Siah1a
entrez
20437
canonical
uniprot
P61092
canonical
ensembl
ENSMUSG00000036840
resolver
ensp
ENSMUSP00000044123
resolver
enst
ENSMUST00000045296
resolver
genesymbol
Siah1a
resolver
uniprot
Q06984
resolver
uniprot_entry
SIA1A_MOUSE
resolver
uniprot_sec
Q06984
resolver
amino_acid_sequence
MSRQTATALPTGTSKCPPSQRVPALTGTTASNNDLASLFECPVCFDYVLPPILQCQSGHLVCSNCRPKLTCCPTCRGPLGSIRNLAMEKVANSVLFPCKYASSGCEITLPHTEKAEHEELCEFRPYSCPCPGASCKWQGSLDAVMPHLMHQHKSITTLQGEDIVFLATDINLPGAVDWVMMQSCFGFHFMLVLEKQEKYDGHQQFFAIVQLIGTRKQAENFAYRLELNGHRRRLTWEATPRSIHEGIATAIMNSDCLVFDTSIAQLFAENGNLGINVTISMC
uniprot
proteins
ec_number
2.3.2.27
uniprot
proteins
function
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), in transcriptional restart after DNA damage (AFF1), 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 (By similarity). 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 signaling. Has some overlapping function with SIAH2 (By similarity). Required for completion of meiosis I in males (PubMed:11884614). Induces apoptosis in cooperation with PEG3 (PubMed:10681424). 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 (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 (PubMed:24809345). Also part of the Wnt signaling pathway in which it mediates the Wnt-induced ubiquitin-mediated proteasomal degradation of AXIN1. {ECO:0000250|UniProtKB:Q8IUQ4, ECO:0000250|UniProtKB:Q920M9, ECO:0000269|PubMed:10681424, ECO:0000269|PubMed:11884614, ECO:0000269|PubMed:24809345, ECO:0000269|PubMed:28546513}.
uniprot
proteins
mass_dalton
31137
uniprot
proteins
mutagenesis
MUTAGEN 156; /note="T->E: Strongly reduced binding and degradation of target proteins; when associated with D-158."; /evidence="ECO:0000269|PubMed:16615911"; MUTAGEN 158; /note="L->D,K: Strongly reduced binding of target proteins. Strongly reduced degradation of target proteins."; /evidence="ECO:0000269|PubMed:16615911"; MUTAGEN 166; /note="L->K: Minor effect on binding and degradation of target proteins."; /evidence="ECO:0000269|PubMed:16615911"; MUTAGEN 176..178; /note="VDW->AAA: Loss of interaction with AXIN1. Loss of function in AXIN1 degradation. Loss of function in Wnt signaling."; /evidence="ECO:0000269|PubMed:28546513"; MUTAGEN 180; /note="M->K: Strongly reduced binding of target proteins. Strongly reduced degradation of target proteins."; /evidence="ECO:0000269|PubMed:16615911
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:28546513}.
uniprot
proteins
post_translational_modification
PTM: Phosphorylated on Ser-19 by ATM and ATR. This phosphorylation disrupts SIAH1 interaction with HIPK2, and subsequent proteasomal degradation of HIPK2 (By similarity). {ECO:0000250|UniProtKB:Q8IUQ4}.
uniprot
proteins
protein_family
SINA (Seven in absentia) family
uniprot
proteins
pubmed
10681424
uniprot
proteins
pubmed
11742346
uniprot
proteins
pubmed
11884614
uniprot
proteins
pubmed
12417719
uniprot
proteins
pubmed
12646221
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16615911
uniprot
proteins
pubmed
24809345
uniprot
proteins
pubmed
28546513
uniprot
proteins
pubmed
8404535
uniprot
proteins
sequence_length
282
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Predominantly cytoplasmic. Partially nuclear.
uniprot
proteins