SIAH1
entrez
6477
canonical
uniprot
Q8IUQ4
canonical
ensembl
ENSG00000196470
resolver
ensp
ENSP00000349156
resolver
ensp
ENSP00000378214
resolver
ensp
ENSP00000563263
resolver
ensp
ENSP00000563265
resolver
genesymbol
SIAH1
resolver
genesymbol_syn
HUMSIAH
resolver
hgnc
HGNC:10857
resolver
uniprot
A0FKF3
resolver
uniprot
O43269
resolver
uniprot
Q49A58
resolver
uniprot
Q92880
resolver
uniprot_entry
SIAH1_HUMAN
resolver
uniprot_sec
A0FKF3
resolver
uniprot_sec
O43269
resolver
uniprot_sec
Q49A58
resolver
uniprot_sec
Q92880
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by interaction with SNCAIP (isoform 2, but not isoform 1). May be inhibited by interaction with PEG10. {ECO:0000269|PubMed:19224863}.
uniprot
proteins
amino_acid_sequence
MSRQTATALPTGTSKCPPSQRVPALTGTTASNNDLASLFECPVCFDYVLPPILQCQSGHLVCSNCRPKLTCCPTCRGPLGSIRNLAMEKVANSVLFPCKYASSGCEITLPHTEKADHEELCEFRPYSCPCPGASCKWQGSLDAVMPHLMHQHKSITTLQGEDIVFLATDINLPGAVDWVMMQSCFGFHFMLVLEKQEKYDGHQQFFAIVQLIGTRKQAENFAYRLELNGHRRRLTWEATPRSIHEGIATAIMNSDCLVFDTSIAQLFAENGNLGINVTISMC
uniprot
proteins
disease_involvement
DISEASE: Buratti-Harel syndrome (BURHAS) [MIM:619314]: An autosomal dominant neurodevelopmental disorder characterized by hypotonia apparent in early infancy, global developmental delay, delayed walking, language and speech delay, impaired intellectual development, and dysmorphic facial features. {ECO:0000269|PubMed:32430360}. Note=The disease is caused by variants affecting the gene represented in this entry.
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 (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:28546513, PubMed:32430360, PubMed:33591310, PubMed:9334332, PubMed:9858595, PubMed:41062835). 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 (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595). Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595). 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 (PubMed:10747903, PubMed:11146551, PubMed:11389839, PubMed:11389840, PubMed:11483517, PubMed:11483518, PubMed:11752454, PubMed:12072443, PubMed:41062835). Confers constitutive instability to HIPK2 through proteasomal degradation (PubMed:18536714, PubMed:33591310). It is thereby involved in many cellular processes such as apoptosis, tumor suppression, cell cycle, axon guidance, transcription regulation, spermatogenesis and TNF signaling (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595). Has some overlapping function with SIAH2 (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595). 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). Also part of the Wnt signaling pathway in which it mediates the Wnt-induced ubiquitin-mediated proteasomal degradation of AXIN1 (PubMed:28546513, PubMed:32430360). {ECO:0000250|UniProtKB:P61092, ECO:0000250|UniProtKB:Q920M9, ECO:0000269|PubMed:10747903, ECO:0000269|PubMed:11146551, ECO:0000269|PubMed:11389839, ECO:0000269|PubMed:11389840, ECO:0000269|PubMed:11483517, ECO:0000269|PubMed:11483518, ECO:0000269|PubMed:11752454, ECO:0000269|PubMed:12072443, ECO:0000269|PubMed:14506261, ECO:0000269|PubMed:14645235, ECO:0000269|PubMed:14654780, ECO:0000269|PubMed:15064394, ECO:0000269|PubMed:16085652, ECO:0000269|PubMed:18536714, ECO:0000269|PubMed:19224863, ECO:0000269|PubMed:20508617, ECO:0000269|PubMed:22483617, ECO:0000269|PubMed:28546513, ECO:0000269|PubMed:32430360, ECO:0000269|PubMed:41062835, ECO:0000269|PubMed:9334332, ECO:0000269|PubMed:9858595}.
