ARIH1
entrez
25820
canonical
uniprot
Q9Y4X5
canonical
ensembl
ENSG00000166233
resolver
ensp
ENSP00000369217
resolver
enst
ENST00000379887
resolver
genesymbol
ARIH1
resolver
genesymbol_syn
ARI
resolver
genesymbol_syn
MOP6
resolver
genesymbol_syn
UBCH7BP
resolver
hgnc
HGNC:689
resolver
uniprot
B2R6U3
resolver
uniprot
O76026
resolver
uniprot
Q9H3T6
resolver
uniprot
Q9UEN0
resolver
uniprot
Q9UP39
resolver
uniprot_entry
ARI1_HUMAN
resolver
uniprot_sec
B2R6U3
resolver
uniprot_sec
O76026
resolver
uniprot_sec
Q9H3T6
resolver
uniprot_sec
Q9UEN0
resolver
uniprot_sec
Q9UP39
resolver
activity_regulation
ACTIVITY REGULATION: Autoinhibited by the ariadne domain, which masks the second RING-type zinc finger that contains the active site and inhibits the E3 activity (PubMed:23707686). Inhibition is relieved upon binding to neddylated cullin-RING ubiquitin ligase complexes, which activate the E3 ligase activity of ARIH1 (PubMed:24076655, PubMed:27565346). {ECO:0000269|PubMed:23707686, ECO:0000269|PubMed:24076655, ECO:0000269|PubMed:27565346}.
uniprot
proteins
amino_acid_sequence
MDSDEGYNYEFDEDEECSEEDSGAEEEEDEDDDEPDDDTLDLGEVELVEPGLGVGGERDGLLCGETGGGGGSALGPGGGGGGGGGGGGGGPGHEQEEDYRYEVLTAEQILQHMVECIREVNEVIQNPATITRILLSHFNWDKEKLMERYFDGNLEKLFAECHVINPSKKSRTRQMNTRSSAQDMPCQICYLNYPNSYFTGLECGHKFCMQCWSEYLTTKIMEEGMGQTISCPAHGCDILVDDNTVMRLITDSKVKLKYQHLITNSFVECNRLLKWCPAPDCHHVVKVQYPDAKPVRCKCGRQFCFNCGENWHDPVKCKWLKKWIKKCDDDSETSNWIAANTKECPKCHVTIEKDGGCNHMVCRNQNCKAEFCWVCLGPWEPHGSAWYNCNRYNEDDAKAARDAQERSRAALQRYLFYCNRYMNHMQSLRFEHKLYAQVKQKMEEMQQHNMSWIEVQFLKKAVDVLCQCRATLMYTYVFAFYLKKNNQSIIFENNQADLENATEVLSGYLERDISQDSLQDIKQKVQDKYRYCESRRRVLLQHVHEGYEKDLWEYIED
uniprot
proteins
disease_involvement
DISEASE: Note=Defects in ARIH1 have been found in several individuals with thoracic aortic aneurysms and cerebrovascular disease. {ECO:0000269|PubMed:29689197}.
uniprot
proteins
ec_number
2.3.2.31
uniprot
proteins
function
FUNCTION: E3 ubiquitin-protein ligase, which catalyzes ubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3 (PubMed:15236971, PubMed:21532592, PubMed:23707686, PubMed:24076655, PubMed:27565346). Acts as an atypical E3 ubiquitin-protein ligase by working together with cullin-RING ubiquitin ligase (CRL) complexes and initiating ubiquitination of CRL substrates: associates with CRL complexes and specifically mediates addition of the first ubiquitin on CRLs targets (PubMed:27565346). The initial ubiquitin is then elongated by CDC34/UBE2R1 and UBE2R2 (PubMed:27565346). E3 ubiquitin-protein ligase activity is activated upon binding to neddylated cullin-RING ubiquitin ligase complexes (PubMed:24076655, PubMed:27565346). Plays a role in protein translation in response to DNA damage by mediating ubiquitination of EIF4E2, the consequences of EIF4E2 ubiquitination are however unclear (PubMed:25624349). According to a report, EIF4E2 ubiquitination leads to promote EIF4E2 cap-binding and protein translation arrest (PubMed:25624349). According to another report EIF4E2 ubiquitination leads to its subsequent degradation (PubMed:14623119). Acts as the ligase involved in ISGylation of EIF4E2 (PubMed:17289916). In vitro, controls the degradation of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex member SUN2 and may therefore have a role in the formation and localization of the LINC complex, and as a consequence, nuclear subcellular localization and nuclear morphology (PubMed:29689197). {ECO:0000269|PubMed:14623119, ECO:0000269|PubMed:15236971, ECO:0000269|PubMed:17289916, ECO:0000269|PubMed:21532592, ECO:0000269|PubMed:23707686, ECO:0000269|PubMed:24076655, ECO:0000269|PubMed:25624349, ECO:0000269|PubMed:27565346, ECO:0000269|PubMed:29689197}.
