CDD Conserved Protein Domain Family: RING-HC

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 it for degradation. The CDK2 phosphorylation-mediated 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.

Feature 1 # # # # # # # # Q8IUQ4 34 DLASLFECPVCFDYvLPPILQCQSGHLVCSNCRPKLtCCPTCRGP 78 human Q7ZVG6 34 DLASLFECPVCFDYvLPPILQCQSGHLVCSNCRPKLtCCPTCRGP 78 zebrafish XP_005998413 34 DLASLFECPVCFDYvLPPILQCQSGHLVCSNCRPKLtCCPTCRGP 78 coelacanth XP_007887616 34 DLASLFECPVCFDYvLPPILQCQSGHLVCSNCRPKLtCCPTCRGP 78 elephant shark XP_002127743 34 DLASLFECPVCFDYvLPPILQCQSGHLVCTNCRPKLtCCPTCRGA 78 vase tunicate XP_797311 20 DLASLFECPVCFDYvLPPILQCQSGHLVCSNCRPKLnCCPTCRGP 64 purple urchin XP_002740720 30 DLASLFECPVCFDYvLPPILQCQAGHLVCSNCRPKLsCCPTCRGP 74 Saccoglossus kowalevskii EDO45001 4 DLTSIFECPVCFDYvLPPILQCSSGHLVCSNCRPKLtCCPTCRGP 48 starlet sea anemone Q965X6 149 EILSVFECPVCLEYmLPPYMQCSSGHLVCSNCRPKLqCCPTCRGP 193 Caenorhabditis elegans XP_013422072 38 DLAGLFECPVCFDYaLPPIMQCQSGHIVCSSCRPKLsCCPTCRGP 82 Lingula anatina NP_001085438 34 DLASLFECPVCFDYvLPPILQCQSGHLVCSNCRPKLtCCPTCRGP 78 African clawed frog

Conserved Protein Domain FamilyRING-HC_SIAH1

Conserved Protein Domain Family
RING-HC_SIAH1