UHRF2_HUMAN
ID UHRF2_HUMAN Reviewed; 802 AA.
AC Q96PU4; Q5VYR1; Q5VYR3; Q659C8; Q8TAG7;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=E3 ubiquitin-protein ligase UHRF2;
DE EC=2.3.2.27 {ECO:0000269|PubMed:29923055};
DE AltName: Full=Np95/ICBP90-like RING finger protein;
DE Short=Np95-like RING finger protein;
DE AltName: Full=Nuclear protein 97;
DE AltName: Full=Nuclear zinc finger protein Np97;
DE AltName: Full=RING finger protein 107;
DE AltName: Full=RING-type E3 ubiquitin transferase UHRF2;
DE AltName: Full=Ubiquitin-like PHD and RING finger domain-containing protein 2;
DE AltName: Full=Ubiquitin-like-containing PHD and RING finger domains protein 2;
GN Name=UHRF2; Synonyms=NIRF, RNF107;
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 [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, INDUCTION,
RP FUNCTION, AND INTERACTION WITH PCNP.
RC TISSUE=Fetal brain;
RX PubMed=12176013; DOI=10.1016/s0006-291x(02)00890-2;
RA Mori T., Li Y., Hata H., Ono K., Kochi H.;
RT "NIRF, a novel RING finger protein, is involved in cell-cycle regulation.";
RL Biochem. Biophys. Res. Commun. 296:530-536(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Davenport J.W., Fernandes E.R., Neale G.A.M., Goorha R.M.;
RT "LMO2-induced T cell leukemias overexpress a novel gene, Uhr1, containing
RT RING and PHD zinc fingers and an ubiquitin-like domain.";
RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 636-802 (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP FUNCTION IN CELL CYCLE, AND PHOSPHORYLATION.
RX PubMed=15178429; DOI=10.1016/j.bbrc.2004.04.190;
RA Li Y., Mori T., Hata H., Homma Y., Kochi H.;
RT "NIRF induces G1 arrest and associates with Cdk2.";
RL Biochem. Biophys. Res. Commun. 319:464-468(2004).
RN [7]
RP UBIQUITINATION, INTERACTION WITH PCNP, AND FUNCTION.
RX PubMed=14741369; DOI=10.1016/s0014-5793(03)01495-9;
RA Mori T., Li Y., Hata H., Kochi H.;
RT "NIRF is a ubiquitin ligase that is capable of ubiquitinating PCNP, a PEST-
RT containing nuclear protein.";
RL FEBS Lett. 557:209-214(2004).
RN [8]
RP FUNCTION, AND INTERACTION WITH HDAC1.
RX PubMed=15361834; DOI=10.1038/sj.onc.1208053;
RA Unoki M., Nishidate T., Nakamura Y.;
RT "ICBP90, an E2F-1 target, recruits HDAC1 and binds to methyl-CpG through
RT its SRA domain.";
RL Oncogene 23:7601-7610(2004).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-667, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP FUNCTION, INTERACTION WITH CCDN1; CCNE1; TP53 AND RB1, AND ASSOCIATION WITH
RP TUMORIGENESIS.
RX PubMed=21952639; DOI=10.4161/cc.10.19.17176;
RA Mori T., Ikeda D.D., Fukushima T., Takenoshita S., Kochi H.;
RT "NIRF constitutes a nodal point in the cell cycle network and is a
RT candidate tumor suppressor.";
RL Cell Cycle 10:3284-3299(2011).
RN [12]
RP FUNCTION, AUTOSUMOYLATION, INTERACTION WITH UBE2I, SUBCELLULAR LOCATION,
RP AND MUTAGENESIS OF LYS-307; LYS-548 AND CYS-735.
RX PubMed=23404503; DOI=10.1074/jbc.m112.438234;
RA Oh Y., Chung K.C.;
RT "UHRF2, a ubiquitin E3 ligase, acts as a small ubiquitin-like modifier E3
RT ligase for zinc finger protein 131.";
RL J. Biol. Chem. 288:9102-9111(2013).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [14]
RP FUNCTION, INTERACTION WITH ZNF618, AND SUBCELLULAR LOCATION.
RX PubMed=27129234; DOI=10.1074/jbc.m116.717314;
RA Liu Y., Zhang B., Kuang H., Korakavi G., Lu L.Y., Yu X.;
RT "Zinc Finger Protein 618 Regulates the Function of UHRF2 (Ubiquitin-like
RT with PHD and Ring Finger Domains 2) as a Specific 5-Hydroxymethylcytosine
RT Reader.";
RL J. Biol. Chem. 291:13679-13688(2016).
