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Q8IUQ4

- SIAH1_HUMAN

UniProt

Q8IUQ4 - SIAH1_HUMAN

Protein

E3 ubiquitin-protein ligase SIAH1

Gene

SIAH1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 126 (01 Oct 2014)
      Sequence version 2 (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 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.19 Publications

    Enzyme regulationi

    Inhibited by interaction with SNCAIP (isoform 2, but not isoform 1). May be inhibited by interaction with PEG10.1 Publication

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi98 – 981Zinc 1By similarity
    Metal bindingi105 – 1051Zinc 1By similarity
    Metal bindingi117 – 1171Zinc 1By similarity
    Metal bindingi121 – 1211Zinc 1By similarity
    Metal bindingi128 – 1281Zinc 2
    Metal bindingi135 – 1351Zinc 2
    Metal bindingi147 – 1471Zinc 2
    Metal bindingi152 – 1521Zinc 2

    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 C-terminus binding Source: UniProtKB
    4. ubiquitin-protein transferase activity Source: UniProtKB
    5. zinc ion binding Source: UniProtKB

    GO - Biological processi

    1. anatomical structure morphogenesis Source: ProtInc
    2. apoptotic process Source: ProtInc
    3. axon guidance Source: Reactome
    4. cell cycle Source: UniProtKB-KW
    5. nervous system development Source: ProtInc
    6. neuron apoptotic process Source: UniProtKB
    7. positive regulation of apoptotic process Source: UniProtKB
    8. positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
    9. proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
    10. protein catabolic process Source: UniProtKB
    11. protein destabilization Source: Ensembl
    12. protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: UniProtKB
    13. proteolysis Source: ProtInc
    14. spermatogenesis Source: UniProtKB-KW
    15. ubiquitin-dependent protein catabolic process 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

    ReactomeiREACT_22237. Netrin-1 signaling.
    UniPathwayiUPA00143.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    E3 ubiquitin-protein ligase SIAH1 (EC:6.3.2.-)
    Alternative name(s):
    Seven in absentia homolog 1
    Short name:
    Siah-1
    Siah-1a
    Gene namesi
    Name:SIAH1
    Synonyms:HUMSIAH
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 16

    Organism-specific databases

    HGNCiHGNC:10857. SIAH1.

    Subcellular locationi

    Cytoplasm. Nucleus
    Note: Predominantly cytoplasmic. Partially nuclear.

