UHRF1_XENTR
ID UHRF1_XENTR Reviewed; 775 AA.
AC F6UA42;
DT 31-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 60.
DE RecName: Full=E3 ubiquitin-protein ligase UHRF1;
DE EC=2.3.2.27;
DE AltName: Full=RING-type E3 ubiquitin transferase UHRF1;
DE AltName: Full=Ubiquitin-like PHD and RING finger domain-containing protein 1;
DE AltName: Full=Ubiquitin-like-containing PHD and RING finger domains protein 1;
GN Name=uhrf1;
OS Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX NCBI_TaxID=8364;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=20431018; DOI=10.1126/science.1183670;
RA Hellsten U., Harland R.M., Gilchrist M.J., Hendrix D., Jurka J.,
RA Kapitonov V., Ovcharenko I., Putnam N.H., Shu S., Taher L., Blitz I.L.,
RA Blumberg B., Dichmann D.S., Dubchak I., Amaya E., Detter J.C., Fletcher R.,
RA Gerhard D.S., Goodstein D., Graves T., Grigoriev I.V., Grimwood J.,
RA Kawashima T., Lindquist E., Lucas S.M., Mead P.E., Mitros T., Ogino H.,
RA Ohta Y., Poliakov A.V., Pollet N., Robert J., Salamov A., Sater A.K.,
RA Schmutz J., Terry A., Vize P.D., Warren W.C., Wells D., Wills A.,
RA Wilson R.K., Zimmerman L.B., Zorn A.M., Grainger R., Grammer T.,
RA Khokha M.K., Richardson P.M., Rokhsar D.S.;
RT "The genome of the Western clawed frog Xenopus tropicalis.";
RL Science 328:633-636(2010).
CC -!- FUNCTION: Multidomain protein that acts as a key epigenetic regulator
CC by bridging DNA methylation and chromatin modification. Specifically
CC recognizes and binds hemimethylated DNA at replication forks via its
CC YDG domain and recruits dnmt1 methyltransferase to ensure faithful
CC propagation of the DNA methylation patterns through DNA replication. In
CC addition to its role in maintenance of DNA methylation, also plays a
CC key role in chromatin modification: through its tudor-like regions and
CC PHD-type zinc fingers, specifically recognizes and binds histone H3
CC trimethylated at 'Lys-9' (H3K9me3) and unmethylated at 'Arg-2'
CC (H3R2me0), respectively, and recruits chromatin proteins. Enriched in
CC pericentric heterochromatin where it recruits different chromatin
CC modifiers required for this chromatin replication. Also localizes to
CC euchromatic regions where it negatively regulates transcription
CC possibly by impacting DNA methylation and histone modifications. Has E3
CC ubiquitin-protein ligase activity by mediating the ubiquitination of
CC target proteins. However, it is still unclear how E3 ubiquitin-protein
CC ligase activity is related to its role in chromatin in vivo.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00358}.
CC Note=Localizes to replication foci. Enriched in pericentric
CC heterochromatin. Also localizes to euchromatic regions (By similarity).
CC {ECO:0000250}.
CC -!- DOMAIN: The tudor-like regions specifically recognize and bind histone
CC H3 unmethylated at 'Arg-2' (H3R2me0), while the PHD-type zinc finger
CC specifically recognizes and binds histone H3 trimethylated at 'Lys-9'
CC (H3K9me3). {ECO:0000250}.
CC -!- DOMAIN: The YDG domain (also named SRA domain) specifically recognizes
CC and binds hemimethylated DNA at replication forks (DNA that is only
CC methylated on the mother strand of replicating DNA). {ECO:0000250}.
CC -!- DOMAIN: The RING finger is required for ubiquitin ligase activity.
CC {ECO:0000250}.
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DR EMBL; AAMC01100082; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01100083; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01100084; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01100085; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01100086; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01100087; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; F6UA42; -.
DR SMR; F6UA42; -.
DR STRING; 8364.ENSXETP00000048273; -.
DR PaxDb; F6UA42; -.
DR eggNOG; ENOG502QRDQ; Eukaryota.
DR InParanoid; F6UA42; -.
DR OrthoDB; 705927at2759; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000008143; Genome assembly.
DR Proteomes; UP000790000; Unplaced.
DR GO; GO:0000785; C:chromatin; ISS:UniProtKB.
DR GO; GO:0000791; C:euchromatin; ISS:UniProtKB.
DR GO; GO:0000792; C:heterochromatin; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005657; C:replication fork; ISS:UniProtKB.
DR GO; GO:0044729; F:hemi-methylated DNA-binding; ISS:UniProtKB.
DR GO; GO:0042393; F:histone binding; ISS:UniProtKB.
DR GO; GO:0035064; F:methylated histone binding; ISS:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0010390; P:histone monoubiquitination; IBA:GO_Central.
DR GO; GO:0016574; P:histone ubiquitination; ISS:UniProtKB.
DR GO; GO:0010216; P:maintenance of DNA methylation; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR Gene3D; 2.30.280.10; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR015947; PUA-like_sf.
DR InterPro; IPR036987; SRA-YDG_sf.
DR InterPro; IPR003105; SRA_YDG.
DR InterPro; IPR021991; TTD_dom.
DR InterPro; IPR000626; Ubiquitin-like_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR InterPro; IPR045134; UHRF1/2-like.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR001965; Znf_PHD.
