Human Gene SIAH1 (ENST00000394725.3) from GENCODE V44
  Description: Homo sapiens siah E3 ubiquitin protein ligase 1 (SIAH1), transcript variant 1, mRNA. (from RefSeq NM_003031)
RefSeq Summary (NM_003031): This gene encodes a protein that is a member of the seven in absentia homolog (SIAH) family. The protein is an E3 ligase and is involved in ubiquitination and proteasome-mediated degradation of specific proteins. The activity of this ubiquitin ligase has been implicated in the development of certain forms of Parkinson's disease, the regulation of the cellular response to hypoxia and induction of apoptosis. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized. [provided by RefSeq, Jul 2008].
Gencode Transcript: ENST00000394725.3
Gencode Gene: ENSG00000196470.12
Transcript (Including UTRs)
   Position: hg38 chr16:48,360,531-48,385,413 Size: 24,883 Total Exon Count: 2 Strand: -
Coding Region
   Position: hg38 chr16:48,361,580-48,362,428 Size: 849 Coding Exon Count: 1 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr16:48,360,531-48,385,413)mRNA (may differ from genome)Protein (282 aa)
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-  Comments and Description Text from UniProtKB
  ID: SIAH1_HUMAN
DESCRIPTION: RecName: Full=E3 ubiquitin-protein ligase SIAH1; EC=6.3.2.-; AltName: Full=Seven in absentia homolog 1; Short=Siah-1; AltName: Full=Siah-1a;
FUNCTION: 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 (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.
ENZYME REGULATION: Inhibited by interaction with SNCAIP (isoform 2, but not isoform 1). May be inhibited by interaction with PEG10.
PATHWAY: Protein modification; protein ubiquitination.
SUBUNIT: 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.
INTERACTION: O15265:ATXN7; NbExp=2; IntAct=EBI-747107, EBI-708350; Q99836:MYD88; NbExp=3; IntAct=EBI-747107, EBI-447677; O43236-6:SEPT4; NbExp=2; IntAct=EBI-747107, EBI-4372019; Q69ZI1:Sh3rf1 (xeno); NbExp=5; IntAct=EBI-747107, EBI-957380; P98170:XIAP; NbExp=3; IntAct=EBI-747107, EBI-517127;
SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Predominantly cytoplasmic. Partially nuclear.
TISSUE SPECIFICITY: Widely expressed at a low level. Down- regulated in advanced hepatocellular carcinomas.
INDUCTION: 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.
DOMAIN: The RING-type zinc finger domain is essential for ubiquitin ligase activity.
DOMAIN: The SBD domain (substrate-binding domain) mediates the homodimerization and the interaction with substrate proteins. It is related to the TRAF family (By similarity).
PTM: Phosphorylated on Ser-19 by ATM and ATR. This phosphorylation disrupts SIAH1 interaction with HIPK2, and subsequent proteasomal degradation of HIPK2.
SIMILARITY: Belongs to the SINA (Seven in absentia) family.
SIMILARITY: Contains 1 RING-type zinc finger.
SIMILARITY: Contains 1 SIAH-type zinc finger.

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: SIAH1
Diseases sorted by gene-association score: parkinson disease, late-onset (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 3.21 RPKM in Testis
Total median expression: 24.19 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -116.50212-0.550 Picture PostScript Text
3' UTR -212.301049-0.202 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR004162 - 7-in-absentia-prot
IPR018121 - 7-in-absentia-prot_TRAF-dom
IPR013323 - SIAH-type
IPR008974 - TRAF-like
IPR013322 - TRAF-type
IPR001841 - Znf_RING
IPR013083 - Znf_RING/FYVE/PHD
IPR013010 - Znf_SIAH

Pfam Domains:
PF03145 - Seven in absentia protein family

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2A25 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q8IUQ4
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004842 ubiquitin-protein transferase activity
GO:0005515 protein binding
GO:0008022 protein C-terminus binding
GO:0008270 zinc ion binding
GO:0016740 transferase activity
GO:0042802 identical protein binding
GO:0046872 metal ion binding
GO:0061630 ubiquitin protein ligase activity

Biological Process:
GO:0000209 protein polyubiquitination
GO:0006511 ubiquitin-dependent protein catabolic process
GO:0006915 apoptotic process
GO:0007049 cell cycle
GO:0007275 multicellular organism development
GO:0007283 spermatogenesis
GO:0007399 nervous system development
GO:0007411 axon guidance
GO:0009653 anatomical structure morphogenesis
GO:0016567 protein ubiquitination
GO:0030154 cell differentiation
GO:0030163 protein catabolic process
GO:0031648 protein destabilization
GO:0043065 positive regulation of apoptotic process
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0044267 cellular protein metabolic process
GO:0051402 neuron apoptotic process
GO:2001244 positive regulation of intrinsic apoptotic signaling pathway

Cellular Component:
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005769 early endosome
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0030877 beta-catenin destruction complex


