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P61092

- SIA1A_MOUSE

UniProt

P61092 - SIA1A_MOUSE

Protein

E3 ubiquitin-protein ligase SIAH1A

Gene

Siah1a

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 108 (01 Oct 2014)
      Sequence version 1 (26 Apr 2004)
      Previous versions | rss
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    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. 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.3 Publications

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi98 – 981Zinc 12 Publications
    Metal bindingi105 – 1051Zinc 12 Publications
    Metal bindingi117 – 1171Zinc 12 Publications
    Metal bindingi121 – 1211Zinc 12 Publications
    Metal bindingi128 – 1281Zinc 22 Publications
    Metal bindingi135 – 1351Zinc 22 Publications
    Metal bindingi147 – 1471Zinc 22 Publications
    Metal bindingi152 – 1521Zinc 22 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri41 – 7636RING-typePROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri93 – 15361SIAH-typePROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. ligase activity Source: UniProtKB-KW
    2. protein binding Source: UniProtKB
    3. protein homodimerization activity Source: UniProtKB
    4. ubiquitin-protein transferase activity Source: UniProtKB
    5. zinc ion binding Source: UniProtKB

    GO - Biological processi

    1. cell differentiation Source: UniProtKB-KW
    2. male meiosis I Source: MGI
    3. neuron apoptotic process Source: UniProtKB
    4. post-embryonic development Source: MGI
    5. proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
    6. protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: UniProtKB
    7. regulation of multicellular organism growth Source: MGI
    8. spermatogenesis Source: MGI

    Keywords - Molecular functioni

    Developmental protein, Ligase

    Keywords - Biological processi

    Apoptosis, Cell cycle, Differentiation, Spermatogenesis, Ubl conjugation pathway

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    UniPathwayiUPA00143.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    E3 ubiquitin-protein ligase SIAH1A (EC:6.3.2.-)
    Alternative name(s):
    Seven in absentia homolog 1a
    Short name:
    Siah-1a
    Short name:
    Siah1a
    Short name:
    mSiah-1a
    Gene namesi
    Name:Siah1a
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 8

    Organism-specific databases

    MGIiMGI:108064. Siah1a.

    Subcellular locationi

    Cytoplasm. Nucleus
    Note: Predominantly cytoplasmic. Partially nuclear.

    GO - Cellular componenti

    1. cytosol Source: UniProtKB
    2. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi156 – 1561T → E: Strongly reduced binding and degradation of target proteins; when associated with D-158. 1 Publication
    Mutagenesisi158 – 1581L → D or K: Strongly reduced binding of target proteins. Strongly reduced degradation of target proteins. 1 Publication
    Mutagenesisi166 – 1661L → K: Minor effect on binding and degradation of target proteins. 1 Publication
    Mutagenesisi180 – 1801M → K: Strongly reduced binding of target proteins. Strongly reduced degradation of target proteins. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 282282E3 ubiquitin-protein ligase SIAH1APRO_0000056164Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei19 – 191Phosphoserine; by ATM and ATRBy similarity

    Post-translational modificationi

    Phosphorylated on Ser-19 by ATM and ATR. This phosphorylation disrupts SIAH1 interaction with HIPK2, and subsequent proteasomal degradation of HIPK2 By similarity.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PRIDEiP61092.

    PTM databases

    PhosphoSiteiP61092.

    Expressioni

    Tissue specificityi

    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.1 Publication

    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

    BgeeiP61092.
    CleanExiMM_SIAH1A.
    GenevestigatoriP61092.

    Interactioni

    Subunit structurei

    Homodimer. Interacts with group 1 glutamate receptors GRM1 and GRM5. Interacts with SNCAIP and HIPK2. Interacts with GAPDH; leading to stabilize SIAH1 By similarity. Interacts with UBE2E2. Component of some large E3 complex composed of UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X. Interacts with UBE2I. Interacts with alpha-tubulin. Interacts with PEG10, which may inhibit its activity By similarity. Interacts with DAB1, which may inhibit its activity. Interacts with PEG3 and KLF10.By similarity4 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Dab1P973183EBI-446761,EBI-81680

    Protein-protein interaction databases

    BioGridi203231. 7 interactions.
    DIPiDIP-29100N.
    IntActiP61092. 3 interactions.
    STRINGi10090.ENSMUSP00000044123.

    Structurei

    Secondary structure

    1
    282
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi101 – 1033
    Helixi111 – 1133
    Helixi114 – 1196
    Beta strandi130 – 1323
    Helixi141 – 1433
    Helixi144 – 1507
    Beta strandi156 – 16712
    Beta strandi177 – 1848
    Beta strandi187 – 19812
    Turni199 – 2013
    Beta strandi202 – 21312
    Helixi215 – 2184
    Beta strandi221 – 2299
    Beta strandi232 – 2387
    Turni243 – 2453
    Helixi248 – 2525
    Beta strandi256 – 2605
    Helixi261 – 2677
    Beta strandi272 – 28110

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1K2FX-ray2.60A/B93-282[»]
    2AN6X-ray3.00A/B/C/D92-282[»]
    ProteinModelPortaliP61092.
    SMRiP61092. Positions 35-81, 93-282.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP61092.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni90 – 282193SBDAdd
    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.

    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 fingeri41 – 7636RING-typePROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri93 – 15361SIAH-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Zinc-finger

    Phylogenomic databases

    eggNOGiNOG264215.
    GeneTreeiENSGT00390000005434.
    HOGENOMiHOG000231487.
    HOVERGENiHBG055701.
    InParanoidiP61092.
    KOiK04506.
    OMAiHEETCEF.
    OrthoDBiEOG7JT6XC.
    PhylomeDBiP61092.
    TreeFamiTF312976.

