General Information of the m6A Target Gene (ID: M6ATAR00392)
Target Name E3 ubiquitin-protein ligase SIAH1 (SIAH1)
Synonyms
RING-type E3 ubiquitin transferase SIAH1; Seven in absentia homolog 1; Siah-1; Siah-1a; HUMSIAH
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Gene Name SIAH1
Chromosomal Location 16q12.1
Family SINA (Seven in absentia) family
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 (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 (By similarity). Upon nitric oxid (NO) generation that follows apoptotic stimulation, interacts with S-nitrosylated GAPDH, mediating the translocation of GAPDH to the nucleus (By similarity). GAPDH acts as a stabilizer of SIAH1, facilitating the degradation of nuclear proteins (By similarity). Mediates ubiquitination and degradation of EGLN2 and EGLN3 in response to the unfolded protein response (UPR), leading to their degradation and subsequent stabilization of ATF4 (By similarity).
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Gene ID 6477
Uniprot ID
SIAH1_HUMAN
HGNC ID
HGNC:10857
Ensembl Gene ID
ENSG00000196470
KEGG ID
hsa:6477
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
SIAH1 can be regulated by the following regulator(s), and cause disease/drug response(s). You can browse detail information of regulator(s) or disease/drug response(s).
Browse Regulator
Browse Disease
Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) [READER]
Representative RNA-seq result indicating the expression of this target gene regulated by HNRNPA2B1
Cell Line c2c12 cell line Mus musculus
Treatment: HNRNPA2B1 knockout c2c12 cells
Control: WT c2c12 cells
GSE152467
Regulation
logFC: 1.19E+00
p-value: 5.63E-11
More Results Click to View More RNA-seq Results
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary The RP11/hnRNPA2B1/mRNA complex accelerated the mRNA degradation of two E3 ligases, E3 ubiquitin-protein ligase SIAH1 (SIAH1) and Fbxo45, and subsequently prevented the proteasomal degradation of Zeb1. m6A can regulate the expression of RP11, further, RP11 regulated Siah1-Fbxo45/Zeb1 was involved in the development of Colorectal cancer.
Target Regulation Down regulation
Responsed Disease Colorectal cancer ICD-11: 2B91
Pathway Response Proteasome hsa03050
Cell Process Proteasomal degradation
In-vitro Model DLD-1 Colon adenocarcinoma Homo sapiens CVCL_0248
HCT 15 Colon adenocarcinoma Homo sapiens CVCL_0292
HCT 8 Colon adenocarcinoma Homo sapiens CVCL_2478
RKO Colon carcinoma Homo sapiens CVCL_0504
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
In-vivo Model HCT-15 RP11 stable overexpression or control cells (2 × 106 per mouse) diluted in 100 uL normal medium + 100 uL Matrigel (BD Biosciences) were subcutaneously injected into immunodeficient mice to investigate tumour growth.
Colorectal cancer [ICD-11: 2B91]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary The RP11/hnRNPA2B1/mRNA complex accelerated the mRNA degradation of two E3 ligases, E3 ubiquitin-protein ligase SIAH1 (SIAH1) and Fbxo45, and subsequently prevented the proteasomal degradation of Zeb1. m6A can regulate the expression of RP11, further, RP11 regulated Siah1-Fbxo45/Zeb1 was involved in the development of Colorectal cancer.
Responsed Disease Colorectal cancer [ICD-11: 2B91]
Target Regulator Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) READER
Target Regulation Down regulation
Pathway Response Proteasome hsa03050
Cell Process Proteasomal degradation
In-vitro Model DLD-1 Colon adenocarcinoma Homo sapiens CVCL_0248
HCT 15 Colon adenocarcinoma Homo sapiens CVCL_0292
HCT 8 Colon adenocarcinoma Homo sapiens CVCL_2478
RKO Colon carcinoma Homo sapiens CVCL_0504
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
In-vivo Model HCT-15 RP11 stable overexpression or control cells (2 × 106 per mouse) diluted in 100 uL normal medium + 100 uL Matrigel (BD Biosciences) were subcutaneously injected into immunodeficient mice to investigate tumour growth.
References
Ref 1 m(6)A-induced lncRNA RP11 triggers the dissemination of colorectal cancer cells via upregulation of Zeb1. Mol Cancer. 2019 Apr 13;18(1):87. doi: 10.1186/s12943-019-1014-2.