    GO - Cellular componenti

    1. beta-catenin destruction complex Source: UniProtKB
    2. cytoplasm Source: ProtInc
    3. cytosol Source: Reactome
    4. early endosome Source: Ensembl
    5. nucleus Source: UniProtKB
    6. plasma membrane Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi19 – 191S → A: Impaired ATM mediated phosphorylation, but normal interaction with HIPK2 and HIPK2 subsequent proteasomal degradation. 1 Publication
    Mutagenesisi19 – 191S → D: Reduced interaction with HIPK2 and HIPK2 subsequent proteasomal degradation. 1 Publication
    Mutagenesisi40 – 401E → R: Loss of function. 1 Publication
    Mutagenesisi41 – 411C → S: Loss of function; when associated with S-44. 1 Publication
    Mutagenesisi44 – 441C → S: Loss of function. 2 Publications
    Mutagenesisi55 – 551C → A: Loss of function; when associated with A-59 and S-72. 2 Publications
    Mutagenesisi55 – 551C → S: Loss of function; when associated with Y-59. 2 Publications
    Mutagenesisi59 – 591H → A: Loss of function; when associated with A-55 and S-72. 2 Publications
    Mutagenesisi59 – 591H → Y: Loss of function. 2 Publications
    Mutagenesisi66 – 661R → L: Decreased activity; when associated with T-68. 1 Publication
    Mutagenesisi68 – 681K → T: Decreased activity; when associated with L-66. 1 Publication
    Mutagenesisi72 – 721C → S: Loss of function; when associated with A-55 and A-59. 1 Publication
    Mutagenesisi76 – 761R → E: Decreased activity. 1 Publication
    Mutagenesisi124 – 1241R → A in D; does not impair its ability to interact with CACYBP and degrade CTNNB1 and PML; when associated with A-214; A-215; A-231 and A-232.
    Mutagenesisi142 – 1421D → A in E; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-151.
    Mutagenesisi151 – 1511Q → A in E; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-142.
    Mutagenesisi152 – 1521H → Y: Abolishes ability to degrade DCC. 1 Publication
    Mutagenesisi161 – 1622ED → AA in A; does not impair its ability to degrade PML while it abolishes its ability to interact with CACYBP and degrade CTNNB1; when associated with A-226 and A-237.
    Mutagenesisi198 – 2003KYD → GDG: Impairs CTNNB1 degradation.
    Mutagenesisi202 – 2021H → Y: No effect. 1 Publication
    Mutagenesisi211 – 2111L → R: Abolishes ability to degrade DCC. 1 Publication
    Mutagenesisi214 – 2152TR → AA in D; does not impair its ability to interact with CACYBP and degrade CTNNB1 and PML; when associated with A-124; A-231 and A-232.
    Mutagenesisi224 – 2241R → A in C; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-233.
    Mutagenesisi226 – 2261E → A in A; does not impair its ability to degrade PML while it abolishes its ability to interact with CACYBP and degrade CTNNB1; when associated with A-161; A-162 and A-237.
    Mutagenesisi231 – 2322RR → AA in D; does not impair its ability to interact with CACYBP and degrade CTNNB1 and PML; when associated with A-124; A-214 and A-215.
    Mutagenesisi233 – 2331R → A in C; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-233.
    Mutagenesisi237 – 2371E → A in A; does not impair its ability to degrade PML while it abolishes its ability to interact with CACYBP and degrade CTNNB1; when associated with A-161; A-162 and A-226.
    Mutagenesisi252 – 2521M → D or K: Impairs CTNNB1 degradation. 1 Publication
    Mutagenesisi253 – 2531N → A in B; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-265.
    Mutagenesisi265 – 2651Q → A in B; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-253.

    Organism-specific databases

    PharmGKBiPA35759.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 282282E3 ubiquitin-protein ligase SIAH1PRO_0000056163Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei19 – 191Phosphoserine; by ATM and ATR1 Publication

    Post-translational modificationi

    Phosphorylated on Ser-19 by ATM and ATR. This phosphorylation disrupts SIAH1 interaction with HIPK2, and subsequent proteasomal degradation of HIPK2.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ8IUQ4.
    PaxDbiQ8IUQ4.
    PRIDEiQ8IUQ4.

    PTM databases

    PhosphoSiteiQ8IUQ4.

    Expressioni

    Tissue specificityi

    Widely expressed at a low level. Down-regulated in advanced hepatocellular carcinomas.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.

    Gene expression databases

    ArrayExpressiQ8IUQ4.
    BgeeiQ8IUQ4.
    CleanExiHS_SIAH1.
    GenevestigatoriQ8IUQ4.

    Organism-specific databases

    HPAiCAB018724.

    Interactioni

    Subunit structurei

    Homodimer. Interacts with group 1 glutamate receptors GRM1 and GRM5. Interacts with DAB1, which may inhibit its activity. Interacts with UBE2E2. Interacts with PEG3. Interacts with GAPDH; leading to stabilize SIAH1 By similarity. 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. Interacts with KHDRBS3. Interacts with SNCAIP and HIPK2.By similarity11 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ATXN7O152652EBI-747107,EBI-708350
    MYD88Q998363EBI-747107,EBI-447677
    OPRM1P353724EBI-747107,EBI-2624570
    POU2AF1Q166332EBI-747107,EBI-943588
    Pou2af1Q646935EBI-747107,EBI-943530From a different organism.
    SEPT4O43236-62EBI-747107,EBI-4372019
    Sh3rf1Q69ZI15EBI-747107,EBI-957380From a different organism.
    XP697134EBI-747107,EBI-7088789From a different organism.
    XIAPP981703EBI-747107,EBI-517127

    Protein-protein interaction databases

    BioGridi112372. 84 interactions.
    IntActiQ8IUQ4. 42 interactions.
    MINTiMINT-156060.
    STRINGi9606.ENSP00000349156.

