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 determine... See more...

Aliases for ARIH2 Gene

Aliases for ARIH2 Gene

  • Ariadne RBR E3 Ubiquitin Protein Ligase 2 2 3 5
  • TRIAD1 2 3 4
  • All-Trans Retinoic Acid Inducible RING Finger 2 3
  • RING-Type E3 Ubiquitin Transferase ARIH2 3 4
  • E3 Ubiquitin-Protein Ligase ARIH2 3 4
  • Protein Ariadne-2 Homolog 3 4
  • ARI2 3 4
  • Ariadne (Drosophila) Homolog 2 2
  • Ariadne Homolog 2 (Drosophila) 2
  • Ariadne Homolog 2 3
  • Triad1 Protein 4
  • EC 2.3.2.31 4
  • ARIH2 5
  • ARI-2 4

External Ids for ARIH2 Gene

Previous GeneCards Identifiers for ARIH2 Gene

  • GC03U990111
  • GC03P048231
  • GC03P048810
  • GC03P048915
  • GC03P048931

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. Diseases associated with ARIH2 include Parkinson Disease, Late-Onset. 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 Summary 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 , Rfam classification and piRNA Summary for ARIH2 Gene

Genomics for ARIH2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for ARIH2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ARIH2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ARIH2

Top Transcription factor binding sites by QIAGEN in the ARIH2 gene promoter:
  • AhR
  • Arnt
  • Elk-1
  • Nkx3-1
  • Nkx3-1 v1
  • Nkx3-1 v2
  • Nkx3-1 v3
  • Pax-5
  • POU2F1
  • POU2F1a

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)
Size:
67,562 bases
Orientation:
Plus strand

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; Evidence={ECO:0000305};

neXtProt entry for ARIH2 Gene

Post-translational modifications for ARIH2 Gene

  • Ubiquitinated. Ubiquitination promotes proteasomal degradation.
  • Ubiquitination at Lys364, Lys377, and Lys460
  • 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):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for ARIH2 Gene

InterPro:
Blocks:
  • Zn-finger, RING
  • Zn-finger, cysteine-rich C6HC
ProtoNet:

Suggested Antigen Peptide Sequences for ARIH2 Gene

GenScript: Design optimal peptide antigens:
  • Triad1 protein (ARI2_HUMAN)
  • cDNA, FLJ93973, Homo sapiens ariadne homolog 2 (Drosophila) (ARIH2), mRNA (Q6IBL8_HUMAN)

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 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 CatalyticActivity:
Reaction=[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.; EC=2.3.2.31; Evidence={ECO:0000269|PubMed:16118314, ECO:0000269|PubMed:17646546, ECO:0000269|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.
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).

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 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:
  • Arih2 Arih2<tm1.1(KOMP)Vlcg>
  • Arih2 Arih2<tm1Mak>

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ARIH2

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
plasma membrane 1
extracellular 1
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1
lysosome 1
golgi apparatus 1

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:0000151 ubiquitin ligase complex IBA 21873635
GO:0005634 nucleus IEA,IDA 16118314
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IBA,IDA 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 IBA,IDA 16118314
GO:0007275 multicellular organism development TAS 10422847
GO:0016567 protein ubiquitination IDA 24076655
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process IBA 21873635
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

mRNA/cDNA for ARIH2 Gene

25 REFSEQ mRNAs :
21 NCBI additional mRNA sequence :
31 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ARIH2

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

Expression for ARIH2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and 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, MaxQB, and MOPED for ARIH2 Gene



Protein tissue co-expression partners for ARIH2 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for 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(4.6)
  • Skin(3.2)
  • Eye(3)
  • Intestine(2.9)
  • Liver(2.8)
  • Bone marrow(2.2)
  • Lung(2.2)
  • Heart(2.1)
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 30 31
  • 99.59 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia ARIH2 30 31
  • 94.37 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia ARIH2 31
  • 94 (a)
OneToOne
Cow
(Bos Taurus)
Mammalia ARIH2 30 31
  • 93.01 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Arih2 30
  • 91.87 (n)
Mouse
(Mus musculus)
Mammalia Arih2 30 17 31
  • 91.67 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia ARIH2 31
  • 84 (a)
OneToOne
Chicken
(Gallus gallus)
Aves ARIH2 30 31
  • 84.22 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia ARIH2 31
  • 93 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia arih2 30
  • 81.33 (n)
Str.746 30
African clawed frog
(Xenopus laevis)
Amphibia MGC68617 30
Zebrafish
(Danio rerio)
Actinopterygii arih2 30 31
  • 76.65 (n)
OneToOne
Dr.25750 30
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.8799 30
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP005977 30
  • 61.04 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta ari-2 30 31 32
  • 60.58 (n)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea T12E12.1 30 31 32
  • 52.28 (n)
OneToOne
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes -- 31
  • 23 (a)
OneToMany
Rice
(Oryza sativa)
Liliopsida Os08g0540300 30
  • 44.58 (n)
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 55 (a)
OneToOne
Sea Vase
(Ciona intestinalis)
Ascidiacea Cin.1806 30
Species where no ortholog for ARIH2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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)
Aminode:
Evolutionary constrained regions (ECRs) for ARIH2: view image

Paralogs for ARIH2 Gene

Paralogs for ARIH2 Gene

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

  • ARI2_HUMAN
  • C9JAU2_HUMAN
  • C9JBC5_HUMAN
  • C9JCL4_HUMAN
  • C9JZ71_HUMAN
  • F8WCS4_HUMAN
  • Q6IBL8_HUMAN

Pseudogenes.org Pseudogenes for ARIH2 Gene

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

Variants for ARIH2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ARIH2 Gene

SNP ID Clinical significance and condition Chr 03 pos Variation AA Info Type
rs11507 - p.Glu24Lys
rs34221642 - p.Glu29Asp

Additional dbSNP identifiers (rs#s) for ARIH2 Gene

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

MalaCards: The human disease database

(1) MalaCards diseases for ARIH2 Gene - From: DISEASES

Disorder Aliases PubMed IDs
parkinson disease, late-onset
  • pd
- elite association - COSMIC cancer census association via MalaCards
Search ARIH2 in MalaCards View complete list of genes associated with diseases
genes like me logo Genes that share disorders with ARIH2: view

No data available for 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 23
  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
  3. 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
  4. Structure of the HHARI catalytic domain shows glimpses of a HECT E3 ligase. (PMID: 24058416) Spratt DE … Shaw GS (PloS one 2013) 2 3
  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

Products for ARIH2 Gene

  • Signalway Proteins for ARIH2

Sources for ARIH2 Gene