DR InterPro; IPR019787; Znf_PHD-finger.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR14140; PTHR14140; 1.
DR Pfam; PF00628; PHD; 1.
DR Pfam; PF02182; SAD_SRA; 1.
DR Pfam; PF12148; TTD; 1.
DR Pfam; PF00240; ubiquitin; 1.
DR SMART; SM00249; PHD; 1.
DR SMART; SM00184; RING; 2.
DR SMART; SM00466; SRA; 1.
DR SMART; SM00213; UBQ; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR SUPFAM; SSF88697; SSF88697; 1.
DR PROSITE; PS50053; UBIQUITIN_2; 1.
DR PROSITE; PS51015; YDG; 1.
DR PROSITE; PS01359; ZF_PHD_1; 1.
DR PROSITE; PS50016; ZF_PHD_2; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 2.
PE 3: Inferred from homology;
KW Cell cycle; Chromatin regulator; DNA-binding; Metal-binding; Nucleus;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Transferase; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..775
FT /note="E3 ubiquitin-protein ligase UHRF1"
FT /id="PRO_0000419990"
FT DOMAIN 1..77
FT /note="Ubiquitin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT DOMAIN 419..582
FT /note="YDG"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00358"
FT ZN_FING 299..366
FT /note="PHD-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT ZN_FING 706..745
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 81..128
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 131..207
FT /note="Tudor-like 1"
FT REGION 214..283
FT /note="Tudor-like 2"
FT REGION 293..301
FT /note="Linker"
FT /evidence="ECO:0000250"
FT REGION 333..337
FT /note="Histone H3R2me0 binding"
FT /evidence="ECO:0000250"
FT REGION 353..355
FT /note="Histone H3R2me0 binding"
FT /evidence="ECO:0000250"
FT REGION 445..446
FT /note="Required to promote base flipping"
FT /evidence="ECO:0000250"
FT REGION 466..469
FT /note="Required for formation of a 5-methylcytosine-binding
FT pocket"
FT /evidence="ECO:0000250"
FT REGION 478..481
FT /note="Required for formation of a 5-methylcytosine-binding
FT pocket"
FT /evidence="ECO:0000250"
FT REGION 616..655
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 96..113
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 616..645
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 463..464
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_part="5-methylcytosine group"
FT /ligand_part_id="ChEBI:CHEBI:65274"
FT /evidence="ECO:0000250"
FT BINDING 469
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_part="5-methylcytosine group"
FT /ligand_part_id="ChEBI:CHEBI:65274"
FT /evidence="ECO:0000250"
FT SITE 316
FT /note="Histone H3K4me0 binding"
FT /evidence="ECO:0000250"
FT SITE 327
FT /note="Histone H3R2me0 binding"
FT /evidence="ECO:0000250"
FT SITE 330
FT /note="Histone H3R2me0 binding"
FT /evidence="ECO:0000250"
FT SITE 479
FT /note="Required to confer preferential recognition of
FT cytosine over thymine"
FT /evidence="ECO:0000250"
FT SITE 489
FT /note="Required to discriminate between hemimethylated DNA
FT versus symmetrically methylated DNA"
FT /evidence="ECO:0000250"
FT SITE 491
FT /note="Required for affinity and specificity for 5-mCpG
FT sequence"
FT /evidence="ECO:0000250"
SQ SEQUENCE 775 AA; 86990 MW; 6F49DCB4B7221B89 CRC64;
MWIQVRTMDG RDTRRIDSLS KLTKVEDLRA RIQQIFGVAL ESQRLFYRGK QMENGHTLFD
YSVGLNDIVQ LLVRQIPDSV PTKDKECGIS DADSGCGSGQ GESDKNSSCG EGATDVDGQP
AGINSENVGP SLYKKNDLVD ARDLNMGAWF EAQIVSVSKR VNPDGMSAEI LDTSAASDDI
IYHVKYEDYP ENGVVQLTYK DVRLRARTTL PWHDLKVGQV VMVNYNPDEP KERGYWYDAE
ILRKRETRTI KEIYVKVLLG DAGDSLNDCR IRFVDEIYKI EEPGSAYITT ESPQKRQNGP
ECKHCKDNPK RACRMCACYV CGGKQDPEKQ LLCDECDMAF HIYCLKPPLS AIPQDEDWYC
PDCRNDASEV VLAGEKLKES KKKAKMASAS SSSQRDWGKG MACVGRSREC TIVPSNHYGP
IPGVPVGTLW KFRVQVSESG VHRPHVAGIH GRSNDGSYSL VLAGGYEDDV DNGSEFTYTG
SGGRDLSGNK RTAEQSCDQK LTNMNRALAL NCSAPINDKE GAVAKDWRAG KPVRVVRNTK
GKKHSKYAPE DGNRYDGIYK VVKYWPEKGK SGFLVWRYLL RRDDEEPAPW SKEGKERIKK
LGLVMQYPDG YLESLASKER EKENKTEDEL SESPSKGKRK RNSAGSGLSD AKSTPKKTKV
ESYKLSLDQK TLIKQDDLNA KLWREVMSFL KEGPKFLSKV EETFLCICCQ EVVYEPITTE
CHHNICKGCL DRSFKALVHN CPACRHDLGK NYSLNVNKPL QAILSQLFPG YERGR
