ID ARI2_HUMAN Reviewed; 493 AA. AC O95376; Q9HBZ6; Q9UEM9; DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 1. DT 27-MAR-2024, entry version 198. 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:0000269|PubMed:16118314, ECO:0000269|PubMed:17646546, ECO:0000269|PubMed:19340006}; DE AltName: Full=RING-type E3 ubiquitin transferase ARIH2 {ECO:0000305}; DE AltName: Full=Triad1 protein {ECO:0000303|PubMed:10422847}; GN Name=ARIH2; Synonyms=ARI2, TRIAD1 {ECO:0000303|PubMed:16118314}; GN ORFNames=HT005; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=10422847; DOI=10.1110/ps.8.7.1557; RA van der Reijden B.A., Erpelinck-Verschueren C.A.J., Loewenberg B., RA Jansen J.H.; RT "TRIADs: a new class of proteins with a novel cysteine-rich signature."; RL Protein Sci. 8:1557-1561(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. 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 TISSUE=Hypothalamus; RX PubMed=10931946; DOI=10.1073/pnas.160270997; RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J., RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., RA Chen M.-D., Chen J.-L.; RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis RT and full-length cDNA cloning."; RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Muscle; 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 [5] RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH UBE2L3, SUBCELLULAR RP LOCATION, UBIQUITINATION, MUTAGENESIS OF HIS-158 AND CYS-161, TISSUE RP SPECIFICITY, AND INDUCTION BY ATRA. RX PubMed=16118314; DOI=10.1182/blood-2005-04-1450; RA Marteijn J.A., van Emst L., Erpelinck-Verschueren C.A., Nikoloski G., RA Menke A., de Witte T., Loewenberg B., Jansen J.H., van der Reijden B.A.; RT "The E3 ubiquitin-protein ligase Triad1 inhibits clonogenic growth of RT primary myeloid progenitor cells."; RL Blood 106:4114-4123(2005). RN [6] RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH GFI1 AND GFI1B. RX PubMed=17646546; DOI=10.1182/blood-2006-11-058602; RA Marteijn J.A., van der Meer L.T., van Emst L., van Reijmersdal S., RA Wissink W., de Witte T., Jansen J.H., Van der Reijden B.A.; RT "Gfi1 ubiquitination and proteasomal degradation is inhibited by the RT ubiquitin ligase Triad1."; RL Blood 110:3128-3135(2007). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-353, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [8] RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH UBE2L3 AND UBE2N, AND RP SUBCELLULAR LOCATION. RX PubMed=19340006; DOI=10.1038/leu.2009.57; RA Marteijn J.A., van der Meer L.T., Smit J.J., Noordermeer S.M., Wissink W., RA Jansen P., Swarts H.G., Hibbert R.G., de Witte T., Sixma T.K., Jansen J.H., RA van der Reijden B.A.; RT "The ubiquitin ligase Triad1 inhibits myelopoiesis through UbcH7 and Ubc13 RT interacting domains."; RL Leukemia 23:1480-1489(2009). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [10] RP FUNCTION, INTERACTION WITH UBE2L3 AND CUL5, INTERACTION WITH ECS COMPLEX, RP ACTIVITY REGULATION, AND MUTAGENESIS OF 84-LEU--VAL-86; TRP-100; HIS-158; RP CYS-257; CYS-300 AND CYS-310. RX PubMed=24076655; DOI=10.1038/emboj.2013.209; RA Kelsall I.R., Duda D.M., Olszewski J.L., Hofmann K., Knebel A., RA Langevin F., Wood N., Wightman M., Schulman B.A., Alpi A.F.; RT "TRIAD1 and HHARI bind to and are activated by distinct neddylated Cullin- RT RING ligase complexes."; RL EMBO J. 32:2848-2860(2013). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-353, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [12] RP INTERACTION WITH DCUN1D1. RX PubMed=30587576; DOI=10.1074/jbc.ra118.005861; RA Kelsall I.R., Kristariyanto Y.A., Knebel A., Wood N.T., Kulathu Y., RA Alpi A.F.; RT "Coupled monoubiquitylation of the co-E3 ligase DCNL1 by Ariadne-RBR E3 RT ubiquitin ligases promotes cullin-RING ligase complex remodeling."; RL J. Biol. Chem. 294:2651-2664(2019). CC -!