Conserved Protein Domain Family
RING-HC_SIAH1

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cd16751: RING-HC_SIAH1 
RING finger, HC subclass, found in seven in absentia homolog 1 (SIAH1) and similar proteins
SIAH1, also known as Siah-1a, is an inducible E3 ubiquitin-protein ligase that contributes to proteasome-mediated degradation of multiple targets in numerous cellular processes including apoptosis, tumor suppression, cell cycle, axon guidance, transcription regulation, and tumor necrosis factor signaling. SIAH1 functions as a scaffolding protein and interacts with a variety of different substrates for ubiquitination and subsequent degradation. It regulates the oncoprotein p34SEI-1 polyubiquitination and its subsequent degradation in a p53-dependent manner, which mediates p53 preferential vitamin C cytotoxicity. It targets the nonreceptor tyrosine kinase activated Cdc42-associated kinase 1 (ACK1), a valid target in cancer therapy, for ubiquitinylation and proteasomal degradation. It also interacts with KLF10 and targets for its degradation. The CDK2 phosphorylation-mediates KLF10 dissociation from SIAH1 is linked to cell cycle progression. Moreover, Siah1 is downregulated and associated with apoptosis and invasion in human breast cancer. It targets TAp73, a homolog of the tumor suppressor p53, for degradation. It is suppressed by hypoxia-inducible factor 1-alpha (HIF-1alpha) under hypoxic conditions to regulate TAp73 levels. It also promotes the migration and invasion of human glioma cells by regulating HIF-1alpha signaling under hypoxia. Furthermore, Siah1 forms a protein complex with glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The apoptosis signal-regulating kinase 1 (ASK1) functions as an activator of the GAPDH-Siah1 stress-signaling cascade. It also plays an important role in ethanol-induced apoptosis in neural crest cells (NCCs). SIAH1 contains an N-terminal C3HC4-type RING-HC finger, two zinc-finger subdomains, and a C-terminal tumor necrosis factor (TNF) receptor associated factor (TRAF)-like substrate-binding domain (SBD) responsible for dimer formation.
Statistics
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PSSM-Id: 319665
View PSSM: cd16751
Aligned: 12 rows
Threshold Bit Score: 83.4363
Threshold Setting Gi: 22652328
Created: 2-Aug-2013
Updated: 18-Aug-2016
Structure
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Aligned Rows:
 
Zn binding siteRING-HC finger
Feature 1:Zn binding site [ion binding site]
Evidence:
  • Comment:Based on the structural evidence that Homo sapiens Parkin (5C1Z) binds two Zn2+ ions through its RING-HC finger.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
Feature 1          #  #          #   #  #  #      #  #   
gi 46577493   39 FECPVCFDYvLPPILQCQSGHLVCSNCRPKLtCCPTCRGP 78
gi 46577417   39 FECPVCFDYvLPPILQCQSGHLVCSNCRPKLtCCPTCRGP 78
gi 22652328   10 FECPVCFDYvLPPILQCQSGHLVCSNCRPKLtCCPTCRGP 49
gi 556985327  39 FECPVCFDYvLPPILQCQSGHLVCSNCRPKLtCCPTCRGP 78
gi 632944642  39 FECPVCFDYvLPPILQCQSGHLVCSNCRPKLtCCPTCRGP 78
gi 198436455  39 FECPVCFDYvLPPILQCQSGHLVCTNCRPKLtCCPTCRGA 78
gi 390356002  25 FECPVCFDYvLPPILQCQSGHLVCSNCRPKLnCCPTCRGP 64
gi 260829225  29 FECPVCFDYvLPPILQCQSGHLVCSSCRPKLsCCPTCRGP 68
gi 585707543  35 FECPVCFDYvLPPILQCQAGHLVCSNCRPKLsCCPTCRGP 74
gi 156224173   9 FECPVCFDYvLPPILQCSSGHLVCSNCRPKLtCCPTCRGP 48
gi 363548505 154 FECPVCLEYmLPPYMQCSSGHLVCSNCRPKLqCCPTCRGP 193
gi 919082021  43 FECPVCFDYaLPPIMQCQSGHIVCSSCRPKLsCCPTCRGP 82

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