uniprot
proteins
mass_dalton
64118
uniprot
proteins
mutagenesis
MUTAGEN 123; /note="V->A: Strongly decreased ability to initiate ubiquitination of cullin-RING complexes."; /evidence="ECO:0000269|PubMed:27565346"; MUTAGEN 150; /note="F->A: Strongly decreased ability to initiate ubiquitination of cullin-RING complexes."; /evidence="ECO:0000269|PubMed:27565346"; MUTAGEN 156..158; /note="KLF->AAA: Strongly decreased ability to initiate ubiquitination of cullin-RING complexes."; /evidence="ECO:0000269|PubMed:27565346"; MUTAGEN 187..188; /note="QI->HV: No loss of interaction with UBE2L3."; /evidence="ECO:0000269|PubMed:11278816"; MUTAGEN 188; /note="I->A: Loss of interaction with UBE2L3. Decreased E3 ligase activity. Strongly decreased ability to initiate ubiquitination of cullin-RING complexes."; /evidence="ECO:0000269|PubMed:11278816, ECO:0000269|PubMed:23707686, ECO:0000269|PubMed:27565346"; MUTAGEN 205; /note="H->A: Impaired interaction with UBE2L3 without affecting interaction with neddylated cullin-RING complexes."; /evidence="ECO:0000269|PubMed:24076655"; MUTAGEN 208; /note="C->A,H: Loss of interaction with UBE2L3."; /evidence="ECO:0000269|PubMed:11278816"; MUTAGEN 257..258; /note="KY->AAA: Strongly decreased ability to initiate ubiquitination of cullin-RING complexes."; /evidence="ECO:0000269|PubMed:27565346"; MUTAGEN 258; /note="Y->A: No loss of interaction with UBE2L3."; /evidence="ECO:0000269|PubMed:11278816"; MUTAGEN 265..267; /note="SFV->AAA: Strongly decreased ability to initiate ubiquitination of cullin-RING complexes."; /evidence="ECO:0000269|PubMed:27565346"; MUTAGEN 340..341; /note="NT->AA: Strongly decreased ability to initiate ubiquitination of cullin-RING complexes."; /evidence="ECO:0000269|PubMed:27565346"; MUTAGEN 342..343; /note="KE->AA: Strongly decreased ability to initiate ubiquitination of cullin-RING complexes."; /evidence="ECO:0000269|PubMed:27565346"; MUTAGEN 347; /note="C->A: Impairs zinc-binding and folding. Abolishes E3 ubiquitin-protein ligase activity."; /evidence="ECO:0000269|PubMed:15236971"; MUTAGEN 351..352; /note="IE->AA: Strongly decreased ability to initiate ubiquitination of cullin-RING complexes."; /evidence="ECO:0000269|PubMed:27565346"; MUTAGEN 351; /note="I->A: Disrupts the hydrophobic network. Abolishes E3 ubiquitin-protein ligase activity."; /evidence="ECO:0000269|PubMed:15236971"; MUTAGEN 357; /note="C->A,S: Does not affect zinc binding and folding. Abolishes ability to transfer ubiquitin and E3 ubiquitin-protein ligase activity."; /evidence="ECO:0000269|PubMed:15236971, ECO:0000269|PubMed:21532592, ECO:0000269|PubMed:24058416, ECO:0000269|PubMed:24076655"; MUTAGEN 358; /note="N->A: Defects in ligation."; /evidence="ECO:0000269|PubMed:27565346"; MUTAGEN 359; /note="H->A: Defects in ligation. Does not affect zinc binding, folding. Does not impair E3 ubiquitin-protein ligase activity."; /evidence="ECO:0000269|PubMed:15236971, ECO:0000269|PubMed:27565346"; MUTAGEN 367; /note="C->A: Impairs zinc-binding and folding. Abolishes E3 ubiquitin-protein ligase activity."; /evidence="ECO:0000269|PubMed:15236971"; MUTAGEN 371; /note="F->A: Disrupts the hydrophobic network. Abolishes E3 ubiquitin-protein ligase activity."; /evidence="ECO:0000269|PubMed:15236971"; MUTAGEN 372; /note="C->A: Impairs E3 ubiquitin-protein ligase activity."; /evidence="ECO:0000269|PubMed:15236971"; MUTAGEN 373; /note="W->A: Abolishes E3 ubiquitin-protein ligase activity."; /evidence="ECO:0000269|PubMed:15236971"; MUTAGEN 378..379; /note="PW->AA: Defects in ligation."; /evidence="ECO:0000269|PubMed:27565346"; MUTAGEN 379; /note="W->A: Does not affect E3 ubiquitin-protein ligase activity."; /evidence="ECO:0000269|PubMed:15236971"; MUTAGEN 383..385; /note="GSA->AAD: Defects in ligation."; /evidence="ECO:0000269|PubMed:27565346"; MUTAGEN 386; /note="W->A: Does not affect E3 ubiquitin-protein ligase activity. Strongly decreased