nucleolus.
CC Note=Mainly found throughout the nucleoplasm outside of regions
CC containing heterochromatic DNA, with some localization in
CC nucleolus. During mitosis, excluded from the nucleus and reappears
CC in the telophase of the cell cycle.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Alpha;
CC IsoId=Q6NYC1-1; Sequence=Displayed;
CC Name=2; Synonyms=Beta;
CC IsoId=Q6NYC1-2; Sequence=VSP_014022, VSP_014023;
CC Name=3;
CC IsoId=Q6NYC1-3; Sequence=VSP_014023;
CC -!- TISSUE SPECIFICITY: Highly expressed in the heart, skeletal muscle
CC and kidney. Expressed at moderate or low level in brain, placenta,
CC lung, liver, pancreas, spleen, thymus, prostate, testis and ovary.
CC Up-regulated in many patients with chronic pancreatitis. Expressed
CC in nursing thymic epithelial cells.
CC -!- INDUCTION: Up-regulated upon cytokine treatment, but not upon TNF
CC treatment.
CC -!- DOMAIN: The nuclear localization signal motifs are necessary and
CC sufficient to target it into the nucleus.
CC -!- SIMILARITY: Belongs to the JMJD6 family.
CC -!- SIMILARITY: Contains 1 JmjC domain.
CC -!- CAUTION: Was initially thought to constitute the
CC phosphatidylserine receptor, a receptor that mediates recognition
CC of phosphatidylserine, a specific marker only present at the
CC surface of apoptotic cells. Phosphatidylserine receptor probably
CC participates in apoptotic cell phagocytosis. This protein was
CC identified using phage display expressing mAb 217, an antibody
CC that specifically recognizes phosphatidylserine receptor. However,
CC its nuclear localization and the fact that mAb 217 antibody still
CC recognizes the phosphatidylserine receptor in mice lacking JMJD6,
CC strongly suggest that it does not constitute the receptor for
CC phosphatidylserine and is not involved in apoptotic cell removal.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH47003.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=BAA25511.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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DR EMBL; AB073711; BAC16755.1; -; mRNA.
DR EMBL; AB011157; BAA25511.1; ALT_INIT; mRNA.
DR EMBL; AK021780; BAG51050.1; -; mRNA.
DR EMBL; AK294816; BAG57932.1; -; mRNA.
DR EMBL; AC005837; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471099; EAW89434.1; -; Genomic_DNA.
DR EMBL; BC047003; AAH47003.1; ALT_INIT; mRNA.
DR EMBL; BC066654; AAH66654.1; -; mRNA.
DR RefSeq; NP_001074930.1; NM_001081461.1.
DR RefSeq; NP_055982.2; NM_015167.2.
DR UniGene; Hs.514505; -.
DR PDB; 3K2O; X-ray; 1.75 A; A/B=1-335.
DR PDB; 3LD8; X-ray; 2.70 A; A=1-334.
DR PDB; 3LDB; X-ray; 2.70 A; A=1-334.
DR PDBsum; 3K2O; -.
DR PDBsum; 3LD8; -.
DR PDBsum; 3LDB; -.
DR ProteinModelPortal; Q6NYC1; -.
DR SMR; Q6NYC1; 1-335.
DR IntAct; Q6NYC1; 26.
DR MINT; MINT-3086431; -.
DR STRING; 9606.ENSP00000394085; -.
DR PhosphoSite; Q6NYC1; -.
DR DMDM; 67461014; -.
DR PaxDb; Q6NYC1; -.
DR PRIDE; Q6NYC1; -.
DR Ensembl; ENST00000397625; ENSP00000380750; ENSG00000070495.
DR Ensembl; ENST00000445478; ENSP00000394085; ENSG00000070495.
DR GeneID; 23210; -.
DR KEGG; hsa:23210; -.
DR UCSC; uc002jso.3; human.
DR CTD; 23210; -.
DR GeneCards; GC17M074708; -.
DR HGNC; HGNC:19355; JMJD6.
DR HPA; CAB004548; -.
DR MIM; 604914; gene.
DR neXtProt; NX_Q6NYC1; -.
DR PharmGKB; PA162392513; -.
DR eggNOG; NOG124833; -.
DR HOGENOM; HOG000265824; -.
DR HOVERGEN; HBG054774; -.
DR InParanoid; Q6NYC1; -.
DR KO; K11323; -.
DR EvolutionaryTrace; Q6NYC1; -.
