UniProt:O95376 ARIH2

chain
  • chain:1-493
checksum 30AFFDD327B51013
comment
  • FUNCTION E3 ubiquitin-protein ligase, which catalyzes ubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3 (PubMed:16118314, PubMed:17646546, PubMed:19340006, PubMed:24076655, PubMed:33268465, PubMed:34518685, PubMed:38418882). Acts as an atypical E3 ubiquitin-protein ligase by working together with cullin-5-RING ubiquitin ligase complex (ECS complex, also named CRL5 complex) and initiating ubiquitination of ECS substrates: associates with ECS complex and specifically mediates addition of the first ubiquitin on ECS targets (PubMed:33268465, PubMed:34518685, PubMed:38418882). The initial ubiquitin is then elongated (PubMed:33268465). E3 ubiquitin-protein ligase activity is activated upon binding to neddylated form of the cullin-5 (CUL5) component of the ECS complex (PubMed:24076655). Together with the ECS(ASB9) complex, catalyzes ubiquitination of CKB (PubMed:33268465). Promotes ubiquitination of DCUN1D1 (PubMed:30587576). Mediates 'Lys-6', 'Lys-48'- and 'Lys-63'-linked polyubiquitination (PubMed:16118314, PubMed:17646546, PubMed:19340006). May play a role in myelopoiesis (PubMed:19340006).FUNCTION (Microbial infection) Following infection by HIV-1 virus, acts together with a cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex) hijacked by the HIV-1 Vif protein, to catalyze ubiquitination and degradation of APOBEC3F and APOBEC3G.CATALYTIC ACTIVITY [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-N(6)-ubiquitinyl-L-lysine.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:34518685). Inhibition is relieved upon binding to neddylated cullin-RING ubiquitin ligase complexes, which activate the E3 ligase activity of ARIH1 (PubMed:24076655, PubMed:33268465, PubMed:34518685).PATHWAY Protein modification; protein ubiquitination.SUBUNIT Interacts with (neddylated) CUL5; promoting association with cullin-5-RING ubiquitin ligase complexes (ECS complexes) (PubMed:24076655, PubMed:33268465). Does not interact with other neddylated cullins (CUL1, CUL2, CUL3, CUL4A or CUL4B) (PubMed:24076655). Interacts (via RING-type zinc finger 1) with UBE2L3 (PubMed:16118314, PubMed:19340006, PubMed:24076655). Interacts (via RING-type zinc finger 2) with UBE2N (PubMed:19340006). Interacts (via RING-type 2) with GFI1B (PubMed:17646546). Interacts with GFI1; prevents its ubiquitination and proteasomal degradation (PubMed:17646546).INTERACTION Widely expressed with higher expression in granulocytes.INDUCTION Up-regulated by all-trans retinoic acid (ATRA). Up-regulated during differentiation of immature blood cells toward monocytes and granulocytes.DOMAIN Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING-type zinc finger, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved active site Cys residue in the second RING-type zinc finger. The active site probably forms a thioester intermediate with ubiquitin taken from the active-site cysteine of the E2 before ultimately transferring it to a Lys residue on the substrate.DOMAIN The Ariadne domain inhibits activity by masking the second RING-type zinc finger that contains the active site.PTM Ubiquitinated. Ubiquitination promotes proteasomal degradation.SIMILARITY Belongs to the RBR family. Ariadne subfamily.
crossReference
databaseName UniProt
dbId 50269
description
  • recommendedName: fullName evidence="17"E3 ubiquitin-protein ligase ARIH2 shortName: ARI-2 shortName: Protein ariadne-2 homolog ecNumber evidence="4 5 6 10"2.3.2.31 alternativeName: fullName evidence="14"Triad1 protein
displayName UniProt:O95376 ARIH2
geneName
  • ARIH2
  • ARI2
  • TRIAD1
  • HT005
identifier O95376
isSequenceChanged false
keyword
  • 3D-structure
  • Cytoplasm
  • Metal-binding
  • Nucleus
  • Phosphoprotein
  • Proteomics identification
  • Reference proteome
  • Repeat
  • Transferase
  • Ubl conjugation
  • Ubl conjugation pathway
  • Zinc
  • Zinc-finger
modified [InstanceEdit:9926675] Weiser, Joel, 2024-11-03
moleculeType Protein
name
  • ARIH2
otherIdentifier
  • 10425
  • 11717394_at
  • 11717395_a_at
  • 11754979_x_at
  • 16940557
  • 201228_PM_s_at
  • 201228_s_at
  • 201229_PM_s_at
  • 201229_s_at
  • 201230_PM_s_at
  • 201230_s_at
  • 216008_PM_s_at
  • 216008_s_at
  • 227932_PM_at
  • 227932_at
  • 2621828
  • 2621829
  • 2621830
  • 2621831
  • 2621832
  • 2621833
  • 2621834
  • 2621835
  • 2621836
  • 2621837
  • 2621838
  • 2621842
  • 2621843
  • 2621846
  • 2621847
  • 2621848
  • 2621849
  • 2621850
  • 2621851
  • 2621852
  • 2621854
  • 2621855
  • 2621857
  • 2621858
  • 2621859
  • 2621862
  • 2621863
  • 2621864
  • 2621866
  • 2621867
  • 2621868
  • 2621869
  • 2621872
  • 2621873
  • 2621874
  • 2621875
  • 2621876
  • 2621877
  • 3783118
  • 3783119
  • 3783123
  • 39164_at
  • 56846_at
  • 8079662
  • A_14_P105620
  • A_23_P61881
  • A_23_P73279
  • A_24_P94651
  • GE61552
  • GE61709
  • GO:0000151
  • GO:0000209
  • GO:0002376
  • GO:0003824
  • GO:0004842
  • GO:0005515
  • GO:0005634
  • GO:0005654
  • GO:0005737
  • GO:0006511
  • GO:0008270
  • GO:0016567
  • GO:0016740
  • GO:0030163
  • GO:0031466
  • GO:0031624
  • GO:0043161
  • GO:0045087
  • GO:0046872
  • GO:0048588
  • GO:0051607
  • GO:0061630
  • GO:0070534
  • GO:0070936
  • GO:0071425
  • GO:0098542
  • GO:0140096
  • GO:1903955
  • HMNXSV003046972
  • HMNXSV003056238
  • Hs.241558.1.S1_3p_at
  • Hs.241558.2.S1_3p_a_at
  • ILMN_1792825
  • PH_hs_0012955
  • TC03002330.hg
  • g12653306_3p_a_at
  • g5453556_3p_a_at
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • ARI2_HUMAN
  • Q9HBZ6
  • Q9UEM9
sequenceLength 493
species [Species:48887] Homo sapiens
stId uniprot:O95376
url http://purl.uniprot.org/uniprot/O95376
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