JMJD7_HUMAN
ID JMJD7_HUMAN Reviewed; 316 AA.
AC P0C870; A5D6V5; O95712; Q59GF9; Q8TB10; Q9UKV7;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 02-SEP-2008, sequence version 1.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=Bifunctional peptidase and (3S)-lysyl hydroxylase JMJD7 {ECO:0000305|PubMed:28847961, ECO:0000305|PubMed:29915238};
DE EC=1.14.11.63 {ECO:0000269|PubMed:29915238};
DE EC=3.4.-.- {ECO:0000269|PubMed:28847961};
DE AltName: Full=JmjC domain-containing protein 7 {ECO:0000303|PubMed:28847961};
DE AltName: Full=Jumonji domain-containing protein 7 {ECO:0000303|PubMed:28847961};
DE AltName: Full=L-lysine (3S)-hydroxylase JMJD7 {ECO:0000303|PubMed:29915238};
GN Name=JMJD7 {ECO:0000303|PubMed:28847961, ECO:0000312|HGNC:HGNC:34397};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Hippocampus;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, AND MUTAGENESIS OF HIS-178; ASP-180 AND HIS-277.
RX PubMed=28847961; DOI=10.1073/pnas.1706831114;
RA Liu H., Wang C., Lee S., Deng Y., Wither M., Oh S., Ning F., Dege C.,
RA Zhang Q., Liu X., Johnson A.M., Zang J., Chen Z., Janknecht R., Hansen K.,
RA Marrack P., Li C.Y., Kappler J.W., Hagman J., Zhang G.;
RT "Clipping of arginine-methylated histone tails by JMJD5 and JMJD7.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E7717-E7726(2017).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.17 ANGSTROMS) IN COMPLEX WITH 2-OXOGLUTARATE,
RP DISULFIDE BOND, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR
RP LOCATION, SUBSTRATE SPECIFICITY, AND MUTAGENESIS OF CYS-47 AND HIS-178.
RX PubMed=29915238; DOI=10.1038/s41589-018-0071-y;
RA Markolovic S., Zhuang Q., Wilkins S.E., Eaton C.D., Abboud M.I., Katz M.J.,
RA McNeil H.E., Lesniak R.K., Hall C., Struwe W.B., Konietzny R., Davis S.,
RA Yang M., Ge W., Benesch J.L.P., Kessler B.M., Ratcliffe P.J., Cockman M.E.,
RA Fischer R., Wappner P., Chowdhury R., Coleman M.L., Schofield C.J.;
RT "The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC
RT GTPases.";
RL Nat. Chem. Biol. 14:688-695(2018).
RN [5]
RP VARIANT VAL-160.
RX PubMed=23033978; DOI=10.1056/nejmoa1206524;
RA de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G.,
RA Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C.,
RA del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G.,
RA Veltman J.A., Vissers L.E.;
RT "Diagnostic exome sequencing in persons with severe intellectual
RT disability.";
RL N. Engl. J. Med. 367:1921-1929(2012).
CC -!- FUNCTION: Bifunctional enzyme that acts both as an endopeptidase and 2-
CC oxoglutarate-dependent monooxygenase (PubMed:28847961,
CC PubMed:29915238). Endopeptidase that cleaves histones N-terminal tails
CC at the carboxyl side of methylated arginine or lysine residues, to
CC generate 'tailless nucleosomes', which may trigger transcription
CC elongation (PubMed:28847961). Preferentially recognizes and cleaves
CC monomethylated and dimethylated arginine residues of histones H2, H3
CC and H4 (PubMed:28847961). After initial cleavage, continues to digest
CC histones tails via its aminopeptidase activity (PubMed:28847961).
CC Additionally, may play a role in protein biosynthesis by modifying the
CC translation machinery (PubMed:29915238). Acts as Fe(2+) and 2-
CC oxoglutarate-dependent monooxygenase, catalyzing (S)-stereospecific
CC hydroxylation at C-3 of 'Lys-22' of DRG1 and 'Lys-21' of DRG2
CC translation factors (TRAFAC), promoting their interaction with
CC ribonucleic acids (RNA) (PubMed:29915238).
