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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

UHRF1 Gene

protein-coding GIFtS: 52
GCID: GC19P004910

ubiquitin-like with PHD and ring finger domains 1

Explore 6 diseases affiliated with
UHRF1 via

MalaCards

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Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Ubiquitin-Like With PHD And Ring Finger Domains 1¹ ²		RING Finger Protein 106² ³
ICBP90¹ ² ³ ⁵		NP95³ ⁵
RNF106¹ ² ³		FLJ21925¹
Np95¹ ²		E3 Ubiquitin-Protein Ligase UHRF1²
Inverted CCAAT Box-Binding Protein Of 90 KDa² ³		HNP95¹
Nuclear Protein 95² ³		HuNp95³
Nuclear Zinc Finger Protein Np95² ³		Ubiquitin-Like, Containing PHD And RING Finger Domains, 1²
Transcription Factor ICBP90² ³		EC 6.3.2.-³
Ubiquitin-Like PHD And RING Finger Domain-Containing Protein 1² ³		HuNp95³
Ubiquitin-Like-Containing PHD And RING Finger Domains Protein 1² ³		HNp95¹
HUHRF1¹		EC 6.3.2⁸

External Ids:	HGNC: 12556¹	Entrez Gene: 29128²	Ensembl: ENSG00000034063⁷	OMIM: 607990⁵	UniProtKB: Q96T88³

Export aliases for UHRF1 gene to outside databases

Previous GC identifers: GC19P005001 GC19P004849 GC19P004860 GC19P004861 GC19P004671

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for UHRF1:

This gene encodes a member of a subfamily of RING-finger type E3 ubiquitin ligases. The protein binds to specific DNA

sequences, and recruits a histone deacetylase to regulate gene expression. Its expression peaks at late G1 phase and

continues during G2 and M phases of the cell cycle. It plays a major role in the G1/S transition by regulating

topoisomerase IIalpha and retinoblastoma gene expression, and functions in the p53-dependent DNA damage checkpoint.

Multiple transcript variants encoding different isoforms have been found for this gene. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: UHRF1_HUMAN, Q96T88

Function: Multidomain protein that acts as a key epigenetic regulator by bridging DNA methylation and chromatin

modification. Specifically recognizes and binds hemimethylated DNA at replication forks via its YDG domain and

recruits DNMT1 methyltransferase to ensure faithful propagation of the DNA methylation patterns through DNA

replication. In addition to its role in maintenance of DNA methylation, also plays a key role in chromatin

modification: through its tudor-like regions and PHD-type zinc fingers, specifically recognizes and binds histone H3

trimethylated at 'Lys-9' (H3K9me3) and unmethylated at 'Arg-2' (H3R2me0), respectively, and recruits chromatin

proteins. Enriched in pericentric heterochromatin where it recruits different chromatin modifiers required for this

chromatin replication. Also localizes to euchromatic regions where it negatively regulates transcription possibly by

impacting DNA methylation and histone modifications. Has E3 ubiquitin-protein ligase activity by mediating the

ubiquitination of target proteins such as histone H3 and PML. It is still unclear how E3 ubiquitin-protein ligase

activity is related to its role in chromatin in vivo. May be involved in DNA repair

Gene Wiki entry for UHRF1

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000019.9 NC_018930.1 NT_011255.14

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the UHRF1 gene promoter:
Egr-3 MZF-1 PPAR-gamma1 AML1a PPAR-gamma2
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 3): UHRF1 promoter sequence

Search SABiosciences Chromatin IP Primers for UHRF1

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat UHRF1

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 19p13.3 Ensembl cytogenetic band: 19p13.3 HGNC cytogenetic band: 19p13.3

UHRF1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
UHRF1 gene location

GeneLoc information about chromosome 19 GeneLoc Exon Structure

GeneLoc location for GC19P004910: view genomic region (about GC identifiers)

Start:	4,903,092 bp from pter	End:	4,962,165 bp from pter
Size:	59,074 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: UHRF1_HUMAN, Q96T88 (See protein sequence)

Recommended Name: E3 ubiquitin-protein ligase UHRF1

Size: 793 amino acids; 89814 Da

Subunit: Interacts with DNMT3A and DNMT3B (By similarity). Interacts with DNMT1; the interaction is direct. Interacts

with USP7; leading to its deubiquitination. Interacts with histone H3. Interacts with HDAC1, but not with HDAC2.