uniprot
proteins
mass_dalton
31123
uniprot
proteins
mutagenesis
MUTAGEN 19; /note="S->A: Impaired ATM mediated phosphorylation, but normal interaction with HIPK2 and HIPK2 subsequent proteasomal degradation."; /evidence="ECO:0000269|PubMed:18536714"; MUTAGEN 19; /note="S->D: Reduced interaction with HIPK2 and HIPK2 subsequent proteasomal degradation."; /evidence="ECO:0000269|PubMed:18536714"; MUTAGEN 40; /note="E->R: Loss of function."; /evidence="ECO:0000269|PubMed:9858595"; MUTAGEN 41; /note="C->S: Loss of function; when associated with S-44."; /evidence="ECO:0000269|PubMed:9858595"; MUTAGEN 44; /note="C->S: Loss of function."; /evidence="ECO:0000269|PubMed:18536714, ECO:0000269|PubMed:9858595"; MUTAGEN 55; /note="C->A: Loss of function; when associated with A-59 and S-72."; /evidence="ECO:0000269|PubMed:15064394, ECO:0000269|PubMed:9858595"; MUTAGEN 55; /note="C->S: Loss of function; when associated with Y-59."; /evidence="ECO:0000269|PubMed:15064394, ECO:0000269|PubMed:9858595"; MUTAGEN 59; /note="H->A: Loss of function; when associated with A-55 and S-72."; /evidence="ECO:0000269|PubMed:15064394, ECO:0000269|PubMed:9858595"; MUTAGEN 59; /note="H->Y: Loss of function."; /evidence="ECO:0000269|PubMed:15064394, ECO:0000269|PubMed:9858595"; MUTAGEN 66; /note="R->L: Decreased activity; when associated with T-68."; /evidence="ECO:0000269|PubMed:9858595"; MUTAGEN 68; /note="K->T: Decreased activity; when associated with L-66."; /evidence="ECO:0000269|PubMed:9858595"; MUTAGEN 72; /note="C->S: Loss of function; when associated with A-55 and A-59."; /evidence="ECO:0000269|PubMed:15064394"; MUTAGEN 76; /note="R->E: Decreased activity."; /evidence="ECO:0000269|PubMed:9858595"; MUTAGEN 124; /note="R->A: In D; does not impair its ability to interact with CACYBP and degrade CTNNB1 and PML; when associated with A-214; A-215; A-231 and A-232."; /evidence="ECO:0000269|PubMed:12421809, ECO:0000269|PubMed:14645235"; MUTAGEN 142; /note="D->A: In E; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-151."; /evidence="ECO:0000269|PubMed:12421809"; MUTAGEN 151; /note="Q->A: In E; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-142."; /evidence="ECO:0000269|PubMed:12421809"; MUTAGEN 152; /note="H->Y: Abolishes ability to degrade DCC."; /evidence="ECO:0000269|PubMed:9858595"; MUTAGEN 161..162; /note="ED->AA: In A; does not impair its ability to degrade PML while it abolishes its ability to interact with CACYBP and degrade CTNNB1; when associated with A-226 and A-237."; /evidence="ECO:0000269|PubMed:12421809, ECO:0000269|PubMed:14645235"; MUTAGEN 198..200; /note="KYD->GDG: Impairs CTNNB1 degradation."; /evidence="ECO:0000269|PubMed:16085652"; MUTAGEN 202; /note="H->Y: No effect."; /evidence="ECO:0000269|PubMed:9858595"; MUTAGEN 211; /note="L->R: Abolishes ability to degrade DCC."; /evidence="ECO:0000269|PubMed:9858595"; MUTAGEN 214..215; /note="TR->AA: In D; does not impair its ability to interact with CACYBP and degrade CTNNB1 and PML; when associated with A-124; A-231 and A-232."; /evidence="ECO:0000269|PubMed:12421809, ECO:0000269|PubMed:14645235"; MUTAGEN 224; /note="R->A: In C; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-233."; /evidence="ECO:0000269|PubMed:12421809"; MUTAGEN 226; /note="E->A: In A; does not impair its ability to degrade PML while it abolishes its ability to interact with CACYBP and degrade CTNNB1; when associated with A-161; A-162 and A-237."; /evidence="ECO:0000269|PubMed:12421809, ECO:0000269|PubMed:14645235"; MUTAGEN 231..232; /note="RR->AA: In D; does not impair its ability to interact with CACYBP and degrade CTNNB1 and PML; when associated with A-124; A-214 and A-215."; /evidence="ECO:0000269|PubMed:12421809, ECO:0000269|PubMed:14645235"; MUTAGEN 233; /note="R->A: In C; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-233."; /evidence="ECO:0000269|PubMed:12421809"; MUTAGEN 237; /note="E->A: In A; does not impair its ability to degrade PML while it abolishes its ability to interact with CACYBP and degrade CTNNB1; when associated with A-161; A-162 and A-226."; /evidence="ECO:0000269|PubMed:12421809, ECO:0000269|PubMed:14645235"; MUTAGEN 252; /note="M->D,K: Impairs CTNNB1 degradation."; /evidence="ECO:0000269|PubMed:16085652"; MUTAGEN 253; /note="N->A: In B; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-265."; /evidence="ECO:0000269|PubMed:12421809"; MUTAGEN 265; /note="Q->A: In B; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-253."; /evidence="ECO:0000269|PubMed:12421809
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:19224863, 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. {ECO:0000269|PubMed:18536714}.
uniprot
proteins
protein_family
SINA (Seven in absentia) family
uniprot
proteins
pubmed
10747903
uniprot
proteins
pubmed
10956387
uniprot
proteins
pubmed
11146551
uniprot
proteins
pubmed
11389839
uniprot
proteins
pubmed
11389840
uniprot
proteins
pubmed
11483517
uniprot
proteins
pubmed
11483518
uniprot
proteins
pubmed
11752454
uniprot
proteins
pubmed
12072443
uniprot
proteins
pubmed
12421809
uniprot
proteins
pubmed
12557228
uniprot
proteins
pubmed
12810624
uniprot
proteins
pubmed
14506261
uniprot
proteins
pubmed
14645235
uniprot
proteins
pubmed
14654780
uniprot
proteins
pubmed
15064394
uniprot
proteins
pubmed
15163637
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16085652
uniprot
proteins
pubmed
17420721
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18536714
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19224863
uniprot
proteins
pubmed
20508617
uniprot
proteins
pubmed
22483617
uniprot
proteins
pubmed
28546513
uniprot
proteins
pubmed
32430360
uniprot
proteins
pubmed
33591310
uniprot
proteins
pubmed
41062835
uniprot
proteins
pubmed
8799150
uniprot
proteins
pubmed
9334332
uniprot
proteins
pubmed
9403064
uniprot
proteins
pubmed
9582267
uniprot
proteins
pubmed
9858595
uniprot
proteins
sequence_length
282
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Predominantly cytoplasmic. Partially nuclear.
uniprot
proteins