UHRF1_BOVIN
ID UHRF1_BOVIN Reviewed; 786 AA.
AC A7E320; F1MY11;
DT 31-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 11-SEP-2007, sequence version 1.
DT 03-AUG-2022, entry version 104.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Hereford;
RX PubMed=19393038; DOI=10.1186/gb-2009-10-4-r42;
RA Zimin A.V., Delcher A.L., Florea L., Kelley D.R., Schatz M.C., Puiu D.,
RA Hanrahan F., Pertea G., Van Tassell C.P., Sonstegard T.S., Marcais G.,
RA Roberts M., Subramanian P., Yorke J.A., Salzberg S.L.;
RT "A whole-genome assembly of the domestic cow, Bos taurus.";
RL Genome Biol. 10:R42.01-R42.10(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal skin;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-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 such as histone H3 and PML. It is still unclear how E3
CC ubiquitin-protein ligase activity is related to its role in chromatin
CC in vivo. Plays a role in DNA repair by cooperating with UHRF1 to ensure
CC recruitment of FANCD2 to interstrand crosslinks (ICLs) leading to
CC FANCD2 activation (By similarity). {ECO:0000250|UniProtKB:Q96T88}.
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 -!- SUBUNIT: Interacts with DNMT3A and DNMT3B. Interacts with DNMT1; the
CC interaction is direct. Interacts with USP7; leading to its
CC deubiquitination. Interacts with histone H3. Interacts with HDAC1, but
CC not with HDAC2. Interacts with UHRF1BP1. Interacts with PML. Interacts
CC with EHMT2. Binds methylated CpG containing oligonucleotides (By
CC similarity). Interacts with ZNF263; recruited to the SIX3 promoter
CC along with other proteins involved in chromatin modification and
CC transcriptional corepression where it contributes to transcriptional
CC repression (By similarity). Interacts with UHRF2 (By similarity).
CC Interacts with FANCD2 (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q96T88}.
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). The tudor-like regions simultaneously recognizes H3K9me3
CC through a conserved aromatic cage in the first tudor-like subdomain and
CC unmodified H3K4 (H3K4me0) within a groove between the tandem
CC subdomains. The linker region plays a role in the formation of a
CC histone H3-binding hole between the reader modules formed by the tudor-
CC like regions and the PHD-type zinc finger by making extended contacts
CC with the tandem tudor-like regions (By similarity). {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). It contains a
CC binding pocket that accommodates the 5-methylcytosine that is flipped
CC out of the duplex DNA. 2 specialized loops reach through the resulting
CC gap in the DNA from both the major and the minor grooves to read the
CC other 3 bases of the CpG duplex. The major groove loop confers both
CC specificity for the CpG dinucleotide and discrimination against
CC methylation of deoxycytidine of the complementary strand. The YDG
CC domain also recognizes and binds 5-hydroxymethylcytosine (5hmC) (By
CC similarity). {ECO:0000250}.
CC -!- DOMAIN: The RING finger is required for ubiquitin ligase activity.
CC {ECO:0000250}.
CC -!- PTM: Phosphorylation at Ser-302 of the linker region decreases the
CC binding to H3K9me3. Phosphorylation at Ser-645 by CDK1 during M phase
CC impairs interaction with USP7, preventing deubiquitination and leading
CC to degradation by the proteasome (By similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated; which leads to proteasomal degradation.
CC Autoubiquitinated; interaction with USP7 leads to deubiquitination and
CC prevents degradation. Ubiquitination and degradation takes place during
CC M phase, when phosphorylation at Ser-645 prevents interaction with USP7
CC and subsequent deubiquitination. Polyubiquitination may be stimulated
CC by DNA damage (By similarity). {ECO:0000250}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; DAAA02019593; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; DAAA02019594; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC151671; AAI51672.1; -; mRNA.
DR RefSeq; NP_001096568.1; NM_001103098.1.
DR RefSeq; XP_010805284.1; XM_010806982.2.
DR AlphaFoldDB; A7E320; -.
DR SMR; A7E320; -.
DR STRING; 9913.ENSBTAP00000042353; -.
DR PaxDb; A7E320; -.
DR PRIDE; A7E320; -.
DR Ensembl; ENSBTAT00000044908; ENSBTAP00000042353; ENSBTAG00000002224.
DR GeneID; 530411; -.
DR KEGG; bta:530411; -.
DR CTD; 29128; -.
DR VEuPathDB; HostDB:ENSBTAG00000002224; -.
DR VGNC; VGNC:36654; UHRF1.
DR eggNOG; ENOG502QRDQ; Eukaryota.
DR GeneTree; ENSGT00390000008296; -.
DR HOGENOM; CLU_022357_0_0_1; -.
DR InParanoid; A7E320; -.
DR OMA; WYDAEIC; -.
DR OrthoDB; 705927at2759; -.
DR TreeFam; TF106434; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000009136; Chromosome 7.
DR Bgee; ENSBTAG00000002224; Expressed in oocyte and 102 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:0016363; C:nuclear matrix; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005657; C:replication fork; ISS:UniProtKB.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0044729; F:hemi-methylated DNA-binding; ISS:UniProtKB.