DR GeneWiki; JMJD6; -.
DR GenomeRNAi; 23210; -.
DR NextBio; 44753; -.
DR PRO; PR:Q6NYC1; -.
DR ArrayExpress; Q6NYC1; -.
DR Bgee; Q6NYC1; -.
DR CleanEx; HS_JMJD6; -.
DR Genevestigator; Q6NYC1; -.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0033746; F:histone demethylase activity (H3-R2 specific); IDA:UniProtKB.
DR GO; GO:0033749; F:histone demethylase activity (H4-R3 specific); IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:BHF-UCL.
DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB.
DR GO; GO:0070815; F:peptidyl-lysine 5-dioxygenase activity; IDA:UniProtKB.
DR GO; GO:0004872; F:receptor activity; IEA:Ensembl.
DR GO; GO:0003727; F:single-stranded RNA binding; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:Ensembl.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0048821; P:erythrocyte development; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR GO; GO:0030324; P:lung development; IEA:Ensembl.
DR GO; GO:0042116; P:macrophage activation; IEA:Ensembl.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0018395; P:peptidyl-lysine hydroxylation to 5-hydroxy-L-lysine; IDA:UniProtKB.
DR GO; GO:0043654; P:recognition of apoptotic cell; IEA:Ensembl.
DR GO; GO:0048024; P:regulation of mRNA splicing, via spliceosome; IMP:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0060041; P:retina development in camera-type eye; IEA:Ensembl.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR GO; GO:0002040; P:sprouting angiogenesis; ISS:UniProtKB.
DR GO; GO:0033077; P:T cell differentiation in thymus; IEA:Ensembl.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR InterPro; IPR003347; JmjC_dom.
DR Pfam; PF02373; JmjC; 1.
DR SMART; SM00558; JmjC; 1.
DR PROSITE; PS51184; JMJC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromatin regulator;
KW Complete proteome; Developmental protein; Differentiation;
KW Dioxygenase; Iron; Metal-binding; mRNA processing; mRNA splicing;
KW Nucleus; Oxidoreductase; Reference proteome; RNA-binding;
KW Transcription; Transcription regulation.
FT CHAIN 1 403 Bifunctional arginine demethylase and
FT lysyl-hydroxylase JMJD6.
FT /FTId=PRO_0000129369.
FT DOMAIN 141 305 JmjC.
FT MOTIF 6 10 Nuclear localization signal 1.
FT MOTIF 91 95 Nuclear localization signal 2.
FT MOTIF 141 145 Nuclear localization signal 3.
FT MOTIF 167 170 Nuclear localization signal 4.
FT MOTIF 373 378 Nuclear localization signal 5.
FT COMPBIAS 340 365 Ser-rich.
FT METAL 187 187 Iron; catalytic.
FT METAL 189 189 Iron; catalytic.
FT METAL 273 273 Iron; catalytic.
FT BINDING 184 184 Substrate (By similarity).
FT BINDING 197 197 2-oxoglutarate.
FT BINDING 204 204 Substrate (By similarity).
FT BINDING 285 285 2-oxoglutarate.
FT VAR_SEQ 361 402 Missing (in isoform 2).
FT /FTId=VSP_014022.
FT VAR_SEQ 403 403 R -> RIRDTCGGRAHP (in isoform 2 and
FT isoform 3).
FT /FTId=VSP_014023.
FT MUTAGEN 131 131 Y->F: Abolishes 2-oxoglutarate-binding
FT and enzyme activity.
FT MUTAGEN 187 187 H->A: Loss of catalytic activity; when
FT associated with A-189 and A-273.
FT MUTAGEN 189 189 D->A: Loss of catalytic activity; when
FT associated with A-187 and A-273.
FT MUTAGEN 204 204 K->A: Impairs enzyme activity without
FT affecting 2-oxoglutarate-binding.
FT MUTAGEN 231 231 E->A: Impairs both hydroxylation activity
FT and 2-oxoglutarate turnover assays.
FT MUTAGEN 273 273 H->A: Loss of catalytic activity; when
FT associated with A-187 and A-189.
FT MUTAGEN 285 285 T->A: Impairs enzyme activity and 2-
FT oxoglutarate-binding.
FT MUTAGEN 287 287 N->A: Impairs enzyme activity.
FT CONFLICT 136 136 S -> G (in Ref. 3; BAG51050).
