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Aliases for ARIH2 Gene

Aliases for ARIH2 Gene

  • Ariadne RBR E3 Ubiquitin Protein Ligase 2 2 3 5
  • All-Trans Retinoic Acid Inducible RING Finger 2 3
  • RING-Type E3 Ubiquitin Transferase ARIH2 3 4
  • Protein Ariadne-2 Homolog 3 4
  • TRIAD1 3 4
  • ARI2 3 4
  • E3 Ubiquitin-Protein Ligase ARIH2 3
  • Ariadne (Drosophila) Homolog 2 2
  • Ariadne Homolog 2 (Drosophila) 2
  • Ariadne Homolog 2 3
  • Triad1 Protein 4
  • EC 2.3.2.27 4
  • ARI-2 4

External Ids for ARIH2 Gene

Previous GeneCards Identifiers for ARIH2 Gene

  • GC03U990111
  • GC03P048231
  • GC03P048810
  • GC03P048915

Summaries for ARIH2 Gene

Entrez Gene Summary for ARIH2 Gene

  • The protein encoded by this gene is an E3 ubiquitin-protein ligase that polyubiquitinates some proteins, tagging them for degradation. The encoded protein upregulates p53 in some cancer cells and may inhibit myelopoiesis. Several transcript variants encoding different isoforms have been found for this gene, although the full-length nature of some of them have not been determined yet. [provided by RefSeq, Nov 2015]

GeneCards Summary for ARIH2 Gene

ARIH2 (Ariadne RBR E3 Ubiquitin Protein Ligase 2) is a Protein Coding gene. Among its related pathways are Innate Immune System and Class I MHC mediated antigen processing and presentation. Gene Ontology (GO) annotations related to this gene include nucleic acid binding and ubiquitin-protein transferase activity. An important paralog of this gene is ARIH1.

UniProtKB/Swiss-Prot for ARIH2 Gene

  • 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).

Gene Wiki entry for ARIH2 Gene

Additional gene information for ARIH2 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for ARIH2 Gene

Genomics for ARIH2 Gene

GeneHancer (GH) Regulatory Elements for ARIH2 Gene

Promoters and enhancers for ARIH2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH03I048917 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 550.8 0.0 -3 3.4 HDGF PKNOX1 SMAD1 FOXA2 ARID4B SIN3A DMAP1 IRF4 YY1 POLR2B ARIH2OS ARIH2 WDR6 QRICH1 CCDC71 IP6K2 ZNF589 AMT SLC25A20
GH03I048926 Promoter 1 EPDnew 550.4 +8.1 8062 0.1 NR2F1 CEBPB DPF2 BCL11B RARA HIC1 ZFHX2 BCL11A EGR1 HDAC2 PIR40585 ARIH2 ARIH2OS
GH03I049016 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 11.4 +101.4 101440 6.8 CLOCK ZFP64 FEZF1 IRF4 YY1 E2F8 ZNF143 SP3 NFYC ZFP41 DALRD3 GC03M049024 MIR191 NDUFAF3 MIR425 WDR6 ENSG00000235236 NICN1 ENSG00000223343 P4HTM
GH03I048896 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 13 -20.5 -20533 3.2 HDGF PKNOX1 FOXA2 SMAD1 MLX ARID4B SIN3A FEZF1 DMAP1 ZNF2 SLC25A20 WDR6 ARIH2OS ARIH2 QARS MST1 IP6K2 PRKAR2A
GH03I048682 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE dbSUPER 10.9 -233.2 -233211 5.8 HDGF ARID4B SIN3A DMAP1 ZNF2 ZBTB7B ZNF207 ZNF143 MXD4 REST NCKIPSD WDR6 AMT CELSR3-AS1 CELSR3 ARIH2 ENSG00000235236 ENSG00000223343 P4HTM IP6K2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around ARIH2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the ARIH2 gene promoter:

Genomic Locations for ARIH2 Gene

Genomic Locations for ARIH2 Gene
chr3:48,918,821-48,986,382
(GRCh38/hg38)
Size:
67,562 bases
Orientation:
Plus strand
chr3:48,956,254-49,023,815
(GRCh37/hg19)

Genomic View for ARIH2 Gene

Genes around ARIH2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ARIH2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ARIH2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ARIH2 Gene

Proteins for ARIH2 Gene

  • Protein details for ARIH2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O95376-ARI2_HUMAN
    Recommended name:
    E3 ubiquitin-protein ligase ARIH2
    Protein Accession:
    O95376
    Secondary Accessions:
    • Q9HBZ6
    • Q9UEM9

