ARI2_MOUSE
ID ARI2_MOUSE Reviewed; 492 AA.
AC Q9Z1K6;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=E3 ubiquitin-protein ligase ARIH2;
DE Short=ARI-2;
DE Short=Protein ariadne-2 homolog;
DE EC=2.3.2.31 {ECO:0000250|UniProtKB:O95376};
DE AltName: Full=RING-type E3 ubiquitin transferase ARIH2 {ECO:0000305};
DE AltName: Full=Triad1 protein;
DE AltName: Full=UbcM4-interacting protein 48;
GN Name=Arih2; Synonyms=Ari2, Triad1, Uip48;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Liver;
RX PubMed=10431818; DOI=10.1016/s0014-5793(99)00823-6;
RA Martinez-Noel G., Niedenthal R., Tamura T., Harbers K.;
RT "A family of structurally related RING finger proteins interacts
RT specifically with the ubiquitin-conjugating enzyme UbcM4.";
RL FEBS Lett. 454:257-261(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain, and Embryo;
RX PubMed=10880484; DOI=10.1093/genetics/155.3.1231;
RA Aguilera M., Oliveros M., Martinez-Padron M., Barbas J.A., Ferrus A.;
RT "Ariadne-1: a vital Drosophila gene is required in development and defines
RT a new conserved family of ring-finger proteins.";
RL Genetics 155:1231-1244(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-352, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Liver, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: E3 ubiquitin-protein ligase, which catalyzes ubiquitination
CC of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3
CC (By similarity). Acts as an atypical E3 ubiquitin-protein ligase by
CC working together with cullin-5-RING ubiquitin ligase complex (ECS
CC complex, also named CRL5 complex) and initiating ubiquitination of ECS
CC substrates: associates with ECS complex and specifically mediates
CC addition of the first ubiquitin on ECS targets (By similarity). The
CC initial ubiquitin is then elongated (By similarity). E3 ubiquitin-
CC protein ligase activity is activated upon binding to neddylated form of
CC the ECS complex. Mediates 'Lys-6', 'Lys-48'- and 'Lys-63'-linked
CC polyubiquitination. May play a role in myelopoiesis (By similarity).
CC {ECO:0000250|UniProtKB:O95376, ECO:0000250|UniProtKB:Q9Y4X5}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + [acceptor protein]-N(6)-ubiquitinyl-L-lysine.;
CC EC=2.3.2.31; Evidence={ECO:0000250|UniProtKB:O95376};
CC -!- ACTIVITY REGULATION: Autoinhibited by the ariadne domain, which masks
CC the second RING-type zinc finger that contains the active site and
CC inhibits the E3 activity (By similarity). Inhibition is relieved upon
CC binding to neddylated cullin-RING ubiquitin ligase complexes, which
CC activate the E3 ligase activity of ARIH1 (By similarity).
CC {ECO:0000250|UniProtKB:O95376, ECO:0000250|UniProtKB:Q9Y4X5}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts (via RING-type zinc finger 1) with UBE2L3. Interacts
CC (via RING-type zinc finger 2) with UBE2N. Interacts with neddylated
CC CUL5. Interacts (via RING-type 2) with GFI1B. Interacts with GFI1;
CC prevents its ubiquitination and proteasomal degradation. Interacts with
CC DCUN1D1 (via UBA-like domain); promotes DCUN1D1 ubiquitination (By
CC similarity). {ECO:0000250|UniProtKB:O95376}.
CC -!- INTERACTION:
CC Q9Z1K6; Q60778: Nfkbib; NbExp=2; IntAct=EBI-6861719, EBI-644469;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O95376}. Cytoplasm
CC {ECO:0000250|UniProtKB:O95376}.
CC -!- DOMAIN: Members of the RBR family are atypical E3 ligases. They
CC interact with the E2 conjugating enzyme UBE2L3 and function like HECT-
CC type E3 enzymes: they bind E2s via the first RING-type zinc finger, but
CC require an obligate trans-thiolation step during the ubiquitin
CC transfer, requiring a conserved active site Cys residue in the second
CC RING-type zinc finger. The active site probably forms a thioester
CC intermediate with ubiquitin taken from the active-site cysteine of the
CC E2 before ultimately transferring it to a Lys residue on the substrate.
CC {ECO:0000250|UniProtKB:Q9Y4X5}.
CC -!- DOMAIN: The Ariadne domain inhibits activity by masking the second
CC RING-type zinc finger that contains the active site.
CC {ECO:0000250|UniProtKB:Q9Y4X5}.
CC -!- PTM: Ubiquitinated. Ubiquitination promotes proteasomal degradation.
CC {ECO:0000250|UniProtKB:O95376}.
CC -!- SIMILARITY: Belongs to the RBR family. Ariadne subfamily.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF124664; AAD24573.1; -; mRNA.
DR EMBL; AJ130975; CAA10273.1; -; mRNA.
DR EMBL; BC051998; AAH51998.1; -; mRNA.
DR EMBL; BC052422; AAH52422.1; -; mRNA.
DR CCDS; CCDS23534.1; -.
DR RefSeq; NP_035920.1; NM_011790.4.