    Structurei

    Secondary structure

    1
    282
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi101 – 1033
    Helixi111 – 12010
    Beta strandi122 – 1243
    Beta strandi130 – 1345
    Helixi141 – 1433
    Helixi144 – 1518
    Beta strandi156 – 16712
    Beta strandi172 – 18413
    Beta strandi187 – 19711
    Beta strandi203 – 21311
    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
    2A25X-ray2.20A90-282[»]
    4C9ZX-ray1.95A/B91-282[»]
    4CA1X-ray1.58A/B91-282[»]
    4I7BX-ray3.00A/C90-282[»]
    4I7CX-ray2.80A/C90-282[»]
    4I7DX-ray2.40A/C90-282[»]
    ProteinModelPortaliQ8IUQ4.
    SMRiQ8IUQ4. Positions 35-81, 95-282.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ8IUQ4.

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

    Keywords - Domaini

    Zinc-finger

    Phylogenomic databases

    eggNOGiNOG264215.
    HOGENOMiHOG000231487.
    HOVERGENiHBG055701.
    KOiK04506.
    OMAiHEETCEF.
    OrthoDBiEOG7JT6XC.
    PhylomeDBiQ8IUQ4.
    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]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q8IUQ4-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MSRQTATALP TGTSKCPPSQ RVPALTGTTA SNNDLASLFE CPVCFDYVLP    50
    PILQCQSGHL VCSNCRPKLT CCPTCRGPLG SIRNLAMEKV ANSVLFPCKY 100
    ASSGCEITLP HTEKADHEEL 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):31,123
    Last modified:April 26, 2004 - v2
    Checksum:iFA0698D0DC1B0A15
    GO
    Isoform 2 (identifier: Q8IUQ4-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-1: M → MTGKATPPSLYSWRGVLFTCLPAARTRKRKEM

    Show »
    Length:313
    Mass (Da):34,628
    Checksum:iBE3085493B0ABEC1
    GO
    Isoform 3 (identifier: Q8IUQ4-3) [UniParc]FASTAAdd to Basket

    Also known as: Siah-1S

    The sequence of this isoform differs from the canonical sequence as follows:
         193-195: LEK → DLS
         196-282: Missing.

    Show »
    Length:195
    Mass (Da):21,215
    Checksum:iB5AB8D4079A7C723
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti173 – 1731P → S in CAE46191. (PubMed:17974005)Curated
    Sequence conflicti245 – 2451E → G in CAE46191. (PubMed:17974005)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 11M → MTGKATPPSLYSWRGVLFTC LPAARTRKRKEM in isoform 2. 2 PublicationsVSP_010166
    Alternative sequencei193 – 1953LEK → DLS in isoform 3. 1 PublicationVSP_029210
    Alternative sequencei196 – 28287Missing in isoform 3. 1 PublicationVSP_029211Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U63295 mRNA. Translation: AAC12950.1.
    U76247 mRNA. Translation: AAC51907.1.
    AJ400626 Genomic DNA. Translation: CAC35542.1.
    EF026094 mRNA. Translation: ABK15529.1.
    BX647064 mRNA. Translation: CAE46191.1.
    BC035562 mRNA. Translation: AAH35562.1.
    BC042550 mRNA. Translation: AAH42550.1.
    BC044920 mRNA. Translation: AAH44920.1.
    CCDSiCCDS10735.1. [Q8IUQ4-1]
    CCDS32444.1. [Q8IUQ4-2]
    RefSeqiNP_001006611.1. NM_001006610.1. [Q8IUQ4-2]
    NP_003022.3. NM_003031.3. [Q8IUQ4-1]
    XP_006721309.1. XM_006721246.1. [Q8IUQ4-1]
    UniGeneiHs.706828.

