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FLASH GENE
Symbol SIAH1 contributors: mct - updated : 18-01-2016
HGNC name seven in absentia homolog 1 (Drosophila)
HGNC id 10857
Location 16q12.1      Physical location : 48.394.445 - 48.419.229
Synonym name
  • sonic hedgehog (Drosophila) homolog
  • E3 ubiquitin-protein ligase SIAH1
  • Synonym symbol(s) Siah-1, HUMSIAH, Siah-1a, FLJ08065
    EC.number 6.3.2.-
    DNA
    TYPE functioning gene
    STRUCTURE 87.91 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site
    text structure one Sp1 site responsible of the basal promoter activity
    MAPPING cloned Y linked N status provisional
    Physical map
    LOC124149 16q11.2 similar to KIAA0565 protein LOC390728 16 similar to Rab31-like SHCBP1 16q11.2 likely ortholog of mouse Shc SH2-domain binding protein 1 LOC388271 16q11.2 similar to RAB41 VPS35 16q13-q21 vacuolar protein sorting 35 (yeast) ORC6L 16q12 origin recognition complex, subunit 6 homolog-like (yeast) LOC91807 16q11.2 myosin light chain kinase (MLCK) LOC388272 16 similar to RIKEN cDNA 4921524J17 LOC124144 16q11.2 brain creatine kinase pseudogene GPT2 16q12.1 glutamic pyruvate transaminase (alanine aminotransferase) 2 DNAJA2 16q11.1-q11.2 DnaJ (Hsp40) homolog, subfamily A, member 2 NETO2 16q11.2 neuropilin (NRP) and tolloid (TLL)-like 2 LOC342451 16q11.2 similar to 60S ribosomal protein L23a CDA08 16q11.2 T-cell immunomodulatory protein PHKB 16q12.1 phosphorylase kinase, beta ABCC12 16q11-q12 ATP-binding cassette, sub-family C (CFTR/MRP), member 12 ABCC11 16q11-q12 ATP-binding cassette, sub-family C (CFTR/MRP), member 11 LONP 16q12.1 peroxisomal lon protease SIAH1 16q12 seven in absentia homolog 1 (Drosophila) LOC255896 16q12.1 similar to molybdenum cofactor synthesis-step 1 protein isoform 2 FLJ31821 16q12.1 hypothetical protein FLJ31821 N4BP1 16q12.1 hypothetical protein FLJ31821 LOC388273 16 LOC388273 CBLN1 16q11.2-q12.2 cerebellin 1 precursor MGC33367 16q12.1 hypothetical protein MGC32905 OAZ 16q12 hypothetical protein MGC32905 ADAM3B 16q12.1 a disintegrin and metalloproteinase domain 3b (cyritestin 2) MRPS21P7 16q12.1 mitochondrial ribosomal protein S21 pseudogene 7 MRPS21P8 16q12.1 mitochondrial ribosomal protein S21 pseudogene 8 FLJ38101 16q12.1 hypothetical protein FLJ38101 FLJ20718 16q12.1 hypothetical protein FLJ20718 LOC390729 16 similar to 60S ribosomal protein L10 (QM protein homolog)
    RNA
    TRANSCRIPTS type messenger
    text may be three transcripts (Mips)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 splicing 2003 31.1 282 - 2007 17420721
  • also called variant 1, or SIAH1S
  • interact with SIAH1 to form heterodimer or with itself to form homodimer
  • displays a promotion effect on cells tumorigenicity
  • - - 33200 - 299 - Mips
    - - 36900 - 344 - Mips
    2 - 2393 - 313 - 2007 17420721
  • also called variant 2, or SIAH1L
  • upregulated by TP53
  • induced in response to TP53 and plays an important role in the regulation of beta-catenin activity in tumor cells
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouthtongue  highly
    Endocrinethyroid   highly
    Reproductivefemale systemovary   
     male systemprostate   
    Urinarykidney    
    Visualeyeanterior segmentiris highly
     eyeretina  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    NervousPurkinje cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text eye
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal RING zinc finger motif confering its ability to work as an E3 ubiquitin-ligase and required for the transactivation
  • conserved ALF domain
  • C-terminal domain implicated in the binding of different substrate proteins (the presynaptic protein synaptophysin), and may regulate substrate binding ability
  • HOMOLOGY
    interspecies homolog to Drosophila seven in absentia (sina) 1
    Homologene
    FAMILY
  • E3 ligase family
  • CATEGORY regulatory , tumor suppressor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm,nuclear bodies
    text
  • co-localized with PHC2 in nuclei
  • HIPK2 colocalizes with its ubiquitin ligase SIAH1 at nuclear bodies, suggesting that these nuclear domains are the site of HIPK2 ubiquitination
  • basic FUNCTION
  • involved in external sensory organ development
  • requiring for specification of r7 photoreceptor cell fate in the Drosophila eye
  • involved in a variety of cellular processes such as apoptosis and tumor suppression
  • contributing to death of neurons and other cell types by activating the JNK pathway, activity that requires its E3 ligase activity