DR RefSeq; XP_006511788.1; XM_006511725.2.
DR AlphaFoldDB; Q9Z1K6; -.
DR SMR; Q9Z1K6; -.
DR BioGRID; 204727; 4.
DR IntAct; Q9Z1K6; 1.
DR STRING; 10090.ENSMUSP00000013338; -.
DR iPTMnet; Q9Z1K6; -.
DR PhosphoSitePlus; Q9Z1K6; -.
DR EPD; Q9Z1K6; -.
DR MaxQB; Q9Z1K6; -.
DR PaxDb; Q9Z1K6; -.
DR PRIDE; Q9Z1K6; -.
DR ProteomicsDB; 265093; -.
DR Antibodypedia; 13411; 362 antibodies from 36 providers.
DR DNASU; 23807; -.
DR Ensembl; ENSMUST00000013338; ENSMUSP00000013338; ENSMUSG00000064145.
DR GeneID; 23807; -.
DR KEGG; mmu:23807; -.
DR UCSC; uc009rqo.1; mouse.
DR CTD; 10425; -.
DR MGI; MGI:1344361; Arih2.
DR VEuPathDB; HostDB:ENSMUSG00000064145; -.
DR eggNOG; KOG1812; Eukaryota.
DR GeneTree; ENSGT00940000154875; -.
DR HOGENOM; CLU_009823_0_1_1; -.
DR InParanoid; Q9Z1K6; -.
DR OMA; ICKVCHT; -.
DR OrthoDB; 469819at2759; -.
DR PhylomeDB; Q9Z1K6; -.
DR TreeFam; TF300805; -.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 23807; 11 hits in 71 CRISPR screens.
DR ChiTaRS; Arih2; mouse.
DR PRO; PR:Q9Z1K6; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q9Z1K6; protein.
DR Bgee; ENSMUSG00000064145; Expressed in paneth cell and 253 other tissues.
DR ExpressionAtlas; Q9Z1K6; baseline and differential.
DR Genevisible; Q9Z1K6; MM.
DR GO; GO:0031466; C:Cul5-RING ubiquitin ligase complex; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0000151; C:ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; ISO:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0048588; P:developmental cell growth; ISS:UniProtKB.
DR GO; GO:0071425; P:hematopoietic stem cell proliferation; ISS:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IPI:MGI.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR045840; Ariadne.
DR InterPro; IPR031126; Ariadne-2.
DR InterPro; IPR031127; E3_UB_ligase_RBR.
DR InterPro; IPR002867; IBR_dom.
DR InterPro; IPR044066; TRIAD_supradom.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR11685; PTHR11685; 1.
DR PANTHER; PTHR11685:SF210; PTHR11685:SF210; 1.
DR Pfam; PF19422; Ariadne; 1.
DR Pfam; PF01485; IBR; 2.
DR SMART; SM00647; IBR; 2.
DR SMART; SM00184; RING; 2.
DR PROSITE; PS51873; TRIAD; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 2.
PE 1: Evidence at protein level;
KW Cytoplasm; Metal-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Transferase; Ubl conjugation; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..492
FT /note="E3 ubiquitin-protein ligase ARIH2"
FT /id="PRO_0000055756"
FT ZN_FING 138..187
FT /note="RING-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT ZN_FING 207..269
FT /note="IBR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT ZN_FING 296..325
FT /note="RING-type 2; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 64..111
FT /note="UBA-like"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4X5"
FT REGION 134..343
FT /note="TRIAD supradomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT REGION 358..492
FT /note="Ariadne domain"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4X5"
FT COMPBIAS 15..35
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 309
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 138
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 141
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 155
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 157
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 160
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 163
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 182
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 187
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 227
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 232
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 248
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 251
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 256
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 259
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 264
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 269
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 296
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 299
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 314
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 317
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 322
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 325
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 332
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 339
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT MOD_RES 352
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 492 AA; 57697 MW; B55EA54FE8C3ADAF CRC64;
MSVDMNSQGS DSNEEDYDPN CEEEEEEEED PGDIEDYYVG VASDVEQQGA DAFDPEEYQF
TCLTYKESEG ALHEHMTSLA SVLKVSHSVA KLILVNFHWQ VSEILDRYRS NSAQLLVEAR
VQPNPSKHVP TAHPPHHCAV CMQFVRKENL LSLACQHQFC RSCWEQHCSV LVKDGVGVGI
SCMAQDCPLR TPEDFVFPLL PNEELRDKYR RYLFRDYVES HFQLQLCPGA DCPMVIRVQE
PRARRVQCNR CSEVFCFKCR QMYHAPTDCA TIRKWLTKCA DDSETANYIS AHTKDCPKCN
ICIEKNGGCN HMQCSKCKHD FCWMCLGDWK THGSEYYECS RYKENPDIVN QSQQAQAREA
LKKYLFYFER WENHNKSLQL EAQTYERIHE KIQERVMNNL GTWIDWQYLQ NAAKLLAKCR
YTLQYTYPYA YYMESGPRKK LFEYQQAQLE AEIENLSWKV ERADSYDRGD LENQMHIAEQ
RRRTLLKDFH DT
