Protein: Q8IUQ4

UniprotKB AC UniprotKB ID Gene name Full name Species Curated set
Q8IUQ4 (Uniprot) SIAH1_HUMAN SIAH1 E3 ubiquitin-protein ligase SIAH1 human No
Uniprot: 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. more..
MoonDB Dissimilar Functions
GO ID 1 Function 1 Module ID 1 GO ID 2 Function 2 Module ID 2 Association Probability (PrOnto) Interaction Probability (PrOnto)
GO:0034641 cellular nitrogen compound metabolic process 35 GO:0006928 movement of cell or subcellular component 496 7.55e-40 5.63e-168
GO:0006725 cellular aromatic compound metabolic process 342 GO:0006928 movement of cell or subcellular component 496 1.24e-32 2.63e-196
GO:0006139 nucleobase-containing compound metabolic process 354 GO:0006928 movement of cell or subcellular component 496 1.95e-31 6.36e-195
GO:0006928 movement of cell or subcellular component 496 GO:0032446 protein modification by small protein conjugation 575 8.80e-04 1.11e-80
Biological Processes
Module ID (MoonGO) GO ID (BP) GO Name
35 GO:0044271 cellular nitrogen compound biosynthetic process
35 GO:0044267 cellular protein metabolic process
35 GO:0090304 nucleic acid metabolic process
35 GO:0010468 regulation of gene expression
35 GO:0009966 regulation of signal transduction
59 GO:0016070 RNA metabolic process
59 GO:0006464 cellular protein modification process
59 GO:0010467 gene expression
59 GO:2000112 regulation of cellular macromolecule biosynthetic process
79 GO:0007165 signal transduction
107 GO:0016070 RNA metabolic process
107 GO:0044267 cellular protein metabolic process
107 GO:0034654 nucleobase-containing compound biosynthetic process
107 GO:2000112 regulation of cellular macromolecule biosynthetic process
107 GO:0010468 regulation of gene expression
107 GO:0019219 regulation of nucleobase-containing compound metabolic process
107 GO:0007165 signal transduction
125 GO:0044248 cellular catabolic process
125 GO:0016567 protein ubiquitination
125 GO:0060255 regulation of macromolecule metabolic process
207 GO:0007165 signal transduction
283 GO:0006464 cellular protein modification process
283 GO:0060255 regulation of macromolecule metabolic process
297 GO:0007165 signal transduction
342 GO:0006139 nucleobase-containing compound metabolic process
342 GO:0060255 regulation of macromolecule metabolic process
354 GO:0090304 nucleic acid metabolic process
359 GO:0044248 cellular catabolic process
359 GO:0000209 protein polyubiquitination
359 GO:0007165 signal transduction
375 GO:0070647 protein modification by small protein conjugation or removal
375 GO:0060255 regulation of macromolecule metabolic process
496 GO:0048870 cell motility
496 GO:0071310 cellular response to organic substance
496 GO:0090304 nucleic acid metabolic process
496 GO:0034654 nucleobase-containing compound biosynthetic process
496 GO:0043085 positive regulation of catalytic activity
496 GO:0031325 positive regulation of cellular metabolic process
