3VK6,2MQ1


Conserved Protein Domain Family
RING-HC_HAKAI_like

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cd16508: RING-HC_HAKAI_like 
Click on image for an interactive view with Cn3D
RING finger, HC subclass, found in E3 ubiquitin-protein ligase Hakai, zinc finger protein 645 (ZNF645), and similar proteins
Hakai, also known as Casitas B-lineage lymphoma-transforming sequence-like protein 1, RING finger protein 188 (RNF188), or c-Cbl-like protein 1 (CBLL1), is an E3 ubiquitin ligase that disrupts cell-cell contacts in epithelial cells and is upregulated in human colon and gastric adenocarcinomas. It was identified to mediate the posttranslational downregulation of E-cadherin (CDH1), a major component of adherens junctions in epithelial cells and a potent tumor suppressor. It also promotes ubiquitination of several other tyrosine-phosphorylated Src substrates, including cortactin (CTTN) and DOK1. Hakai acts as a homodimer with a novel HYB (Hakai pTyr-binding) domain that forms a phosphotyrosine-binding pocket upon, and consists of a pair of monomers arranged in an anti-parallel configuration. Each monomer contains a C3HC4-type RING-HC finger and a short pTyr-B domain that incorporates a novel, atypical C2H2-type Zn-finger coordination motif. Both domains are important for dimerization. ZNF645 is a novel testis-specific E3 ubiquitin-protein ligase that plays a role in sperm production and quality control. It has a structure similar to that of the c-Cbl-like protein Hakai. In contrast to Hakai, its HYB domain demonstrates different target specificities. It interacts with v-Src-phosphorylated E-cadherin, but not to cortactin.
Statistics
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PSSM-Id: 319422
View PSSM: cd16508
Aligned: 19 rows
Threshold Bit Score: 65.0911
Threshold Setting Gi: 672885534
Created: 31-Jul-2013
Updated: 18-Aug-2016
Structure
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Program:
Drawing:
Aligned Rows:
 
Zn binding siteRING-HC 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          #  #            # #  #  #           #  #
3VK6_A         2 HFCDKCGLPIkVYGRMIPCKHVFCYDCAIlhekkgDKMCPgC 43
gi 15240902   70 HFCVRCDFPIaIYGRLIPCDHAFCLECARs-----DSICYlC 106
gi 74759980   55 HFCDKCDLPIkIYGRIIPCKHAFCYHCANlydkvgYKVCPrC 96
gi 215507051  15 HCCDKCSLPIiIYGRNIPCKHVFCFDCAKk----sDKICYrC 52
gi 313228967  27 HNCDTCRLPIvTYGRMIPCKHVFCFNCSCqsr-ktGGSCArC 67
gi 340370372  77 HICEQCDLPIlIYGRMKHCRHTFCRDCAKk----aGGECPkC 114
gi 353230450 176 HFCDICDLPIvIYGRLLPCKHVLCYTCAMn----lMKKCNrC 213
gi 405970378  61 HCCDKCKLPIlIYGRMIPCKHVFCYDCARk----tDKVCArC 98
gi 442628450 178 HCCDQCDKPIlVYGRMIPCKHVFCLKCARae---pIKSCPrC 216
gi 585686408 104 HCCSKCDLPIlIYGRMIPCKHVVCFDCAKr----tDKNCPrC 141

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