RN [15]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=27743347; DOI=10.1007/s13238-016-0324-z;
RA Zeng S., Wang Y., Zhang T., Bai L., Wang Y., Duan C.;
RT "E3 ligase UHRF2 stabilizes the acetyltransferase TIP60 and regulates
RT H3K9ac and H3K14ac via RING finger domain.";
RL Protein Cell 8:202-218(2017).
RN [16]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=29506131; DOI=10.1093/nar/gky151;
RA Vaughan R.M., Dickson B.M., Cornett E.M., Harrison J.S., Kuhlman B.,
RA Rothbart S.B.;
RT "Comparative biochemical analysis of UHRF proteins reveals molecular
RT mechanisms that uncouple UHRF2 from DNA methylation maintenance.";
RL Nucleic Acids Res. 46:4405-4416(2018).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY.
RX PubMed=29923055; DOI=10.1007/s10529-018-2577-5;
RA Wang Y., Yan X., Zeng S., Zhang T., Cheng F., Chen R., Duan C.;
RT "UHRF2 promotes DNA damage response by decreasing p21 via RING finger
RT domain.";
RL Biotechnol. Lett. 40:1181-1188(2018).
RN [18]
RP FUNCTION, INTERACTION WITH UHRF1 AND FANCD2, AND SUBCELLULAR LOCATION.
RX PubMed=30335751; DOI=10.1371/journal.pgen.1007643;
RA Motnenko A., Liang C.C., Yang D., Lopez-Martinez D., Yoshikawa Y., Zhan B.,
RA Ward K.E., Tian J., Haas W., Spingardi P., Kessler B.M., Kriaucionis S.,
RA Gygi S.P., Cohn M.A.;
RT "Identification of UHRF2 as a novel DNA interstrand crosslink sensor
RT protein.";
RL PLoS Genet. 14:e1007643-e1007643(2018).
RN [19]
RP FUNCTION, AND INTERACTION WITH ATR.
RX PubMed=33848395; DOI=10.1111/gtc.12851;
RA Hanaki S., Habara M., Shimada M.;
RT "UV-induced activation of ATR is mediated by UHRF2.";
RL Genes Cells 26:447-454(2021).
RN [20]
RP STRUCTURE BY NMR OF 1-76.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the N-terminal ubiquitin-like domain in human
RT NP95/ICBP90-like RING finger protein (NIRF).";
RL Submitted (AUG-2005) to the PDB data bank.
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 672-802 IN COMPLEX WITH ZINC IONS.
RG Structural genomics consortium (SGC);
RT "2.1 Angstrom crystal structure of the human ubiquitin ligase NIRF.";
RL Submitted (JAN-2006) to the PDB data bank.
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 672-802, SUBUNIT, AND DISULFIDE
RP BOND.
RG Structural genomics consortium (SGC);
RT "2.1 Angstrom crystal structure of the human ubiquitin ligase NIRF.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [23] {ECO:0007744|PDB:4PW5, ECO:0007744|PDB:4PW6, ECO:0007744|PDB:4PW7}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 419-648,
RP HYDROXYMETHYLCYTOSINE-BINDING, AND FUNCTION.
RX PubMed=24813944; DOI=10.1016/j.molcel.2014.04.003;
RA Zhou T., Xiong J., Wang M., Yang N., Wong J., Zhu B., Xu R.M.;
RT "Structural basis for hydroxymethylcytosine recognition by the SRA domain
RT of UHRF2.";
RL Mol. Cell 54:879-886(2014).
RN [24] {ECO:0007744|PDB:5YCO}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 784-800, AND INTERACTION WITH
RP PCNA.
RX PubMed=28951215; DOI=10.1016/j.bbrc.2017.09.102;
RA Chen W., Wu M., Hang T., Wang C., Zhang X., Zang J.;
RT "Structure insights into the molecular mechanism of the interaction between
RT UHRF2 and PCNA.";
RL Biochem. Biophys. Res. Commun. 494:575-580(2017).
RN [25]
RP VARIANT [LARGE SCALE ANALYSIS] ASN-87.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: E3 ubiquitin ligase that plays important roles in DNA
CC methylation, histone modifications, cell cycle and DNA repair
CC (PubMed:15178429, PubMed:29506131, PubMed:27743347, PubMed:23404503).
