UniProtKB - O95376 (ARI2_HUMAN)
Protein
E3 ubiquitin-protein ligase ARIH2
Gene
ARIH2
Organism
Homo sapiens (Human)
Status
Functioni
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). 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 (By similarity). The initial ubiquitin is then elongated (By similarity). E3 ubiquitin-protein ligase activity is activated upon binding to neddylated form of the ECS complex (PubMed:24076655). Mediates 'Lys-6', 'Lys-48'-and 'Lys-63'-linked polyubiquitination (PubMed:16118314, PubMed:17646546, PubMed:19340006). May play a role in myelopoiesis (PubMed:19340006).By similarity4 Publications
Catalytic activityi
- [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.3 Publications EC:2.3.2.31
Activity regulationi
Autoinhibited by the ariadne domain, which masks the second RING-type zinc finger that contains the active site and inhibits the E3 activity (By similarity). Inhibition is relieved upon binding to neddylated cullin-RING ubiquitin ligase complexes, which activate the E3 ligase activity of ARIH1 (PubMed:24076655).By similarity1 Publication
: protein ubiquitination Pathwayi
This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 139 | Zinc 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 142 | Zinc 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 156 | Zinc 2PROSITE-ProRule annotation | 1 | |
Metal bindingi | 158 | Zinc 2; via pros nitrogenPROSITE-ProRule annotation | 1 | |
Metal bindingi | 161 | Zinc 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 164 | Zinc 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 183 | Zinc 2PROSITE-ProRule annotation | 1 | |
Metal bindingi | 188 | Zinc 2PROSITE-ProRule annotation | 1 | |
Metal bindingi | 228 | Zinc 3PROSITE-ProRule annotation | 1 | |
Metal bindingi | 233 | Zinc 3PROSITE-ProRule annotation | 1 | |
Metal bindingi | 249 | Zinc 3PROSITE-ProRule annotation | 1 | |
Metal bindingi | 252 | Zinc 3PROSITE-ProRule annotation | 1 | |
Metal bindingi | 257 | Zinc 4PROSITE-ProRule annotation | 1 | |
Metal bindingi | 260 | Zinc 4PROSITE-ProRule annotation | 1 | |
Metal bindingi | 265 | Zinc 4; via tele nitrogenPROSITE-ProRule annotation | 1 | |
Metal bindingi | 270 | Zinc 4PROSITE-ProRule annotation | 1 | |
Metal bindingi | 297 | Zinc 5PROSITE-ProRule annotation | 1 | |
Metal bindingi | 300 | Zinc 5PROSITE-ProRule annotation | 1 | |
Active sitei | 310 | PROSITE-ProRule annotation1 Publication | 1 | |
Metal bindingi | 315 | Zinc 5PROSITE-ProRule annotation | 1 | |
Metal bindingi | 318 | Zinc 5PROSITE-ProRule annotation | 1 | |
Metal bindingi | 323 | Zinc 6PROSITE-ProRule annotation | 1 | |
Metal bindingi | 326 | Zinc 6PROSITE-ProRule annotation | 1 | |
Metal bindingi | 333 | Zinc 6; via tele nitrogenPROSITE-ProRule annotation | 1 | |
Metal bindingi | 340 | Zinc 6PROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 139 – 188 | RING-type 1PROSITE-ProRule annotationAdd BLAST | 50 | |
Zinc fingeri | 208 – 270 | IBR-typePROSITE-ProRule annotationAdd BLAST | 63 | |
Zinc fingeri | 297 – 326 | RING-type 2; atypicalPROSITE-ProRule annotationAdd BLAST | 30 |
GO - Molecular functioni
- ubiquitin conjugating enzyme binding Source: UniProtKB
- ubiquitin protein ligase activity Source: GO_Central
- ubiquitin-protein transferase activity Source: UniProtKB
- zinc ion binding Source: ProtInc
GO - Biological processi
- developmental cell growth Source: UniProtKB
- hematopoietic stem cell proliferation Source: UniProtKB
- multicellular organism development Source: ProtInc
- positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: GO_Central
- positive regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL
- protein K48-linked ubiquitination Source: UniProtKB
