Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

E3 ubiquitin-protein ligase ARIH2

Gene

ARIH2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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]-N6-ubiquitinyl-L-lysine.3 Publications

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

Pathwayi: protein ubiquitination

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 keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi139Zinc 1PROSITE-ProRule annotation1
Metal bindingi142Zinc 1PROSITE-ProRule annotation1
Metal bindingi156Zinc 2PROSITE-ProRule annotation1
Metal bindingi158Zinc 2; via pros nitrogenPROSITE-ProRule annotation1
Metal bindingi161Zinc 1PROSITE-ProRule annotation1
Metal bindingi164Zinc 1PROSITE-ProRule annotation1
Metal bindingi183Zinc 2PROSITE-ProRule annotation1
Metal bindingi188Zinc 2PROSITE-ProRule annotation1
Metal bindingi228Zinc 3PROSITE-ProRule annotation1
Metal bindingi233Zinc 3PROSITE-ProRule annotation1
Metal bindingi249Zinc 3PROSITE-ProRule annotation1
Metal bindingi252Zinc 3PROSITE-ProRule annotation1
Metal bindingi257Zinc 4PROSITE-ProRule annotation1
Metal bindingi260Zinc 4PROSITE-ProRule annotation1
Metal bindingi265Zinc 4; via tele nitrogenPROSITE-ProRule annotation1
Metal bindingi270Zinc 4PROSITE-ProRule annotation1
Metal bindingi297Zinc 5PROSITE-ProRule annotation1
Metal bindingi300Zinc 5PROSITE-ProRule annotation1
Active sitei310PROSITE-ProRule annotation1 Publication1
Metal bindingi315Zinc 5PROSITE-ProRule annotation1
Metal bindingi318Zinc 5PROSITE-ProRule annotation1
Metal bindingi323Zinc 6PROSITE-ProRule annotation1
Metal bindingi326Zinc 6PROSITE-ProRule annotation1
Metal bindingi333Zinc 6; via tele nitrogenPROSITE-ProRule annotation1
Metal bindingi340Zinc 6PROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri139 – 188RING-type 1PROSITE-ProRule annotationAdd BLAST50
Zinc fingeri208 – 270IBR-typePROSITE-ProRule annotationAdd BLAST63
Zinc fingeri297 – 326RING-type 2; atypicalPROSITE-ProRule annotationAdd BLAST30

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

Keywordsi

Molecular functionTransferase
Biological processUbl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000177479.19
HGNCiHGNC:690 ARIH2
MIMi605615 gene
neXtProtiNX_O95376

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi84 – 86LKV → AKA: Reduced interaction with neddylated CUL5; when associated with A-100. 1 Publication3
Mutagenesisi100W → A: Reduced interaction with neddylated CUL5; when associated with 84-A--A-86. 1 Publication1
Mutagenesisi158H → A: Loss of effect in myelopoiesis. Abolishes interaction with UBE2L3. 2 Publications1
Mutagenesisi161C → A: Loss of effect in myelopoiesis. 1 Publication1
Mutagenesisi257C → A: Does not affect interaction with UBE2L3. 1 Publication1
Mutagenesisi300C → A: Does not affect interaction with UBE2L3. 1 Publication1
Mutagenesisi310C → A: Abolishes E3 ubiquitin-protein ligase activity. 1 Publication1

Organism-specific databases

DisGeNETi10425
OpenTargetsiENSG00000177479
PharmGKBiPA24983

Polymorphism and mutation databases

BioMutaiARIH2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000557551 – 493E3 ubiquitin-protein ligase ARIH2Add BLAST493

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei353PhosphoserineCombined sources1

Post-translational modificationi

Ubiquitinated. Ubiquitination promotes proteasomal degradation.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO95376
MaxQBiO95376
PaxDbiO95376
PeptideAtlasiO95376
PRIDEiO95376
ProteomicsDBi50829

PTM databases

iPTMnetiO95376
PhosphoSitePlusiO95376

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

BgeeiENSG00000177479 Expressed in 231 organ(s), highest expression level in muscle of leg
CleanExiHS_ARIH2
ExpressionAtlasiO95376 baseline and differential
GenevisibleiO95376 HS

Organism-specific databases

HPAiHPA067381
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

Protein-protein interaction databases

BioGridi115694, 74 interactors
IntActiO95376, 49 interactors
MINTiO95376
STRINGi9606.ENSP00000348769

Structurei

3D structure databases

ProteinModelPortaliO95376
SMRiO95376
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni65 – 112UBA-likeBy similarityAdd BLAST48
Regioni135 – 344TRIAD supradomainPROSITE-ProRule annotationAdd BLAST210
Regioni359 – 493Ariadne domainBy similarityAdd BLAST135

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

Belongs to the RBR family. Ariadne subfamily.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri139 – 188RING-type 1PROSITE-ProRule annotationAdd BLAST50
Zinc fingeri208 – 270IBR-typePROSITE-ProRule annotationAdd BLAST63
Zinc fingeri297 – 326RING-type 2; atypicalPROSITE-ProRule annotationAdd BLAST30