    Protein attributes for ARIH2 Gene

    Size:
    493 amino acids
    Molecular mass:
    57819 Da
    Quaternary structure:
    • 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).
    SequenceCaution:
    • Sequence=AAG09696.1; Type=Frameshift; Positions=Several; Evidence={ECO:0000305};

neXtProt entry for ARIH2 Gene

Post-translational modifications for ARIH2 Gene

  • Ubiquitinated. Ubiquitination promotes proteasomal degradation.
  • Ubiquitination at posLast=364364, posLast=377377, and posLast=460460
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for ARIH2 Gene

Domains & Families for ARIH2 Gene

Gene Families for ARIH2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Suggested Antigen Peptide Sequences for ARIH2 Gene

Graphical View of Domain Structure for InterPro Entry

O95376

UniProtKB/Swiss-Prot:

ARI2_HUMAN :
  • 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.
  • Belongs to the RBR family. Ariadne subfamily.
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.
  • The Ariadne domain inhibits activity by masking the second RING-type zinc finger that contains the active site.
Family:
  • Belongs to the RBR family. Ariadne subfamily.
genes like me logo Genes that share domains with ARIH2: view

Function for ARIH2 Gene

Molecular function for ARIH2 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.
UniProtKB/Swiss-Prot EnzymeRegulation:
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).
UniProtKB/Swiss-Prot 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). 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).
UniProtKB/Swiss-Prot Induction:
Up-regulated by all-trans retinoic acid (ATRA). Up-regulated during differentiation of immature blood cells toward monocytes and granulocytes.

Enzyme Numbers (IUBMB) for ARIH2 Gene

Phenotypes From GWAS Catalog for ARIH2 Gene

Gene Ontology (GO) - Molecular Function for ARIH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004842 ubiquitin-protein transferase activity IDA,IEA 16118314
GO:0005515 protein binding IPI 16118314
GO:0008270 zinc ion binding TAS 10422847
GO:0016740 transferase activity IEA --
GO:0031624 ubiquitin conjugating enzyme binding IPI 24076655
genes like me logo Genes that share ontologies with ARIH2: view
genes like me logo Genes that share phenotypes with ARIH2: view

Animal Models for ARIH2 Gene

MGI Knock Outs for ARIH2:

Clone Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for ARIH2 Gene

Localization for ARIH2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ARIH2 Gene

Nucleus. Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ARIH2 gene
Compartment Confidence
nucleus 5
cytosol 2

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for ARIH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA,IDA 16118314
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IDA,IEA 19340006
GO:0031466 colocalizes_with Cul5-RING ubiquitin ligase complex IDA 24076655
genes like me logo Genes that share ontologies with ARIH2: view

Pathways & Interactions for ARIH2 Gene

genes like me logo Genes that share pathways with ARIH2: view

Pathways by source for ARIH2 Gene

UniProtKB/Swiss-Prot O95376-ARI2_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

Gene Ontology (GO) - Biological Process for ARIH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000209 protein polyubiquitination IDA 16118314
GO:0006511 ubiquitin-dependent protein catabolic process IEA --
GO:0007275 multicellular organism development TAS 10422847
GO:0016567 protein ubiquitination IEA,IDA 24076655
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process IBA --
genes like me logo Genes that share ontologies with ARIH2: view

No data available for SIGNOR curated interactions for ARIH2 Gene

Drugs & Compounds for ARIH2 Gene

No Compound Related Data Available

Transcripts for ARIH2 Gene

Unigene Clusters for ARIH2 Gene

Ariadne homolog 2 (Drosophila):
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for ARIH2 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10a · 10b ^ 11 ^ 12 ^ 13a · 13b ^ 14 ^ 15a · 15b ^ 16
SP1:
SP2: -
SP3: - -
SP4:
SP5:
SP6:

Relevant External Links for ARIH2 Gene

GeneLoc Exon Structure for
ARIH2
ECgene alternative splicing isoforms for
ARIH2

Expression for ARIH2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for ARIH2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for ARIH2 Gene

This gene is overexpressed in Lung (24.1) and Peripheral blood mononuclear cells (6.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for ARIH2 Gene



Protein tissue co-expression partners for ARIH2 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of ARIH2 Gene:

ARIH2

SOURCE GeneReport for Unigene cluster for ARIH2 Gene:

Hs.633601

mRNA Expression by UniProt/SwissProt for ARIH2 Gene:

O95376-ARI2_HUMAN
Tissue specificity: Widely expressed with higher expression in granulocytes.