- protein K63-linked ubiquitination Source: UniProtKB
- protein polyubiquitination Source: UniProtKB
- protein ubiquitination Source: UniProtKB
- ubiquitin-dependent protein catabolic process Source: UniProtKB
Keywordsi
Molecular function | Transferase |
Biological process | Ubl conjugation pathway |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
Reactomei | R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation |
UniPathwayi | UPA00143 |
Names & Taxonomyi
Protein namesi | Recommended name: E3 ubiquitin-protein ligase ARIH2 (EC:2.3.2.313 Publications)Short name: ARI-2 Short name: Protein ariadne-2 homolog Alternative name(s): RING-type E3 ubiquitin transferase ARIH2Curated Triad1 protein1 Publication |
Gene namesi | Name:ARIH2 Synonyms:ARI2, TRIAD11 Publication ORF Names:HT005 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000177479.19 |
HGNCi | HGNC:690 ARIH2 |
MIMi | 605615 gene |
neXtProti | NX_O95376 |
Subcellular locationi
Nucleus
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
- ubiquitin ligase complex Source: GO_Central
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 84 – 86 | LKV → AKA: Reduced interaction with neddylated CUL5; when associated with A-100. 1 Publication | 3 | |
Mutagenesisi | 100 | W → A: Reduced interaction with neddylated CUL5; when associated with 84-A--A-86. 1 Publication | 1 | |
Mutagenesisi | 158 | H → A: Loss of effect in myelopoiesis. Abolishes interaction with UBE2L3. 2 Publications | 1 | |
Mutagenesisi | 161 | C → A: Loss of effect in myelopoiesis. 1 Publication | 1 | |
Mutagenesisi | 257 | C → A: Does not affect interaction with UBE2L3. 1 Publication | 1 | |
Mutagenesisi | 300 | C → A: Does not affect interaction with UBE2L3. 1 Publication | 1 | |
Mutagenesisi | 310 | C → A: Abolishes E3 ubiquitin-protein ligase activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 10425 |
OpenTargetsi | ENSG00000177479 |
PharmGKBi | PA24983 |
Polymorphism and mutation databases
BioMutai | ARIH2 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000055755 | 1 – 493 | E3 ubiquitin-protein ligase ARIH2Add BLAST | 493 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 353 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Ubiquitinated. Ubiquitination promotes proteasomal degradation.1 Publication
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
EPDi | O95376 |
jPOSTi | O95376 |
MaxQBi | O95376 |
PaxDbi | O95376 |
PeptideAtlasi | O95376 |
PRIDEi | O95376 |
ProteomicsDBi | 50829 |
PTM databases
iPTMneti | O95376 |
PhosphoSitePlusi | O95376 |
Expressioni
Tissue specificityi
Widely expressed with higher expression in granulocytes.1 Publication
Inductioni
Up-regulated by all-trans retinoic acid (ATRA). Up-regulated during differentiation of immature blood cells toward monocytes and granulocytes.1 Publication
Gene expression databases
Bgeei | ENSG00000177479 Expressed in 231 organ(s), highest expression level in muscle of leg |
ExpressionAtlasi | O95376 baseline and differential |
Genevisiblei | O95376 HS |
Organism-specific databases
HPAi | HPA067381 HPA069715 HPA070963 |
Interactioni
Subunit structurei
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 with neddylated CUL5 (PubMed:24076655). Interacts (via RING-type 2) with GFI1B (PubMed:17646546). Interacts with GFI1; prevents its ubiquitination and proteasomal degradation (PubMed:17646546).4 Publications
Binary interactionsi
GO - Molecular functioni
- ubiquitin conjugating enzyme binding Source: UniProtKB
Protein-protein interaction databases
BioGridi | 115694, 73 interactors |
IntActi | O95376, 49 interactors |
MINTi | O95376 |
STRINGi | 9606.ENSP00000348769 |
Structurei
3D structure databases
ProteinModelPortali | O95376 |
