CPLM-016958

Genbank Nucleotide ID

E3 ubiquitin-protein ligase SIAH1

Protein Synonyms/Alias

Seven in absentia homolog 1; Siah-1; Siah-1a

Homo sapiens (Human)

Position	Peptide	Type	References
46	ALPTGTSKCPPSQRV	ubiquitination	[1]

[1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]

Functional Description

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.

ZN_FING 41 76 RING-type.
ZN_FING 93 153 SIAH-type.
REGION 90 282 SBD.
METAL 98 98 Zinc 1 (By similarity).
METAL 105 105 Zinc 1 (By similarity).
METAL 117 117 Zinc 1 (By similarity).
METAL 121 121 Zinc 1 (By similarity).
METAL 128 128 Zinc 2.
METAL 135 135 Zinc 2.
METAL 147 147 Zinc 2.
METAL 152 152 Zinc 2.
MOD_RES 19 19 Phosphoserine; by ATM and ATR.

3D-structure; Alternative splicing; Apoptosis; Cell cycle; Complete proteome; Cytoplasm; Developmental protein; Differentiation; Ligase; Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Spermatogenesis; Ubl conjugation pathway; Zinc; Zinc-finger.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0030877; C:beta-catenin destruction complex; IDA:UniProtKB.
GO:0005829; C:cytosol; TAS:Reactome.
GO:0005769; C:early endosome; IEA:Compara.
GO:0005634; C:nucleus; ISS:UniProtKB.
GO:0005886; C:plasma membrane; IEA:Compara.
GO:0004842; F:ubiquitin-protein ligase activity; IMP:UniProtKB.
GO:0008270; F:zinc ion binding; IDA:UniProtKB.
GO:0007411; P:axon guidance; TAS:Reactome.
GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
GO:0051402; P:neuron apoptotic process; ISS:UniProtKB.
GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; IMP:UniProtKB.
GO:0043161; P:proteasomal ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
GO:0031648; P:protein destabilization; IEA:Compara.
GO:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW.

IPR004162; 7-in-absentia-prot.
IPR018121; 7-in-absentia-prot_TRAF-dom.
IPR013323; SIAH-type.
IPR008974; TRAF-like.
IPR001841; Znf_RING.
IPR013083; Znf_RING/FYVE/PHD.
IPR013010; Znf_SIAH.

PS00518; ZF_RING_1
PS50089; ZF_RING_2
PS51081; ZF_SIAH