CC Acts as a specific reader for 5-hydroxymethylcytosine (5hmC) and
CC thereby recruits various substrates to these sites to ubiquitinate them
CC (PubMed:27129234, PubMed:24813944). This activity also allows the
CC maintenance of 5mC levels at specific genomic loci and regulates
CC neuron-related gene expression (By similarity). Participates in cell
CC cycle regulation by ubiquitinating cyclins CCND1 and CCNE1 and thereby
CC inducing G1 arrest (PubMed:15178429, PubMed:15361834, PubMed:21952639).
CC Ubiquitinates also PCNP leading to its degradation by the proteasome
CC (PubMed:14741369, PubMed:12176013). Plays an active role in DNA damage
CC repair by ubiquitinating p21/CDKN1A leading to its proteosomal
CC degradation (PubMed:29923055). Promotes also DNA repair by acting as an
CC interstrand cross-links (ICLs) sensor. Mechanistically, cooperates with
CC UHRF1 to ensure recruitment of FANCD2 to ICLs, leading to FANCD2
CC monoubiquitination and subsequent activation (PubMed:30335751).
CC Contributes to UV-induced DNA damage response by physically interacting
CC with ATR in response to irradiation, thereby promoting ATR activation
CC (PubMed:33848395). {ECO:0000250|UniProtKB:Q7TMI3,
CC ECO:0000269|PubMed:12176013, ECO:0000269|PubMed:14741369,
CC ECO:0000269|PubMed:15178429, ECO:0000269|PubMed:15361834,
CC ECO:0000269|PubMed:21952639, ECO:0000269|PubMed:23404503,
CC ECO:0000269|PubMed:24813944, ECO:0000269|PubMed:27129234,
CC ECO:0000269|PubMed:27743347, ECO:0000269|PubMed:29506131,
CC ECO:0000269|PubMed:29923055, ECO:0000269|PubMed:30335751,
CC ECO:0000269|PubMed:33848395}.
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; Evidence={ECO:0000269|PubMed:29923055};
CC -!- ACTIVITY REGULATION: E3 ligase activity is robustly activated by 5-
CC hydroxymethylcytosine. {ECO:0000269|PubMed:29506131}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Binds methylated CpG containing
CC oligonucleotides. Interacts with H3; the interaction has a preference
CC for the 'Lys-9' trimethylated form of H3 (H3K9me3) (By similarity).
CC Interacts with PCNP (PubMed:12176013, PubMed:14741369). Interacts with
CC HDAC1 (PubMed:15361834). Interacts directly with CCNE1; the interaction
CC ubiquitinates CCNE1 and appears independent of CCNE1 phosphorylation
CC (PubMed:21952639). Interacts with CCND1; the interaction ubiquitinates
CC CCND1 and appears independent of CCND1 phosphorylation
CC (PubMed:21952639). Interacts with p53/TP53 and RB1 (PubMed:21952639).
CC Interacts with UBE2I (PubMed:23404503). Interacts with ZNF618
CC (PubMed:27129234). Interacts with UHRF1 (PubMed:30335751). Interacts
CC with FANCD2 (PubMed:30335751). Interacts with ATR (PubMed:33848395).
CC Interacts with PCNA (PubMed:28951215). {ECO:0000250,
CC ECO:0000269|PubMed:12176013, ECO:0000269|PubMed:14741369,
CC ECO:0000269|PubMed:15361834, ECO:0000269|PubMed:21952639,
CC ECO:0000269|PubMed:23404503, ECO:0000269|PubMed:27129234,
CC ECO:0000269|PubMed:28951215, ECO:0000269|PubMed:30335751,
CC ECO:0000269|PubMed:33848395, ECO:0000269|Ref.21, ECO:0000269|Ref.22}.