CC {ECO:0000269|PubMed:28847961, ECO:0000269|PubMed:29915238}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + L-lysyl-[protein] + O2 = (3S)-3-hydroxy-L-
CC lysyl-[protein] + CO2 + succinate; Xref=Rhea:RHEA:57152, Rhea:RHEA-
CC COMP:9752, Rhea:RHEA-COMP:15133, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:141492; EC=1.14.11.63;
CC Evidence={ECO:0000269|PubMed:29915238};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:57153;
CC Evidence={ECO:0000269|PubMed:29915238};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:29915238};
CC -!- SUBUNIT: Homodimer; disulfide-linked. Interacts with DRG1 and DRG2.
CC {ECO:0000269|PubMed:29915238}.
CC -!- INTERACTION:
CC P0C870; P55212: CASP6; NbExp=3; IntAct=EBI-9090173, EBI-718729;
CC P0C870; P55039: DRG2; NbExp=3; IntAct=EBI-9090173, EBI-750565;
CC P0C870; Q12951-2: FOXI1; NbExp=3; IntAct=EBI-9090173, EBI-12018822;
CC P0C870; O75603: GCM2; NbExp=3; IntAct=EBI-9090173, EBI-10188645;
CC P0C870; O14964: HGS; NbExp=3; IntAct=EBI-9090173, EBI-740220;
CC P0C870; P04792: HSPB1; NbExp=3; IntAct=EBI-9090173, EBI-352682;
CC P0C870; O60333-2: KIF1B; NbExp=3; IntAct=EBI-9090173, EBI-10975473;
CC P0C870; P13473-2: LAMP2; NbExp=3; IntAct=EBI-9090173, EBI-21591415;
CC P0C870; Q8TDS5: OXER1; NbExp=3; IntAct=EBI-9090173, EBI-12813389;
CC P0C870; Q7Z3K3: POGZ; NbExp=3; IntAct=EBI-9090173, EBI-1389308;
CC P0C870; Q96HA1-2: POM121; NbExp=3; IntAct=EBI-9090173, EBI-11956563;
CC P0C870; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-9090173, EBI-5280197;
CC P0C870; P62826: RAN; NbExp=3; IntAct=EBI-9090173, EBI-286642;
CC P0C870; Q96NU1: SAMD11; NbExp=3; IntAct=EBI-9090173, EBI-14067109;
CC P0C870; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-9090173, EBI-2623095;
CC P0C870; P09234: SNRPC; NbExp=5; IntAct=EBI-9090173, EBI-766589;
CC P0C870; Q5T6F2: UBAP2; NbExp=3; IntAct=EBI-9090173, EBI-2514383;
CC P0C870; Q08AM6: VAC14; NbExp=3; IntAct=EBI-9090173, EBI-2107455;
CC P0C870; O76024: WFS1; NbExp=3; IntAct=EBI-9090173, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:29915238}. Cytoplasm
CC {ECO:0000269|PubMed:29915238}.
CC -!- CAUTION: This sequence was first thought to be an alternatively spliced
CC isoform of PLA2G4B. It is derived from JMJD7 which is located upstream
CC of PLA2G4B. Most tissues also express read-through transcripts from
CC JMJD7 into the downstream PLA2G4B gene, some of which may encode fusion
CC proteins combining the N-terminus of this protein with PLA2G4B protein.
CC {ECO:0000305}.
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DR EMBL; AK289833; BAF82522.1; -; mRNA.
DR EMBL; AK290051; BAF82740.1; -; mRNA.
DR EMBL; BC025290; AAH25290.1; -; mRNA.
DR EMBL; BC139899; AAI39900.1; -; mRNA.
DR CCDS; CCDS45240.1; -.
DR RefSeq; NP_001108104.1; NM_001114632.1.
DR PDB; 5NFN; X-ray; 2.98 A; A/B/C/D=1-316.
DR PDB; 5NFO; X-ray; 2.17 A; A/B=1-316.
DR PDBsum; 5NFN; -.
DR PDBsum; 5NFO; -.
DR AlphaFoldDB; P0C870; -.
DR SMR; P0C870; -.
DR BioGRID; 936684; 20.
DR IntAct; P0C870; 29.
DR MINT; P0C870; -.
DR STRING; 9606.ENSP00000380467; -.
DR iPTMnet; P0C870; -.