FT HELIX 3 16
FT HELIX 23 27
FT HELIX 31 34
FT HELIX 39 41
FT STRAND 48 50
FT HELIX 51 53
FT HELIX 56 62
FT TURN 63 67
FT STRAND 70 74
FT TURN 75 78
FT HELIX 81 84
FT HELIX 87 93
FT STRAND 98 103
FT STRAND 109 113
FT HELIX 114 123
FT STRAND 132 135
FT HELIX 137 139
FT HELIX 143 149
FT HELIX 154 156
FT HELIX 160 164
FT TURN 166 168
FT STRAND 173 178
FT STRAND 183 187
FT HELIX 190 192
FT STRAND 194 202
FT STRAND 204 209
FT HELIX 215 218
FT HELIX 222 225
FT HELIX 226 228
FT HELIX 232 238
FT HELIX 240 244
FT HELIX 250 252
FT STRAND 255 259
FT STRAND 264 267
FT STRAND 272 279
FT STRAND 281 288
FT TURN 291 293
FT HELIX 294 304
FT HELIX 306 319
FT HELIX 321 333
SQ SEQUENCE 403 AA; 46462 MW; 9C9AADA98B24B035 CRC64;
MNHKSKKRIR EAKRSARPEL KDSLDWTRHN YYESFSLSPA AVADNVERAD ALQLSVEEFV
ERYERPYKPV VLLNAQEGWS AQEKWTLERL KRKYRNQKFK CGEDNDGYSV KMKMKYYIEY
MESTRDDSPL YIFDSSYGEH PKRRKLLEDY KVPKFFTDDL FQYAGEKRRP PYRWFVMGPP
RSGTGIHIDP LGTSAWNALV QGHKRWCLFP TSTPRELIKV TRDEGGNQQD EAITWFNVIY
PRTQLPTWPP EFKPLEILQK PGETVFVPGG WWHVVLNLDT TIAITQNFAS STNFPVVWHK
TVRGRPKLSR KWYRILKQEH PELAVLADSV DLQESTGIAS DSSSDSSSSS SSSSSDSDSE
CESGSEGDGT VHRRKKRRTC SMVGNGDTTS QDDCVSKERS SSR
//
MIM
604914
*RECORD*
*FIELD* NO
604914
*FIELD* TI
*604914 JUMONJI DOMAIN-CONTAINING PROTEIN 6; JMJD6
;;PHOSPHATIDYLSERINE RECEPTOR; PSR
read more*FIELD* TX
CLONING
The culmination of apoptosis in vivo is phagocytosis of cellular
corpses. During apoptosis, the asymmetry of plasma membrane
phospholipids is lost, which exposes phosphatidylserine externally. The
phagocytosis of apoptotic cells can be inhibited stereospecifically by
phosphatidylserine and its structural analogs, but not by other anionic
phospholipids, suggesting that phosphatidylserine is specifically
recognized. Fadok et al. (2000) used phage display to clone a gene that
appeared to recognize phosphatidylserine on apoptotic cells. Fadok et
al. (2000) showed that this gene, phosphatidylserine receptor or PSR,
when transfected into B and T lymphocytes, enabled them to recognize and
engulf apoptotic cells in a phosphatidylserine-specific manner. Flow
cytometric analysis using a monoclonal antibody suggested that the
protein is expressed on the surface of macrophages, fibroblasts, and
epithelial cells; this antibody, like phosphatidylserine liposomes,
inhibited the phagocytosis of apoptotic cells and, in macrophages,
induced an antiinflammatory state. This candidate phosphatidylserine
receptor is highly homologous to genes in Caenorhabditis elegans and
Drosophila, suggesting that phosphatidylserine recognition on apoptotic
cells during their removal by phagocytes is highly conserved throughout
phylogeny.
Nagase et al. (1998) cloned the phosphatidylserine receptor from a human
brain cDNA library and designated it KIAA0585. They demonstrated that
KIAA0585 was highly homologous to an uncharacterized open reading frame
in C. elegans. Using RT-PCR, Nagase et al. (1998) found that expression
was high in heart, skeletal muscle, and kidney, and moderate or low in
brain, placenta, lung, liver, pancreas, spleen, thymus, prostate,
testis, and ovary. A number of homologous sequences were present in
human, mouse, Drosophila, and C. elegans EST databases. The predicted
427-amino acid protein has 1 predicted transmembrane domain and an area
in the C terminus that contains a series of serines that represent
potential O-glycosylation sites. The predicted molecular weight for this
protein based on sequence analysis was 47 to 48 kD for human, mouse, and
Drosophila gene products and 40 kD for that of the nematode. Western
blot analysis suggested an apparent molecular weight of 70 kD;
deglycosylation reduces the apparent size to approximately 50 kD, which
is compatible with the predicted molecular weight of 47 kD.
