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Protein

E3 ubiquitin-protein ligase SIAH2

Gene

Siah2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. 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 (POU2AF1, PML, NCOR1), a cell surface receptor (DCC), an antiapoptotic protein (BAG1), and a protein involved in synaptic vesicle function in neurons (SYP). 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 similarity5 Publications

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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi139 – 1391Zinc 1By similarity
Metal bindingi146 – 1461Zinc 1By similarity
Metal bindingi158 – 1581Zinc 1By similarity
Metal bindingi162 – 1621Zinc 1By similarity
Metal bindingi169 – 1691Zinc 2By similarity
Metal bindingi176 – 1761Zinc 2By similarity
Metal bindingi188 – 1881Zinc 2By similarity
Metal bindingi193 – 1931Zinc 2By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri81 – 11636RING-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri134 – 19461SIAH-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Apoptosis, Cell cycle, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-373752. Netrin-1 signaling.
R-MMU-983168. Antigen processing: Ubiquitination & Proteasome degradation.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase SIAH2 (EC:6.3.2.-)
Alternative name(s):
Seven in absentia homolog 2
Short name:
Siah-2
Short name:
mSiah2
Gene namesi
Name:Siah2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:108062. Siah2.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity

  • Note: Predominantly cytoplasmic. Partially nuclear.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 325325E3 ubiquitin-protein ligase SIAH2PRO_0000056169Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei6 – 61PhosphoserineBy similarity
Modified residuei16 – 161Phosphoserine; by DYRK2By similarity
Modified residuei24 – 241Phosphothreonine; by MAPK141 Publication
Modified residuei29 – 291Phosphoserine; by DYRK2 and MAPK141 Publication
Modified residuei69 – 691Phosphoserine; by DYRK2By similarity
Modified residuei120 – 1201Phosphothreonine; by DYRK2By similarity

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.
PhosphoSiteiQ06986.

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

BgeeiQ06986.
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

WithEntry#Exp.IntActNotes
Akap1O087156EBI-957413,EBI-7838029
ARP102756EBI-957413,EBI-608057From a different organism.

Protein-protein interaction databases

BioGridi203233. 8 interactions.
IntActiQ06986. 5 interactions.
STRINGi10090.ENSMUSP00000067496.

Structurei

3D structure databases

ProteinModelPortaliQ06986.
SMRiQ06986. Positions 70-323.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni131 – 323193SBDAdd
BLAST

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).By similarity

Sequence similaritiesi

Belongs to the SINA (Seven in absentia) family.Curated
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation
Contains 1 SIAH-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri81 – 11636RING-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri134 – 19461SIAH-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3002. Eukaryota.
ENOG410XVP0. LUCA.
HOGENOMiHOG000231487.
HOVERGENiHBG055701.
InParanoidiQ06986.
KOiK08742.
OMAiKQCRQKL.
OrthoDBiEOG7JT6XC.
TreeFamiTF312976.

Family and domain databases

Gene3Di2.60.210.10. 1 hit.
3.30.40.10. 1 hit.
3.90.890.10. 1 hit.
InterProiIPR018121. 7-in-absentia-prot_TRAF-dom.
IPR013323. SIAH-type.
IPR004162. SINA-like.
IPR008974. TRAF-like.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR013010. Znf_SIAH.
[Graphical view]
PANTHERiPTHR10315. PTHR10315. 1 hit.
PfamiPF03145. Sina. 1 hit.
[Graphical view]
SUPFAMiSSF49599. SSF49599. 1 hit.
PROSITEiPS50089. ZF_RING_2. 1 hit.
PS51081. ZF_SIAH. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti203 – 2042DI → ET in CAA79632 (PubMed:8404535).Curated

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ06986.
SMRiQ06986. Positions 70-323.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi203233. 8 interactions.
IntActiQ06986. 5 interactions.
STRINGi10090.ENSMUSP00000067496.

PTM databases

iPTMnetiQ06986.
PhosphoSiteiQ06986.

Proteomic databases

PaxDbiQ06986.
PeptideAtlasiQ06986.
PRIDEiQ06986.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi6478.
MGIiMGI:108062. Siah2.

Phylogenomic databases

eggNOGiKOG3002. Eukaryota.
ENOG410XVP0. LUCA.
HOGENOMiHOG000231487.
HOVERGENiHBG055701.
InParanoidiQ06986.
KOiK08742.
OMAiKQCRQKL.
OrthoDBiEOG7JT6XC.
TreeFamiTF312976.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-MMU-373752. Netrin-1 signaling.
R-MMU-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

PROiQ06986.
SOURCEiSearch...

Gene expression databases

BgeeiQ06986.
CleanExiMM_SIAH2.
ExpressionAtlasiQ06986. baseline and differential.
GenevisibleiQ06986. MM.

Family and domain databases

Gene3Di2.60.210.10. 1 hit.
3.30.40.10. 1 hit.
3.90.890.10. 1 hit.
InterProiIPR018121. 7-in-absentia-prot_TRAF-dom.
IPR013323. SIAH-type.
IPR004162. SINA-like.
IPR008974. TRAF-like.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR013010. Znf_SIAH.
[Graphical view]
PANTHERiPTHR10315. PTHR10315. 1 hit.
PfamiPF03145. Sina. 1 hit.
[Graphical view]
SUPFAMiSSF49599. SSF49599. 1 hit.
PROSITEiPS50089. ZF_RING_2. 1 hit.
PS51081. ZF_SIAH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Isolation and characterisation of murine homologues of the Drosophila seven in absentia gene (sina)."
    Della N.G., Senior P.V., Bowtell D.D.L.
    Development 117:1333-1343(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    Strain: SWR/J.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Brain.
  3. "Expression of Siah-2, a vertebrate homologue of Drosophila sina, in germ cells of the mouse ovary and testis."
    Della N.G., Bowtell D.D.L., Beck F.
    Cell Tissue Res. 279:411-419(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  4. "Proteasomal regulation of nuclear receptor corepressor-mediated repression."
    Zhang J., Guenther M.G., Carthew R.W., Lazar M.A.
    Genes Dev. 12:1775-1780(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN DEGRADATION OF NCOR1.
  5. "Pw1/Peg3 is a potential cell death mediator and cooperates with Siah1a in p53-mediated apoptosis."
    Relaix F., Wei X., Li W., Pan J., Lin Y., Bowtell D.D., Sassoon D.A., Wu X.
    Proc. Natl. Acad. Sci. U.S.A. 97:2105-2110(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PEG3.
  6. "Alteration of the stability of Bag-1 protein in the control of olfactory neuronal apoptosis."
    Sourisseau T., Desbois C., Debure L., Bowtell D.D.L., Cato A.C.B., Schneikert J., Moyse E., Michel D.
    J. Cell Sci. 114:1409-1416(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN DEGRADATION OF BAG1.
  7. Cited for: INDUCTION.
  8. Cited for: FUNCTION.
  9. "The coiled-coil domain is the structural determinant for mammalian homologues of Drosophila Sina-mediated degradation of promyelocytic leukemia protein and other tripartite motif proteins by the proteasome."
    Fanelli M., Fantozzi A., De Luca P., Caprodossi S., Matsuzawa S., Lazar M.A., Pelicci P.G., Minucci S.
    J. Biol. Chem. 279:5374-5379(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN DEGRADATION OF PML.
  10. Cited for: PHOSPHORYLATION AT THR-24 AND SER-29, FUNCTION.

Entry informationi

Entry nameiSIAH2_MOUSE
AccessioniPrimary (citable) accession number: Q06986
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: April 26, 2004
Last modified: July 6, 2016
This is version 140 of the entry and version 2 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.