-  Descriptions from all associated GenBank mRNAs
  BC044920 - Homo sapiens seven in absentia homolog 1 (Drosophila), mRNA (cDNA clone MGC:44340 IMAGE:5295925), complete cds.
BC042550 - Homo sapiens seven in absentia homolog 1 (Drosophila), mRNA (cDNA clone MGC:34550 IMAGE:5198176), complete cds.
BC018193 - Homo sapiens seven in absentia homolog 1 (Drosophila), mRNA (cDNA clone IMAGE:3857590), containing frame-shift errors.
U76247 - Human hSIAH1 mRNA, complete cds.
BC035562 - Homo sapiens seven in absentia homolog 1 (Drosophila), mRNA (cDNA clone MGC:40343 IMAGE:5224755), complete cds.
AK225895 - Homo sapiens mRNA for seven in absentia homolog 1 isoform a variant, clone: FCC120G04.
AK313861 - Homo sapiens cDNA, FLJ94493, highly similar to Homo sapiens seven in absentia homolog 1 (Drosophila) (SIAH1),mRNA.
BX647064 - Homo sapiens mRNA; cDNA DKFZp686L1897 (from clone DKFZp686L1897); complete cds.
U63295 - Homo sapiens seven in absentia homolog mRNA, complete cds.
JD044796 - Sequence 25820 from Patent EP1572962.
JD262339 - Sequence 243363 from Patent EP1572962.
JD297059 - Sequence 278083 from Patent EP1572962.
JD317115 - Sequence 298139 from Patent EP1572962.
JD509200 - Sequence 490224 from Patent EP1572962.
JD088525 - Sequence 69549 from Patent EP1572962.
JD091341 - Sequence 72365 from Patent EP1572962.
AK094663 - Homo sapiens cDNA FLJ37344 fis, clone BRAMY2021139, highly similar to Ubiquitin ligase SIAH1 (EC 6.3.2.-).
JD566237 - Sequence 547261 from Patent EP1572962.
JD304449 - Sequence 285473 from Patent EP1572962.
JD310674 - Sequence 291698 from Patent EP1572962.
JD166989 - Sequence 148013 from Patent EP1572962.
KJ892138 - Synthetic construct Homo sapiens clone ccsbBroadEn_01532 SIAH1 gene, encodes complete protein.
AB451253 - Homo sapiens SIAH1 mRNA for seven in absentia homolog 1 isoform a, complete cds, clone: FLJ08065AAAN.
DQ890990 - Synthetic construct clone IMAGE:100003620; FLH168308.01X; RZPDo839F0292D seven in absentia homolog 1 (Drosophila) (SIAH1) gene, encodes complete protein.
DQ894167 - Synthetic construct Homo sapiens clone IMAGE:100008627; FLH168304.01L; RZPDo839F0291D seven in absentia homolog 1 (Drosophila) (SIAH1) gene, encodes complete protein.
KJ905919 - Synthetic construct Homo sapiens clone ccsbBroadEn_15589 SIAH1 gene, encodes complete protein.
AB451377 - Homo sapiens SIAH1 mRNA for seven in absentia homolog 1 isoform a, partial cds, clone: FLJ08065AAAF.
AB528467 - Synthetic construct DNA, clone: pF1KE0921, Homo sapiens SIAH1 gene for seven in absentia homolog 1, without stop codon, in Flexi system.
CU690108 - Synthetic construct Homo sapiens gateway clone IMAGE:100020769 5' read SIAH1 mRNA.
CU692094 - Synthetic construct Homo sapiens gateway clone IMAGE:100021123 5' read SIAH1 mRNA.
EF026094 - Homo sapiens SIAH1 short protein (SIAH1) mRNA, complete cds, alternatively spliced.
LF383079 - JP 2014500723-A/190582: Polycomb-Associated Non-Coding RNAs.
MA618656 - JP 2018138019-A/190582: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04115 - p53 signaling pathway
hsa04120 - Ubiquitin mediated proteolysis
hsa04310 - Wnt signaling pathway

Reactome (by CSHL, EBI, and GO)

Protein Q8IUQ4 (Reactome details) participates in the following event(s):

R-HSA-374665 DCC interaction with SIAH1
R-HSA-5660753 SIAH1:UBE2L6:Ubiquitin ubiquitinates SNCA
R-HSA-983157 Interaction of E3 with substrate and E2-Ub complex
R-HSA-983147 Release of E3 from polyubiquitinated substrate
R-HSA-5658092 SIAH1, SIAH2 bind SNCAIP
R-HSA-983140 Transfer of Ub from E2 to substrate and release of E2
R-HSA-5658496 SIAH1:UBE2L6:Ubiquitin binds SNCA
R-HSA-373752 Netrin-1 signaling
R-HSA-977225 Amyloid fiber formation
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-422475 Axon guidance
R-HSA-392499 Metabolism of proteins
R-HSA-983169 Class I MHC mediated antigen processing & presentation
R-HSA-1266738 Developmental Biology
R-HSA-1280218 Adaptive Immune System
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: A0FKF3, ENST00000394725.1, ENST00000394725.2, HUMSIAH, NM_003031, O43269, Q49A58, Q8IUQ4, Q92880, SIAH1_HUMAN, uc002efo.1, uc002efo.2, uc002efo.3, uc002efo.4
UCSC ID: ENST00000394725.3
RefSeq Accession: NM_003031
Protein: Q8IUQ4 (aka SIAH1_HUMAN or SIH1_HUMAN)
CCDS: CCDS10735.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.