Protein: E3 ubiquitin-protein ligase UHRF2 (EC 2.3.2.27) (Np95/ICBP90-like RING finger protein) (Np95-like RING finger protein) (Nuclear protein 97) (Nuclear zinc finger protein Np97) (RING finger protein 107) (RING-type E3 ubiquitin transferase UHRF2) (Ubiquitin-like PHD and RING finger domain-containing protein 2) (Ubiquitin-like-containing PHD and RING finger domains protein 2) (Q96PU4)
Organism: Homo sapiens (Human)
Function: E3 ubiquitin ligase that plays important roles in DNA methylation, histone modifications, cell cycle and DNA repair. Acts as a specific reader for 5-hydroxymethylcytosine (5hmC) and thereby recruits various substrates to these sites to ubiquitinate them. This activity also allows the maintenance of 5mC levels at specific genomic loci and regulates neuron-related gene expression (By similarity). Participates in cell cycle regulation by ubiquitinating cyclins CCND1 and CCNE1 and thereby inducing G1 arrest. Ubiquitinates also PCNP leading to its degradation by the proteasome. Plays an active role in DNA damage repair by ubiquitinating p21/CDKN1A leading to its proteosomal degradation. Promotes also DNA repair by acting as an interstrand cross-links (ICLs) sensor. Mechanistically, cooperates with UHRF1 to ensure recruitment of FANCD2 to ICLs, leading to FANCD2 monoubiquitination and subsequent activation. Contributes to UV-induced DNA damage response by physically interacting with ATR in response to irradiation, thereby promoting ATR activation.
Subcellular location: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00358, ECO:0000269|PubMed:12176013, ECO:0000269|PubMed:23404503, ECO:0000269|PubMed:27129234, ECO:0000269|PubMed:27743347, ECO:0000269|PubMed:29923055, ECO:0000269|PubMed:30335751}. Chromosome {ECO:0000269|PubMed:27129234}. Note=Enriched at genomic loci that are enriched for 5-hydroxymethylcytosine (5hmC). {ECO:0000269|PubMed:27129234}.
Sequence: MWIQVRTIDGSKTCTIEDVSRKATIEELRERVWALFDVRPECQRLFYRGKQLENGYTLFDYDVGLNDIIQLLVRPDPDHLPGTSTQIEAKPCSNSPPKVKKAPRVGPSNQPSTSARARLIDPGFGIYKVNELVDARDVGLGAWFEAHIHSVTRASDGQSRGKTPLKNGSSCKRTNGNIKHKSKENTNKLDSVPSTSNSDCVAADEDVIYHIQYDEYPESGTLEMNVKDLRPRARTILKWNELNVGDVVMVNYNVESPGQRGFWFDAEITTLKTISRTKKELRVKIFLGGSEGTLNDCKIISVDEIFKIERPGAHPLSFADGKFLRRNDPECDLCGGDPEKKCHSCSCRVCGGKHEPNMQLLCDECNVAYHIYCLNPPLDKVPEEEYWYCPSCKTDSSEVVKAGERLKMSKKKAKMPSASTESRRDWGRGMACVGRTRECTIVPSNHYGPIPGIPVGSTWRFRVQVSEAGVHRPHVGGIHGRSNDGAYSLVLAGGFADEVDRGDEFTYTGSGGKNLAGNKRIGAPSADQTLTNMNRALALNCDAPLDDKIGAESRNWRAGKPVRVIRSFKGRKISKYAPEEGNRYDGIYKVVKYWPEISSSHGFLVWRYLLRRDDVEPAPWTSEGIERSRRLCLRLQYPAGYPSDKEGKKPKGQSKKQPSGTTKRPISDDDCPSASKVYKASDSAEAIEAFQLTPQQQHLIREDCQNQKLWDEVLSHLVEGPNFLKKLEQSFMCVCCQELVYQPVTTECFHNVCKDCLQRSFKAQVFSCPACRHDLGQNYIMIPNEILQTLLDLFFPGYSKGR
InterPro domains: - IPR045134: UHRF1/2-like (family) [41-796]
- IPR017907: Zinc finger, RING-type, conserved site (conserved_site) [748-757]
- IPR000626: Ubiquitin-like domain (domain) [1-75]
- IPR029071: Ubiquitin-like domain superfamily (homologous_superfamily) [1-84]
- IPR047466: E3 ubiquitin-protein ligase UHRF2, RING finger, HC subclass (domain) [728-792]
- IPR011011: Zinc finger, FYVE/PHD-type (homologous_superfamily) [343-397]
- IPR003105: SRA-YDG (domain) [443-616]
- IPR019787: Zinc finger, PHD-finger (domain) [344-395]
- IPR047468: E3 ubiquitin-protein ligase UHRF2, ubiquitin-like domain (domain) [1-74]
- IPR021991: UHRF1, tandem tudor domain (domain) [125-312]
- IPR036987: SRA-YDG superfamily (homologous_superfamily) [428-639]
- IPR013083: Zinc finger, RING/FYVE/PHD-type (homologous_superfamily) [688-802]
- IPR047407: E3 ubiquitin-protein ligase UHRF2, first Tudor domain (domain) [111-237]
- IPR047467: E3 ubiquitin-protein ligase UHRF2, PHD finger (domain) [346-392]
- IPR015947: PUA-like superfamily (homologous_superfamily) [429-633]
