UHRF1_XENLA
ID UHRF1_XENLA Reviewed; 772 AA.
AC B6CHA3;
DT 31-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=E3 ubiquitin-protein ligase UHRF1;
DE EC=2.3.2.27;
DE AltName: Full=Nuclear zinc finger protein Np95;
DE Short=XNp95;
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; Synonyms=np95;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Lindsay H.D.;
RT "Xenopus Homolog of XNp95.";
RL Submitted (SEP-2007) to the EMBL/GenBank/DDBJ databases.
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; EU177101; ABY28114.1; -; mRNA.
DR RefSeq; NP_001129236.1; NM_001135764.1.
DR RefSeq; XP_018091852.1; XM_018236363.1.
DR AlphaFoldDB; B6CHA3; -.
DR SMR; B6CHA3; -.
DR BioGRID; 101600; 3.
DR IntAct; B6CHA3; 1.
DR MINT; B6CHA3; -.
DR GeneID; 432234; -.
DR KEGG; xla:432234; -.
DR CTD; 432234; -.
DR Xenbase; XB-GENE-5821540; uhrf1.S.
DR OrthoDB; 705927at2759; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000186698; Chromosome 1S.
DR Bgee; 432234; Expressed in egg cell and 19 other tissues.
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: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: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: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; 1.
PE 2: Evidence at transcript level;
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..772
FT /note="E3 ubiquitin-protein ligase UHRF1"
FT /id="PRO_0000419989"
FT DOMAIN 1..77
FT /note="Ubiquitin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT DOMAIN 417..580
FT /note="YDG"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00358"
FT ZN_FING 297..364
FT /note="PHD-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT ZN_FING 703..742
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 90..111
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 129..205
FT /note="Tudor-like 1"
FT REGION 212..281
FT /note="Tudor-like 2"
FT REGION 291..299
FT /note="Linker"
FT /evidence="ECO:0000250"
FT REGION 331..335
FT /note="Histone H3R2me0 binding"
FT /evidence="ECO:0000250"
FT REGION 351..353
FT /note="Histone H3R2me0 binding"
FT /evidence="ECO:0000250"
FT REGION 443..444
FT /note="Required to promote base flipping"
FT /evidence="ECO:0000250"
FT REGION 464..467
FT /note="Required for formation of a 5-methylcytosine-binding
FT pocket"
FT /evidence="ECO:0000250"
FT REGION 476..479
FT /note="Required for formation of a 5-methylcytosine-binding
FT pocket"
FT /evidence="ECO:0000250"
FT REGION 615..649
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 615..644
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 461..462
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 467
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 314
FT /note="Histone H3K4me0 binding"
FT /evidence="ECO:0000250"
FT SITE 325
FT /note="Histone H3R2me0 binding"
FT /evidence="ECO:0000250"
FT SITE 328
FT /note="Histone H3R2me0 binding"
FT /evidence="ECO:0000250"
FT SITE 477
FT /note="Required to confer preferential recognition of
FT cytosine over thymine"
FT /evidence="ECO:0000250"
FT SITE 487
FT /note="Required to discriminate between hemimethylated DNA
FT versus symmetrically methylated DNA"
FT /evidence="ECO:0000250"
FT SITE 489
FT /note="Required for affinity and specificity for 5-mCpG
FT sequence"
FT /evidence="ECO:0000250"
SQ SEQUENCE 772 AA; 86974 MW; 202D7F91C7CEFBCD CRC64;
MWIQVRTMDG RDTRRIDSLS KLTKVDDLRD RIQQLFGVAL ESQRLFYRGK QMENGHTLFD
YSVGLNDIVQ LLVRQIPDSF PTKHKECELS DASAGCGSGQ RDSDSGSGEG AMDVDGQSIS
IIGENVGTSL YKKNDLVDAR DLNMGAWFEA QIVNVSKKVG PYGTLPEVSD TSVTSDAIIY
HVKYEDYPEN GVVQLTCKDV RLRARTTLPW HEIKVGQVVM VNYNPDEPKE RGYWYDAEIL
RKHESKKIKE IYAKVLLGDA GDSLNDCRIR FVNEIYKIEE PGSTYLNTES PQKRQNGPEC
KHCKDNPKRA CRMCACCICG GKQDPEKQLL CDECDLAFHI YCLKPPLSVI PQDEDWYCPD
CRNDASEVVL AGEKLKESKK KARMASANSS SQRDWGKGMA CVGRSRECTI VPSNHYGPIP
GVPVGTLWKF RVQVSESGVH RPHVAGIHGR SNDGSYSLVL AGGYEDDVDN GNEFTYTGSG
GRDLSGNKRT AEQSCDQKLS NMNRALALNC SAPINDKEGS IAKDWRAGKP VRVVRNSKGR
KHSKYAPEEG NRYDGIYKVV KYWPEKGKSG FLVWRYLLRR DDYEPAPWSK EGKERIKKLG
LTMQYPDGYL ETLASKEREK ENKTEDEPID SPSKGKRKRN SDNEQTAAKS IPKKMKVASY
KLTLEQKTLI KQDVLNAKLW SEVMLFLKEG PKFVNKVEET FLCICCQEVV YEPVTTECHH
NICKGCLDRS FKALVHSCPA CRHDLGKNYP LNVNKPLQAI LSQLFPGYES GR
