Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

E3 ubiquitin-protein ligase SIAH2

Gene

Siah2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:11257006, PubMed:14645235, PubMed:14645526, PubMed:17003045, PubMed:9637679, PubMed:26070566). 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 (PubMed:11257006, PubMed:14645235, PubMed:14645526, PubMed:17003045, PubMed:9637679, PubMed:26070566). Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes. Mediates ubiquitination and proteasomal degradation of DYRK2 in response to hypoxia. Promotes monoubiquitination of SNCA (By similarity). Triggers the ubiquitin-mediated degradation of many substrates, including proteins involved in transcription regulation (GPS2, POU2AF1, PML, NCOR1), a cell surface receptor (DCC), an antiapoptotic protein (BAG1), and a protein involved in synaptic vesicle function in neurons (SYP) (PubMed:11257006, PubMed:14645235, PubMed:14645526, PubMed:17003045, PubMed:9637679, PubMed:26070566). 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 does not.By similarity6 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.1 Publication

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi139Zinc 1By similarity1
Metal bindingi146Zinc 1By similarity1
Metal bindingi158Zinc 1By similarity1
Metal bindingi162Zinc 1By similarity1
Metal bindingi169Zinc 2By similarity1
Metal bindingi176Zinc 2By similarity1
Metal bindingi188Zinc 2By similarity1
Metal bindingi193Zinc 2By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri81 – 116RING-typePROSITE-ProRule annotationAdd BLAST36
Zinc fingeri134 – 194SIAH-typePROSITE-ProRule annotationAdd BLAST61

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processApoptosis, Cell cycle, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-373752 Netrin-1 signaling
R-MMU-5689880 Ub-specific processing proteases
R-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase SIAH2 (EC:2.3.2.271 Publication)
Alternative name(s):
RING-type E3 ubiquitin transferase SIAH2Curated
Seven in absentia homolog 2
Short name:
Siah-2
Short name:
mSiah2
Gene namesi
Name:Siah2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:108062 Siah2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000561691 – 325E3 ubiquitin-protein ligase SIAH2Add BLAST325

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei6PhosphoserineBy similarity1
Modified residuei16Phosphoserine; by DYRK2By similarity1
Modified residuei24Phosphothreonine; by MAPK141 Publication1
Modified residuei29Phosphoserine; by DYRK2 and MAPK141 Publication1
Modified residuei69Phosphoserine; by DYRK2By similarity1
Modified residuei120Phosphothreonine; by DYRK2By similarity1

Post-translational modificationi

Phosphorylated at Ser-29 by DYRK2; this increases the ubiquitin ligase activity and promotes degradation of EGLN3 (By similarity). Phosphorylated at Thr-24 and Ser-29 by MAPK14, which mediates the degradation by the proteasome of EGLN3.By similarity1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ06986
PeptideAtlasiQ06986
PRIDEiQ06986

PTM databases

iPTMnetiQ06986
PhosphoSitePlusiQ06986

Expressioni

Tissue specificityi

Widely expressed at low level in embryos and adults. Expressed in a specific population of germ cells within both the mouse ovary and testis. Absent in primordial oocytes but expressed in all growing oocytes, coincident with their recruitment from the pool of quiescent cells. Its level of expression increases as the oocytes mature. Expressed in Graafian follicles and in fertilized zygotes up until the two cell stage, a time of extensive maternal transcript degradation and zygotic gene activation. Expressed in the testis from postmeiotic spermatids.2 Publications

Inductioni

May be induced by p53/TP53, suggesting that it may be required to modulate p53/TP53 response. The relevance of such activity in vivo is however unclear and may not exist.1 Publication

Gene expression databases

BgeeiENSMUSG00000036432
CleanExiMM_SIAH2
ExpressionAtlasiQ06986 baseline and differential
GenevisibleiQ06986 MM

