JBP1_LEITA
ID JBP1_LEITA Reviewed; 827 AA.
AC Q9U6M1;
DT 16-JUN-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 51.
DE RecName: Full=Thymine dioxygenase JBP1;
DE EC=1.14.11.6 {ECO:0000269|PubMed:17389644};
DE AltName: Full=J-binding protein 1;
DE AltName: Full=Thymidine hydroxylase JBP1;
GN Name=JBP1;
OS Leishmania tarentolae (Sauroleishmania tarentolae).
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Leishmaniinae; Leishmania;
OC lizard Leishmania.
OX NCBI_TaxID=5689;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND DNA-BINDING.
RC STRAIN=tarIVa;
RX PubMed=10562569; DOI=10.1093/emboj/18.22.6573;
RA Cross M., Kieft R., Sabatini R., Wilm M., de Kort M., van der Marel G.A.,
RA van Boom J.H., van Leeuwen F., Borst P.;
RT "The modified base J is the target for a novel DNA-binding protein in
RT kinetoplastid protozoans.";
RL EMBO J. 18:6573-6581(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=TarII;
RX PubMed=15781496; DOI=10.1093/nar/gki304;
RA Genest P.-A., ter Riet B., Dumas C., Papadopoulou B., van Luenen H.G.A.M.,
RA Borst P.;
RT "Formation of linear inverted repeat amplicons following targeting of an
RT essential gene in Leishmania.";
RL Nucleic Acids Res. 33:1699-1709(2005).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF HIS-189; ASP-191;
RP HIS-239; ARG-255 AND VAL-259.
RX PubMed=17389644; DOI=10.1093/nar/gkm049;
RA Yu Z., Genest P.-A., ter Riet B., Sweeney K., DiPaolo C., Kieft R.,
RA Christodoulou E., Perrakis A., Simmons J.M., Hausinger R.P.,
RA van Luenen H.G.A.M., Rigden D.J., Sabatini R., Borst P.;
RT "The protein that binds to DNA base J in trypanosomatids has features of a
RT thymidine hydroxylase.";
RL Nucleic Acids Res. 35:2107-2115(2007).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 392-561, DNA-BINDING, MUTAGENESIS
RP OF GLU-391; LYS-436; ASP-465; GLU-468; 487-GLU-GLU-488; LYS-518; LYS-522;
RP LYS-524; ASP-525; ARG-532; LYS-535; ASP-536; 540-GLU-GLU-541 AND GLU-553,
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=21415010; DOI=10.1093/nar/gkr125;
RA Heidebrecht T., Christodoulou E., Chalmers M.J., Jan S., Ter Riet B.,
RA Grover R.K., Joosten R.P., Littler D., van Luenen H., Griffin P.R.,
RA Wentworth P. Jr., Borst P., Perrakis A.;
RT "The structural basis for recognition of base J containing DNA by a novel
RT DNA binding domain in JBP1.";
RL Nucleic Acids Res. 39:5715-5728(2011).
CC -!- FUNCTION: Dioxygenase that catalyzes the first step of DNA base J
CC (beta-d-glucosyl-HOMedU) biosynthesis by converting thymine to 5-
CC hydroxymethyluracil (HOMedU). DNA base J is a hypermodified thymidine
CC residue found in the genome of kinetoplastid parasites, which is
CC localized primarily to repetitive DNA, namely the telomeres, and is
CC implicated in the regulation of antigenic variation. Also specifically
CC binds to base J-containing DNA (J-DNA). Involved in propagation and
CC maintenance of DNA base J synthesis initiated by JBP2 by specifically
CC binding already synthesized DNA base J and propagating J synthesis.
CC Thymine dioxygenase activity and J-DNA-binding are independent
CC functions. {ECO:0000269|PubMed:17389644}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + O2 + thymine = 5-hydroxymethyluracil + CO2 +
CC succinate; Xref=Rhea:RHEA:10316, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:16964,
CC ChEBI:CHEBI:17821, ChEBI:CHEBI:30031; EC=1.14.11.6;
CC Evidence={ECO:0000269|PubMed:17389644};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000250|UniProtKB:Q6N021};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250|UniProtKB:Q6N021};
CC -!- SUBUNIT: Monomer. Binds to DNA as a monomer.