Evidence on tissue expression from TISSUES for ARIH2 Gene

  • Nervous system(4.9)
  • Muscle(4.4)
  • Eye(2.8)
  • Intestine(2.5)
  • Skin(2.5)
  • Liver(2.4)
  • Lung(2.2)
genes like me logo Genes that share expression patterns with ARIH2: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for ARIH2 Gene

Orthologs for ARIH2 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for ARIH2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia ARIH2 33 34
  • 99.59 (n)
dog
(Canis familiaris)
Mammalia ARIH2 33 34
  • 94.37 (n)
oppossum
(Monodelphis domestica)
Mammalia ARIH2 34
  • 94 (a)
OneToOne
cow
(Bos Taurus)
Mammalia ARIH2 33 34
  • 93.01 (n)
rat
(Rattus norvegicus)
Mammalia Arih2 33
  • 91.87 (n)
mouse
(Mus musculus)
Mammalia Arih2 33 16 34
  • 91.67 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia ARIH2 34
  • 84 (a)
OneToOne
chicken
(Gallus gallus)
Aves ARIH2 33 34
  • 84.22 (n)
lizard
(Anolis carolinensis)
Reptilia ARIH2 34
  • 93 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia arih2 33
  • 81.33 (n)
Str.746 33
African clawed frog
(Xenopus laevis)
Amphibia MGC68617 33
zebrafish
(Danio rerio)
Actinopterygii arih2 33 34
  • 76.65 (n)
Dr.25750 33
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.8799 33
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP005977 33
  • 61.04 (n)
fruit fly
(Drosophila melanogaster)
Insecta ari-2 35 33 34
  • 60.58 (n)
worm
(Caenorhabditis elegans)
Secernentea T12E12.1 35 33 34
  • 52.28 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes -- 34
  • 23 (a)
OneToMany
rice
(Oryza sativa)
Liliopsida Os08g0540300 33
  • 44.58 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 55 (a)
OneToOne
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.1806 33
Species where no ortholog for ARIH2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for ARIH2 Gene

ENSEMBL:
Gene Tree for ARIH2 (if available)
TreeFam:
Gene Tree for ARIH2 (if available)

Paralogs for ARIH2 Gene

Paralogs for ARIH2 Gene

(1) SIMAP similar genes for ARIH2 Gene using alignment to 7 proteins:

Pseudogenes.org Pseudogenes for ARIH2 Gene

genes like me logo Genes that share paralogs with ARIH2: view

Variants for ARIH2 Gene

Sequence variations from dbSNP and Humsavar for ARIH2 Gene

SNP ID Clin Chr 03 pos Variation AA Info Type
rs1000051643 -- 48,942,715(+) G/A genic_upstream_transcript_variant, intron_variant, upstream_transcript_variant
rs1000120498 -- 48,954,228(+) G/A genic_upstream_transcript_variant, intron_variant
rs1000124074 -- 48,929,174(+) G/A genic_upstream_transcript_variant, intron_variant
rs1000169002 -- 48,933,995(+) C/G genic_upstream_transcript_variant, intron_variant
rs1000210837 -- 48,958,831(+) A/G genic_upstream_transcript_variant, intron_variant

Structural Variations from Database of Genomic Variants (DGV) for ARIH2 Gene

Variant ID Type Subtype PubMed ID
esv2473053 CNV deletion 19546169
esv2725249 CNV deletion 23290073
esv3561855 CNV deletion 23714750
esv3596116 CNV loss 21293372
esv3893694 CNV loss 25118596
nsv1073224 CNV deletion 25765185
nsv1118970 CNV deletion 24896259

Variation tolerance for ARIH2 Gene

Residual Variation Intolerance Score: 15.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.36; 8.00% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ARIH2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
ARIH2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ARIH2 Gene

Disorders for ARIH2 Gene

Additional Disease Information for ARIH2

No disorders were found for ARIH2 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for ARIH2 Gene

Publications for ARIH2 Gene

  1. The ubiquitin ligase Triad1 inhibits myelopoiesis through UbcH7 and Ubc13 interacting domains. (PMID: 19340006) Marteijn JA … van der Reijden BA (Leukemia 2009) 3 4 22 58
  2. TRIADs: a new class of proteins with a novel cysteine-rich signature. (PMID: 10422847) van der Reijden BA … Jansen JH (Protein science : a publication of the Protein Society 1999) 2 3 4 58
  3. Structure of the HHARI catalytic domain shows glimpses of a HECT E3 ligase. (PMID: 24058416) Spratt DE … Shaw GS (PloS one 2013) 2 3 58
  4. TRIAD1 and HHARI bind to and are activated by distinct neddylated Cullin-RING ligase complexes. (PMID: 24076655) Kelsall IR … Alpi AF (The EMBO journal 2013) 3 4 58
  5. Gfi1 ubiquitination and proteasomal degradation is inhibited by the ubiquitin ligase Triad1. (PMID: 17646546) Marteijn JA … Van der Reijden BA (Blood 2007) 3 4 58

Products for ARIH2 Gene

Sources for ARIH2 Gene

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