InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Siah1a

Summary

InnateDB Protein

IDBP-178089.6

Last Modified

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

Gene Symbol

Siah1a

Protein Name

seven in absentia 1A

Synonyms

AA982064; AI853500; Sinh1a;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000044123

InnateDB Gene

IDBG-178087 (Siah1a)

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, spermatogenesis and TNF-alpha signaling. Has some overlapping function with SIAH2. Required for completion of meiosis I in males. 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:10681424, ECO:0000269PubMed:11884614, ECO:0000269PubMed:16615911}.

Subcellular Localization

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

Disease Associations

Tissue Specificity

Widely expressed at low level in embryos and adults. Expressed at higher level in testis. Due to the high similarity between SIAH1A and SIAH1B, it is difficult to distinguish its own tissue specificity. {ECO:0000269PubMed:8404535}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 12 experimentally validated interaction(s) in this database.
They are also associated with 80 interaction(s) predicted by orthology.

Experimentally validated
Total	12 [view]
Protein-Protein	12 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	80 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004842	ubiquitin-protein transferase activity
GO:0005515	protein binding
GO:0008270	zinc ion binding
GO:0016874	ligase activity
GO:0042803	protein homodimerization activity

Biological Process

GO:0006511	ubiquitin-dependent protein catabolic process
GO:0007141	male meiosis I
GO:0007275	multicellular organismal development
GO:0007283	spermatogenesis
GO:0009791	post-embryonic development
GO:0030154	cell differentiation
GO:0040014	regulation of multicellular organism growth
GO:0042787	protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0051402	neuron apoptotic process