ability to initiate ubiquitination of cullin-RING complexes."; /evidence="ECO:0000269|PubMed:15236971, ECO:0000269|PubMed:27565346"; MUTAGEN 416; /note="F->A: Slightly relieves autoinhibition of the E3 ligase activity by the ariadne domain."; /evidence="ECO:0000269|PubMed:23707686"; MUTAGEN 417; /note="Y->A: Hyperactive 'open' mutant that displays enhanced E3 ubiquitin-protein ligase activity."; /evidence="ECO:0000269|PubMed:27565346"; MUTAGEN 420..423; /note="RYMN->AYMA: Slightly relieves autoinhibition of the E3 ligase activity by the ariadne domain. Hyperactive 'open' mutant that displays enhanced E3 ubiquitin-protein ligase activity; when associated with A-503."; /evidence="ECO:0000269|PubMed:23707686, ECO:0000269|PubMed:27565346"; MUTAGEN 427; /note="S->A: Slightly relieves autoinhibition of the E3 ligase activity by the ariadne domain."; /evidence="ECO:0000269|PubMed:23707686"; MUTAGEN 430..431; /note="FE->AA: Relieves autoinhibition of the E3 ligase activity by the ariadne domain; when associated with A-503. Hyperactive 'open' mutant that displays enhanced E3 ubiquitin-protein ligase activity; when associated with A-503."; /evidence="ECO:0000269|PubMed:23707686, ECO:0000269|PubMed:24076655, ECO:0000269|PubMed:27565346"; MUTAGEN 476; /note="Y->A: Hyperactive 'open' mutant that displays enhanced E3 ubiquitin-protein ligase activity."; /evidence="ECO:0000269|PubMed:27565346"; MUTAGEN 492; /note="E->A: Hyperactive 'open' mutant that displays enhanced E3 ubiquitin-protein ligase activity."; /evidence="ECO:0000269|PubMed:27565346"; MUTAGEN 493; /note="N->A: Hyperactive 'open' mutant that displays enhanced E3 ubiquitin-protein ligase activity."; /evidence="ECO:0000269|PubMed:27565346"; MUTAGEN 495; /note="Q->A: Hyperactive 'open' mutant that displays enhanced E3 ubiquitin-protein ligase activity."; /evidence="ECO:0000269|PubMed:27565346"; MUTAGEN 499; /note="E->A: Hyperactive 'open' mutant that displays enhanced E3 ubiquitin-protein ligase activity."; /evidence="ECO:0000269|PubMed:27565346"; MUTAGEN 503; /note="E->A: Relieves autoinhibition of the E3 ligase activity by the ariadne domain; when associated with 430-A-A-431. Hyperactive 'open' mutant that displays enhanced E3 ubiquitin-protein ligase activity; when associated with 430-A-A-431. Hyperactive 'open' mutant that displays enhanced E3 ubiquitin-protein ligase activity; when associated with 420-A--A-423."; /evidence="ECO:0000269|PubMed:23707686, ECO:0000269|PubMed:24076655, ECO:0000269|PubMed:27565346"; MUTAGEN 531; /note="Y->A: Strongly decreased ability to initiate ubiquitination of cullin-RING complexes."; /evidence="ECO:0000269|PubMed:27565346
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination.
uniprot
proteins
protein_family
Ariadne subfamily
uniprot
proteins
protein_family
RBR family
uniprot
proteins
pubmed
10521492
uniprot
proteins
pubmed
10880484
uniprot
proteins
pubmed
11124525
uniprot
proteins
pubmed
11124703
uniprot
proteins
pubmed
11278816
uniprot
proteins
pubmed
14623119
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15236971
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16572171
uniprot
proteins
pubmed
17289916
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21532592
uniprot
proteins
pubmed
21590270
uniprot
proteins
pubmed
23059369
uniprot
proteins
pubmed
23707686
uniprot
proteins
pubmed
24058416
uniprot
proteins
pubmed
24076655
uniprot
proteins
pubmed
25624349
uniprot
proteins
pubmed
27565346
uniprot
proteins
pubmed
29689197
uniprot
proteins
sequence_length
557
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11278816, ECO:0000269|PubMed:21590270, ECO:0000269|PubMed:23059369}. Nucleus {ECO:0000269|PubMed:23059369}. Nucleus, Cajal body {ECO:0000269|PubMed:23059369}. Note=Mainly cytoplasmic (PubMed:11278816). Present in Lewy body (PubMed:21590270). {ECO:0000269|PubMed:11278816, ECO:0000269|PubMed:21590270}.
uniprot
proteins