Interactioni

Subunit structurei

Homodimer. Interacts with UBE2E2. Interacts with VAV1, without mediating its ubiquitin-mediated degradation. Interacts with CACYBP/SIP. Probable component of some large E3 complex possibly composed of UBE2D1, SIAH2, CACYBP/SIP, SKP1, APC and TBL1X. Interacts with UBE2I. Interacts with PEG10, which may inhibit its activity. Interacts with EGLN2 and SNCAIP. Interacts with DYRK2 (By similarity). Interacts with PEG3.By similarity1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi203233, 8 interactors
IntActiQ06986, 4 interactors
MINTiQ06986
STRINGi10090.ENSMUSP00000067496

Structurei

3D structure databases

ProteinModelPortaliQ06986
SMRiQ06986
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni131 – 323SBDBy similarityAdd BLAST193

Domaini

The RING-type zinc finger domain is essential for ubiquitin ligase activity.
The SBD domain (substrate-binding domain) mediates the homodimerization and the interaction with substrate proteins. It is related to the TRAF family.By similarity

Sequence similaritiesi

Belongs to the SINA (Seven in absentia) family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri81 – 116RING-typePROSITE-ProRule annotationAdd BLAST36
Zinc fingeri134 – 194SIAH-typePROSITE-ProRule annotationAdd BLAST61

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3002 Eukaryota
ENOG410XVP0 LUCA
GeneTreeiENSGT00390000005434
HOGENOMiHOG000231487
HOVERGENiHBG055701
InParanoidiQ06986
KOiK08742
OMAiIDPPQNE
OrthoDBiEOG091G0BPY
TreeFamiTF312976

Family and domain databases

Gene3Di2.60.210.10, 1 hit
3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR018121 7-in-absentia-prot_TRAF-dom
IPR004162 SINA-like
IPR008974 TRAF-like
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR013010 Znf_SIAH
PANTHERiPTHR10315 PTHR10315, 1 hit
PfamiView protein in Pfam
PF03145 Sina, 1 hit
SUPFAMiSSF49599 SSF49599, 1 hit
PROSITEiView protein in PROSITE
PS50089 ZF_RING_2, 1 hit
PS51081 ZF_SIAH, 1 hit

Sequencei

Sequence statusi: Complete.

Q06986-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSRPSSTGPS ANKPCSKQPP PPQTPHAPSP AAPPAAATIS AAGPGSSAVP
60 70 80 90 100
AAAAVISGPG AGGGADPVSP QHHELTSLFE CPVCFDYVLP PILQCQAGHL
110 120 130 140 150
VCNQCRQKLS CCPTCRGALT PSIRNLAMEK VASAVLFPCK YATTGCSLTL
160 170 180 190 200
HHTEKPEHED ICEYRPYSCP CPGASCKWQG SLEAVMSHLM HAHKSITTLQ
210 220 230 240 250
GEDIVFLATD INLPGAVDWV MMQSCFGHHF MLVLEKQEKY EGHQQFFAIV
260 270 280 290 300
LLIGTRKQAE NFAYRLELNG NRRRLTWEAT PRSIHDGVAA AIMNSDCLVF
310 320
DTAIAHLFAD NGNLGINVTI STCCQ
Length:325
Mass (Da):34,758
Last modified:April 26, 2004 - v2
Checksum:i1CB73AD3B4C9982F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti203 – 204DI → ET in CAA79632 (PubMed:8404535).Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z19581 mRNA Translation: CAA79632.1
BC058400 mRNA Translation: AAH58400.1
CCDSiCCDS17368.1
PIRiI48765
RefSeqiNP_033200.2, NM_009174.3
UniGeneiMm.2847

Genome annotation databases

EnsembliENSMUST00000070368; ENSMUSP00000067496; ENSMUSG00000036432
GeneIDi20439
KEGGimmu:20439
UCSCiuc008pia.1 mouse

Similar proteinsi

Entry informationi

Entry nameiSIAH2_MOUSE
AccessioniPrimary (citable) accession number: Q06986
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: April 26, 2004
Last modified: May 23, 2018
This is version 152 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health