CC -!- INTERACTION:
CC Q96PU4; P20248: CCNA2; NbExp=2; IntAct=EBI-625304, EBI-457097;
CC Q96PU4; P14635: CCNB1; NbExp=2; IntAct=EBI-625304, EBI-495332;
CC Q96PU4; P24385: CCND1; NbExp=4; IntAct=EBI-625304, EBI-375001;
CC Q96PU4; P24864: CCNE1; NbExp=4; IntAct=EBI-625304, EBI-519526;
CC Q96PU4; P24941: CDK2; NbExp=5; IntAct=EBI-625304, EBI-375096;
CC Q96PU4; P06400: RB1; NbExp=4; IntAct=EBI-625304, EBI-491274;
CC Q96PU4; P04637: TP53; NbExp=3; IntAct=EBI-625304, EBI-366083;
CC Q96PU4-2; Q6ICB0: DESI1; NbExp=3; IntAct=EBI-12878912, EBI-2806959;
CC Q96PU4-2; Q86VK4-3: ZNF410; NbExp=3; IntAct=EBI-12878912, EBI-11741890;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00358,
CC ECO:0000269|PubMed:12176013, ECO:0000269|PubMed:23404503,
CC ECO:0000269|PubMed:27129234, ECO:0000269|PubMed:27743347,
CC ECO:0000269|PubMed:29923055, ECO:0000269|PubMed:30335751}. Chromosome
CC {ECO:0000269|PubMed:27129234}. Note=Enriched at genomic loci that are
CC enriched for 5-hydroxymethylcytosine (5hmC).
CC {ECO:0000269|PubMed:27129234}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96PU4-1; Sequence=Displayed;
CC Name=2; Synonyms=a;
CC IsoId=Q96PU4-2; Sequence=VSP_013874, VSP_013875;
CC -!- INDUCTION: Up-regulated in proliferating fetal lung fibroblasts and in
CC U-937 myeloid leukemia cells. Down-regulated in these cells by growth
CC arrest and differentiation. In other cell types which cannot leave the
CC cell cycle, such as tumoral HT-1080 and Hep-G2, levels are consistently
CC up-regulated. {ECO:0000269|PubMed:12176013}.
CC -!- DOMAIN: The YDG domain recognizes and binds 5-hydroxymethylcytosine
CC (5hmC). {ECO:0000269|PubMed:24813944}.
CC -!- PTM: May be autoubiquitinated; which may lead to proteasomal
CC degradation. {ECO:0000269|PubMed:14741369}.
CC -!- PTM: Phosphorylated. Phosphorylation may be mediated by CDK2.
CC {ECO:0000269|PubMed:15178429}.
CC -!- PTM: Autosumoylated.
CC -!- DISEASE: Note=Associated with various cancers. DNA copy number loss is
CC found in multiple kinds of malignancies originating from the brain,
CC breast, stomach, kidney, hematopoietic tissue and lung.
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DR EMBL; AB071698; BAB68317.1; -; mRNA.
DR EMBL; AF274049; AAM33799.1; -; mRNA.
DR EMBL; AL133480; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL353718; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC028397; AAH28397.1; -; mRNA.
DR EMBL; AL137728; CAH56383.1; -; mRNA.
DR CCDS; CCDS6469.1; -. [Q96PU4-1]
DR RefSeq; NP_690856.1; NM_152896.2. [Q96PU4-1]
DR PDB; 1WY8; NMR; -; A=1-76.
DR PDB; 1Z6U; X-ray; 2.10 A; A/B=672-802.
DR PDB; 2E6S; NMR; -; A=326-395.
DR PDB; 3OLN; X-ray; 2.30 A; A/B=419-648.
DR PDB; 4PW5; X-ray; 2.20 A; A/B/E/F=419-648.
DR PDB; 4PW6; X-ray; 3.79 A; A/B=419-648.
DR PDB; 4PW7; X-ray; 2.00 A; A/B/E/F=419-648.
DR PDB; 4TVR; X-ray; 2.29 A; A=109-395.
DR PDB; 5YCO; X-ray; 2.20 A; E/F=784-800.
DR PDBsum; 1WY8; -.
DR PDBsum; 1Z6U; -.
DR PDBsum; 2E6S; -.
DR PDBsum; 3OLN; -.
DR PDBsum; 4PW5; -.
DR PDBsum; 4PW6; -.
DR PDBsum; 4PW7; -.
DR PDBsum; 4TVR; -.
DR PDBsum; 5YCO; -.
DR AlphaFoldDB; Q96PU4; -.
DR BMRB; Q96PU4; -.
DR SMR; Q96PU4; -.
DR BioGRID; 125434; 127.
DR IntAct; Q96PU4; 41.
DR MINT; Q96PU4; -.
DR STRING; 9606.ENSP00000276893; -.
DR GlyGen; Q96PU4; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96PU4; -.
DR PhosphoSitePlus; Q96PU4; -.
DR BioMuta; UHRF2; -.
DR DMDM; 67462076; -.
DR EPD; Q96PU4; -.
