InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SIAH1

Summary

InnateDB Protein

IDBP-752664.3

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

SIAH1

Protein Name

Synonyms

SIAH1A;

Species

Homo sapiens

Ensembl Protein

ENSP00000456421

InnateDB Gene

IDBG-30112 (SIAH1)

Protein Structure

UniProt Annotation

Function

E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin- conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes. Triggers the ubiquitin-mediated degradation of many substrates, including proteins involved in transcription regulation (ELL2, MYB, POU2AF1, PML and RBBP8), a cell surface receptor (DCC), the cell-surface receptor-type tyrosine kinase FLT3, the cytoplasmic signal transduction molecules (KLF10/TIEG1 and NUMB), an antiapoptotic protein (BAG1), a microtubule motor protein (KIF22), a protein involved in synaptic vesicle function in neurons (SYP), a structural protein (CTNNB1) and SNCAIP. Confers constitutive instability to HIPK2 through proteasomal degradation. It is thereby involved in many cellular processes such as apoptosis, tumor suppression, cell cycle, axon guidance, transcription regulation, spermatogenesis and TNF-alpha signaling. Has some overlapping function with SIAH2. Induces apoptosis in cooperation with PEG3. Upon nitric oxid (NO) generation that follows apoptotic stimulation, interacts with S- nitrosylated GAPDH, mediating the translocation of GAPDH to the nucleus. GAPDH acts as a stabilizer of SIAH1, facilitating the degradation of nuclear proteins. {ECO:0000269PubMed:10747903, ECO:0000269PubMed:11146551, ECO:0000269PubMed:11389839, ECO:0000269PubMed:11389840, ECO:0000269PubMed:11483517, ECO:0000269PubMed:11483518, ECO:0000269PubMed:11752454, ECO:0000269PubMed:12072443, ECO:0000269PubMed:14506261, ECO:0000269PubMed:14645235, ECO:0000269PubMed:14654780, ECO:0000269PubMed:15064394, ECO:0000269PubMed:16085652, ECO:0000269PubMed:18536714, ECO:0000269PubMed:19224863, ECO:0000269PubMed:20508617, ECO:0000269PubMed:22483617, ECO:0000269PubMed:9334332, ECO:0000269PubMed:9858595}.

Subcellular Localization

Cytoplasm. Nucleus. Note=Predominantly cytoplasmic. Partially nuclear.

Disease Associations

Tissue Specificity

Widely expressed at a low level. Down- regulated in advanced hepatocellular carcinomas. {ECO:0000269PubMed:12557228, ECO:0000269PubMed:9403064}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 125 experimentally validated interaction(s) in this database.
They are also associated with 4 interaction(s) predicted by orthology.

Experimentally validated
Total	125 [view]
Protein-Protein	124 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	4 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004842	ubiquitin-protein transferase activity
GO:0005515	protein binding
GO:0008022	protein C-terminus binding
GO:0008270	zinc ion binding
GO:0016874	ligase activity

Biological Process

GO:0006508	proteolysis
GO:0006511	ubiquitin-dependent protein catabolic process
GO:0006915	apoptotic process
GO:0007049	cell cycle
GO:0007275	multicellular organismal development
GO:0007283	spermatogenesis
GO:0007399	nervous system development
GO:0007411	axon guidance
GO:0009653	anatomical structure morphogenesis
GO:0030163	protein catabolic process
GO:0042787	protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:0043065	positive regulation of apoptotic process
GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0045087	innate immune response (InnateDB)
GO:0051402	neuron apoptotic process
GO:2001244	positive regulation of intrinsic apoptotic signaling pathway