Conserved Protein Domain Family
RING-H2_RNF12

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cd16674: RING-H2_RNF12 
RING finger, H2 subclass, found in RING finger protein 12 (RNF12) and similar proteins
RNF12, also known as LIM domain-interacting RING finger protein or RING finger LIM domain-binding protein (R-LIM), is an E3 ubiquitin-protein ligase encoded by gene RLIM that is crucial for normal embryonic development in some species and for normal X inactivation in mice. It thus functions as a major sex-specific epigenetic regulator of female mouse nurturing tissues. RNF12 is widely expressed during embryogenesis, and mainly localizes to the cell nucleus, where it regulates the levels of many proteins, including CLIM, LMO, HDAC2, TRF1, SMAD7, and REX1, by proteasomal degradation. Its functional activity is regulated by phosphorylation-dependent nucleocytoplasmic shuttling. It is negatively regulated by pluripotency factors in embryonic stem cells. p53 represses its transcription through Sp1. RNF12 is the primary factor responsible for X chromosome inactivation (XCI) in female placental mammals. It is an indispensable factor in up-regulation of Xist transcription, thereby leading to initiation of random XCI. It also targets REX1, an inhibitor of XCI, for proteasomal degradation. Moreover, RNF12 acts as a co-regulator of a range of transcription factors, particularly those containing a LIM homeodomain, and modulates the formation of transcriptional multiprotein complexes. It is a negative regulator of Smad7, which in turn negatively regulates the type I receptors in transforming growth factor beta (TGF-beta) superfamily signaling. In addition, paternal RNF12 is a critical survival factor for milk-producing alveolar cells. RNF12 contains an nuclear localization signal (NLS) and a C3H2C3-type RING-H2 finger.
Statistics
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PSSM-Id: 319588
View PSSM: cd16674
Aligned: 7 rows
Threshold Bit Score: 101.292
Threshold Setting Gi: 143811451
Created: 6-May-2013
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 RNF38 (4V3K) binds two Zn2+ ions through its RING-H2 finger.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
Feature 1          #  #              # #  #  #          #  #  
gi 143811451 568 KTCSVCITEYTEGNKLRKLPCSHEYHVHCIDRWLSENSTCPICRR 612
gi 45382265  537 KTCSVCITEYTEGNKLRKLPCSHEYHVHCIARWLSENSTCPICRR 581
gi 82208071  701 KTCSVCITEYTEGNKLRKLPCSHEYHIHCIDRWLSENSTCPICRR 745
gi 82198038  566 KTCSVCITEYTEGNKLRKLPCSHEYHIHCIDRWLSENSTCPICRR 610
gi 556974183 563 KTCSVCITEYTEGNKLRKLPCSHEYHVHCIDRWLSENSTCPICRR 607
gi 528499462 582 KTCSVCITEYAEGNKLRKLPCSHEYHVHCIDRWLSENSTCPICRR 626
gi 632935964 616 KTCSVCISEYTAGNKLRKLPCSHEYHVHCIDRWLSENSTCPICRQ 660

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