DR jPOST; Q96PU4; -.
DR MassIVE; Q96PU4; -.
DR MaxQB; Q96PU4; -.
DR PaxDb; Q96PU4; -.
DR PeptideAtlas; Q96PU4; -.
DR PRIDE; Q96PU4; -.
DR ProteomicsDB; 77750; -. [Q96PU4-1]
DR ProteomicsDB; 77751; -. [Q96PU4-2]
DR Antibodypedia; 9697; 310 antibodies from 30 providers.
DR DNASU; 115426; -.
DR Ensembl; ENST00000276893.10; ENSP00000276893.5; ENSG00000147854.17. [Q96PU4-1]
DR Ensembl; ENST00000468435.6; ENSP00000434182.1; ENSG00000147854.17. [Q96PU4-2]
DR GeneID; 115426; -.
DR KEGG; hsa:115426; -.
DR MANE-Select; ENST00000276893.10; ENSP00000276893.5; NM_152896.3; NP_690856.1.
DR UCSC; uc003zjy.4; human. [Q96PU4-1]
DR CTD; 115426; -.
DR DisGeNET; 115426; -.
DR GeneCards; UHRF2; -.
DR HGNC; HGNC:12557; UHRF2.
DR HPA; ENSG00000147854; Low tissue specificity.
DR MIM; 615211; gene.
DR neXtProt; NX_Q96PU4; -.
DR OpenTargets; ENSG00000147854; -.
DR PharmGKB; PA37197; -.
DR VEuPathDB; HostDB:ENSG00000147854; -.
DR eggNOG; ENOG502QRDQ; Eukaryota.
DR GeneTree; ENSGT00390000008296; -.
DR HOGENOM; CLU_022357_0_0_1; -.
DR InParanoid; Q96PU4; -.
DR OMA; CHMCSCH; -.
DR OrthoDB; 705927at2759; -.
DR PhylomeDB; Q96PU4; -.
DR TreeFam; TF106434; -.
DR PathwayCommons; Q96PU4; -.
DR Reactome; R-HSA-3899300; SUMOylation of transcription cofactors.
DR SignaLink; Q96PU4; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 115426; 10 hits in 1124 CRISPR screens.
DR ChiTaRS; UHRF2; human.
DR EvolutionaryTrace; Q96PU4; -.
DR GeneWiki; UHRF2; -.
DR GenomeRNAi; 115426; -.
DR Pharos; Q96PU4; Tbio.
DR PRO; PR:Q96PU4; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q96PU4; protein.
DR Bgee; ENSG00000147854; Expressed in secondary oocyte and 188 other tissues.
DR ExpressionAtlas; Q96PU4; baseline and differential.
DR Genevisible; Q96PU4; HS.
DR GO; GO:0000792; C:heterochromatin; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:HGNC-UCL.
DR GO; GO:0005721; C:pericentric heterochromatin; IDA:ARUK-UCL.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0042393; F:histone binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:ARUK-UCL.
DR GO; GO:0019789; F:SUMO transferase activity; EXP:Reactome.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:HGNC-UCL.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEP:HGNC-UCL.
DR GO; GO:0010216; P:maintenance of DNA methylation; IBA:GO_Central.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:HGNC-UCL.
DR GO; GO:0016567; P:protein ubiquitination; IDA:HGNC-UCL.
DR GO; GO:0051726; P:regulation of cell cycle; IDA: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 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell cycle; Chromosome; Disulfide bond;
KW DNA-binding; Metal-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Transferase; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..802
FT /note="E3 ubiquitin-protein ligase UHRF2"
FT /id="PRO_0000056147"
FT DOMAIN 1..78
FT /note="Ubiquitin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT DOMAIN 448..612
FT /note="YDG"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00358"
FT ZN_FING 344..395
FT /note="PHD-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT ZN_FING 733..772
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 80..116
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 117..311
FT /note="Required for interaction with histone H3"
FT /evidence="ECO:0000250"
FT REGION 153..197
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 194..288
FT /note="Interaction with PCNP"
FT REGION 414..644
FT /note="Methyl-CpG binding and interaction with HDAC1"
FT /evidence="ECO:0000269|PubMed:15361834"
FT REGION 640..674
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 153..175
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 654..668
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 667
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT DISULFID 704
FT /note="Interchain"
FT /evidence="ECO:0000269|Ref.22"
FT VAR_SEQ 500..503
FT /note="DRGD -> LTEL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013874"
FT VAR_SEQ 504..802
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013875"
FT VARIANT 87
FT /note="I -> N (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs147971931)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035961"
FT MUTAGEN 307
FT /note="K->R: No effect on autosumoylation."