    Genome annotation databases

    EnsembliENST00000356721; ENSP00000349156; ENSG00000196470. [Q8IUQ4-2]
    ENST00000380006; ENSP00000369343; ENSG00000196470. [Q8IUQ4-1]
    ENST00000394725; ENSP00000378214; ENSG00000196470. [Q8IUQ4-1]
    ENST00000568007; ENSP00000456421; ENSG00000196470. [Q8IUQ4-1]
    GeneIDi6477.
    KEGGihsa:6477.
    UCSCiuc002efn.1. human. [Q8IUQ4-2]
    uc002efo.1. human. [Q8IUQ4-1]

    Polymorphism databases

    DMDMi46577493.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U63295 mRNA. Translation: AAC12950.1 .
    U76247 mRNA. Translation: AAC51907.1 .
    AJ400626 Genomic DNA. Translation: CAC35542.1 .
    EF026094 mRNA. Translation: ABK15529.1 .
    BX647064 mRNA. Translation: CAE46191.1 .
    BC035562 mRNA. Translation: AAH35562.1 .
    BC042550 mRNA. Translation: AAH42550.1 .
    BC044920 mRNA. Translation: AAH44920.1 .
    CCDSi CCDS10735.1. [Q8IUQ4-1 ]
    CCDS32444.1. [Q8IUQ4-2 ]
    RefSeqi NP_001006611.1. NM_001006610.1. [Q8IUQ4-2 ]
    NP_003022.3. NM_003031.3. [Q8IUQ4-1 ]
    XP_006721309.1. XM_006721246.1. [Q8IUQ4-1 ]
    UniGenei Hs.706828.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2A25 X-ray 2.20 A 90-282 [» ]
    4C9Z X-ray 1.95 A/B 91-282 [» ]
    4CA1 X-ray 1.58 A/B 91-282 [» ]
    4I7B X-ray 3.00 A/C 90-282 [» ]
    4I7C X-ray 2.80 A/C 90-282 [» ]
    4I7D X-ray 2.40 A/C 90-282 [» ]
    ProteinModelPortali Q8IUQ4.
    SMRi Q8IUQ4. Positions 35-81, 95-282.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112372. 84 interactions.
    IntActi Q8IUQ4. 42 interactions.
    MINTi MINT-156060.
    STRINGi 9606.ENSP00000349156.

    PTM databases

    PhosphoSitei Q8IUQ4.

    Polymorphism databases

    DMDMi 46577493.

    Proteomic databases

    MaxQBi Q8IUQ4.
    PaxDbi Q8IUQ4.
    PRIDEi Q8IUQ4.

    Protocols and materials databases

    DNASUi 6477.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000356721 ; ENSP00000349156 ; ENSG00000196470 . [Q8IUQ4-2 ]
    ENST00000380006 ; ENSP00000369343 ; ENSG00000196470 . [Q8IUQ4-1 ]
    ENST00000394725 ; ENSP00000378214 ; ENSG00000196470 . [Q8IUQ4-1 ]
    ENST00000568007 ; ENSP00000456421 ; ENSG00000196470 . [Q8IUQ4-1 ]
    GeneIDi 6477.
    KEGGi hsa:6477.
    UCSCi uc002efn.1. human. [Q8IUQ4-2 ]
    uc002efo.1. human. [Q8IUQ4-1 ]

    Organism-specific databases

    CTDi 6477.
    GeneCardsi GC16M048443.
    HGNCi HGNC:10857. SIAH1.
    HPAi CAB018724.
    MIMi 602212. gene.
    neXtProti NX_Q8IUQ4.
    PharmGKBi PA35759.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG264215.
    HOGENOMi HOG000231487.
    HOVERGENi HBG055701.
    KOi K04506.
    OMAi HEETCEF.
    OrthoDBi EOG7JT6XC.
    PhylomeDBi Q8IUQ4.
    TreeFami TF312976.

    Enzyme and pathway databases

    UniPathwayi UPA00143 .
    Reactomei REACT_22237. Netrin-1 signaling.

    Miscellaneous databases

    EvolutionaryTracei Q8IUQ4.
    GeneWikii SIAH1.
    GenomeRNAii 6477.
    NextBioi 25161.
    PROi Q8IUQ4.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8IUQ4.
    Bgeei Q8IUQ4.
    CleanExi HS_SIAH1.
    Genevestigatori Q8IUQ4.

