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
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

E3 ubiquitin-protein ligase, which catalyzes ubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3 (By similarity). 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. Mediates 'Lys-6', 'Lys-48'-and 'Lys-63'-linked polyubiquitination. May play a role in myelopoiesis (By similarity).By similarity

Catalytic activityi

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.By similarity

Enzyme 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 (By similarity).By similarity

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 bindingi138Zinc 1By similarity1
Metal bindingi141Zinc 1By similarity1
Metal bindingi155Zinc 2By similarity1
Metal bindingi157Zinc 2; via pros nitrogenBy similarity1
Metal bindingi160Zinc 1By similarity1
Metal bindingi163Zinc 1By similarity1
Metal bindingi182Zinc 2By similarity1
Metal bindingi187Zinc 2By similarity1
Metal bindingi227Zinc 3By similarity1
Metal bindingi232Zinc 3By similarity1
Metal bindingi248Zinc 3By similarity1
Metal bindingi251Zinc 3By similarity1
Metal bindingi256Zinc 4By similarity1
Metal bindingi259Zinc 4By similarity1
Metal bindingi264Zinc 4; via tele nitrogenBy similarity1
Metal bindingi269Zinc 4By similarity1
Metal bindingi296Zinc 5By similarity1
Metal bindingi299Zinc 5By similarity1
Active sitei309By similarity1
Metal bindingi314Zinc 5By similarity1
Metal bindingi317Zinc 5By similarity1
Metal bindingi322Zinc 6By similarity1
Metal bindingi325Zinc 6By similarity1
Metal bindingi332Zinc 6; via tele nitrogenBy similarity1
Metal bindingi339Zinc 6By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri138 – 187RING-type 1; atypicalPROSITE-ProRule annotationAdd BLAST50
Zinc fingeri207 – 269IBR-typeAdd BLAST63
Zinc fingeri296 – 325RING-type 2PROSITE-ProRule annotationAdd BLAST30

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase ARIH2 (EC:2.3.2.-By similarity)
Short name:
ARI-2
Short name:
Protein ariadne-2 homolog
Alternative name(s):
RING-type E3 ubiquitin transferase ARIH2Curated
Triad1 protein
UbcM4-interacting protein 48
Gene namesi
Name:Arih2
Synonyms:Ari2, Triad1, Uip48
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1344361. Arih2.

Subcellular locationi

  • Nucleus By similarity
  • Cytoplasm By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000557561 – 492E3 ubiquitin-protein ligase ARIH2Add BLAST492

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei352PhosphoserineCombined sources1

Post-translational modificationi

Ubiquitinated. Ubiquitination promotes proteasomal degradation.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9Z1K6.
MaxQBiQ9Z1K6.
PaxDbiQ9Z1K6.
PRIDEiQ9Z1K6.

PTM databases

iPTMnetiQ9Z1K6.
PhosphoSitePlusiQ9Z1K6.

Expressioni

Gene expression databases

BgeeiENSMUSG00000064145.
CleanExiMM_ARIH2.
ExpressionAtlasiQ9Z1K6. baseline and differential.
GenevisibleiQ9Z1K6. MM.

Interactioni

Subunit structurei

Interacts (via RING-type zinc finger 1) with UBE2L3. Interacts (via RING-type zinc finger 2) with UBE2N. Interacts with neddylated CUL5. Interacts (via RING-type 2) with GFI1B. Interacts with GFI1; prevents its ubiquitination and proteasomal degradation.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
NfkbibQ607782EBI-6861719,EBI-644469

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204727. 4 interactors.
IntActiQ9Z1K6. 1 interactor.
STRINGi10090.ENSMUSP00000013338.

Structurei

3D structure databases

ProteinModelPortaliQ9Z1K6.
SMRiQ9Z1K6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni64 – 111UBA-likeBy similarityAdd BLAST48
Regioni358 – 492Ariadne 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
Contains 1 IBR-type zinc finger.Curated
Contains 2 RING-type zinc fingers.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri138 – 187RING-type 1; atypicalPROSITE-ProRule annotationAdd BLAST50
Zinc fingeri207 – 269IBR-typeAdd BLAST63
Zinc fingeri296 – 325RING-type 2PROSITE-ProRule annotationAdd BLAST30

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1815. Eukaryota.
ENOG410XP9Y. LUCA.
GeneTreeiENSGT00840000129790.
HOGENOMiHOG000216611.
HOVERGENiHBG018737.
InParanoidiQ9Z1K6.
KOiK11969.
OMAiFRDYVEX.
OrthoDBiEOG091G06CV.
PhylomeDBiQ9Z1K6.
TreeFamiTF300805.

