Conserved Protein Domain Family

cd20387: Tudor_UHRF_rpt1 
first Tudor domain found in the UHRF (ubiquitin-like PHD and RING finger domain-containing protein) family
The UHRF family includes UHRF1 and UHRF2. UHRF1 is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma (LSCC), gastric cancer (GC), esophageal squamous cell carcinoma (ESCC), colorectal cancer, prostate cancer, and breast cancer. UHRF1 acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumour suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF2 was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Both UHRF1 and UHRF2 contain an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain(PHD) finger, a SET- and RING-associated (SRA) domain, and a C-terminal RING finger. The model corresponds to the first Tudor domain. The tandem Tudor domain directs binding of UHRF to the heterochromatin mark histone H3K9me3.
PSSM-Id: 410458
Aligned: 28 rows
Threshold Bit Score: 66.9479
Created: 30-Mar-2007
Updated: 25-Oct-2021
Aligned Rows:
peptide binding
Conserved site includes 8 residues -Click on image for an interactive view with Cn3D
Feature 1:peptide binding site [polypeptide binding site]
  • Structure:4GY5; Homo sapiens UHRF1 in complex with Histone H3k9me3, contacts at 4A
    View structure with Cn3D
  • Structure:2L3R; Homo sapiens UHRF1 in complex with Histone H3 peptide, contacts at 4A
    View structure with Cn3D
  • Structure:3DB3; Homo sapiens UHRF1 in complex with Histone H3K9me3 peptide, contacts at 4A
    View structure with Cn3D

Sequence Alignment
Format: Row Display: Color Bits: Type Selection:
Feature 1                    #  #   #                                                             
4GY5_A          9 LYKVNEYVDARDtnMGAWFEAQVVRVTRKApsrdepcs------------------------------------------ 46   human
XP_008488317  129 YYKVGDYVDAILetEGAWFESQITHILVDInkek---------------------------------------------- 162  Asian citrus ...
XP_025830555  112 YFKVGDLVDAHDpeYTAWFEGILVAVWENNvglqs--------------------------------------------- 146  emerald ash b...
KRT83940      105 YYRIDDNVDVQDt-LGAWFEGKIKRITRKIga------------------------------------------------ 135  Oryctes borbo...
XP_018572895  111 FYKVEDLIDVRLeeNGAWYEAVISKIFTKGlnnen--------------------------------------------- 145  Asian longhor...
XP_009351373  109 LYSIGDLIDMKDreQGAWFEGEIVRIVKDPsyippepieetvntkedseneppsqsssksppkkkgiaeyfskmaklstr 188  Chinese white...
XP_017774481  104 YYKVGDKIDMRDt-NGCWFEAKVEKIYSNGddtg---------------------------------------------- 136  Nicrophorus v...
XP_025017518   23 YYLIGDHVDCLHpeIGAWFEGIVCGLYKLNs------------------------------------------------- 53   two-spotted s...
RZC38251      112 YYENGDRIDVIDynHGAWFEAKILNISTRKtqn----------------------------------------------- 144  Asbolus verru...
OTF71479      118 YYSVGDHVDAFNpeTGSWYPAQIVRMTKSSp------------------------------------------------- 148  Euroglyphus m...
Feature 1                                   # ## ##                   
4GY5_A         47 ----------stsrpaleEDVIYHVKYDDYPENGVVQMNs-rDVRARARTII 87   human
XP_008488317  163 --------------pydeDDLIFKVVHLKYKDDGSSTMKf-dDIRPLPKHLI 199  Asian citrus psyllid
XP_025830555  147 --------------tlnnEDVLFQIKLENFEHFADLEVEf-kDIRPRSYYTY 183  emerald ash borer
KRT83940      136 ----------------deSDLTFHVTRLSELQRDPLVVNs-sEIRPRSHQVL 170  Oryctes borbonicus
XP_018572895  146 --------------tpeeSNLIFKVKGAEHVITFEGEASf-iDIRPRSYYTY 182  Asian longhorned beetle
XP_009351373  189 kkqiqntqrhleeknspeCGLLYTVHLDAEEDPESKYYCklkEIRPRSRHEI 240  Chinese white pear
XP_017774481  137 --------------akeePELFFKCLQETNFLPVRLEVSf-dNLRPRSYKMY 173  Nicrophorus vespilloides
XP_025017518   54 -----------------sNQTLYEVKFWKSSLPETVKVSi-nGIRPQSYQQI 87   two-spotted spider mite
RZC38251      145 ---------------aqeSDLVFKIRMDRNVETAPIEVKf-dDIRPRACYTY 180  Asbolus verrucosus
OTF71479      149 ------------------TQVNYHVTFRKSSLGSDQIRSl-aQIRPQPYRMI 181  Euroglyphus maynei

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