CC {ECO:0000269|PubMed:21415010}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17389644,
CC ECO:0000269|PubMed:21415010}. Note=Localizes to discrete spots in the
CC nucleus, probably the J-rich telomeres.
CC -!- DOMAIN: The DNA-binding JBP1 domain (DB-JBP1) is necessary and
CC sufficient for binding to J-DNA.
CC -!- SIMILARITY: Belongs to the TET family. JBP1 subfamily. {ECO:0000305}.
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DR EMBL; AF182401; AAF01743.1; -; Genomic_DNA.
DR EMBL; AY842844; AAX81332.1; -; Genomic_DNA.
DR PDB; 2XSE; X-ray; 1.90 A; A=392-561.
DR PDBsum; 2XSE; -.
DR AlphaFoldDB; Q9U6M1; -.
DR SASBDB; Q9U6M1; -.
DR SMR; Q9U6M1; -.
DR PRIDE; Q9U6M1; -.
DR ABCD; Q9U6M1; 1 sequenced antibody.
DR VEuPathDB; TriTrypDB:LtaPh_1400300; -.
DR PhylomeDB; Q9U6M1; -.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050341; F:thymine dioxygenase activity; TAS:UniProtKB.
DR GO; GO:0070580; P:base J metabolic process; IMP:UniProtKB.
DR Gene3D; 1.20.120.1440; -; 1.
DR InterPro; IPR024779; 2OGFeDO_noxygenase_dom.
DR InterPro; IPR041241; DB_JBP1.
DR InterPro; IPR043111; DB_JBP1_sf.
DR Pfam; PF18526; DB_JBP1; 1.
DR Pfam; PF12851; Tet_JBP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Dioxygenase; DNA-binding; Iron; Metal-binding; Nucleus;
KW Oxidoreductase.
FT CHAIN 1..827
FT /note="Thymine dioxygenase JBP1"
FT /id="PRO_0000377554"
FT REGION 62..264
FT /note="Thymine dioxygenase"
FT /evidence="ECO:0000269|PubMed:17389644"
FT REGION 364..383
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 392..561
FT /note="DNA-binding JBP1 domain"
FT /evidence="ECO:0000269|PubMed:17389644"
FT REGION 539..568
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 539..564
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 189
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305|PubMed:17389644"
FT BINDING 191
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305|PubMed:17389644"
FT BINDING 239
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305|PubMed:17389644"
FT BINDING 255
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000305|PubMed:17389644"
FT SITE 525
FT /note="Involved in J base recognition and binding,
FT conferring specificity towards J-DNA"
FT MUTAGEN 189
FT /note="H->A: Impairs DNA base J biosynthesis."
FT /evidence="ECO:0000269|PubMed:17389644"
FT MUTAGEN 191
FT /note="D->A: Impairs DNA base J biosynthesis."
FT /evidence="ECO:0000269|PubMed:17389644"
FT MUTAGEN 239
FT /note="H->A: Impairs DNA base J biosynthesis."
FT /evidence="ECO:0000269|PubMed:17389644"
FT MUTAGEN 255
FT /note="R->A: Impairs DNA base J biosynthesis."
FT /evidence="ECO:0000269|PubMed:17389644"
FT MUTAGEN 259
FT /note="V->A: No effect."
FT /evidence="ECO:0000269|PubMed:17389644"
FT MUTAGEN 391
FT /note="E->A: No effect."
FT /evidence="ECO:0000269|PubMed:21415010"
FT MUTAGEN 436
FT /note="K->A: No effect."
FT /evidence="ECO:0000269|PubMed:21415010"
FT MUTAGEN 465
FT /note="D->A: No effect."
FT /evidence="ECO:0000269|PubMed:21415010"
FT MUTAGEN 468
FT /note="E->A: No effect."
FT /evidence="ECO:0000269|PubMed:21415010"
FT MUTAGEN 487..488
FT /note="EE->AA: No effect."
FT /evidence="ECO:0000269|PubMed:21415010"
FT MUTAGEN 518
FT /note="K->A: Decreases binding affinity for both J-DNA and
FT normal DNA."
FT /evidence="ECO:0000269|PubMed:21415010"
FT MUTAGEN 522
FT /note="K->A: Decreases binding affinity for both J-DNA and
FT normal DNA."