Family and domain databases

Gene3Di3.30.40.10. 2 hits.
InterProiIPR031127. E3_UB_ligase_RBR.
IPR002867. IBR_dom.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PANTHERiPTHR11685. PTHR11685. 1 hit.
PfamiPF01485. IBR. 2 hits.
[Graphical view]
SMARTiSM00647. IBR. 2 hits.
SM00184. RING. 2 hits.
[Graphical view]
PROSITEiPS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9Z1K6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSVDMNSQGS DSNEEDYDPN CEEEEEEEED PGDIEDYYVG VASDVEQQGA
60 70 80 90 100
DAFDPEEYQF TCLTYKESEG ALHEHMTSLA SVLKVSHSVA KLILVNFHWQ
110 120 130 140 150
VSEILDRYRS NSAQLLVEAR VQPNPSKHVP TAHPPHHCAV CMQFVRKENL
160 170 180 190 200
LSLACQHQFC RSCWEQHCSV LVKDGVGVGI SCMAQDCPLR TPEDFVFPLL
210 220 230 240 250
PNEELRDKYR RYLFRDYVES HFQLQLCPGA DCPMVIRVQE PRARRVQCNR
260 270 280 290 300
CSEVFCFKCR QMYHAPTDCA TIRKWLTKCA DDSETANYIS AHTKDCPKCN
310 320 330 340 350
ICIEKNGGCN HMQCSKCKHD FCWMCLGDWK THGSEYYECS RYKENPDIVN
360 370 380 390 400
QSQQAQAREA LKKYLFYFER WENHNKSLQL EAQTYERIHE KIQERVMNNL
410 420 430 440 450
GTWIDWQYLQ NAAKLLAKCR YTLQYTYPYA YYMESGPRKK LFEYQQAQLE
460 470 480 490
AEIENLSWKV ERADSYDRGD LENQMHIAEQ RRRTLLKDFH DT
Length:492
Mass (Da):57,697
Last modified:May 1, 1999 - v1
Checksum:iB55EA54FE8C3ADAF
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF124664 mRNA. Translation: AAD24573.1.
AJ130975 mRNA. Translation: CAA10273.1.
BC051998 mRNA. Translation: AAH51998.1.
BC052422 mRNA. Translation: AAH52422.1.
CCDSiCCDS23534.1.
RefSeqiNP_035920.1. NM_011790.4.
XP_006511788.1. XM_006511725.2.
UniGeneiMm.290447.

Genome annotation databases

EnsembliENSMUST00000013338; ENSMUSP00000013338; ENSMUSG00000064145.
GeneIDi23807.
KEGGimmu:23807.
UCSCiuc009rqo.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF124664 mRNA. Translation: AAD24573.1.
AJ130975 mRNA. Translation: CAA10273.1.
BC051998 mRNA. Translation: AAH51998.1.
BC052422 mRNA. Translation: AAH52422.1.
CCDSiCCDS23534.1.
RefSeqiNP_035920.1. NM_011790.4.
XP_006511788.1. XM_006511725.2.
UniGeneiMm.290447.

3D structure databases

ProteinModelPortaliQ9Z1K6.
SMRiQ9Z1K6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204727. 4 interactors.
IntActiQ9Z1K6. 1 interactor.
STRINGi10090.ENSMUSP00000013338.

PTM databases

iPTMnetiQ9Z1K6.
PhosphoSitePlusiQ9Z1K6.

Proteomic databases

EPDiQ9Z1K6.
MaxQBiQ9Z1K6.
PaxDbiQ9Z1K6.
PRIDEiQ9Z1K6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000013338; ENSMUSP00000013338; ENSMUSG00000064145.
GeneIDi23807.
KEGGimmu:23807.
UCSCiuc009rqo.1. mouse.

Organism-specific databases

CTDi10425.
MGIiMGI:1344361. Arih2.

Phylogenomic databases

eggNOGiKOG1815. Eukaryota.
ENOG410XP9Y. LUCA.
GeneTreeiENSGT00840000129790.
HOGENOMiHOG000216611.
HOVERGENiHBG018737.
InParanoidiQ9Z1K6.
KOiK11969.
OMAiFRDYVEX.
OrthoDBiEOG091G06CV.
PhylomeDBiQ9Z1K6.
TreeFamiTF300805.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

PROiQ9Z1K6.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000064145.
CleanExiMM_ARIH2.
ExpressionAtlasiQ9Z1K6. baseline and differential.
GenevisibleiQ9Z1K6. MM.

Family and domain databases

Gene3Di3.30.40.10. 2 hits.
InterProiIPR031127. E3_UB_ligase_RBR.
IPR002867. IBR_dom.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PANTHERiPTHR11685. PTHR11685. 1 hit.
PfamiPF01485. IBR. 2 hits.
[Graphical view]
SMARTiSM00647. IBR. 2 hits.
SM00184. RING. 2 hits.
[Graphical view]
PROSITEiPS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiARI2_MOUSE
AccessioniPrimary (citable) accession number: Q9Z1K6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: May 1, 1999
Last modified: November 30, 2016
This is version 137 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.