496 GO:1902533 positive regulation of intracellular signal transduction
496 GO:0010604 positive regulation of macromolecule metabolic process
496 GO:0051173 positive regulation of nitrogen compound metabolic process
496 GO:0051128 regulation of cellular component organization
496 GO:2000112 regulation of cellular macromolecule biosynthetic process
496 GO:0010468 regulation of gene expression
496 GO:0043549 regulation of kinase activity
496 GO:0019219 regulation of nucleobase-containing compound metabolic process
496 GO:0001932 regulation of protein phosphorylation
496 GO:0009719 response to endogenous stimulus
496 GO:1901700 response to oxygen-containing compound
496 GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway
552 GO:0044267 cellular protein metabolic process
571 GO:0019538 protein metabolic process
571 GO:0060255 regulation of macromolecule metabolic process
575 GO:0016567 protein ubiquitination
575 GO:0060255 regulation of macromolecule metabolic process
591 GO:0016070 RNA metabolic process
591 GO:0010467 gene expression
591 GO:0060255 regulation of macromolecule metabolic process
606 GO:0019538 protein metabolic process
606 GO:0006355 regulation of transcription, DNA-templated
606 GO:0007165 signal transduction
606 GO:0006366 transcription from RNA polymerase II promoter
742 GO:0031325 positive regulation of cellular metabolic process
742 GO:0010604 positive regulation of macromolecule metabolic process
742 GO:0051173 positive regulation of nitrogen compound metabolic process
742 GO:0006357 regulation of transcription from RNA polymerase II promoter
807 GO:0070647 protein modification by small protein conjugation or removal
Cellular Components
Module ID (MoonGO) GO ID (CC) GO Name
35 GO:0005829 cytosol
35 GO:0005634 nucleus
35 GO:0005886 plasma membrane
59 GO:0005634 nucleus
79 GO:0005634 nucleus
107 GO:0005829 cytosol
107 GO:0005654 nucleoplasm
125 GO:0005829 cytosol
125 GO:0005634 nucleus
207 GO:0005829 cytosol
207 GO:0005654 nucleoplasm
283 GO:0012505 endomembrane system
283 GO:0044428 nuclear part
297 GO:0005634 nucleus
342 GO:0012505 endomembrane system
342 GO:0044428 nuclear part
354 GO:0005634 nucleus
359 GO:0005634 nucleus
375 GO:0005829 cytosol
375 GO:0005634 nucleus
496 GO:0005829 cytosol
496 GO:0005634 nucleus
496 GO:0005886 plasma membrane
552 GO:0005634 nucleus
571 GO:0005634 nucleus
575 GO:0005654 nucleoplasm
591 GO:0031981 nuclear lumen
606 GO:0005829 cytosol
606 GO:0031981 nuclear lumen
721 GO:0043232 intracellular non-membrane-bounded organelle
721 GO:0005634 nucleus
742 GO:0005654 nucleoplasm
805 GO:0005634 nucleus
812 GO:0005634 nucleus
GO ID (BP) GO Name Evidence Code (GO EC)
GO:0000209 protein polyubiquitination TAS
GO:0006511 ubiquitin-dependent protein catabolic process IDA
GO:0006915 apoptotic process TAS
GO:0007049 cell cycle IEA
GO:0007283 spermatogenesis IEA
GO:0007399 nervous system development TAS
GO:0007411 axon guidance TAS