DR PhosphoSitePlus; P0C870; -.
DR BioMuta; JMJD7; -.
DR DMDM; 205783894; -.
DR EPD; P0C870; -.
DR jPOST; P0C870; -.
DR MassIVE; P0C870; -.
DR MaxQB; P0C870; -.
DR PaxDb; P0C870; -.
DR PeptideAtlas; P0C870; -.
DR PRIDE; P0C870; -.
DR Antibodypedia; 35028; 101 antibodies from 27 providers.
DR DNASU; 100137047; -.
DR Ensembl; ENST00000397299.9; ENSP00000380467.4; ENSG00000243789.11.
DR GeneID; 100137047; -.
DR KEGG; hsa:100137047; -.
DR MANE-Select; ENST00000397299.9; ENSP00000380467.4; NM_001114632.2; NP_001108104.1.
DR UCSC; uc001zon.3; human.
DR CTD; 100137047; -.
DR DisGeNET; 100137047; -.
DR GeneCards; JMJD7; -.
DR HGNC; HGNC:34397; JMJD7.
DR HPA; ENSG00000243789; Low tissue specificity.
DR neXtProt; NX_P0C870; -.
DR PharmGKB; PA162392530; -.
DR VEuPathDB; HostDB:ENSG00000243789; -.
DR eggNOG; KOG2508; Eukaryota.
DR GeneTree; ENSGT00900000141196; -.
DR HOGENOM; CLU_016785_6_0_1; -.
DR InParanoid; P0C870; -.
DR OMA; YWHDMEF; -.
DR PhylomeDB; P0C870; -.
DR TreeFam; TF329946; -.
DR BioCyc; MetaCyc:G66-32545-MON; -.
DR BRENDA; 1.14.11.27; 2681.
DR BRENDA; 1.14.11.63; 2681.
DR PathwayCommons; P0C870; -.
DR SignaLink; P0C870; -.
DR BioGRID-ORCS; 100137047; 16 hits in 1049 CRISPR screens.
DR GenomeRNAi; 100137047; -.
DR Pharos; P0C870; Tbio.
DR PRO; PR:P0C870; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P0C870; protein.
DR Bgee; ENSG00000243789; Expressed in lower esophagus mucosa and 99 other tissues.
DR ExpressionAtlas; P0C870; baseline and differential.
DR Genevisible; P0C870; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016706; F:2-oxoglutarate-dependent dioxygenase activity; IBA:GO_Central.
DR GO; GO:0004177; F:aminopeptidase activity; IDA:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB.
DR GO; GO:0004497; F:monooxygenase activity; IDA:UniProtKB.
DR GO; GO:0106155; F:peptidyl-lysine 3-dioxygenase activity; IEA:UniProtKB-EC.
DR GO; GO:0018126; P:protein hydroxylation; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 2.60.120.10; -; 1.
DR InterPro; IPR041667; Cupin_8.
DR InterPro; IPR003347; JmjC_dom.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR Pfam; PF13621; Cupin_8; 1.
DR SMART; SM00558; JmjC; 1.
DR PROSITE; PS51184; JMJC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aminopeptidase; Cytoplasm; Disulfide bond; Hydrolase; Iron;
KW Metal-binding; Monooxygenase; Nucleus; Oxidoreductase; Protease;
KW Reference proteome.
FT CHAIN 1..316
FT /note="Bifunctional peptidase and (3S)-lysyl hydroxylase
FT JMJD7"
FT /id="PRO_0000349374"
FT DOMAIN 128..307
FT /note="JmjC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT BINDING 178
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:29915238"
FT BINDING 180
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:29915238"
FT BINDING 277
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:29915238"
FT DISULFID 47
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:29915238,
FT ECO:0007744|PDB:5NFN, ECO:0007744|PDB:5NFO"
FT VARIANT 28
FT /note="A -> G (in dbSNP:rs7174710)"
FT /id="VAR_027046"
FT VARIANT 160
FT /note="M -> V"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069392"
FT MUTAGEN 47
FT /note="C->A: Impairs homodimer formation."
FT /evidence="ECO:0000269|PubMed:29915238"
FT MUTAGEN 178
FT /note="H->A: Loss of peptidase activity toward methylated
FT histones and reduced anchorage-independent growth of
FT transformed cells; when associated with A-180 and A-277.
