3L1Z,2KR4,2KRE


Conserved Protein Domain Family
RING-Ubox_UBE4B

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cd16658: RING-Ubox_UBE4B 
Click on image for an interactive view with Cn3D
U-box domain, a modified RING finger, found in ubiquitin conjugation factor E4 B (UBE4B) and similar proteins
UBE4B, also known as UFD2a, is a U-box-type ubiquitin-protein ligase that functions as an E3 ubiquitin ligase and an E4 polyubiquitin chain elongation factor, which catalyzes formation of Lys27- and Lys33-linked polyubiquitin chains rather than the Lys48-linked chain. It is a mammalian homolog of yeast UFD2 ubiquitination factor and participates in the proteasomal degradation of misfolded or damaged proteins through association with chaperones. It is located in common neuroblastoma deletion regions and may be subject to mutations in tumors. UBE4B has contradictory functions upon tumorigenesis as an oncogene or tumor suppressor in different types of cancers. It is essential for Hdm2 (also known as Mdm2)-mediated p53 degradation. It mediates p53 polyubiquitination and degradation, as well as inhibits p53-dependent transactivation and apoptosis, and thus plays an important role in regulating phosphorylated p53 following DNA damage. UBE4B is also associated with other pathways independent of the p53 family, such as polyglutamine aggregation and Wallerian degeneration, both of which are critical in neurodegenerative diseases. Moreover, UBE4B acts as a regulator of epidermal growth factor receptor (EGFR) degradation. It is recruited to endosomes in response to EGFR activation by binding to Hrs, a key component of endosomal sorting complex required for transport (ESCRT) 0, and then regulates endosomal sorting, affecting cellular levels of the EGFR and its downstream signaling. UBE4B contains a ubiquitin elongating factor core and a RING-like U-box domain at the C-terminus.
Statistics
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PSSM-Id: 319572
View PSSM: cd16658
Aligned: 26 rows
Threshold Bit Score: 127.416
Threshold Setting Gi: 313219478
Created: 13-Apr-2015
Updated: 18-Aug-2016
Structure
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Program:
Drawing:
Aligned Rows:
 
polypeptideU-box domain, a
Conserved site includes 8 residues -Click on image for an interactive view with Cn3D
Feature 1:polypeptide substrate binding site [polypeptide binding site]
Evidence:
  • Structure:3L1Z; Homo sapiens E4b ubiquitin ligase in complex with Ubch5c E2 ubiquitin conjugating enzyme, contacts at 4A.
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
Feature 1         #                 #                                             ##  #  ##  #
3L1Z_B         22 DYSDAPDEFRDPLMDTLMTDPVRLP-SGTIMDRSIILRHLLNSpTDPFNRQTLtESMLEPVPELKEQIQAWMREKQ 96
gi 405970866 1034 DYGEIPEEFKDPLMDTLMNDPVILP-SGTVMDRPIITRHLLNSqTDPFNRQPLtEEELKPANEIKLKIEAWKQSKT 1108
gi 919062484 1038 DFGDIPDDFRDPLMDTLMTDPVILP-SGTVMDRPIIQRHLLNSsTDPFNRQHLtEEMLIPATDLKKRIEQWKREKT 1112
gi 761906441  922 VISDVPDEFKDPIMDTLMNDPVQLP-SGVIVDRPVIVRHLLNSsQDPFNRQRLtIDMLQPATELLGRINKWKADRG 996
gi 158276742  374 MGEDVPEEFSCAILSTIMKDPVKLP-SGVVVDRPNIQRHLLSDpTDPFSRQPLtEDQLEPLPELTARITAWRKQRS 448
gi 262106262  971 TLGEIPEEFLDPLVFTLMKDPVLLP-SGYTMDRSCITQHLMNDqSDPFTRVPLtVDQLQPNTDLKTKIEQWVQEQQ 1045
gi 313219478  272 FEEEPPDEFCDPIMGSLMEDPVELPrSGAILCRNTIARQLLVTpIDPFNRQPLsLDEVIPRQDLKEKIKEWKREQR 347
gi 919029353  959 LLGDVPEEFQDAIMGTVMKDPVILP-SGQVVDRSTIARHLLSDqTDPFNRSPLtMEMLKPHDELREKIKLWIQDNK 1033
gi 2497002    902 EYDDVPEEFKDPIMDAIMVDPVKLP-SGHVMDRAVIERHLLSTpNNPFNRAPLsHNELSPDSELKAKIQEWICQKR 976
gi 402591350  165 FGDDVPDDFRDPVMNTLMTDPVILP-SGHKMDRKHIMRHLLSSqTDPFTRQPLsETQLVSDDALKTKIRAWIKEKL 239

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