GENE FUNCTION
Fadok et al. (2000) transiently transfected cells from 2 cell lines that
are not capable of binding or phagocytosing apoptotic cells (the mouse
class II-negative B cell line M12.C3 and human Jurkat T cells), with PSR
DNA and demonstrated binding of specific antibody. About 25% of M12.C3
cells were able to bind antibody and apoptotic targets, and about 12.5%
were able to engulf apoptotic cells. Stably transfected Jurkat T cells
bound reliably to apoptotic cells only when PS receptor expression was
increased with PMA.
Chang et al. (2007) demonstrated that JMJD6 is a JmjC-containing iron-
and 2-oxoglutarate-dependent dioxygenase that demethylates histone H3
(see 602810) at arginine-2 (H3R2) and histone H4 (see 602822) at
arginine-3 (H4R3) in both biochemical and cell-based assays. The authors
suggested that their findings may help explain the many developmental
defects observed in the Jmjd6-null mice.
Webby et al. (2009) discovered that the splicing factor U2 small nuclear
ribonucleoprotein auxiliary factor 65-kD subunit (U2AF65; 191318)
undergoes posttranslational lysyl-5-hydroxylation catalyzed by the
Fe(II)- and 2-oxoglutarate-dependent dioxygenase JMJD6. JMJD6 is a
nuclear protein that has an important role in vertebrate development and
is a human homolog of the HIF asparaginyl-hydroxylase (factor-inhibiting
HIF; 606615). JMJD6 was shown to change alternative RNA splicing of
some, but not all, of the endogenous and reporter genes, supporting a
specific role for JMJD6 in the regulation of RNA splicing.
*FIELD* RF
1. Chang, B.; Chen, Y.; Zhao, Y.; Bruick, R. K.: JMJD6 is a histone
arginine demethylase. Science 318: 444-447, 2007.
2. Fadok, V. A.; Bratton, D. L.; Rose, D. M.; Pearson, A.; Ezekewitz,
R. A. B.; Henson, P. M.: A receptor for phosphatidylserine-specific
clearance of apoptotic cells. Nature 405: 85-90, 2000.
3. Nagase, T.; Ishikawa, K.; Miyajima, N.; Tanaka, A.; Kotani, H.;
Nomura, N.; Ohara, O.: 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. DNA Res. 5: 31-39,
1998.
4. 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.; Bottger, A.: Jmjd6 catalyses lysyl-hydroxylation
of U2AF65, a protein associated with RNA splicing. Science 325:
90-93, 2009.
*FIELD* CN
Ada Hamosh - updated: 8/14/2009
Ada Hamosh - updated: 11/26/2007
*FIELD* CD
Ada Hamosh: 5/3/2000
*FIELD* ED
mgross: 02/05/2013
alopez: 8/17/2009
terry: 8/14/2009
alopez: 11/29/2007
terry: 11/26/2007
joanna: 11/12/2007
alopez: 5/3/2000
*RECORD*
*FIELD* NO
604914
*FIELD* TI
*604914 JUMONJI DOMAIN-CONTAINING PROTEIN 6; JMJD6
;;PHOSPHATIDYLSERINE RECEPTOR; PSR
read more*FIELD* TX
CLONING
The culmination of apoptosis in vivo is phagocytosis of cellular
corpses. During apoptosis, the asymmetry of plasma membrane
phospholipids is lost, which exposes phosphatidylserine externally. The
phagocytosis of apoptotic cells can be inhibited stereospecifically by
phosphatidylserine and its structural analogs, but not by other anionic
phospholipids, suggesting that phosphatidylserine is specifically
recognized. Fadok et al. (2000) used phage display to clone a gene that
appeared to recognize phosphatidylserine on apoptotic cells. Fadok et
al. (2000) showed that this gene, phosphatidylserine receptor or PSR,
when transfected into B and T lymphocytes, enabled them to recognize and
engulf apoptotic cells in a phosphatidylserine-specific manner. Flow
cytometric analysis using a monoclonal antibody suggested that the
protein is expressed on the surface of macrophages, fibroblasts, and
epithelial cells; this antibody, like phosphatidylserine liposomes,
inhibited the phagocytosis of apoptotic cells and, in macrophages,
induced an antiinflammatory state. This candidate phosphatidylserine
receptor is highly homologous to genes in Caenorhabditis elegans and
Drosophila, suggesting that phosphatidylserine recognition on apoptotic
cells during their removal by phagocytes is highly conserved throughout
phylogeny.