    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. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Intestinal epithelium.
    2. "Characterization of human homologs of the Drosophila seven in absentia (sina) gene."
      Hu G., Chung Y.-L., Glover T., Valentine V., Look A.T., Fearon E.R.
      Genomics 46:103-111(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      Tissue: Fetal brain.
    3. "Lack of somatic mutation in the coding sequence of SIAH1 in tumors hemizygous for this candidate tumor suppressor gene."
      Medhioub M., Vaury C., Hamelin R., Thomas G.
      Int. J. Cancer 87:794-797(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    4. "Siah-1S, a novel splice variant of Siah-1 (seven in absentia homolog), counteracts Siah-1-mediated downregulation of beta-catenin."
      Mei Y., Xie C., Xie W., Wu Z., Wu M.
      Oncogene 26:6319-6331(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Tissue: Retina.
    6. "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] (ISOFORMS 1 AND 2).
      Tissue: Brain, Pancreas and Testis.
    7. "Mammalian homologs of seven in absentia regulate DCC via the ubiquitin-proteasome pathway."
      Hu G., Zhang S., Vidal M., Baer J.L., Xu T., Fearon E.R.
      Genes Dev. 11:2701-2714(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN DEGRADATION OF DCC, SUBCELLULAR LOCATION, INTERACTION WITH UBE2I.
    8. "p53-inducible human homologue of Drosophila seven in absentia (Siah) inhibits cell growth: suppression by BAG-1."
      Matsuzawa S., Takayama S., Froesch B.A., Zapata J.M., Reed J.C.
      EMBO J. 17:2736-2747(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH BAG1, SUBCELLULAR LOCATION.
    9. "Siah-1 N-terminal RING domain is required for proteolysis function, and C-terminal sequences regulate oligomerization and binding to target proteins."
      Hu G., Fearon E.R.
      Mol. Cell. Biol. 19:724-732(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF GLU-40; CYS-41; CYS-44; CYS-55; HIS-59; ARG-66; LYS-68; ARG-76; HIS-152; HIS-202 AND LEU-211.
    10. "SIAH-1 interacts with alpha-tubulin and degrades the kinesin Kid by the proteasome pathway during mitosis."
      Germani A., Bruzzoni-Giovanelli H., Fellous A., Gisselbrecht S., Varin-Blank N., Calvo F.
      Oncogene 19:5997-6006(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN DEGRADATION OF KIF22, INTERACTION WITH ALPHA-TUBULIN.
    11. "p53 suppresses the c-Myb-induced activation of heat shock transcription factor 3."
      Tanikawa J., Ichikawa-Iwata E., Kanei-Ishii C., Nakai A., Matsuzawa S., Reed J.C., Ishii S.
      J. Biol. Chem. 275:15578-15585(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN DEGRADATION OF MYB.
    12. "Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses."
      Matsuzawa S., Reed J.C.
      Mol. Cell 7:915-926(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN DEGRADATION OF CTNNB1, SUBUNIT OF A COMPLEX WITH UBE2D1; CACYBP; SKP1; APC AND TBL1X.
    13. "Siah-1 mediates a novel beta-catenin degradation pathway linking p53 to the adenomatous polyposis coli protein."
      Liu J., Stevens J., Rote C.A., Yost H.J., Hu Y., Neufeld K.L., White R.L., Matsunami N.
      Mol. Cell 7:927-936(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN DEGRADATION OF CTNNB1.
    14. "The RING finger protein Siah-1 regulates the level of the transcriptional coactivator OBF-1."
      Tiedt R., Bartholdy B.A., Matthias G., Newell J.W., Matthias P.
      EMBO J. 20:4143-4152(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN DEGRADATION OF POU2AF1, SUBCELLULAR LOCATION.
    15. "Regulation of BOB.1/OBF.1 stability by SIAH."
      Boehm J., He Y., Greiner A., Staudt L., Wirth T.
      EMBO J. 20:4153-4162(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN DEGRADATION OF POU2AF1.
    16. Cited for: FUNCTION IN DEGRADATION OF NUMB.
    17. "Modulation of transforming growth factor beta (TGFbeta)/Smad transcriptional responses through targeted degradation of TGFbeta-inducible early gene-1 by human seven in absentia homologue."
      Johnsen S.A., Subramaniam M., Monroe D.G., Janknecht R., Spelsberg T.C.
      J. Biol. Chem. 277:30754-30759(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN DEGRADATION OF KLF10.