FT Impairs L-lysine (3S)-hydroxylase activity. Impairs the
FT interaction with DRG1 and DRG2."
FT /evidence="ECO:0000269|PubMed:28847961,
FT ECO:0000269|PubMed:29915238"
FT MUTAGEN 180
FT /note="D->A: Loss of peptidase activity toward methylated
FT histones and reduced anchorage-independent growth of
FT transformed cells; when associated with A-180 and A-277."
FT /evidence="ECO:0000269|PubMed:28847961"
FT MUTAGEN 277
FT /note="H->A: Loss of peptidase activity toward methylated
FT histones and reduced anchorage-independent growth of
FT transformed cells; when associated with A-180 and A-277."
FT /evidence="ECO:0000269|PubMed:28847961"
FT HELIX 1..24
FT /evidence="ECO:0007829|PDB:5NFO"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:5NFO"
FT HELIX 38..44
FT /evidence="ECO:0007829|PDB:5NFO"
FT TURN 45..49
FT /evidence="ECO:0007829|PDB:5NFO"
FT STRAND 52..58
FT /evidence="ECO:0007829|PDB:5NFO"
FT HELIX 62..66
FT /evidence="ECO:0007829|PDB:5NFO"
FT HELIX 69..76
FT /evidence="ECO:0007829|PDB:5NFO"
FT STRAND 80..95
FT /evidence="ECO:0007829|PDB:5NFO"
FT STRAND 98..101
FT /evidence="ECO:0007829|PDB:5NFO"
FT STRAND 103..108
FT /evidence="ECO:0007829|PDB:5NFO"
FT HELIX 109..116
FT /evidence="ECO:0007829|PDB:5NFO"
FT STRAND 123..128
FT /evidence="ECO:0007829|PDB:5NFO"
FT HELIX 134..138
FT /evidence="ECO:0007829|PDB:5NFO"
FT HELIX 140..145
FT /evidence="ECO:0007829|PDB:5NFO"
FT HELIX 151..157
FT /evidence="ECO:0007829|PDB:5NFO"
FT STRAND 162..169
FT /evidence="ECO:0007829|PDB:5NFO"
FT STRAND 174..178
FT /evidence="ECO:0007829|PDB:5NFO"
FT STRAND 181..198
FT /evidence="ECO:0007829|PDB:5NFO"
FT HELIX 200..205
FT /evidence="ECO:0007829|PDB:5NFO"
FT STRAND 209..218
FT /evidence="ECO:0007829|PDB:5NFO"
FT STRAND 224..228
FT /evidence="ECO:0007829|PDB:5NFO"
FT STRAND 235..237
FT /evidence="ECO:0007829|PDB:5NFO"
FT TURN 247..249
FT /evidence="ECO:0007829|PDB:5NFO"
FT HELIX 251..255
FT /evidence="ECO:0007829|PDB:5NFO"
FT STRAND 259..264
FT /evidence="ECO:0007829|PDB:5NFO"
FT STRAND 268..271
FT /evidence="ECO:0007829|PDB:5NFO"
FT STRAND 276..281
FT /evidence="ECO:0007829|PDB:5NFO"
FT STRAND 286..293
FT /evidence="ECO:0007829|PDB:5NFO"
FT HELIX 298..312
FT /evidence="ECO:0007829|PDB:5NFO"
SQ SEQUENCE 316 AA; 35932 MW; 3C2DFDAD12BBC4E2 CRC64;
MAEAALEAVR SELREFPAAA RELCVPLAVP YLDKPPTPLH FYRDWVCPNR PCIIRNALQH
WPALQKWSLP YFRATVGSTE VSVAVTPDGY ADAVRGDRFM MPAERRLPLS FVLDVLEGRA
QHPGVLYVQK QCSNLPSELP QLLPDLESHV PWASEALGKM PDAVNFWLGE AAAVTSLHKD
HYENLYCVVS GEKHFLFHPP SDRPFIPYEL YTPATYQLTE EGTFKVVDEE AMEKVPWIPL
DPLAPDLARY PSYSQAQALR CTVRAGEMLY LPALWFHHVQ QSQGCIAVNF WYDMEYDLKY
SYFQLLDSLT KASGLD
