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 24-JAN-2024, entry version 190. 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 proteasomal 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. 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; 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; 131. 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 SwissPalm; Q96PU4; -. DR BioMuta; UHRF2; -. DR DMDM; 67462076; -. DR EPD; Q96PU4; -. DR jPOST; Q96PU4; -. DR MassIVE; Q96PU4; -. DR MaxQB; Q96PU4; -. DR PaxDb; 9606-ENSP00000276893; -. DR PeptideAtlas; Q96PU4; -. DR ProteomicsDB; 77750; -. [Q96PU4-1] DR ProteomicsDB; 77751; -. [Q96PU4-2] DR Pumba; Q96PU4; -. DR Antibodypedia; 9697; 362 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 AGR; HGNC:12557; -. 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; 5481936at2759; -. DR PhylomeDB; Q96PU4; -. DR TreeFam; TF106434; -. DR PathwayCommons; Q96PU4; -. DR Reactome; R-HSA-3899300; SUMOylation of transcription cofactors. DR SignaLink; Q96PU4; -. DR SIGNOR; Q96PU4; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 115426; 10 hits in 1212 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 190 other cell types or tissues. DR ExpressionAtlas; Q96PU4; baseline and differential. 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:0051865; P:protein autoubiquitination; IDA:HGNC-UCL. DR GO; GO:0016925; P:protein sumoylation; TAS:Reactome. DR GO; GO:0016567; P:protein ubiquitination; IDA:HGNC-UCL. DR GO; GO:0051726; P:regulation of cell cycle; IDA:UniProtKB. DR CDD; cd15617; PHD_UHRF2; 1. DR CDD; cd16770; RING-HC_UHRF2; 1. DR CDD; cd20456; Tudor_UHRF2_rpt1; 1. DR CDD; cd20458; Tudor_UHRF2_rpt2; 1. DR CDD; cd17123; Ubl_UHRF2; 1. DR Gene3D; 2.30.30.1150; -; 1. DR Gene3D; 2.30.30.140; -; 1. DR Gene3D; 2.30.280.10; SRA-YDG; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR047467; PHD_UHRF2. DR InterPro; IPR015947; PUA-like_sf. DR InterPro; IPR047466; RING-HC_UHRF2. DR InterPro; IPR036987; SRA-YDG_sf. DR InterPro; IPR003105; SRA_YDG. DR InterPro; IPR021991; TTD_dom. DR InterPro; IPR047407; Tudor_UHRF2_rpt1. DR InterPro; IPR000626; Ubiquitin-like_dom. DR InterPro; IPR029071; Ubiquitin-like_domsf. DR InterPro; IPR047468; Ubl_UHRF2. 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; E3 UBIQUITIN-PROTEIN LIGASE UHRF-RELATED; 1. DR PANTHER; PTHR14140:SF3; E3 UBIQUITIN-PROTEIN LIGASE UHRF2; 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; SSF57903; FYVE/PHD zinc finger; 1. DR SUPFAM; SSF88697; PUA domain-like; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR SUPFAM; SSF54236; Ubiquitin-like; 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. DR Genevisible; Q96PU4; HS. 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 //