SMRi | O95376 |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 65 – 112 | UBA-likeBy similarityAdd BLAST | 48 | |
Regioni | 135 – 344 | TRIAD supradomainPROSITE-ProRule annotationAdd BLAST | 210 | |
Regioni | 359 – 493 | Ariadne domainBy similarityAdd BLAST | 135 |
Domaini
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.By similarity
The Ariadne domain inhibits activity by masking the second RING-type zinc finger that contains the active site.By similarity
Sequence similaritiesi
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 139 – 188 | RING-type 1PROSITE-ProRule annotationAdd BLAST | 50 | |
Zinc fingeri | 208 – 270 | IBR-typePROSITE-ProRule annotationAdd BLAST | 63 | |
Zinc fingeri | 297 – 326 | RING-type 2; atypicalPROSITE-ProRule annotationAdd BLAST | 30 |
Keywords - Domaini
Repeat, Zinc-fingerPhylogenomic databases
eggNOGi | KOG1815 Eukaryota ENOG410XP9Y LUCA |
GeneTreei | ENSGT00940000154875 |
HOGENOMi | HOG000216611 |
HOVERGENi | HBG018737 |
InParanoidi | O95376 |
KOi | K11969 |
OMAi | GVCLQVV |
OrthoDBi | 469819at2759 |
PhylomeDBi | O95376 |
TreeFami | TF300805 |
Family and domain databases
Gene3Di | 3.30.40.10, 1 hit |
InterProi | View protein in InterPro IPR031126 Ariadne-2 IPR031127 E3_UB_ligase_RBR IPR002867 IBR_dom IPR001841 Znf_RING IPR013083 Znf_RING/FYVE/PHD IPR017907 Znf_RING_CS |
PANTHERi | PTHR11685 PTHR11685, 1 hit PTHR11685:SF210 PTHR11685:SF210, 1 hit |
Pfami | View protein in Pfam PF01485 IBR, 2 hits |
SMARTi | View protein in SMART SM00647 IBR, 2 hits SM00184 RING, 2 hits |
PROSITEi | View protein in PROSITE PS51873 TRIAD, 1 hit PS00518 ZF_RING_1, 1 hit PS50089 ZF_RING_2, 2 hits |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All
O95376-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MSVDMNSQGS DSNEEDYDPN CEEEEEEEED DPGDIEDYYV GVASDVEQQG
60 70 80 90 100
ADAFDPEEYQ FTCLTYKESE GALNEHMTSL ASVLKVSHSV AKLILVNFHW
110 120 130 140 150
QVSEILDRYK SNSAQLLVEA RVQPNPSKHV PTSHPPHHCA VCMQFVRKEN
160 170 180 190 200
LLSLACQHQF CRSCWEQHCS VLVKDGVGVG VSCMAQDCPL RTPEDFVFPL
210 220 230 240 250
LPNEELREKY RRYLFRDYVE SHYQLQLCPG ADCPMVIRVQ EPRARRVQCN
260 270 280 290 300
RCNEVFCFKC RQMYHAPTDC ATIRKWLTKC ADDSETANYI SAHTKDCPKC
310 320 330 340 350
NICIEKNGGC NHMQCSKCKH DFCWMCLGDW KTHGSEYYEC SRYKENPDIV
360 370 380 390 400
NQSQQAQARE ALKKYLFYFE RWENHNKSLQ LEAQTYQRIH EKIQERVMNN
410 420 430 440 450
LGTWIDWQYL QNAAKLLAKC RYTLQYTYPY AYYMESGPRK KLFEYQQAQL
460 470 480 490
EAEIENLSWK VERADSYDRG DLENQMHIAE QRRRTLLKDF HDT
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketC9JZ71 | C9JZ71_HUMAN | E3 ubiquitin-protein ligase ARIH2 | ARIH2 | 138 | Annotation score: | ||
C9JBC5 | C9JBC5_HUMAN | E3 ubiquitin-protein ligase ARIH2 | ARIH2 | 107 | Annotation score: | ||
C9JCL4 | C9JCL4_HUMAN | E3 ubiquitin-protein ligase ARIH2 | ARIH2 | 85 | Annotation score: | ||
F8WCS4 | F8WCS4_HUMAN | E3 ubiquitin-protein ligase ARIH2 | ARIH2 | 106 | Annotation score: | ||
C9JAU2 | C9JAU2_HUMAN | E3 ubiquitin-protein ligase ARIH2 | ARIH2 | 55 | Annotation score: |
Sequence cautioni
The sequence AAG09696 differs from that shown. Reason: Frameshift at several positions.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 280 – 281 | CA → LQ in CAA10276 (PubMed:10880484).Curated | 2 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_054105 | 24 | E → K. Corresponds to variant dbSNP:rs11507Ensembl. | 1 | |
Natural variantiVAR_054106 | 29 | E → D. Corresponds to variant dbSNP:rs34221642Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF099149 mRNA Translation: AAC82469.1 AJ130978 mRNA Translation: CAA10276.1 AF183427 mRNA Translation: AAG09696.1 Frameshift. BC000422 mRNA Translation: AAH00422.1 |
CCDSi | CCDS2780.1 |
RefSeqi | NP_001304262.1, NM_001317333.1 NP_001304263.1, NM_001317334.1 NP_006312.1, NM_006321.3 XP_016861020.1, XM_017005531.1 XP_016861021.1, XM_017005532.1 |