DR GO; GO:0042393; F:histone binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0008327; F:methyl-CpG binding; IEA:Ensembl.
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:0006281; P:DNA repair; 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:0051247; P:positive regulation of protein metabolic process; IEA:Ensembl.
DR GO; GO:0051865; P:protein autoubiquitination; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0050678; P:regulation of epithelial cell proliferation; IEA:Ensembl.
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 Acetylation; Cell cycle; Chromatin regulator; DNA damage; DNA repair;
KW DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..786
FT /note="E3 ubiquitin-protein ligase UHRF1"
FT /id="PRO_0000419987"
FT DOMAIN 1..78
FT /note="Ubiquitin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT DOMAIN 423..586
FT /note="YDG"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00358"
FT ZN_FING 303..370
FT /note="PHD-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT ZN_FING 717..756
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 82..134
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 139..213
FT /note="Tudor-like 1"
FT REGION 220..287
FT /note="Tudor-like 2"
FT REGION 300..305
FT /note="Linker"
FT /evidence="ECO:0000250"
FT REGION 337..341
FT /note="Histone H3R2me0 binding"
FT /evidence="ECO:0000250"
FT REGION 357..359
FT /note="Histone H3R2me0 binding"
FT /evidence="ECO:0000250"
FT REGION 449..450
FT /note="Required to promote base flipping"
FT /evidence="ECO:0000250"
FT REGION 470..473
FT /note="Required for formation of a 5-methylcytosine-binding
FT pocket"
FT /evidence="ECO:0000250"
FT REGION 482..485
FT /note="Required for formation of a 5-methylcytosine-binding
FT pocket"
FT /evidence="ECO:0000250"
FT REGION 626..679
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 101..121
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 626..657
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 467..468
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 473
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 320
FT /note="Histone H3K4me0 binding"
FT /evidence="ECO:0000250"
FT SITE 331
FT /note="Histone H3R2me0 binding"
FT /evidence="ECO:0000250"
FT SITE 334
FT /note="Histone H3R2me0 binding"
FT /evidence="ECO:0000250"
FT SITE 483
FT /note="Required to confer preferential recognition of
FT cytosine over thymine"
FT /evidence="ECO:0000250"
FT SITE 493
FT /note="Required to discriminate between hemimethylated DNA
FT versus symmetrically methylated DNA"
FT /evidence="ECO:0000250"
FT SITE 495
FT /note="Required for affinity and specificity for 5-mCpG
FT sequence"
FT /evidence="ECO:0000250"
FT MOD_RES 76
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96T88"
FT MOD_RES 98
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96T88"
FT MOD_RES 102
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TPK1"
FT MOD_RES 302
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:Q96T88"
FT MOD_RES 372
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96T88"
FT MOD_RES 403
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q96T88"
FT MOD_RES 550
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q96T88"
FT MOD_RES 645
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:Q96T88"
FT MOD_RES 655
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96T88"
FT MOD_RES 662
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VDF2"
FT CROSSLNK 283
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q96T88"
FT CROSSLNK 389
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q96T88"
FT CROSSLNK 550
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q96T88"
FT CROSSLNK 670
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q96T88"
SQ SEQUENCE 786 AA; 88339 MW; 3026D2764F469AE1 CRC64;
MWIQVRTMDG KVAHTVDSLS RLTKVEELRK KIQELFHVEP GLQRLFYRGK QMEDGHTLFD
YDVRLNDTIQ LLVRQSLVLP VPVPSSSGGS KERDSELSDT DSGCGLAQSE SDKSSNSGEA
ANEPEGKADE DECDETELGL YKVGEYVDAR DTNMGAWFEA KVIRVTRKAP AHDQPSSSSS
KPEDDIIYHV TYDDYPENGV VQMTSQNVRA RARHTIKWED LQVGQVVMVN YNPDLPKDRG
FWYDAEILRK RETRTARELH ANVRIGGDSL NDCRIVFVDE VFKIERPGEG NPMVENPMRR
KSGPSCKHCK DDERKLCRMC ACHVCGGKQD PDKQLMCDEC DMAFHIYCLR PPLSSVPPEE
EWYCPDCRID SSEVVQAGEK LKESKKKAKM ASATSSSQRD WGKGMACVGR TKECTIVPSN
HFGPIPGIPV GTMWRFRVQV SESGVHRPHV AGIHGRSNHG AYSLVLAGGY EDDVDHGNSF
TYTGSGGRDL SGNKRTAEQS CDQKLTNTNR ALALNCFAPI NDLKGAEAKD WRSGKPVRVV
RNVKGRKHSK YAPIEGNRYD GIYKVVRYWP EKGKSGFLVW RFLLRRDDVE PGPWTKEGKD
RIKKLGLTMQ YPEGYLEALA RKEKENSKQA ALDKEEEDGE EGFTSPRKGK RKSKSAGGDG
SSRGTPKKTK VEPYSLTTQQ SSLIKEDKSN MKLWTEILKS LKDGPKFLSK VEETFQCICC
QELVFRPITT VCQHNVCKDC LDRSFKAQVF SCPACRYDLG RSYAMTVNQP LQAVLSQLFP
GYGSGR
