Conserved Protein Domain Family
RING-H2_UBR2

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cd16686: RING-H2_UBR2 
RING finger, H2 subclass, found in ubiquitin-protein ligase E3-alpha-2 (UBR2) and similar proteins
UBR2, also known as N-recognin-2 or E3alpha-II, is an E3 ubiquitin-protein ligase that play an important role in maintaining genome integrity and in homologous recombination repair. It regulates the level of the transcription factor Rpn4 (also known as Son1 and Ufd5) through ubiquitylation. The ubiquitin-conjugating enzyme Rad6, another binding partner of URB2, and an additional factor Mub1, are required for the ubiquitin-dependent degradation of Rpn4. UBR2 associates with Mub1 to form a Mub1/Ubr2 ubiquitin ligase complex that regulates the conserved Dsn1 kinetochore protein levels, which is a part of a quality control system that monitors kinetochore integrity, thus ensuring genomic stability. As the recognition component of a major cellular proteolytic system, UBR2 is associated with chromatin and controls chromatin dynamics and gene expression in both spermatocytes and somatic cells. Moreover, UBR2 mediates transcriptional silencing during spermatogenesis via histone ubiquitination. It functions as a scaffold E3 promoting HR6B/UbcH2-dependent ubiquitylation of H2A and H2B, but not H3 and H4. It also binds to Tex19.1, also known as Tex19, a germ cell-specific protein, and metabolically stabilizes it during spermatogenesis. Furthermore, UBR2 is involved in skeletal muscle (SKM) atrophy. Its expression can be modulated by the mouse ether-a-gogo-related gene 1a (MERG1a) potassium channel. In addition, UBR2 up-regulation in cachectic muscle is mediated by the p38beta-CCAAT/enhancer binding protein (C/EBP)-beta signaling pathway responsible for the bulk of tumor-induced muscle proteolysis. UBR2 contains an N-terminal ubiquitin-recognin (UBR) box involved in binding type-1 (basic) N-end rule substrate, an N-domain (also known as ClpS domain) required for type-2 (bulky hydrophobic) N-end rule substrate recognition, a C3H2C3-type RING-H2 finger, and a C-terminal UBR-specific autoinhibitory (UAIN) domain.
Statistics
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PSSM-Id: 319600
View PSSM: cd16686
Aligned: 4 rows
Threshold Bit Score: 263.45
Threshold Setting Gi: 1040661799
Created: 19-Mar-2015
Updated: 18-Aug-2016
Structure
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Aligned Rows:
 
Zn binding siteRING-H2 finger
Feature 1:Zn binding site [ion binding site]
Evidence:
  • Comment:Based on the structural evidence that Homo sapiens Pirh2 (2JRJ) binds two Zn2+ through its RING-H2 finger.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1           #  #                                                        # #  #  #          
gi 73622073   1107 TCILCQEEQevkvesrAMVLAAFVQRSTVlSKNRskfiqDPEKYDPLFMHPDLscGTHTSSCGHIMHAHCWQRYFDsVQA 1186
gi 148225284  1109 TCILCQEEQaftvdnkAMVLAAFIQRSTVfSKNRsrvitDPEKHDPLCMHPDLacGTHTGSCGHIMHAHCWQRYFDaVQA 1188
gi 632950320  1108 TCILCQEEQeikmnnkAMVLAAFVQRSTVmSKNRmrtiqDPENYDPLFMHPDLacGTHTGSCGHIMHAHCWQSYFDaVQA 1187
gi 1040661799 1127 TCILCQEEQeirsdgkAMVLAAFVQRSTVmSKNRkrpphNPDKYDPLFMHPDLsfGTHTGSCGHIMHSHCWQRYFEaVQA 1206
                           90       100       110
                   ....*....|....*....|....*....|....*.
Feature 1                                 #  #         
gi 73622073   1187 KEQRRQQRLRLHTSYDVENGEFLCPLCECLSNTVIP 1222
gi 148225284  1189 KEQRRQQRLRVHTSYDVENGEFLCPLCECLSNTVIP 1224
gi 632950320  1188 KEQRRQQRLRVHTSYDVENGEFLCPLCECLSNTVIP 1223
gi 1040661799 1207 KEQRRQQRLRVHTSYDVENGEFLCPLCECLSNTVIP 1242

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