UniProt Accession

 UHRF1_HUMAN; Q96T88; A0JBR2; A8K024; B2RBA9; Q2HIX7; Q8J022; Q9H6S6; Q9P115; Q9P1U7 

Genbank Protein ID

 AF129507; AB177623; AB177624; AB075601; AF274048; EF560733; AK025578; AK289389; AK314579; AY787925; AC027319; AC053467; CH471139; BC113875 

Genbank Nucleotide ID

 AAF28469.1; BAF36719.1; BAF36720.1; BAC20576.1; AAK55744.1; ABQ59043.1; BAB15177.1; BAF82078.1; BAG37156.1; AAV40831.1; AAF64067.1; EAW69187.1; AAI13876.2 

Protein Name

 E3 ubiquitin-protein ligase UHRF1 

Protein Synonyms/Alias

 Inverted CCAAT box-binding protein of 90 kDa; Nuclear protein 95; Nuclear zinc finger protein Np95; HuNp95; hNp95; RING finger protein 106; Transcription factor ICBP90; Ubiquitin-like PHD and RING finger domain-containing protein 1; hUHRF1; Ubiquitin-like-containing PHD and RING finger domains protein 1 

Gene Name

 UHRF1 

Gene Synonyms/Alias

 ICBP90; NP95; RNF106 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
24	DSLSRLTKVEELRRK	ubiquitination	[1, 2]
31	KVEELRRKIQELFHV	ubiquitination	[1, 2]
50	QRLFYRGKQMEDGHT	ubiquitination	[1, 2, 3, 4, 5, 6]
84	LVLPHSTKERDSELS	ubiquitination	[1, 4, 7]
136	ETELGLYKVNEYVDA	ubiquitination	[4]
233	NYNPDNPKERGFWYD	ubiquitination	[1, 2, 4]
306	GPSCKHCKDDVNRLC	ubiquitination	[5]
385	RESKKKAKMASATSS	ubiquitination	[8]
399	SSQRDWGKGMACVGR	acetylation	[9]
399	SSQRDWGKGMACVGR	ubiquitination	[1, 2, 5, 10]
408	MACVGRTKECTIVPS	ubiquitination	[1, 2, 5]
500	AEQSCDQKLTNTNRA	ubiquitination	[1, 2, 5, 10]
525	DQEGAEAKDWRSGKP	ubiquitination	[1, 2, 5, 10]
546	VKGGKNSKYAPAEGN	acetylation	[9]
546	VKGGKNSKYAPAEGN	ubiquitination	[1, 2]
560	NRYDGIYKVVKYWPE	ubiquitination	[1, 5]
563	DGIYKVVKYWPEKGK	ubiquitination	[1, 2, 4]
568	VVKYWPEKGKSGFLV	ubiquitination	[1, 2]
570	KYWPEKGKSGFLVWR	ubiquitination	[1, 2, 3, 5]
592	DEPGPWTKEGKDRIK	ubiquitination	[1, 4]
599	KEGKDRIKKLGLTMQ	ubiquitination	[1]
600	EGKDRIKKLGLTMQY	ubiquitination	[1, 2, 3, 4, 6, 11]
622	LANREREKENSKREE	ubiquitination	[5]
626	EREKENSKREEEEQQ	ubiquitination	[4, 10]
670	RRTSKKTKVEPYSLT	ubiquitination	[1, 4]
692	REDKSNAKLWNEVLA	ubiquitination	[1, 2, 3, 4, 6, 11]
702	NEVLASLKDRPASGS	ubiquitination	[10]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [3] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [4] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [5] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [6] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [7] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [8] Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry.
 Denis NJ, Vasilescu J, Lambert JP, Smith JC, Figeys D.
 Proteomics. 2007 Mar;7(6):868-74. [PMID: 17370265]
 [9] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [10] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [11] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 1 78 Ubiquitin-like.
 DOMAIN 419 582 YDG.
 ZN_FING 310 366 PHD-type.
 ZN_FING 724 763 RING-type.
 REGION 133 209 Tudor-like 1.
 REGION 216 283 Tudor-like 2.
 REGION 296 301 Linker.
 REGION 333 337 Histone H3R2me0 binding.
 REGION 353 355 Histone H3R2me0 binding.
 REGION 445 446 Required to promote base flipping (By
 REGION 463 464 Methylcytosine binding.
 REGION 466 469 Required for formation of a 5-
 REGION 478 481 Required for formation of a 5-
 BINDING 316 316 Histone H3K4me0.
 BINDING 327 327 Histone H3R2me0.
 BINDING 330 330 Histone H3R2me0.
 BINDING 469 469 Methylcytosine.
 MOD_RES 76 76 Phosphoserine.
 MOD_RES 91 91 Phosphoserine.
 MOD_RES 287 287 Phosphoserine.
 MOD_RES 298 298 Phosphoserine; by PKA.
 MOD_RES 399 399 N6-acetyllysine.
 MOD_RES 546 546 N6-acetyllysine.
 MOD_RES 639 639 Phosphoserine; by CDK1.
 MOD_RES 651 651 Phosphoserine.
 MOD_RES 707 707 Phosphoserine.
 CROSSLNK 385 385 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 3D-structure; Acetylation; Alternative splicing; Cell cycle; Chromatin regulator; Complete proteome; DNA damage; DNA repair; DNA-binding; Isopeptide bond; Ligase; Metal-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Repressor; Transcription; Transcription regulation; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 793 AA 

