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Protein

E3 ubiquitin-protein ligase ARIH1

Gene

Arih1

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. Acts as an atypical E3 ubiquitin-protein ligase by working together with cullin-RING ubiquitin ligase (CRL) complexes and initiating ubiquitination of CRL substrates: associates with CRL complexes and specifically mediates addition of the first ubiquitin on CRLs targets. The initial ubiquitin is then elongated by CDC34/UBE2R1 and UBE2R2. E3 ubiquitin-protein ligase activity is activated upon binding to neddylated cullin-RING ubiquitin ligase complexes. Plays a role in protein translation in response to DNA damage by mediating ubiquitination of EIF4E2, the consequences of EIF4E2 ubiquitination are however unclear. According to a report, EIF4E2 ubiquitination leads to promote EIF4E2 cap-binding and protein translation arrest. According to another report EIF4E2 ubiquitination leads to its subsequent degradation. Acts as the ligase involved in ISGylation of EIF4E2.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. Inhibition is relieved upon binding to neddylated cullin-RING ubiquitin ligase complexes, which activate the E3 ligase activity of ARIH1.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 bindingi184Zinc 1By similarity1
Metal bindingi187Zinc 1By similarity1
Metal bindingi201Zinc 2By similarity1
Metal bindingi203Zinc 2; via pros nitrogenBy similarity1
Metal bindingi206Zinc 1By similarity1
Metal bindingi209Zinc 1By similarity1
Metal bindingi229Zinc 2By similarity1
Metal bindingi234Zinc 2By similarity1
Metal bindingi274Zinc 3By similarity1
Metal bindingi279Zinc 3By similarity1
Metal bindingi295Zinc 3By similarity1
Metal bindingi297Zinc 3By similarity1
Metal bindingi302Zinc 4By similarity1
Metal bindingi305Zinc 4By similarity1
Metal bindingi310Zinc 4; via tele nitrogenBy similarity1
Metal bindingi315Zinc 4By similarity1
Metal bindingi342Zinc 5By similarity1
Metal bindingi345Zinc 5By similarity1
Active sitei355By similarity1
Metal bindingi360Zinc 5By similarity1
Metal bindingi365Zinc 5By similarity1
Metal bindingi370Zinc 6By similarity1
Metal bindingi373Zinc 6By similarity1
Metal bindingi380Zinc 6; via tele nitrogenBy similarity1
Metal bindingi387Zinc 6By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri184 – 234RING-type 1; atypicalPROSITE-ProRule annotationAdd BLAST51
Zinc fingeri254 – 315IBR-typeAdd BLAST62
Zinc fingeri342 – 373RING-type 2PROSITE-ProRule annotationAdd BLAST32

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

BRENDAi2.3.2.B5. 3474.
ReactomeiR-MMU-1169408. ISG15 antiviral mechanism.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase ARIH1 (EC:2.3.2.-By similarity)
Alternative name(s):
Protein ariadne-1 homolog
Short name:
ARI-1
RING-type E3 ubiquitin transferase ARIH1Curated
UbcH7-binding protein
UbcM4-interacting protein 771 Publication
Ubiquitin-conjugating enzyme E2-binding protein 1
Gene namesi
Name:Arih1
Synonyms:Ari, Ubch7bp1 Publication, Uip771 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1344363. Arih1.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity
  • NucleusCajal body By similarity

  • Note: Mainly cytoplasmic. Present in Lewy body.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000557531 – 555E3 ubiquitin-protein ligase ARIH1Add BLAST555

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei140N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ9Z1K5.
MaxQBiQ9Z1K5.
PaxDbiQ9Z1K5.
PeptideAtlasiQ9Z1K5.
PRIDEiQ9Z1K5.

PTM databases

iPTMnetiQ9Z1K5.
PhosphoSitePlusiQ9Z1K5.

Expressioni

Tissue specificityi

Widely expressed.

Gene expression databases

BgeeiENSMUSG00000025234.
ExpressionAtlasiQ9Z1K5. baseline and differential.
GenevisibleiQ9Z1K5. MM.

Interactioni

Subunit structurei

Interacts (via the first RING-type zinc finger) with UBE2L3. Associates with cullin-RING ubiquitin ligase (CRL) complexes containing CUL1, CUL2 and CUL3. Interacts with neddylated CUL1. Interacts with neddylated CUL2. Interacts with neddylated CUL3. Interacts with neddylated CUL4A.By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204726. 2 interactors.
IntActiQ9Z1K5. 1 interactor.
MINTiMINT-4088309.
STRINGi10090.ENSMUSP00000126531.

Structurei

3D structure databases

ProteinModelPortaliQ9Z1K5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni103 – 151UBA-likeBy similarityAdd BLAST49
Regioni406 – 555Ariadne domainBy similarityAdd BLAST150

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 fingeri184 – 234RING-type 1; atypicalPROSITE-ProRule annotationAdd BLAST51
Zinc fingeri254 – 315IBR-typeAdd BLAST62
Zinc fingeri342 – 373RING-type 2PROSITE-ProRule annotationAdd BLAST32