FT /evidence="ECO:0000269|PubMed:23404503"
FT MUTAGEN 548
FT /note="K->R: No effect on autosumoylation."
FT /evidence="ECO:0000269|PubMed:23404503"
FT MUTAGEN 735
FT /note="C->S: No effect on autosumoylation, nor on ZNF131
FT sumoylation."
FT /evidence="ECO:0000269|PubMed:23404503"
FT CONFLICT 287
FT /note="L -> M (in Ref. 4; AAH28397)"
FT /evidence="ECO:0000305"
FT CONFLICT 329
FT /note="P -> T (in Ref. 4; AAH28397)"
FT /evidence="ECO:0000305"
FT CONFLICT 416
FT /note="P -> Q (in Ref. 4; AAH28397)"
FT /evidence="ECO:0000305"
FT STRAND 1..7
FT /evidence="ECO:0007829|PDB:1WY8"
FT STRAND 13..19
FT /evidence="ECO:0007829|PDB:1WY8"
FT HELIX 25..35
FT /evidence="ECO:0007829|PDB:1WY8"
FT TURN 40..42
FT /evidence="ECO:0007829|PDB:1WY8"
FT STRAND 43..47
FT /evidence="ECO:0007829|PDB:1WY8"
FT STRAND 54..57
FT /evidence="ECO:0007829|PDB:1WY8"
FT HELIX 58..61
FT /evidence="ECO:0007829|PDB:1WY8"
FT STRAND 68..73
FT /evidence="ECO:0007829|PDB:1WY8"
FT STRAND 132..136
FT /evidence="ECO:0007829|PDB:4TVR"
FT TURN 138..140
FT /evidence="ECO:0007829|PDB:4TVR"
FT STRAND 143..153
FT /evidence="ECO:0007829|PDB:4TVR"
FT STRAND 206..213
FT /evidence="ECO:0007829|PDB:4TVR"
FT HELIX 217..219
FT /evidence="ECO:0007829|PDB:4TVR"
FT STRAND 222..224
FT /evidence="ECO:0007829|PDB:4TVR"
FT HELIX 226..228
FT /evidence="ECO:0007829|PDB:4TVR"
FT STRAND 229..231
FT /evidence="ECO:0007829|PDB:4TVR"
FT HELIX 239..241
FT /evidence="ECO:0007829|PDB:4TVR"
FT STRAND 247..252
FT /evidence="ECO:0007829|PDB:4TVR"
FT STRAND 262..273
FT /evidence="ECO:0007829|PDB:4TVR"
FT STRAND 275..277
FT /evidence="ECO:0007829|PDB:4TVR"
FT STRAND 279..286
FT /evidence="ECO:0007829|PDB:4TVR"
FT STRAND 293..298
FT /evidence="ECO:0007829|PDB:4TVR"
FT TURN 318..320
FT /evidence="ECO:0007829|PDB:4TVR"
FT TURN 332..336
FT /evidence="ECO:0007829|PDB:4TVR"
FT STRAND 338..340
FT /evidence="ECO:0007829|PDB:4TVR"
FT TURN 343..345
FT /evidence="ECO:0007829|PDB:4TVR"
FT TURN 348..350
FT /evidence="ECO:0007829|PDB:4TVR"
FT STRAND 356..360
FT /evidence="ECO:0007829|PDB:4TVR"
FT STRAND 363..365
FT /evidence="ECO:0007829|PDB:4TVR"
FT STRAND 368..370
FT /evidence="ECO:0007829|PDB:4TVR"
FT TURN 371..373
FT /evidence="ECO:0007829|PDB:4TVR"
FT STRAND 374..376
FT /evidence="ECO:0007829|PDB:4TVR"
FT TURN 390..392
FT /evidence="ECO:0007829|PDB:4TVR"
FT STRAND 458..461
FT /evidence="ECO:0007829|PDB:4PW7"
FT HELIX 462..467
FT /evidence="ECO:0007829|PDB:4PW7"
FT STRAND 477..481