Interacts with UHRF1BP1. Interacts with PML. Interacts with EHMT2. Binds hemimethylated CpG containing

oligonucleotides

Subcellular location: Nucleus. Note=Localizes to replication foci. Enriched in pericentric heterochromatin. Also

localizes to euchromatic regions

Developmental stage: Expressed in fetal thymus, liver and kidney

Sequence caution: Sequence=BAB15177.1; Type=Erroneous initiation;

6/22 PDB 3D structures from and Proteopedia for UHRF1 (see all 22):

2FAZ (3D)

2L3R (3D)

2LGG (3D)

2LGK (3D)

2LGL (3D)

2PB7 (3D)

Secondary accessions: A0JBR2 A8K024 B2RBA9 Q2HIX7 Q8J022 Q9H6S6 Q9P115 Q9P1U7

Alternative splicing: 2 isoforms: Q96T88-1 Q96T88-2 (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for UHRF1: NX_Q96T88

Post-translational modifications:

Phosphorylation at Ser-298 of the linker region decreases the binding to H3K9me3. Phosphorylation at Ser-639 by CDK1

during M phase impairs interaction with USP7, preventing deubiquitination and leading to degradation by the proteasome¹

Ubiquitinated; which leads to proteasomal degradation. Autoubiquitinated; interaction with USP7 leads to

deubiquitination and prevents degradation. Ubiquitination and degradation takes place during M phase, when

phosphorylation at Ser-639 prevents intereaction with USP7 and subsequent deubiquitination. Polyubiquitination may be

stimulated by DNA damage¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_Q96T88

4/8 DME Specific Peptides for UHRF1 (Q96T88) (see all 8)

GVHRPHV

HNVCKDCL

QRLFYRGKQ

WRFRVQVSE

UHRF1 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (2 alternative transcripts):

NP_001041666.1 NP_037414.3

Human Recombinant Protein Products for UHRF1:

	Browse Purified and Recombinant Proteins at EMD Millipore
	Browse R&D Systems for human recombinant proteins
	Browse recombinant and purified proteins available from Enzo Life Sciences
	OriGene Purified Protein: UHRF1 OriGene Protein Over-expression Lysate (see all 3): UHRF1 OriGene Custom Protein Services for UHRF1
	GenScript Custom Purified and Recombinant Proteins Services for UHRF1
	Novus Biologicals UHRF1 Protein Novus Biologicals UHRF1 Lysate
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for UHRF1

Gene Ontology (GO): 5/6 cellular component terms (GO ID links to tree view) (see all 6): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000790	nuclear chromatin	ISS	--
GO:0000791	euchromatin	IDA	--
GO:0000792	heterochromatin	IDA	--
GO:0005634	nucleus	IDA	--
GO:0005657	replication fork	IDA	17673620

UHRF1 for ontologies About GeneDecksing

UHRF1 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of UHRF1
	Browse R&D Systems for Antibodies
	Browse OriGene Antibodies OriGene Custom Antibody Services for UHRF1
	GenScript Custom Superior Antibodies Services for UHRF1
	Novus Biologicals UHRF1 Antibodies
	Abcam antibodies for UHRF1
	Uscn Antibodies for UHRF1
	Search ThermoFisher Antibodies for UHRF1

Assay Products for UHRF1:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for UHRF1
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for UHRF1

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

UHRF1 for domains About GeneDecksing

5/11 InterPro domains/families (see all 11):

IPR017907 Znf_RING_CS

IPR001841 Znf_RING

IPR001965 Znf_PHD

IPR014722 Rib_L2_dom2

IPR003105 SRA_YDG

Graphical View of Domain Structure for InterPro Entry Q96T88

ProtoNet protein and cluster: Q96T88

2 Blocks protein families:

IPB000626 Ubiquitin domain

IPB001841 Zn-finger

UniProtKB/Swiss-Prot: UHRF1_HUMAN, Q96T88

Domain: The tudor-like regions specifically recognize and bind histone H3 unmethylated at 'Arg-2' (H3R2me0), while the

PHD-type zinc finger specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3). The tudor-like

regions simultaneously recognizes H3K9me3 through a conserved aromatic cage in the first tudor-like subdomain and

unmodified H3K4 (H3K4me0) within a groove between the tandem subdomains (PubMed:21489993, PubMed:21777816 and

PubMed:22100450). The linker region plays a role in the formation of a histone H3-binding hole between the reader

modules formed by the tudor-like regions and the PHD-type zinc finger by making extended contacts with the tandem

tudor-like regions (PubMed:22837395)

Domain: The YDG domain (also named SRA domain) specifically recognizes and binds hemimethylated DNA at replication

forks (DNA that is only methylated on the mother strand of replicating DNA) (PubMed:17673620). It contains a binding

pocket that accommodates the 5-methylcytosine that is flipped out of the duplex DNA. 2 specialized loops reach through

the resulting gap in the DNA from both the major and the minor grooves to read the other 3 bases of the CpG duplex.

The major groove loop confers both specificity for the CpG dinucleotide and discrimination against methylation of

deoxycytidine of the complementary strand (PubMed:18772889). The YDG domain also recognizes and binds

5-hydroxymethylcytosine (5hmC) (PubMed:21731699)

Domain: The RING finger is required for ubiquitin ligase activity (By similarity)

Similarity: Contains 1 PHD-type zinc finger

Similarity: Contains 1 RING-type zinc finger

Similarity: Contains 1 ubiquitin-like domain

Similarity: Contains 1 YDG domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, Sirion Biotech, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, Sirion Biotech, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Molecular Function:

UniProtKB/Swiss-Prot Summary: UHRF1_HUMAN, Q96T88