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Protein

E3 ubiquitin-protein ligase ARIH1

Gene

Arih1

Organism
Mus musculus (Mouse)
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. 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

[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine.By similarity

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. 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 1PROSITE-ProRule annotation1
Metal bindingi187Zinc 1PROSITE-ProRule annotation1
Metal bindingi201Zinc 2PROSITE-ProRule annotation1
Metal bindingi203Zinc 2; via pros nitrogenPROSITE-ProRule annotation1
Metal bindingi206Zinc 1PROSITE-ProRule annotation1
Metal bindingi209Zinc 1PROSITE-ProRule annotation1
Metal bindingi229Zinc 2PROSITE-ProRule annotation1
Metal bindingi234Zinc 2PROSITE-ProRule annotation1
Metal bindingi274Zinc 3PROSITE-ProRule annotation1
Metal bindingi279Zinc 3PROSITE-ProRule annotation1
Metal bindingi295Zinc 3PROSITE-ProRule annotation1
Metal bindingi297Zinc 3PROSITE-ProRule annotation1
Metal bindingi302Zinc 4PROSITE-ProRule annotation1
Metal bindingi305Zinc 4PROSITE-ProRule annotation1
Metal bindingi310Zinc 4; via tele nitrogenPROSITE-ProRule annotation1
Metal bindingi315Zinc 4PROSITE-ProRule annotation1
Metal bindingi342Zinc 5PROSITE-ProRule annotation1
Metal bindingi345Zinc 5PROSITE-ProRule annotation1
Active sitei355PROSITE-ProRule annotation1
Metal bindingi360Zinc 5PROSITE-ProRule annotation1
Metal bindingi365Zinc 5PROSITE-ProRule annotation1
Metal bindingi370Zinc 6PROSITE-ProRule annotation1
Metal bindingi373Zinc 6PROSITE-ProRule annotation1
Metal bindingi380Zinc 6; via tele nitrogenPROSITE-ProRule annotation1
Metal bindingi387Zinc 6PROSITE-ProRule annotation1

Regions

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processUbl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

BRENDAi2.3.2.B5 3474
ReactomeiR-MMU-1169408 ISG15 antiviral mechanism
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase ARIH1 (EC:2.3.2.31By 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1344363 Arih1

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

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 Expressed in 299 organ(s), highest expression level in secondary oocyte
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, 3 interactors
IntActiQ9Z1K5, 4 interactors
MINTiQ9Z1K5
STRINGi10090.ENSMUSP00000126531

Structurei

3D structure databases

ProteinModelPortaliQ9Z1K5
SMRiQ9Z1K5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni103 – 151UBA-likeBy similarityAdd BLAST49
Regioni180 – 391TRIAD supradomainPROSITE-ProRule annotationAdd BLAST212
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

Zinc finger

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

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1815 Eukaryota
ENOG410XP9Y LUCA
GeneTreeiENSGT00890000139392
HOGENOMiHOG000216612
HOVERGENiHBG018737
InParanoidiQ9Z1K5
KOiK11968
OrthoDBiEOG091G01SC
PhylomeDBiQ9Z1K5
TreeFamiTF300805

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR031127 E3_UB_ligase_RBR
IPR002867 IBR_dom
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
PANTHERiPTHR11685 PTHR11685, 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
PS50089 ZF_RING_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H9KV21H9KV21_MOUSE
RBR-type E3 ubiquitin transferase
Arih1
476Annotation score:
H7BWY7H7BWY7_MOUSE
RBR-type E3 ubiquitin transferase
Arih1
381Annotation score:
F7A7T5F7A7T5_MOUSE
E3 ubiquitin-protein ligase ARIH1
Arih1
25Annotation score:

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

Similar proteinsi

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
SMRiQ9Z1K5
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204726, 3 interactors
IntActiQ9Z1K5, 4 interactors
MINTiQ9Z1K5
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
GeneTreeiENSGT00890000139392
HOGENOMiHOG000216612
HOVERGENiHBG018737
InParanoidiQ9Z1K5
KOiK11968
OrthoDBiEOG091G01SC
PhylomeDBiQ9Z1K5
TreeFamiTF300805

Enzyme and pathway databases

UniPathwayi
UPA00143

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

Miscellaneous databases

ChiTaRSiArih1 mouse
PROiPR:Q9Z1K5
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000025234 Expressed in 299 organ(s), highest expression level in secondary oocyte
ExpressionAtlasiQ9Z1K5 baseline and differential
GenevisibleiQ9Z1K5 MM

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR031127 E3_UB_ligase_RBR
IPR002867 IBR_dom
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
PANTHERiPTHR11685 PTHR11685, 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
PS50089 ZF_RING_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiARI1_MOUSE
AccessioniPrimary (citable) accession number: Q9Z1K5
Secondary accession number(s): E9Q1X3, Q6PF92, Q8CFJ4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: August 16, 2004
Last modified: November 7, 2018
This is version 146 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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

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