FT /evidence="ECO:0007829|PDB:4PW7"
FT TURN 482..484
FT /evidence="ECO:0007829|PDB:4PW7"
FT STRAND 485..491
FT /evidence="ECO:0007829|PDB:4PW7"
FT STRAND 502..508
FT /evidence="ECO:0007829|PDB:4PW7"
FT HELIX 532..539
FT /evidence="ECO:0007829|PDB:4PW7"
FT STRAND 541..543
FT /evidence="ECO:0007829|PDB:4PW7"
FT TURN 547..549
FT /evidence="ECO:0007829|PDB:4PW7"
FT HELIX 556..558
FT /evidence="ECO:0007829|PDB:4PW7"
FT STRAND 562..567
FT /evidence="ECO:0007829|PDB:4PW7"
FT HELIX 568..572
FT /evidence="ECO:0007829|PDB:4PW7"
FT STRAND 575..577
FT /evidence="ECO:0007829|PDB:4PW7"
FT STRAND 579..597
FT /evidence="ECO:0007829|PDB:4PW7"
FT TURN 599..601
FT /evidence="ECO:0007829|PDB:4PW7"
FT STRAND 602..612
FT /evidence="ECO:0007829|PDB:4PW7"
FT HELIX 622..630
FT /evidence="ECO:0007829|PDB:4PW7"
FT HELIX 694..702
FT /evidence="ECO:0007829|PDB:1Z6U"
FT HELIX 704..706
FT /evidence="ECO:0007829|PDB:1Z6U"
FT HELIX 707..713
FT /evidence="ECO:0007829|PDB:1Z6U"
FT HELIX 714..722
FT /evidence="ECO:0007829|PDB:1Z6U"
FT HELIX 723..730
FT /evidence="ECO:0007829|PDB:1Z6U"
FT TURN 734..736
FT /evidence="ECO:0007829|PDB:1Z6U"
FT STRAND 737..739
FT /evidence="ECO:0007829|PDB:1Z6U"
FT STRAND 741..745
FT /evidence="ECO:0007829|PDB:1Z6U"
FT STRAND 751..753
FT /evidence="ECO:0007829|PDB:1Z6U"
FT HELIX 754..762
FT /evidence="ECO:0007829|PDB:1Z6U"
FT TURN 769..771
FT /evidence="ECO:0007829|PDB:1Z6U"
FT HELIX 785..794
FT /evidence="ECO:0007829|PDB:1Z6U"
FT TURN 796..801
FT /evidence="ECO:0007829|PDB:1Z6U"
SQ SEQUENCE 802 AA; 89985 MW; 190E26D5A347A7FA CRC64;
MWIQVRTIDG SKTCTIEDVS RKATIEELRE RVWALFDVRP ECQRLFYRGK QLENGYTLFD
YDVGLNDIIQ LLVRPDPDHL PGTSTQIEAK PCSNSPPKVK KAPRVGPSNQ PSTSARARLI
DPGFGIYKVN ELVDARDVGL GAWFEAHIHS VTRASDGQSR GKTPLKNGSS CKRTNGNIKH
KSKENTNKLD SVPSTSNSDC VAADEDVIYH IQYDEYPESG TLEMNVKDLR PRARTILKWN
ELNVGDVVMV NYNVESPGQR GFWFDAEITT LKTISRTKKE LRVKIFLGGS EGTLNDCKII
SVDEIFKIER PGAHPLSFAD GKFLRRNDPE CDLCGGDPEK KCHSCSCRVC GGKHEPNMQL
LCDECNVAYH IYCLNPPLDK VPEEEYWYCP SCKTDSSEVV KAGERLKMSK KKAKMPSAST
ESRRDWGRGM ACVGRTRECT IVPSNHYGPI PGIPVGSTWR FRVQVSEAGV HRPHVGGIHG
RSNDGAYSLV LAGGFADEVD RGDEFTYTGS GGKNLAGNKR IGAPSADQTL TNMNRALALN
CDAPLDDKIG AESRNWRAGK PVRVIRSFKG RKISKYAPEE GNRYDGIYKV VKYWPEISSS
HGFLVWRYLL RRDDVEPAPW TSEGIERSRR LCLRLQYPAG YPSDKEGKKP KGQSKKQPSG
TTKRPISDDD CPSASKVYKA SDSAEAIEAF QLTPQQQHLI REDCQNQKLW DEVLSHLVEG
PNFLKKLEQS FMCVCCQELV YQPVTTECFH NVCKDCLQRS FKAQVFSCPA CRHDLGQNYI
MIPNEILQTL LDLFFPGYSK GR