    Family and domain databases

    Gene3Di3.30.40.10. 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]
    SMARTiSM00184. RING. 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.

    P61092-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSRQTATALP TGTSKCPPSQ RVPALTGTTA SNNDLASLFE CPVCFDYVLP    50
    PILQCQSGHL VCSNCRPKLT CCPTCRGPLG SIRNLAMEKV ANSVLFPCKY 100
    ASSGCEITLP HTEKAEHEEL CEFRPYSCPC PGASCKWQGS LDAVMPHLMH 150
    QHKSITTLQG EDIVFLATDI NLPGAVDWVM MQSCFGFHFM LVLEKQEKYD 200
    GHQQFFAIVQ LIGTRKQAEN FAYRLELNGH RRRLTWEATP RSIHEGIATA 250
    IMNSDCLVFD TSIAQLFAEN GNLGINVTIS MC 282
    Length:282
    Mass (Da):31,137
    Last modified:April 26, 2004 - v1
    Checksum:i852EADC5DD4A4FFA
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Z19579 mRNA. Translation: CAA79630.1.
    BC046317 mRNA. Translation: AAH46317.1.
    CCDSiCCDS22504.1.
    PIRiI48763.
    RefSeqiNP_033198.1. NM_009172.2.
    UniGeneiMm.324553.
    Mm.474080.

    Genome annotation databases

    EnsembliENSMUST00000045296; ENSMUSP00000044123; ENSMUSG00000036840.
    GeneIDi20437.
    KEGGimmu:20437.
    UCSCiuc009mqn.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Z19579 mRNA. Translation: CAA79630.1 .
    BC046317 mRNA. Translation: AAH46317.1 .
    CCDSi CCDS22504.1.
    PIRi I48763.
    RefSeqi NP_033198.1. NM_009172.2.
    UniGenei Mm.324553.
    Mm.474080.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1K2F X-ray 2.60 A/B 93-282 [» ]
    2AN6 X-ray 3.00 A/B/C/D 92-282 [» ]
    ProteinModelPortali P61092.
    SMRi P61092. Positions 35-81, 93-282.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 203231. 7 interactions.
    DIPi DIP-29100N.
    IntActi P61092. 3 interactions.
    STRINGi 10090.ENSMUSP00000044123.

    PTM databases

    PhosphoSitei P61092.

    Proteomic databases

    PRIDEi P61092.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000045296 ; ENSMUSP00000044123 ; ENSMUSG00000036840 .
    GeneIDi 20437.
    KEGGi mmu:20437.
    UCSCi uc009mqn.2. mouse.

    Organism-specific databases

    CTDi 20437.
    MGIi MGI:108064. Siah1a.

    Phylogenomic databases

    eggNOGi NOG264215.
    GeneTreei ENSGT00390000005434.
    HOGENOMi HOG000231487.
    HOVERGENi HBG055701.
    InParanoidi P61092.
    KOi K04506.
    OMAi HEETCEF.
    OrthoDBi EOG7JT6XC.
    PhylomeDBi P61092.
    TreeFami TF312976.

    Enzyme and pathway databases

    UniPathwayi UPA00143 .

    Miscellaneous databases

    ChiTaRSi Siah1a. mouse.
    EvolutionaryTracei P61092.
    NextBioi 298464.
    PROi P61092.
    SOURCEi Search...

    Gene expression databases

    Bgeei P61092.
    CleanExi MM_SIAH1A.
    Genevestigatori P61092.

    Family and domain databases

    Gene3Di 3.30.40.10. 1 hit.
    3.90.890.10. 1 hit.
    InterProi IPR018121. 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 ]
    PANTHERi PTHR10315. PTHR10315. 1 hit.
    Pfami PF03145. Sina. 1 hit.
    [Graphical view ]
    SMARTi SM00184. RING. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49599. SSF49599. 1 hit.
    PROSITEi PS50089. ZF_RING_2. 1 hit.
    PS51081. ZF_SIAH. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: Swiss.
      Tissue: Eye.
    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/6.
      Tissue: Olfactory epithelium.
    3. "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: FUNCTION, INTERACTION WITH PEG3.
    4. Cited for: INTERACTION WITH DAB1.
    5. "The ubiquitin ligase component Siah1a is required for completion of meiosis I in male mice."
      Dickins R.A., Frew I.J., House C.M., O'Bryan M.K., Holloway A.J., Haviv I., Traficante N., de Kretser D.M., Bowtell D.D.L.
      Mol. Cell. Biol. 22:2294-2303(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    6. Cited for: INDUCTION.
    7. "Siah ubiquitin ligase is structurally related to TRAF and modulates TNF-alpha signaling."
      Polekhina G., House C.M., Traficante N., Mackay J.P., Relaix F., Sassoon D.A., Parker M.W., Bowtell D.D.L.
      Nat. Struct. Biol. 9:68-75(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 93-282 IN COMPLEX WITH ZINC, HOMODIMERIZATION.
    8. "Elucidation of the substrate binding site of Siah ubiquitin ligase."
      House C.M., Hancock N.C., Moller A., Cromer B.A., Fedorov V., Bowtell D.D., Parker M.W., Polekhina G.
      Structure 14:695-701(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 92-282 IN COMPLEX WITH ZINC AND PEPTIDE SUBSTRATE, FUNCTION, INTERACTION WITH KLF10, MUTAGENESIS OF THR-156; LEU-158; LEU-166 AND MET-180.

    Entry informationi

    Entry nameiSIA1A_MOUSE
    AccessioniPrimary (citable) accession number: P61092
    Secondary accession number(s): Q06984
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 26, 2004
    Last sequence update: April 26, 2004
    Last modified: October 1, 2014
    This is version 108 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, 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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3