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1815 Eukaryota
ENOG410XP9Y LUCA
GeneTreeiENSGT00890000139392
HOGENOMiHOG000216611
HOVERGENiHBG018737
InParanoidiO95376
KOiK11969
OMAiGVCLQVV
OrthoDBiEOG091G06CV
PhylomeDBiO95376
TreeFamiTF300805

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView 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
PANTHERiPTHR11685 PTHR11685, 1 hit
PTHR11685:SF210 PTHR11685:SF210, 1 hit
PfamiView protein in Pfam
PF01485 IBR, 2 hits
SMARTiView protein in SMART
SM00647 IBR, 2 hits
SM00184 RING, 2 hits
PROSITEiView protein in PROSITE
PS51873 TRIAD, 1 hit
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 2 hits

Sequence (1+)i

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
« Hide
        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
Length:493
Mass (Da):57,819
Last modified:May 1, 1999 - v1
Checksum:i30AFFDD327B51013
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9JZ71C9JZ71_HUMAN
E3 ubiquitin-protein ligase ARIH2
ARIH2
138Annotation score:
C9JBC5C9JBC5_HUMAN
E3 ubiquitin-protein ligase ARIH2
ARIH2
107Annotation score:
C9JCL4C9JCL4_HUMAN
E3 ubiquitin-protein ligase ARIH2
ARIH2
85Annotation score:
F8WCS4F8WCS4_HUMAN
E3 ubiquitin-protein ligase ARIH2
ARIH2
106Annotation score:
C9JAU2C9JAU2_HUMAN
E3 ubiquitin-protein ligase ARIH2
ARIH2
55Annotation score:

Sequence cautioni

The sequence AAG09696 differs from that shown. Reason: Frameshift at several positions.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti280 – 281CA → LQ in CAA10276 (PubMed:10880484).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05410524E → K. Corresponds to variant dbSNP:rs11507Ensembl.1
Natural variantiVAR_05410629E → 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
CCDSiCCDS2780.1
RefSeqiNP_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
UniGeneiHs.633601

Genome annotation databases

EnsembliENST00000356401; ENSP00000348769; ENSG00000177479
ENST00000449376; ENSP00000403222; ENSG00000177479
GeneIDi10425
KEGGihsa:10425

Keywords - Coding sequence diversityi

Polymorphism

Similar 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
CCDSiCCDS2780.1
RefSeqiNP_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
UniGeneiHs.633601

3D structure databases

ProteinModelPortaliO95376
SMRiO95376
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115694, 74 interactors
IntActiO95376, 49 interactors
MINTiO95376
STRINGi9606.ENSP00000348769

PTM databases

iPTMnetiO95376
PhosphoSitePlusiO95376

Polymorphism and mutation databases

BioMutaiARIH2

Proteomic databases

EPDiO95376
MaxQBiO95376
PaxDbiO95376
PeptideAtlasiO95376
PRIDEiO95376
ProteomicsDBi50829

Protocols and materials databases

DNASUi10425
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000356401; ENSP00000348769; ENSG00000177479
ENST00000449376; ENSP00000403222; ENSG00000177479
GeneIDi10425
KEGGihsa:10425

Organism-specific databases

CTDi10425
DisGeNETi10425
EuPathDBiHostDB:ENSG00000177479.19
GeneCardsiARIH2
HGNCiHGNC:690 ARIH2
HPAiHPA067381
HPA069715
HPA070963
MIMi605615 gene
neXtProtiNX_O95376
OpenTargetsiENSG00000177479
PharmGKBiPA24983
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1815 Eukaryota
ENOG410XP9Y LUCA
GeneTreeiENSGT00890000139392
HOGENOMiHOG000216611
HOVERGENiHBG018737
InParanoidiO95376
KOiK11969
OMAiGVCLQVV
OrthoDBiEOG091G06CV
PhylomeDBiO95376
TreeFamiTF300805

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation

Miscellaneous databases

ChiTaRSiARIH2 human
GeneWikiiARIH2
GenomeRNAii10425
PROiPR:O95376
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000177479 Expressed in 231 organ(s), highest expression level in muscle of leg
CleanExiHS_ARIH2
ExpressionAtlasiO95376 baseline and differential
GenevisibleiO95376 HS

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView 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
PANTHERiPTHR11685 PTHR11685, 1 hit
PTHR11685:SF210 PTHR11685:SF210, 1 hit
PfamiView protein in Pfam
PF01485 IBR, 2 hits
SMARTiView protein in SMART
SM00647 IBR, 2 hits
SM00184 RING, 2 hits
PROSITEiView protein in PROSITE
PS51873 TRIAD, 1 hit
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiARI2_HUMAN
AccessioniPrimary (citable) accession number: O95376
Secondary accession number(s): Q9HBZ6, Q9UEM9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: May 1, 1999
Last modified: November 7, 2018
This is version 168 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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 proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PATHWAY comments
    Index of metabolic and biosynthesis pathways
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again