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1815. Eukaryota.
ENOG410XP9Y. LUCA.
GeneTreeiENSGT00840000129790.
HOGENOMiHOG000216612.
HOVERGENiHBG018737.
InParanoidiQ9Z1K5.
KOiK11968.
OMAiGGERDEC.
OrthoDBiEOG091G01SC.
PhylomeDBiQ9Z1K5.
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.
[Graphical view]
PANTHERiPTHR11685. PTHR11685. 1 hit.
PfamiPF01485. IBR. 2 hits.
[Graphical view]
SMARTiSM00647. IBR. 2 hits.
SM00184. RING. 2 hits.
[Graphical view]
PROSITEiPS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9Z1K5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDSDEGYNYE FDEDEECSEE DSGAEEEEDD DEDEPDDDNL DLGEVELVEP
60 70 80 90 100
GLGVGGERDG LLCGETGGGG GSALGPGGGG GGGGGGGGPG HEQEEDYRYE
110 120 130 140 150
VLTAEQILQH MVECIREVNE VIQNPATITR ILLSHFNWDK EKLMERYFDG
160 170 180 190 200
NLEKLFAECH VINPSKKSRT RQMNTRSSAQ DMPCQICYLN YPNSYFTGLE
210 220 230 240 250
CGHKFCMQCW SEYLTTKIME EGMGQTISCP AHGCDILVDD NTVMRLITDS
260 270 280 290 300
KVKLKYQHLI TNSFVECNRL LKWCPAPDCH HVVKVQYPDA KPVRCKCGRQ
310 320 330 340 350
FCFNCGENWH DPVKCKWLKK WIKKCDDDSE TSNWIAANTK ECPKCHVTIE
360 370 380 390 400
KDGGCNHMVC RNQNCKAEFC WVCLGPWEPH GSAWYNCNRY NEDDAKAARD
410 420 430 440 450
AQERSRAALQ RYLFYCNRYM NHMQSLRFEH KLYAQVKQKM EEMQQHNMSW
460 470 480 490 500
IEVQFLKKAV DVLCQCRATL MYTYVFAFYL KKNNQSIIFE NNQADLENAT
510 520 530 540 550
EVLSGYLERD ISQDSLQDIK QKVQDKYRYC ESRRRVLLQH VHEGYEKDLW

EYIED
Length:555
Mass (Da):64,017
Last modified:August 16, 2004 - v3
Checksum:iE322A06806C12C8A
GO

Sequence cautioni

The sequence AAH38034 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti147Y → C in AAK51471 (PubMed:10431818).Curated1
Sequence conflicti324K → R in CAA10275 (PubMed:10880484).Curated1
Sequence conflicti328D → G in CAA10275 (PubMed:10880484).Curated1
Sequence conflicti405S → P in CAA10275 (PubMed:10880484).Curated1
Sequence conflicti478F → YR in CAA10275 (PubMed:10880484).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC113527 Genomic DNA. No translation available.
AC134894 Genomic DNA. No translation available.
BC038034 mRNA. Translation: AAH38034.1. Different initiation.
BC057680 mRNA. Translation: AAH57680.1.
AF361001 mRNA. Translation: AAK51471.1.
AJ130977 mRNA. Translation: CAA10275.1.
CCDSiCCDS52817.1.
RefSeqiNP_064311.2. NM_019927.2.
UniGeneiMm.305925.

Genome annotation databases

EnsembliENSMUST00000171975; ENSMUSP00000126531; ENSMUSG00000025234.
GeneIDi23806.
KEGGimmu:23806.
UCSCiuc009pxs.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC113527 Genomic DNA. No translation available.
AC134894 Genomic DNA. No translation available.
BC038034 mRNA. Translation: AAH38034.1. Different initiation.
BC057680 mRNA. Translation: AAH57680.1.
AF361001 mRNA. Translation: AAK51471.1.
AJ130977 mRNA. Translation: CAA10275.1.
CCDSiCCDS52817.1.
RefSeqiNP_064311.2. NM_019927.2.
UniGeneiMm.305925.

3D structure databases

ProteinModelPortaliQ9Z1K5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204726. 2 interactors.
IntActiQ9Z1K5. 1 interactor.
MINTiMINT-4088309.
STRINGi10090.ENSMUSP00000126531.

PTM databases

iPTMnetiQ9Z1K5.
PhosphoSitePlusiQ9Z1K5.

Proteomic databases

EPDiQ9Z1K5.
MaxQBiQ9Z1K5.
PaxDbiQ9Z1K5.
PeptideAtlasiQ9Z1K5.
PRIDEiQ9Z1K5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000171975; ENSMUSP00000126531; ENSMUSG00000025234.
GeneIDi23806.
KEGGimmu:23806.
UCSCiuc009pxs.2. mouse.

Organism-specific databases

CTDi25820.
MGIiMGI:1344363. Arih1.

Phylogenomic databases

eggNOGiKOG1815. Eukaryota.
ENOG410XP9Y. LUCA.
GeneTreeiENSGT00840000129790.
HOGENOMiHOG000216612.
HOVERGENiHBG018737.
InParanoidiQ9Z1K5.
KOiK11968.
OMAiGGERDEC.
OrthoDBiEOG091G01SC.
PhylomeDBiQ9Z1K5.
TreeFamiTF300805.

Enzyme and pathway databases

UniPathwayiUPA00143.
BRENDAi2.3.2.B5. 3474.
ReactomeiR-MMU-1169408. ISG15 antiviral mechanism.

Miscellaneous databases

ChiTaRSiArih1. mouse.
PROiQ9Z1K5.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000025234.
ExpressionAtlasiQ9Z1K5. baseline and differential.
GenevisibleiQ9Z1K5. 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.
[Graphical view]
PANTHERiPTHR11685. PTHR11685. 1 hit.
PfamiPF01485. IBR. 2 hits.
[Graphical view]
SMARTiSM00647. IBR. 2 hits.
SM00184. RING. 2 hits.
[Graphical view]
PROSITEiPS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiARI1_MOUSE
AccessioniPrimary (citable) accession number: Q9Z1K5
Secondary accession number(s): E9Q1X3, Q6PF92, Q8CFJ4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: August 16, 2004
Last modified: November 30, 2016
This is version 134 of the entry and version 3 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.