CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-000668
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 E3 ubiquitin-protein ligase SIAH2 
Protein Synonyms/Alias
 Seven in absentia homolog 2; Siah-2; hSiah2 
Gene Name
 SIAH2 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
13STGPSANKPCSKQPPubiquitination[1, 2]
107VCNQCRQKLSCCPTCubiquitination[2]
256VLLIGTRKQAENFAYubiquitination[1, 2, 3]
Reference
 [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]
 [2] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [3] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931] 
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 (POU2AF1, PML, NCOR1), a cell surface receptor (DCC), an antiapoptotic protein (BAG1), and a protein involved in synaptic vesicle function in neurons (SYP). Mediates ubiquitination and proteasomal degradation of DYRK2 in response to hypoxia. It is thereby involved in apoptosis, tumor suppression, cell cycle, transcription and signaling processes. Has some overlapping function with SIAH1. Triggers the ubiquitin-mediated degradation of TRAF2, whereas SIAH1 can not. Promotes monoubiquitination of SNCA. 
Sequence Annotation
 ZN_FING 80 115 RING-type.
 ZN_FING 133 193 SIAH-type.
 REGION 130 322 SBD.
 METAL 138 138 Zinc 1 (By similarity).
 METAL 145 145 Zinc 1 (By similarity).
 METAL 157 157 Zinc 1 (By similarity).
 METAL 161 161 Zinc 1 (By similarity).
 METAL 168 168 Zinc 2 (By similarity).
 METAL 175 175 Zinc 2 (By similarity).
 METAL 187 187 Zinc 2 (By similarity).
 METAL 192 192 Zinc 2 (By similarity).
 MOD_RES 16 16 Phosphoserine; by DYRK2.
 MOD_RES 26 26 Phosphothreonine; by DYRK2.
 MOD_RES 28 28 Phosphoserine; by DYRK2 and MAPK14.
 MOD_RES 68 68 Phosphoserine; by DYRK2.
 MOD_RES 119 119 Phosphothreonine; by DYRK2.  
Keyword
 Apoptosis; Cell cycle; Complete proteome; Cytoplasm; Ligase; Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation pathway; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 324 AA 
Protein Sequence
MSRPSSTGPS ANKPCSKQPP PQPQHTPSPA APPAAATISA AGPGSSAVPA AAAVISGPGG 60
GGGAGPVSPQ HHELTSLFEC PVCFDYVLPP ILQCQAGHLV CNQCRQKLSC CPTCRGALTP 120
SIRNLAMEKV ASAVLFPCKY ATTGCSLTLH HTEKPEHEDI CEYRPYSCPC PGASCKWQGS 180
LEAVMSHLMH AHKSITTLQG EDIVFLATDI NLPGAVDWVM MQSCFGHHFM LVLEKQEKYE 240
GHQQFFAIVL LIGTRKQAEN FAYRLELNGN RRRLTWEATP RSIHDGVAAA IMNSDCLVFD 300
TAIAHLFADN GNLGINVTIS TCCP 324 
Gene Ontology
 GO:0005829; C:cytosol; IDA:UniProtKB.
 GO:0005769; C:early endosome; IEA:Compara.
 GO:0043005; C:neuron projection; IEA:Compara.
 GO:0043025; C:neuronal cell body; IEA:Compara.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0003714; F:transcription corepressor activity; TAS:ProtInc.
 GO:0004842; F:ubiquitin-protein ligase activity; IEA:InterPro.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0007411; P:axon guidance; TAS:Reactome.
 GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
 GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
 GO:0090090; P:negative regulation of canonical Wnt receptor signaling pathway; IGI:MGI.
 GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:UniProtKB.
 GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IMP:UniProtKB.
 GO:0031396; P:regulation of protein ubiquitination; IEA:Compara.
 GO:0007264; P:small GTPase mediated signal transduction; TAS:ProtInc.
 GO:0006511; P:ubiquitin-dependent protein catabolic process; TAS:ProtInc. 
Interpro
 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. 
Pfam
 PF03145; Sina 
SMART
 SM00184; RING 
PROSITE
 PS00518; ZF_RING_1
 PS50089; ZF_RING_2
 PS51081; ZF_SIAH 
PRINTS