UniGenei | Hs.633601 |
Genome annotation databases
Ensembli | ENST00000356401; ENSP00000348769; ENSG00000177479 ENST00000449376; ENSP00000403222; ENSG00000177479 |
GeneIDi | 10425 |
KEGGi | hsa:10425 |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF099149 mRNA Translation: AAC82469.1 AJ130978 mRNA Translation: CAA10276.1 AF183427 mRNA Translation: AAG09696.1 Frameshift. BC000422 mRNA Translation: AAH00422.1 |
CCDSi | CCDS2780.1 |
RefSeqi | NP_001304262.1, NM_001317333.1 NP_001304263.1, NM_001317334.1 NP_006312.1, NM_006321.3 XP_016861020.1, XM_017005531.1 XP_016861021.1, XM_017005532.1 |
UniGenei | Hs.633601 |
3D structure databases
ProteinModelPortali | O95376 |
SMRi | O95376 |
ModBasei | Search... |
MobiDBi | Search... |
Protein-protein interaction databases
BioGridi | 115694, 73 interactors |
IntActi | O95376, 49 interactors |
MINTi | O95376 |
STRINGi | 9606.ENSP00000348769 |
PTM databases
iPTMneti | O95376 |
PhosphoSitePlusi | O95376 |
Polymorphism and mutation databases
BioMutai | ARIH2 |
Proteomic databases
EPDi | O95376 |
jPOSTi | O95376 |
MaxQBi | O95376 |
PaxDbi | O95376 |
PeptideAtlasi | O95376 |
PRIDEi | O95376 |
ProteomicsDBi | 50829 |
Protocols and materials databases
DNASUi | 10425 |
Structural Biology Knowledgebase | Search... |
Genome annotation databases
Ensembli | ENST00000356401; ENSP00000348769; ENSG00000177479 ENST00000449376; ENSP00000403222; ENSG00000177479 |
GeneIDi | 10425 |
KEGGi | hsa:10425 |
Organism-specific databases
CTDi | 10425 |
DisGeNETi | 10425 |
EuPathDBi | HostDB:ENSG00000177479.19 |
GeneCardsi | ARIH2 |
HGNCi | HGNC:690 ARIH2 |
HPAi | HPA067381 HPA069715 HPA070963 |
MIMi | 605615 gene |
neXtProti | NX_O95376 |
OpenTargetsi | ENSG00000177479 |
PharmGKBi | PA24983 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1815 Eukaryota ENOG410XP9Y LUCA |
GeneTreei | ENSGT00940000154875 |
HOGENOMi | HOG000216611 |
HOVERGENi | HBG018737 |
InParanoidi | O95376 |
KOi | K11969 |
OMAi | GVCLQVV |
OrthoDBi | 469819at2759 |
PhylomeDBi | O95376 |
TreeFami | TF300805 |
Enzyme and pathway databases
UniPathwayi | UPA00143 |
Reactomei | R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation |
Miscellaneous databases
ChiTaRSi | ARIH2 human |
GeneWikii | ARIH2 |
GenomeRNAii | 10425 |
PROi | PR:O95376 |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000177479 Expressed in 231 organ(s), highest expression level in muscle of leg |
ExpressionAtlasi | O95376 baseline and differential |
Genevisiblei | O95376 HS |
Family and domain databases
Gene3Di | 3.30.40.10, 1 hit |
InterProi | View protein in InterPro IPR031126 Ariadne-2 IPR031127 E3_UB_ligase_RBR IPR002867 IBR_dom IPR001841 Znf_RING IPR013083 Znf_RING/FYVE/PHD IPR017907 Znf_RING_CS |
PANTHERi | PTHR11685 PTHR11685, 1 hit PTHR11685:SF210 PTHR11685:SF210, 1 hit |
Pfami | View protein in Pfam PF01485 IBR, 2 hits |
SMARTi | View protein in SMART SM00647 IBR, 2 hits SM00184 RING, 2 hits |
PROSITEi | View protein in PROSITE PS51873 TRIAD, 1 hit PS00518 ZF_RING_1, 1 hit PS50089 ZF_RING_2, 2 hits |
ProtoNeti | Search... |
Entry informationi
Entry namei | ARI2_HUMAN | |
Accessioni | O95376Primary (citable) accession number: O95376 Secondary accession number(s): Q9HBZ6, Q9UEM9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 26, 2001 |
Last sequence update: | May 1, 1999 | |
Last modified: | February 13, 2019 | |
This is version 171 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Complete proteome, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families - Human chromosome 3
Human chromosome 3: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - PATHWAY comments
Index of metabolic and biosynthesis pathways