TISIDB

Summary
Symbol	UHRF1
Name	ubiquitin-like with PHD and ring finger domains 1
Aliases	Np95; FLJ21925; RNF106; TDRD22; hNP95; hUHRF1; huNp95; RING finger protein 106; inverted CCAAT box-binding p ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Nucleus Note=Localizes to replication foci. Enriched in pericentric heterochromatin. Also localizes to euchromatic regions.
Domain	PF00628 PHD-finger PF02182 SAD/SRA domain PF12148 Tandem tudor domain within UHRF1 PF00240 Ubiquitin family
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 Ontology [ TOP ]
Biological Process	GO:0006342 chromatin silencing GO:0006346 methylation-dependent chromatin silencing GO:0006513 protein monoubiquitination GO:0010216 maintenance of DNA methylation GO:0010390 histone monoubiquitination GO:0010911 regulation of isomerase activity GO:0010912 positive regulation of isomerase activity GO:0016458 gene silencing GO:0016570 histone modification GO:0016574 histone ubiquitination GO:0031935 regulation of chromatin silencing GO:0032781 positive regulation of ATPase activity GO:0040029 regulation of gene expression, epigenetic GO:0042787 protein ubiquitination involved in ubiquitin-dependent protein catabolic process GO:0043462 regulation of ATPase activity GO:0045814 negative regulation of gene expression, epigenetic GO:0051052 regulation of DNA metabolic process GO:0051865 protein autoubiquitination GO:0060968 regulation of gene silencing GO:0090308 regulation of methylation-dependent chromatin silencing GO:1902275 regulation of chromatin organization GO:2000371 regulation of DNA topoisomerase (ATP-hydrolyzing) activity GO:2000373 positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity
Molecular Function	GO:0000987 core promoter proximal region sequence-specific DNA binding GO:0001159 core promoter proximal region DNA binding GO:0003682 chromatin binding GO:0004842 ubiquitin-protein transferase activity GO:0008327 methyl-CpG binding GO:0016874 ligase activity GO:0019787 ubiquitin-like protein transferase activity GO:0031491 nucleosome binding GO:0031493 nucleosomal histone binding GO:0035064 methylated histone binding GO:0042393 histone binding GO:0044729 hemi-methylated DNA-binding GO:0061630 ubiquitin protein ligase activity GO:0061659 ubiquitin-like protein ligase activity
Cellular Component	GO:0000785 chromatin GO:0000790 nuclear chromatin GO:0000791 euchromatin GO:0000792 heterochromatin GO:0005657 replication fork GO:0005720 nuclear heterochromatin GO:0016363 nuclear matrix GO:0034399 nuclear periphery GO:0044454 nuclear chromosome part

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-5334118: DNA methylation R-HSA-212165: Epigenetic regulation of gene expression R-HSA-74160: Gene Expression

Summary
Symbol	UHRF1
Name	ubiquitin-like with PHD and ring finger domains 1
Aliases	Np95; FLJ21925; RNF106; TDRD22; hNP95; hUHRF1; huNp95; RING finger protein 106; inverted CCAAT box-binding p ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between UHRF1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between UHRF1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
23312906	Glioma; Mesothelioma	Promote immunity	In two non epithelial cancers (glioma and mesothelioma), we found that the epigenetic regulation of the NY-ESO1 gene requires the sequential recruitment of the HDAC1-mSin3a-NCOR, Dnmt3b-HDAC1-Egr1 and Dnmt1-PCNA-UHRF1-G9a complexes.The NY-ESO1 gene is a cancer/testis antigen considered to be suitable target for the immunotherapy of human malignancies.

Summary
Symbol	UHRF1
Name	ubiquitin-like with PHD and ring finger domains 1
Aliases	Np95; FLJ21925; RNF106; TDRD22; hNP95; hUHRF1; huNp95; RING finger protein 106; inverted CCAAT box-binding p ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of UHRF1 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	UHRF1
Name	ubiquitin-like with PHD and ring finger domains 1
Aliases	Np95; FLJ21925; RNF106; TDRD22; hNP95; hUHRF1; huNp95; RING finger protein 106; inverted CCAAT box-binding p ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of UHRF1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.797	0.0559
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.671	0.674
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.896	0.487
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	1
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	1
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	1
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.096	0.822
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.352	0.792
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.71	0.594
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0	1
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0	1
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.518	5.46e-05

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of UHRF1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	7.4	1.4	6	0.177
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	7.4	1.7	5.7	0.231
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	UHRF1
Name	ubiquitin-like with PHD and ring finger domains 1
Aliases	Np95; FLJ21925; RNF106; TDRD22; hNP95; hUHRF1; huNp95; RING finger protein 106; inverted CCAAT box-binding p ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of UHRF1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	UHRF1
Name	ubiquitin-like with PHD and ring finger domains 1
Aliases	Np95; FLJ21925; RNF106; TDRD22; hNP95; hUHRF1; huNp95; RING finger protein 106; inverted CCAAT box-binding p ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of UHRF1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by UHRF1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	UHRF1
Name	ubiquitin-like with PHD and ring finger domains 1
Aliases	Np95; FLJ21925; RNF106; TDRD22; hNP95; hUHRF1; huNp95; RING finger protein 106; inverted CCAAT box-binding p ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of UHRF1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	UHRF1
Name	ubiquitin-like with PHD and ring finger domains 1
Aliases	Np95; FLJ21925; RNF106; TDRD22; hNP95; hUHRF1; huNp95; RING finger protein 106; inverted CCAAT box-binding p ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of UHRF1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	UHRF1
Name	ubiquitin-like with PHD and ring finger domains 1
Aliases	Np95; FLJ21925; RNF106; TDRD22; hNP95; hUHRF1; huNp95; RING finger protein 106; inverted CCAAT box-binding p ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between UHRF1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	UHRF1
Name	ubiquitin-like with PHD and ring finger domains 1
Aliases	Np95; FLJ21925; RNF106; TDRD22; hNP95; hUHRF1; huNp95; RING finger protein 106; inverted CCAAT box-binding p ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting UHRF1 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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