GO:0009653 anatomical structure morphogenesis TAS
GO:0030163 protein catabolic process IDA
GO:0031648 protein destabilization IEA
GO:0042787 protein ubiquitination involved in ubiquitin-dependent protein catabolic process ISS
GO:0043065 positive regulation of apoptotic process IDA
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process ISS
GO:0044267 cellular protein metabolic process TAS
GO:0051402 neuron apoptotic process ISS
GO:2001244 positive regulation of intrinsic apoptotic signaling pathway IMP
GO ID (CC) GO Name Evidence Code (GO EC)
GO:0005634 nucleus ISS
GO:0005737 cytoplasm TAS
GO:0005769 early endosome IEA
GO:0005829 cytosol TAS
GO:0005886 plasma membrane IEA
GO:0030877 beta-catenin destruction complex IDA
GO ID 1 Component 1 GO ID 2 Component 2 Association Probability (PrOnto) Interaction Probability (PrOnto)
GO:0005634 nucleus GO:0005886 plasma membrane 5.35e-300 7.52e-165
Interactor Also a MoonDB EMF protein
PRP31_HUMAN No
QRIC1_HUMAN No
ASPP2_HUMAN No
DAB1_HUMAN No
PR20D_HUMAN No
TRI27_HUMAN Yes: P14373 (MoonDB)
KIFC3_HUMAN No
SDCB1_HUMAN Yes: O00560 (MoonDB)
BAG3_HUMAN No
NTAQ1_HUMAN Yes: Q96HA8 (MoonDB)
KHDR3_HUMAN No
APC_HUMAN No
TOLIP_HUMAN No
PR20C_HUMAN No
AQP1_HUMAN No
F90A1_HUMAN No
SPC1L_HUMAN No
A2RRL9_HUMAN No
ACK1_HUMAN No
ADPPT_HUMAN No
AFF1_HUMAN No
AFF4_HUMAN No
ARIP4_HUMAN No
ARMC9_HUMAN No
AROS_HUMAN No
ATN1_HUMAN No
ATX7_HUMAN No
BAG1_HUMAN No
BAG4_HUMAN No
BCL6_HUMAN No
CAPG_HUMAN No
CD5R1_HUMAN No
CDC23_HUMAN No
CN105_HUMAN No
CTIP_HUMAN No
CYBP_HUMAN No
DDX41_HUMAN No
DJC15_HUMAN No
EF1D_HUMAN No
EXAS1_HUMAN No
FLI1_HUMAN No
FZD9_HUMAN No
GDPD5_HUMAN No
GRM5_HUMAN No
H4_HUMAN No
HIPK2_HUMAN No
HIPK3_HUMAN No
IDLC_HUMAN No
IF3M_HUMAN No
INHA_HUMAN No
K1683_HUMAN No
K319L_HUMAN No
KATL1_HUMAN No
KCJ10_HUMAN No
KIF1B_HUMAN No
KIF22_HUMAN No
KLF10_HUMAN No
LACB2_HUMAN No
LANC2_HUMAN No
M1AP_HUMAN No
MABP1_HUMAN No
MARE3_HUMAN No
MB211_HUMAN No
MK12_HUMAN No
MOB3C_HUMAN No
MX1_HUMAN No
MYD88_HUMAN No
NECT2_HUMAN No
NELFA_HUMAN No
NHRF2_HUMAN No
NOL6_HUMAN No
NUMBL_HUMAN No
NUMB_HUMAN No
OBF1_HUMAN No
OPRM_HUMAN No
OTUB2_HUMAN No
PAR6B_HUMAN No
PEG10_HUMAN No
PEG3_HUMAN No
PFKAM_HUMAN No
PHC1_HUMAN No
PHC2_HUMAN Yes: Q8IXK0 (MoonDB)
PIAS1_HUMAN No
PIAS2_HUMAN No
PKD1_HUMAN No
PR20A_HUMAN No
PTPM1_HUMAN No
PUF60_HUMAN No
PYGB_HUMAN No
Q59GP6_HUMAN No
R51A1_HUMAN No
RAPH1_HUMAN No
RB33A_HUMAN No
RL27A_HUMAN No
SIAH2_HUMAN No
SKT_HUMAN No
SPAT4_HUMAN No
STAT3_HUMAN Yes: P40763 (MoonDB)
SYT7_HUMAN No
TB22B_HUMAN No
TFDP1_HUMAN No
THIO_HUMAN No
TMM43_HUMAN No
TRI23_HUMAN No
TRIB3_HUMAN No
TRIM7_HUMAN No
TRIM8_HUMAN Yes: Q9BZR9 (MoonDB)
UB2D1_HUMAN Yes: P51668 (MoonDB)
UB2D2_HUMAN Yes: P62837 (MoonDB)
UB2D3_HUMAN Yes: P61077 (MoonDB)
UB2D4_HUMAN Yes: Q9Y2X8 (MoonDB)
UB2E3_HUMAN Yes: Q969T4 (MoonDB)
UB2R1_HUMAN No
UB2V2_HUMAN No
UBC9_HUMAN Yes: P63279 (MoonDB)
UBE2K_HUMAN Yes: P61086 (MoonDB)
UBE2N_HUMAN Yes: P61088 (MoonDB)