Nagase et al. (1998) cloned the phosphatidylserine receptor from a human
brain cDNA library and designated it KIAA0585. They demonstrated that
KIAA0585 was highly homologous to an uncharacterized open reading frame
in C. elegans. Using RT-PCR, Nagase et al. (1998) found that expression
was high in heart, skeletal muscle, and kidney, and moderate or low in
brain, placenta, lung, liver, pancreas, spleen, thymus, prostate,
testis, and ovary. A number of homologous sequences were present in
human, mouse, Drosophila, and C. elegans EST databases. The predicted
427-amino acid protein has 1 predicted transmembrane domain and an area
in the C terminus that contains a series of serines that represent
potential O-glycosylation sites. The predicted molecular weight for this
protein based on sequence analysis was 47 to 48 kD for human, mouse, and
Drosophila gene products and 40 kD for that of the nematode. Western
blot analysis suggested an apparent molecular weight of 70 kD;
deglycosylation reduces the apparent size to approximately 50 kD, which
is compatible with the predicted molecular weight of 47 kD.
GENE FUNCTION
Fadok et al. (2000) transiently transfected cells from 2 cell lines that
are not capable of binding or phagocytosing apoptotic cells (the mouse
class II-negative B cell line M12.C3 and human Jurkat T cells), with PSR
DNA and demonstrated binding of specific antibody. About 25% of M12.C3
cells were able to bind antibody and apoptotic targets, and about 12.5%
were able to engulf apoptotic cells. Stably transfected Jurkat T cells
bound reliably to apoptotic cells only when PS receptor expression was
increased with PMA.
Chang et al. (2007) demonstrated that JMJD6 is a JmjC-containing iron-
and 2-oxoglutarate-dependent dioxygenase that demethylates histone H3
(see 602810) at arginine-2 (H3R2) and histone H4 (see 602822) at
arginine-3 (H4R3) in both biochemical and cell-based assays. The authors
suggested that their findings may help explain the many developmental
defects observed in the Jmjd6-null mice.
Webby et al. (2009) discovered that the splicing factor U2 small nuclear
ribonucleoprotein auxiliary factor 65-kD subunit (U2AF65; 191318)
undergoes posttranslational lysyl-5-hydroxylation catalyzed by the
Fe(II)- and 2-oxoglutarate-dependent dioxygenase JMJD6. JMJD6 is a
nuclear protein that has an important role in vertebrate development and
is a human homolog of the HIF asparaginyl-hydroxylase (factor-inhibiting
HIF; 606615). JMJD6 was shown to change alternative RNA splicing of
some, but not all, of the endogenous and reporter genes, supporting a
specific role for JMJD6 in the regulation of RNA splicing.
*FIELD* RF
1. Chang, B.; Chen, Y.; Zhao, Y.; Bruick, R. K.: JMJD6 is a histone
arginine demethylase. Science 318: 444-447, 2007.
2. Fadok, V. A.; Bratton, D. L.; Rose, D. M.; Pearson, A.; Ezekewitz,
R. A. B.; Henson, P. M.: A receptor for phosphatidylserine-specific
clearance of apoptotic cells. Nature 405: 85-90, 2000.
3. Nagase, T.; Ishikawa, K.; Miyajima, N.; Tanaka, A.; Kotani, H.;
Nomura, N.; Ohara, O.: 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. DNA Res. 5: 31-39,
1998.
4. 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.; Bottger, A.: Jmjd6 catalyses lysyl-hydroxylation
of U2AF65, a protein associated with RNA splicing. Science 325:
90-93, 2009.
*FIELD* CN
Ada Hamosh - updated: 8/14/2009
Ada Hamosh - updated: 11/26/2007
*FIELD* CD
Ada Hamosh: 5/3/2000
*FIELD* ED
mgross: 02/05/2013
alopez: 8/17/2009
terry: 8/14/2009
alopez: 11/29/2007
terry: 11/26/2007
joanna: 11/12/2007
alopez: 5/3/2000