  • E3 ligase involved in ubiquitination and proteasome-mediated degradation of specific proteins
  • able to facilitate the ubiquitination and degradation of PHC2 via ubiquitin–proteasome pathway
  • plays a critical role in the process of GAPDH nuclear translocation (Chepchumba 2010)
  • SIAH1 ubiquitination pathway provides a fresh avenue for developing strategies to control disease-related transcription
  • SIAH1 and SIAH2 isoforms share high sequence similarity but possess contrary roles in cancer, with SIAH1 more often acting as a tumor suppressor
  • SIAH1 is the key factor that contributes to hypoxia and high glucose mediated synaptophysin degradation
  • E3 ubiquitin ligases SIAH1 and SIAH2 are able to dictate the growth, development, and chemo-/radiosensitivity of breast and prostate cancer cells
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • SIAH1-PARD3 signaling pathway that controls adhesion-dependent exit of neuronal progenitors or immature neurons from a germinal zone niche
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • DCC
  • NCOR
  • POU2AF1 and leading to their destabilization and degradation through the ubiquitin-proteosome pathway
  • interacting with SNCAIP (ubiquitylation of SNCAIP)
  • interacting with RBBP8, leading to RBBP8 degradation by the ubiquitin-proteasome pathway
  • interacts with the scaffold protein SH3RF1 to promote JNK activation and apoptosis
  • interact with the JmjC domain of HIF1AN through its substrate-binding domain and to specifically ubiquitinate HIF1A via its RING finger domain
  • interacting with SNCA and binding the brain-enriched E2 ubiquitin-conjugating enzyme UBE2E2 (facilitates mono- and di-ubiquitination of SNCA, promoting aggregation and apoptotic cell death, and playing a critical role in Lewy body formation and Parkinson pathogenesis)
  • could interact with TRB3 (SIAH1 targeted TRB3 for proteasome-dependent degradation)
  • interacted with, and ubiquitinated HIF1AN
  • interacting with GAPDH (binds SIAH1, forming a complex subsequently promoting translocation of GAPDH from the cytosol to the nucleus and NLS on SIAH1 facilitates the nuclear movement of the complex) (Chepchumba 2010)
  • SIAH1 induces the degradation of Kid (KIF22), a chromokinesin protein implicated in the normal progression of mitosis and meiosis, by the ubiquitin proteasome pathway
  • PRPS1 interacts with the E3 ligase SIAH1 (seven in absentia homolog 1) to induce ubiquitination and degradation of XIAP
  • EEF1D is a SIAH1-interacting protein, and EFF1D functions as a novel negative regulator of SIAH1
  • RING domain protein SIAH1, but not the homologous SIAH2, is the E3 ubiquitin ligase for ELL2 polyubiquitination and proteasomal degradation
  • GAPDH–SIAH1 interaction is augmented by S-nitrosylation of GAPDH
  • NPM1 physiologically bound to both SIAH1 and GAPDH, disrupting the SIAH1–GAPDH complex in the nucleus in response to nitrosative stress
  • interaction of TNK2 with SIAH1 and the induction of proteasomal degradation of TNK2 by SIAH1 are independent of ACK1 kinase activity
  • SIAH1 and SIAH2 are binding partners of USP19, interaction mediated by a SIAH-consensus binding motif and promoting USP19 ubiquitylation and proteasome-dependent degradation
  • PIN1 regulates SIAH1–mediated HIPK2 ubiquitination and degradation
  • a COPS5/CTNNB1/SIAH1 interaction network that might control CTNNB1 degradation in colorectal cancer cells
  • MAP3K5 a representative stress kinase, interacts with both GAPDH and SIAH1 and is likely able to phosphorylate Siah1 at specific amino acid residues
  • CDK2 phosphorylation regulates the protein stability of KLF10 by interfering with binding of the E3 ligase SIAH1
  • ABL1 protected HIPK2 from degradation mediated by the ubiquitin E3 ligase SIAH1
  • dissociation of the GAPDH/SIAH1 pro-apoptotic complex can block high glucose-induced pericyte apoptosis, widely considered a hallmark feature of Diabetic retinopathy (DR)
  • cell & other
    REGULATION
    induced by TP53 and WAF1
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in hepatocellular carcinoma in progression
    Susceptibility
  • to Parkinson disease (role in the formation of cellular inclusion and Lewy bodies)
  • Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    it may be a good molecular therapeutic target to increase the expression level of SIAH1 through promoting cell apoptosis and inhibiting cell invasion in human breast cancer
    cancer  
    viable drug target for antitumor therapies
    ANIMAL & CELL MODELS