UBP19_HUMAN No
UPP2_HUMAN No
UXT_HUMAN No
VAV_HUMAN No
Z512B_HUMAN No
ZBP1_HUMAN No
ZCH10_HUMAN No
ZCH13_HUMAN No
ZFY21_HUMAN No
ZMAT3_HUMAN No
ZN148_HUMAN No
ZN671_HUMAN No
PMID Article Title
8799150 Activation of the human homologue of the Drosophila sina gene in apoptosis and tumor suppression.
9334332 Mammalian homologs of seven in absentia regulate DCC via the ubiquitin-proteasome pathway.
9403064 Characterization of human homologs of the Drosophila seven in absentia (sina) gene.
9582267 p53-inducible human homologue of Drosophila seven in absentia (Siah) inhibits cell growth: suppression by BAG-1.
9858595 Siah-1 N-terminal RING domain is required for proteolysis function, and C-terminal sequences regulate oligomerization and binding to target proteins.
10747903 p53 suppresses the c-Myb-induced activation of heat shock transcription factor 3.
10956387 Lack of somatic mutation in the coding sequence of SIAH1 in tumors hemizygous for this candidate tumor suppressor gene.
11146551 SIAH-1 interacts with alpha-tubulin and degrades the kinesin Kid by the proteasome pathway during mitosis.
11389839 Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses.
11389840 Siah-1 mediates a novel beta-catenin degradation pathway linking p53 to the adenomatous polyposis coli protein.
11483517 The RING finger protein Siah-1 regulates the level of the transcriptional coactivator OBF-1.
11483518 Regulation of BOB.1/OBF.1 stability by SIAH.
11752454 Siah-1 binds and regulates the function of Numb.
12072443 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.
12421809 Structural analysis of Siah1 and its interactions with Siah-interacting protein (SIP).
12557228 SIAH1 inactivation correlates with tumor progression in hepatocellular carcinomas.
12810624 Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1.
14506261 Siah-1 facilitates ubiquitination and degradation of synphilin-1.
14645235 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.
14654780 SIAH-1 interacts with CtIP and promotes its degradation by the proteasome pathway.
15064394 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.
15163637 SIAH1 targets the alternative splicing factor T-STAR for degradation by the proteasome.
15489334 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
16085652 Structural analysis of Siah1-Siah-interacting protein interactions and insights into the assembly of an E3 ligase multiprotein complex.
17420721 Siah-1S, a novel splice variant of Siah-1 (seven in absentia homolog), counteracts Siah-1-mediated downregulation of beta-catenin.
17974005 The full-ORF clone resource of the German cDNA consortium.
18536714 Control of HIPK2 stability by ubiquitin ligase Siah-1 and checkpoint kinases ATM and ATR.
18669648 A quantitative atlas of mitotic phosphorylation.
19224863 Synphilin-1A inhibits seven in absentia homolog (SIAH) and modulates alpha-synuclein monoubiquitylation and inclusion formation.
20508617 Ubiquitin conjugase UBCH8 targets active FMS-like tyrosine kinase 3 for proteasomal degradation.
22483617 The ubiquitin ligase Siah1 controls ELL2 stability and formation of super elongation complexes to modulate gene transcription.
No results found.
Domain Name Domain ID Source
Znf_RING IPR001841 InterPro
SINA-like IPR004162 InterPro
TRAF-like IPR008974 InterPro
Znf_SIAH IPR013010 InterPro
Znf_RING/FYVE/PHD IPR013083 InterPro
7-in-absentia-prot_TRAF-dom IPR018121 InterPro
Sina PF03145 Pfam
ZF_RING_2 PS50089 PROSITE
ZF_SIAH PS51081 PROSITE
PTHR10315 PTHR10315 PANTHER
SSF49599 SSF49599 SUPFAM