2KIZ


Conserved Protein Domain Family
RING-H2_RNF111

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cd16681: RING-H2_RNF111 
Click on image for an interactive view with Cn3D
RING finger, H2 subclass, found in RING finger protein 111 (RNF111) and similar proteins
RNF111, also known as Arkadia, is a nuclear E3 ubiquitin-protein ligase that targets intracellular effectors and modulators of transforming growth factor beta (TGF-beta)/Nodal-related signaling for polyubiquitination and proteasome-dependent degradation. It acts as an amplifier of Nodal signals, and enhances the dorsalizing activity of limiting amounts of Xnr1, a Nodal homolog, and requires Nodal signaling for its function. The loss of RNF111 results in early embryonic lethality, with defects attributed to compromised Nodal signaling. Moreover, RNF111 regulates tumor metastasis by modulation of the TGF-beta pathway. Its ubiquitination can be modulated by the four and a half LIM-only protein 2 (FHL2) that activates TGF-beta signal transduction. Furthermore, RNF111 interacts with the clathrin-adaptor 2 (AP2) complex and regulates endocytosis of certain cell surface receptors, leading to modulation of epidermal growth factor (EGF) and possibly other signaling pathways. In addition, RNF111 has been identified as a small ubiquitin-like modifier (SUMO)-binding protein with clustered SUMO-interacting motifs (SIMs) that together form a SUMO-binding domain (SBD). It thus functions as a SUMO-targeted ubiquitin ligase (STUbL) that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response, as well as triggers degradation of signal-induced polysumoylated proteins, such as the promyelocytic leukemia protein (PML). The N-terminal half of RNF111 harbors three SIMs. Its C-terminal half show high sequence similarity with RING finger protein 165 (RNF165), where it contains two serine rich domains, two nuclear localization signals, a NRG-TIER domain, and a C-terminal C3H2C3-type RING-H2 finger that is required for polyubiqutination and proteasome-dependent degradation of phosphorylated forms of Smad2/3 and three major negative regulators of TGF-beta signaling, Smad7, SnoN and c-Ski.
Statistics
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PSSM-Id: 319595
View PSSM: cd16681
Aligned: 7 rows
Threshold Bit Score: 78.9664
Threshold Setting Gi: 296278272
Created: 19-Mar-2015
Updated: 18-Aug-2016
Structure
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Program:
Drawing:
Aligned Rows:
 
Zn binding siteRING-H2 finger
Conserved site includes 8 residues -Click on image for an interactive view with Cn3D
Feature 1:Zn binding site [ion binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
Feature 1           #  #              # #  #  #          #  #   
2KIZ_A         15 EKCTICLSILEEGEDVRRLPCMHLFHQVCVDQWLiTNKKCPICRVD 60
gi 315075292  931 EKCTICLSILEEGEDVRRLPCMHLFHQVCVDQWLiTNKKCPICRVD 976
gi 308153555  940 EKCTICLSILEEGEDVRRLPCMHLFHQVCVDQWLiTNKKCPICRVD 985
gi 123914777  900 EKCTICLSILEEGEDVRRLPCMHLFHQVCVDQWLiTNKKCPICRVD 945
gi 632938334  898 EKCTICLSILEEGEDVRRLPCMHLFHQVCVDQWLtTNKKCPICRVD 943
gi 556986540  912 EKCTICLSILEEGEDVRRLPCMHLFHQVCVDQWLiTNKKCPICRVD 957
gi 530354708  978 EKCTICLSILEEGEDVRRLPCMHLFHQLCVDQWLlTNKKCPICRVD 1023

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