Protein Sequence

Gene Ontology

 GO:0000791; C:euchromatin; IDA:UniProtKB.
 GO:0000792; C:heterochromatin; IDA:UniProtKB.
 GO:0000790; C:nuclear chromatin; IDA:UniProtKB.
 GO:0016363; C:nuclear matrix; ISS:BHF-UCL.
 GO:0005657; C:replication fork; IDA:UniProtKB.
 GO:0000987; F:core promoter proximal region sequence-specific DNA binding; IDA:BHF-UCL.
 GO:0044729; F:hemi-methylated DNA-binding; IDA:UniProtKB.
 GO:0042802; F:identical protein binding; ISS:BHF-UCL.
 GO:0008327; F:methyl-CpG binding; IDA:UniProtKB.
 GO:0035064; F:methylated histone residue binding; IDA:UniProtKB.
 GO:0031493; F:nucleosomal histone binding; ISS:BHF-UCL.
 GO:0003700; F:sequence-specific DNA binding transcription factor activity; TAS:ProtInc.
 GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; IDA:UniProtKB.
 GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
 GO:0008283; P:cell proliferation; IEP:BHF-UCL.
 GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
 GO:0010390; P:histone monoubiquitination; ISS:BHF-UCL.
 GO:0010216; P:maintenance of DNA methylation; IMP:UniProtKB.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
 GO:0032270; P:positive regulation of cellular protein metabolic process; IDA:BHF-UCL.
 GO:2000373; P:positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity; IC:BHF-UCL.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IC:BHF-UCL.
 GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
 GO:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. 

Interpro

 IPR021991; DUF3590.
 IPR014722; Rib_L2_dom2.
 IPR003105; SRA_YDG.
 IPR000626; Ubiquitin.
 IPR019955; Ubiquitin_supergroup.
 IPR011011; Znf_FYVE_PHD.
 IPR001965; Znf_PHD.
 IPR019787; Znf_PHD-finger.
 IPR001841; Znf_RING.
 IPR013083; Znf_RING/FYVE/PHD.
 IPR017907; Znf_RING_CS. 

Pfam

 PF12148; DUF3590
 PF00628; PHD
 PF00240; ubiquitin
 PF02182; YDG_SRA 

SMART

 SM00249; PHD
 SM00184; RING
 SM00466; SRA
 SM00213; UBQ 

PROSITE

 PS00299; UBIQUITIN_1
 PS50053; UBIQUITIN_2
 PS51015; YDG
 PS01359; ZF_PHD_1
 PS50016; ZF_PHD_2
 PS00518; ZF_RING_1
 PS50089; ZF_RING_2 

PRINTS