Q96PU4 · UHRF2_HUMAN
- ProteinE3 ubiquitin-protein ligase UHRF2
- GeneUHRF2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids802 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Acts as a specific reader for 5-hydroxymethylcytosine (5hmC) and thereby recruits various substrates to these sites to ubiquitinate them (PubMed:24813944, PubMed:27129234).
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 (PubMed:15178429, PubMed:15361834, PubMed:21952639).
Ubiquitinates also PCNP leading to its degradation by the proteasome (PubMed:12176013, PubMed:14741369).
Plays an active role in DNA damage repair by ubiquitinating p21/CDKN1A leading to its proteasomal degradation (PubMed:29923055).
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 (PubMed:30335751).
Contributes to UV-induced DNA damage response by physically interacting with ATR in response to irradiation, thereby promoting ATR activation (PubMed:33848395).
Catalytic activity
Activity regulation
Pathway
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | heterochromatin | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Cellular Component | pericentric heterochromatin | |
Molecular Function | DNA binding | |
Molecular Function | histone binding | |
Molecular Function | metal ion binding | |
Molecular Function | RNA polymerase II-specific DNA-binding transcription factor binding | |
Molecular Function | SUMO transferase activity | |
Molecular Function | ubiquitin protein ligase activity | |
Molecular Function | ubiquitin-protein transferase activity | |
Biological Process | cell differentiation | |
Biological Process | negative regulation of gene expression via chromosomal CpG island methylation | |
Biological Process | protein autoubiquitination | |
Biological Process | protein sumoylation | |
Biological Process | protein ubiquitination | |
Biological Process | regulation of cell cycle |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameE3 ubiquitin-protein ligase UHRF2
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ96PU4
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_035961 | 87 | in a colorectal cancer sample; somatic mutation; dbSNP:rs147971931 | |||
Sequence: I → N | ||||||
Mutagenesis | 307 | No effect on autosumoylation. | ||||
Sequence: K → R | ||||||
Mutagenesis | 548 | No effect on autosumoylation. | ||||
Sequence: K → R | ||||||
Mutagenesis | 735 | No effect on autosumoylation, nor on ZNF131 sumoylation. | ||||
Sequence: C → S |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 633 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue, disulfide bond.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000056147 | 1-802 | UniProt | E3 ubiquitin-protein ligase UHRF2 | |||
Sequence: MWIQVRTIDGSKTCTIEDVSRKATIEELRERVWALFDVRPECQRLFYRGKQLENGYTLFDYDVGLNDIIQLLVRPDPDHLPGTSTQIEAKPCSNSPPKVKKAPRVGPSNQPSTSARARLIDPGFGIYKVNELVDARDVGLGAWFEAHIHSVTRASDGQSRGKTPLKNGSSCKRTNGNIKHKSKENTNKLDSVPSTSNSDCVAADEDVIYHIQYDEYPESGTLEMNVKDLRPRARTILKWNELNVGDVVMVNYNVESPGQRGFWFDAEITTLKTISRTKKELRVKIFLGGSEGTLNDCKIISVDEIFKIERPGAHPLSFADGKFLRRNDPECDLCGGDPEKKCHSCSCRVCGGKHEPNMQLLCDECNVAYHIYCLNPPLDKVPEEEYWYCPSCKTDSSEVVKAGERLKMSKKKAKMPSASTESRRDWGRGMACVGRTRECTIVPSNHYGPIPGIPVGSTWRFRVQVSEAGVHRPHVGGIHGRSNDGAYSLVLAGGFADEVDRGDEFTYTGSGGKNLAGNKRIGAPSADQTLTNMNRALALNCDAPLDDKIGAESRNWRAGKPVRVIRSFKGRKISKYAPEEGNRYDGIYKVVKYWPEISSSHGFLVWRYLLRRDDVEPAPWTSEGIERSRRLCLRLQYPAGYPSDKEGKKPKGQSKKQPSGTTKRPISDDDCPSASKVYKASDSAEAIEAFQLTPQQQHLIREDCQNQKLWDEVLSHLVEGPNFLKKLEQSFMCVCCQELVYQPVTTECFHNVCKDCLQRSFKAQVFSCPACRHDLGQNYIMIPNEILQTLLDLFFPGYSKGR | |||||||
Modified residue (large scale data) | 95 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 643 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 667 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 667 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 673 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 681 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Disulfide bond | 704 | UniProt | Interchain | ||||
Sequence: C |
Post-translational modification
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Induction
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with PCNP (PubMed:12176013, PubMed:14741369).
Interacts with HDAC1 (PubMed:15361834).
Interacts directly with CCNE1; the interaction ubiquitinates CCNE1 and appears independent of CCNE1 phosphorylation (PubMed:21952639).
Interacts with CCND1; the interaction ubiquitinates CCND1 and appears independent of CCND1 phosphorylation (PubMed:21952639).
Interacts with p53/TP53 and RB1 (PubMed:21952639).
Interacts with UBE2I (PubMed:23404503).
Interacts with ZNF618 (PubMed:27129234).
Interacts with UHRF1 (PubMed:30335751).
Interacts with FANCD2 (PubMed:30335751).
Interacts with ATR (PubMed:33848395).