    18. Cited for: FUNCTION IN DEGRADATION OF SNCAIP, SUBCELLULAR LOCATION.
    19. "Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1."
      Okabe H., Satoh S., Furukawa Y., Kato T., Hasegawa S., Nakajima Y., Yamaoka Y., Nakamura Y.
      Cancer Res. 63:3043-3048(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PEG10.
    20. "SIAH1 inactivation correlates with tumor progression in hepatocellular carcinomas."
      Matsuo K., Satoh S., Okabe H., Nomura A., Maeda T., Yamaoka Y., Ikai I.
      Genes Chromosomes Cancer 36:283-291(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    21. Cited for: FUNCTION IN DEGRADATION OF RBBP8.
    22. "Structural analysis of Siah1 and its interactions with Siah-interacting protein (SIP)."
      Matsuzawa S., Li C., Ni C.-Z., Takayama S., Reed J.C., Ely K.R.
      J. Biol. Chem. 278:1837-1840(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CACYBP, MUTANTS A; B; C; D AND E.
    23. "SIAH1 targets the alternative splicing factor T-STAR for degradation by the proteasome."
      Venables J.P., Dalgliesh C., Paronetto M.P., Skitt L., Thornton J.K., Saunders P.T., Sette C., Jones K.T., Elliott D.J.
      Hum. Mol. Genet. 13:1525-1534(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH KHDRBS3.
    24. "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, MUTANTS A AND D.
    25. "Ubiquitylation of synphilin-1 and alpha-synuclein by SIAH and its presence in cellular inclusions and Lewy bodies imply a role in Parkinson's disease."
      Liani E., Eyal A., Avraham E., Shemer R., Szargel R., Berg D., Bornemann A., Riess O., Ross C.A., Rott R., Engelender S.
      Proc. Natl. Acad. Sci. U.S.A. 101:5500-5505(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SNCAIP AND SNCA, MUTAGENESIS OF CYS-55; HIS-59 AND CYS-72.
    26. "Control of HIPK2 stability by ubiquitin ligase Siah-1 and checkpoint kinases ATM and ATR."
      Winter M., Sombroek D., Dauth I., Moehlenbrink J., Scheuermann K., Crone J., Hofmann T.G.
      Nat. Cell Biol. 10:812-824(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF SER-19 AND CYS-44, INTERACTION WITH HIPK2, PHOSPHORYLATION AT SER-19 BY ATM AND ATR.
    27. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    28. "Synphilin-1A inhibits seven in absentia homolog (SIAH) and modulates alpha-synuclein monoubiquitylation and inclusion formation."
      Szargel R., Rott R., Eyal A., Haskin J., Shani V., Balan L., Wolosker H., Engelender S.
      J. Biol. Chem. 284:11706-11716(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SNCAIP, ENZYME REGULATION, FUNCTION.
    29. "Ubiquitin conjugase UBCH8 targets active FMS-like tyrosine kinase 3 for proteasomal degradation."
      Buchwald M., Pietschmann K., Muller J.P., Bohmer F.D., Heinzel T., Kramer O.H.
      Leukemia 24:1412-1421(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN UBIQUITINATION OF FLT3.
    30. "The ubiquitin ligase Siah1 controls ELL2 stability and formation of super elongation complexes to modulate gene transcription."
      Liu M., Hsu J., Chan C., Li Z., Zhou Q.
      Mol. Cell 46:325-334(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    31. "Structural analysis of Siah1-Siah-interacting protein interactions and insights into the assembly of an E3 ligase multiprotein complex."
      Santelli E., Leone M., Li C., Fukushima T., Preece N.E., Olson A.J., Ely K.R., Reed J.C., Pellecchia M., Liddington R.C., Matsuzawa S.
      J. Biol. Chem. 280:34278-34287(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 90-282 IN COMPLEX WITH ZINC IONS AND CACYBP, FUNCTION, MUTAGENESIS OF 198-LYS--ASP-200 AND MET-252, INTERACTION WITH CACYBP.

    Entry informationi

    Entry nameiSIAH1_HUMAN
    AccessioniPrimary (citable) accession number: Q8IUQ4
    Secondary accession number(s): A0FKF3
    , O43269, Q49A58, Q92880
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 26, 2004
    Last sequence update: April 26, 2004
    Last modified: October 1, 2014
    This is version 126 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 16
      Human chromosome 16: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    4. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3