FT /evidence="ECO:0000269|PubMed:21415010"
FT MUTAGEN 524
FT /note="K->A: Slightly decreases binding affinity for both
FT J-DNA and normal DNA."
FT /evidence="ECO:0000269|PubMed:21415010"
FT MUTAGEN 525
FT /note="D->A: Abolishes preference for J-DNA-binding."
FT /evidence="ECO:0000269|PubMed:21415010"
FT MUTAGEN 532
FT /note="R->A: Decreases binding affinity for both J-DNA and
FT normal DNA."
FT /evidence="ECO:0000269|PubMed:21415010"
FT MUTAGEN 535
FT /note="K->A: No effect."
FT /evidence="ECO:0000269|PubMed:21415010"
FT MUTAGEN 536
FT /note="D->A: No effect."
FT /evidence="ECO:0000269|PubMed:21415010"
FT MUTAGEN 540..541
FT /note="EE->AA: No effect."
FT /evidence="ECO:0000269|PubMed:21415010"
FT MUTAGEN 553
FT /note="E->A: No effect."
FT /evidence="ECO:0000269|PubMed:21415010"
FT HELIX 396..401
FT /evidence="ECO:0007829|PDB:2XSE"
FT HELIX 402..406
FT /evidence="ECO:0007829|PDB:2XSE"
FT HELIX 408..411
FT /evidence="ECO:0007829|PDB:2XSE"
FT TURN 412..414
FT /evidence="ECO:0007829|PDB:2XSE"
FT HELIX 417..444
FT /evidence="ECO:0007829|PDB:2XSE"
FT STRAND 455..457
FT /evidence="ECO:0007829|PDB:2XSE"
FT HELIX 458..478
FT /evidence="ECO:0007829|PDB:2XSE"
FT HELIX 485..505
FT /evidence="ECO:0007829|PDB:2XSE"
FT TURN 511..514
FT /evidence="ECO:0007829|PDB:2XSE"
FT HELIX 516..527
FT /evidence="ECO:0007829|PDB:2XSE"
FT HELIX 539..556
FT /evidence="ECO:0007829|PDB:2XSE"
FT TURN 557..559
FT /evidence="ECO:0007829|PDB:2XSE"
SQ SEQUENCE 827 AA; 93403 MW; 5A4B502DE70A4BFE CRC64;
MEPDSKKVKL DIFNFPTTRE TRTPEEVAES YAEAVKSHPF YDNVHSVVDF YDSGTIKDGR
GQIIGVVLRE ALPKYAASMA SELLTSAAVR TSLRSMMFGG EPPLSGIAGY FDYRGSPVEL
KSRKTSFTYE HEAAWPAVFP VVDYVSEIYR HVAPERWKAQ NDAIPDLVRI HGTPFSTLTI
NSRFRTASHT DVGDFDAGYS CIACLDGQFK GLALSFDDFG INVLLQPRDV MIFDSHHFHS
NTEVELSFSG EDWKRLTCVF YYRAALGEPA SYAEYQRRLE KSKTDTRFTP VVHHVRVKEN
GTSVNRPSPV YPISQSPFWV PMVAHCLQHC ASAAQCVHEA MTADGSRLAE MMFGESLSTS
DGIPLRGEDE KVKANGDSTP RPLSRLGGFS ETNLMVSTAV EKKKYLDSEF LLHCISAQLL
DMWKQARARW LELVGKEWAH MLALNPERKD FLWKNQSEMN SAFFDLCEVG KQVMLGLLGK
EVALPKEEQA FWIMYAVHLS AACAEELHMP EVAMSLRKLN VKLKDFNFGG TRYFKDMPPE
EKKRRMERKQ RIEEARRHGM PSGSHEKRAN WLTNDSFDYQ TEDCVIDYAQ HKWVLPALHA
KEVTKTVRTG ELPTTERVVR VLVVIPDPQS KLENVDCKLE VPDMVGSSSE WERLMSSPAV
HRVLSAAQRN LQLPDSVTHG NVQTHFAFHS TLPTDIYDFV VLQHVLSRIP DDAQASAYIR
RAAALCSGCL FVVETDVQCR QYYTLKYSIR CSYDTVAPLF FQQLHRVCYG TKTARVRTKG
ELESLIPTVC CARYKLQGSP LNTTVHVVSP FPSCEVQNLS SALCDRA