- IPR001965: Zinc finger, PHD-type (domain) [346-393]
- IPR001841: Zinc finger, RING-type (domain) [347-772]
Interaction partners: - Proliferating cell nuclear antigen
- DNA
- Histone deacetylase 1
- PEST proteolytic signal-containing nuclear protein
- Retinoblastoma-associated protein
- DNA
- DNA
- Cellular tumor antigen p53
- Zinc finger protein 131
- Ubiquitin-conjugating enzyme E2 D1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0036094 (small molecule binding), GO:1901363 (heterocyclic compound binding), GO:0016740 (transferase activity), GO:0097159 (organic cyclic compound binding), GO:0043167 (ion binding), GO:0140096 (catalytic activity, acting on a protein), GO:0005515 (protein binding), GO:0003676 (nucleic acid binding), GO:0042393 (histone binding), GO:0140030 (modification-dependent protein binding), GO:1901265 (nucleoside phosphate binding), GO:0019787 (ubiquitin-like protein transferase activity), GO:0000166 (nucleotide binding), GO:0043169 (cation binding), GO:0046872 (metal ion binding), GO:0004842 (ubiquitin-protein transferase activity), GO:0001067 (transcription regulatory region nucleic acid binding), GO:0035064 (methylated histone binding), GO:0003677 (DNA binding), GO:0140034 (methylation-dependent protein binding), GO:0008327 (methyl-CpG binding), GO:0003690 (double-stranded DNA binding), GO:0043565 (sequence-specific DNA binding), GO:0046914 (transition metal ion binding), GO:0000976 (transcription cis-regulatory region binding), GO:1990837 (sequence-specific double-stranded DNA binding), GO:0000987 (cis-regulatory region sequence-specific DNA binding), GO:0008270 (zinc ion binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0065007 (biological regulation), GO:0050789 (regulation of biological process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0019222 (regulation of metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0071840 (cellular component organization or biogenesis), GO:0071704 (organic substance metabolic process), GO:0044238 (primary metabolic process), GO:0009892 (negative regulation of metabolic process), GO:1901564 (organonitrogen compound metabolic process), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0019538 (protein metabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0016043 (cellular component organization), GO:0043170 (macromolecule metabolic process), GO:0036211 (protein modification process), GO:0043412 (macromolecule modification), GO:0006325 (chromatin organization), GO:0010629 (negative regulation of gene expression), GO:0010468 (regulation of gene expression), GO:0040029 (epigenetic regulation of gene expression), GO:0045814 (negative regulation of gene expression, epigenetic), GO:0070647 (protein modification by small protein conjugation or removal), GO:0016570 (histone modification), GO:1903507 (negative regulation of nucleic acid-templated transcription), GO:0031507 (heterochromatin formation), GO:0032446 (protein modification by small protein conjugation), GO:0016574 (histone ubiquitination), GO:0070828 (heterochromatin organization), GO:0016567 (protein ubiquitination), GO:0010390 (histone monoubiquitination), GO:0035518 (histone H2A monoubiquitination), GO:0006513 (protein monoubiquitination)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0000785 (chromatin), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:0005657 (replication fork), GO:0000792 (heterochromatin), GO:0043233 (organelle lumen), GO:0000791 (euchromatin), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043228 (non-membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0043232 (intracellular non-membrane-bounded organelle), GO:0031981 (nuclear lumen), GO:0005694 (chromosome), GO:0005634 (nucleus)