Interacts with PCNA (PubMed:28951215).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q96PU4 | CCNA2 P20248 | 2 | EBI-625304, EBI-457097 | |
BINARY | Q96PU4 | CCNB1 P14635 | 2 | EBI-625304, EBI-495332 | |
BINARY | Q96PU4 | CCND1 P24385 | 4 | EBI-625304, EBI-375001 | |
BINARY | Q96PU4 | CCNE1 P24864 | 4 | EBI-625304, EBI-519526 | |
BINARY | Q96PU4 | CDK2 P24941 | 5 | EBI-625304, EBI-375096 | |
BINARY | Q96PU4 | RB1 P06400 | 4 | EBI-625304, EBI-491274 | |
BINARY | Q96PU4 | TP53 P04637 | 3 | EBI-625304, EBI-366083 | |
BINARY | Q96PU4-2 | DESI1 Q6ICB0 | 3 | EBI-12878912, EBI-2806959 | |
BINARY | Q96PU4-2 | ZNF410 Q86VK4-3 | 3 | EBI-12878912, EBI-11741890 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias, zinc finger.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 1-78 | Ubiquitin-like | ||||
Sequence: MWIQVRTIDGSKTCTIEDVSRKATIEELRERVWALFDVRPECQRLFYRGKQLENGYTLFDYDVGLNDIIQLLVRPDPD | ||||||
Region | 80-116 | Disordered | ||||
Sequence: LPGTSTQIEAKPCSNSPPKVKKAPRVGPSNQPSTSAR | ||||||
Region | 117-311 | Required for interaction with histone H3 | ||||
Sequence: ARLIDPGFGIYKVNELVDARDVGLGAWFEAHIHSVTRASDGQSRGKTPLKNGSSCKRTNGNIKHKSKENTNKLDSVPSTSNSDCVAADEDVIYHIQYDEYPESGTLEMNVKDLRPRARTILKWNELNVGDVVMVNYNVESPGQRGFWFDAEITTLKTISRTKKELRVKIFLGGSEGTLNDCKIISVDEIFKIERP | ||||||
Compositional bias | 153-175 | Polar residues | ||||
Sequence: RASDGQSRGKTPLKNGSSCKRTN | ||||||
Region | 153-197 | Disordered | ||||
Sequence: RASDGQSRGKTPLKNGSSCKRTNGNIKHKSKENTNKLDSVPSTSN | ||||||
Region | 194-288 | Interaction with PCNP | ||||
Sequence: STSNSDCVAADEDVIYHIQYDEYPESGTLEMNVKDLRPRARTILKWNELNVGDVVMVNYNVESPGQRGFWFDAEITTLKTISRTKKELRVKIFLG | ||||||
Zinc finger | 344-395 | PHD-type | ||||
Sequence: SCSCRVCGGKHEPNMQLLCDECNVAYHIYCLNPPLDKVPEEEYWYCPSCKTD | ||||||
Region | 414-644 | Methyl-CpG binding and interaction with HDAC1 | ||||
Sequence: KMPSASTESRRDWGRGMACVGRTRECTIVPSNHYGPIPGIPVGSTWRFRVQVSEAGVHRPHVGGIHGRSNDGAYSLVLAGGFADEVDRGDEFTYTGSGGKNLAGNKRIGAPSADQTLTNMNRALALNCDAPLDDKIGAESRNWRAGKPVRVIRSFKGRKISKYAPEEGNRYDGIYKVVKYWPEISSSHGFLVWRYLLRRDDVEPAPWTSEGIERSRRLCLRLQYPAGYPSD | ||||||
Domain | 448-612 | YDG | ||||
Sequence: GPIPGIPVGSTWRFRVQVSEAGVHRPHVGGIHGRSNDGAYSLVLAGGFADEVDRGDEFTYTGSGGKNLAGNKRIGAPSADQTLTNMNRALALNCDAPLDDKIGAESRNWRAGKPVRVIRSFKGRKISKYAPEEGNRYDGIYKVVKYWPEISSSHGFLVWRYLLRR | ||||||
Region | 640-674 | Disordered | ||||
Sequence: GYPSDKEGKKPKGQSKKQPSGTTKRPISDDDCPSA | ||||||
Compositional bias | 654-668 | Polar residues | ||||
Sequence: SKKQPSGTTKRPISD | ||||||
Zinc finger | 733-772 | RING-type | ||||
Sequence: CVCCQELVYQPVTTECFHNVCKDCLQRSFKAQVFSCPACR |
Domain
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q96PU4-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length802
- Mass (Da)89,985
- Last updated2001-12-01 v1
- Checksum190E26D5A347A7FA
Q96PU4-2
- Name2
- Synonymsa
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0A0MSQ3 | A0A0A0MSQ3_HUMAN | UHRF2 | 112 | ||
B1AL33 | B1AL33_HUMAN | UHRF2 | 136 |
Features
Showing features for compositional bias, sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 153-175 | Polar residues | ||||
Sequence: RASDGQSRGKTPLKNGSSCKRTN | ||||||
Sequence conflict | 287 | in Ref. 4; AAH28397 | ||||
Sequence: L → M | ||||||
Sequence conflict | 329 | in Ref. 4; AAH28397 | ||||
Sequence: P → T | ||||||
Sequence conflict | 416 | in Ref. 4; AAH28397 | ||||
Sequence: P → Q | ||||||
Alternative sequence | VSP_013874 | 500-503 | in isoform 2 | |||
Sequence: DRGD → LTEL | ||||||
Alternative sequence | VSP_013875 | 504-802 | in isoform 2 | |||
Sequence: Missing | ||||||
Compositional bias | 654-668 | Polar residues | ||||
Sequence: SKKQPSGTTKRPISD |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB071698 EMBL· GenBank· DDBJ | BAB68317.1 EMBL· GenBank· DDBJ | mRNA | ||
AF274049 EMBL· GenBank· DDBJ | AAM33799.1 EMBL· GenBank· DDBJ | mRNA | ||
AL133480 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL353718 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC028397 EMBL· GenBank· DDBJ | AAH28397.1 EMBL· GenBank· DDBJ | mRNA | ||
AL137728 EMBL· GenBank· DDBJ | CAH56383.1 EMBL· GenBank· DDBJ | mRNA |