- FUNCTION: E3 ubiquitin-protein ligase, which catalyzes ubiquitination CC of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3 CC (PubMed:16118314, PubMed:17646546, PubMed:19340006, PubMed:24076655). CC Acts as an atypical E3 ubiquitin-protein ligase by working together CC with cullin-5-RING ubiquitin ligase complex (ECS complex, also named CC CRL5 complex) and initiating ubiquitination of ECS substrates: CC associates with ECS complex and specifically mediates addition of the CC first ubiquitin on ECS targets (By similarity). The initial ubiquitin CC is then elongated (By similarity). E3 ubiquitin-protein ligase activity CC is activated upon binding to neddylated form of the ECS complex CC (PubMed:24076655). Mediates 'Lys-6', 'Lys-48'- and 'Lys-63'-linked CC polyubiquitination (PubMed:16118314, PubMed:17646546, PubMed:19340006). CC May play a role in myelopoiesis (PubMed:19340006). CC {ECO:0000250|UniProtKB:Q9Y4X5, ECO:0000269|PubMed:16118314, CC ECO:0000269|PubMed:17646546, ECO:0000269|PubMed:19340006, CC ECO:0000269|PubMed:24076655}. 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:0000269|PubMed:16118314, CC ECO:0000269|PubMed:17646546, ECO:0000269|PubMed:19340006}; 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 (PubMed:24076655). CC {ECO:0000250|UniProtKB:Q9Y4X5, ECO:0000269|PubMed:24076655}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Interacts (via RING-type zinc finger 1) with UBE2L3 CC (PubMed:16118314, PubMed:19340006, PubMed:24076655). Interacts (via CC RING-type zinc finger 2) with UBE2N (PubMed:19340006). Interacts with CC neddylated CUL5 (PubMed:24076655). Interacts (via RING-type 2) with CC GFI1B (PubMed:17646546). Interacts with GFI1; prevents its CC ubiquitination and proteasomal degradation (PubMed:17646546). Interacts CC with DCUN1D1 (via UBA-like domain); promotes DCUN1D1 ubiquitination CC (PubMed:30587576). {ECO:0000269|PubMed:16118314, CC ECO:0000269|PubMed:17646546, ECO:0000269|PubMed:19340006, CC ECO:0000269|PubMed:24076655, ECO:0000269|PubMed:30587576}. CC -!- INTERACTION: CC O95376; O43683: BUB1; NbExp=5; IntAct=EBI-711158, EBI-748936; CC O95376; O43186: CRX; NbExp=3; IntAct=EBI-711158, EBI-748171; CC O95376; Q93034: CUL5; NbExp=12; IntAct=EBI-711158, EBI-1057139; CC O95376; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-711158, EBI-16439278; CC O95376; P26367: PAX6; NbExp=3; IntAct=EBI-711158, EBI-747278; CC O95376; Q04864: REL; NbExp=3; IntAct=EBI-711158, EBI-307352; CC O95376; P04637: TP53; NbExp=5; IntAct=EBI-711158, EBI-366083; CC O95376; P68036: UBE2L3; NbExp=11; IntAct=EBI-711158, EBI-711173; CC O95376; O14933: UBE2L6; NbExp=13; IntAct=EBI-711158, EBI-2129974; CC O95376; Q16851: UGP2; NbExp=7; IntAct=EBI-711158, EBI-743729; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16118314}. Cytoplasm CC {ECO:0000269|PubMed:19340006}. CC -!- TISSUE SPECIFICITY: Widely expressed with higher expression in CC granulocytes. {ECO:0000269|PubMed:16118314}. CC -!- INDUCTION: Up-regulated by all-trans retinoic acid (ATRA). Up-regulated CC during differentiation of immature blood cells toward monocytes and CC granulocytes. {ECO:0000269|PubMed:16118314}. 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:0000269|PubMed:16118314}. CC -!- SIMILARITY: Belongs to the RBR family. Ariadne subfamily. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAG09696.1; Type=Frameshift; Evidence={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; AF099149; AAC82469.1; -; mRNA. DR EMBL; AJ130978; CAA10276.1; -; mRNA. DR EMBL; AF183427; AAG09696.1; ALT_FRAME; mRNA. DR EMBL; BC000422; AAH00422.1; -; mRNA. DR CCDS; CCDS2780.1; -. DR RefSeq; NP_001304262.1; NM_001317333.1. DR RefSeq; NP_001304263.1; NM_001317334.1. DR RefSeq; NP_006312.1; NM_006321.3. DR RefSeq; XP_016861020.1; XM_017005531.1. DR RefSeq; XP_016861021.1; XM_017005532.1. DR PDB; 7OD1; X-ray; 2.45 A; A/B=1-493. DR PDB; 7ONI; EM; 3.40 A; H=1-493. DR PDBsum; 7OD1; -. DR PDBsum; 7ONI; -. DR AlphaFoldDB; O95376; -. DR EMDB; EMD-12995; -. DR SMR; O95376; -. DR BioGRID; 115694; 318. DR IntAct; O95376; 57. DR MINT; O95376; -. DR STRING; 9606.ENSP00000348769; -. DR GlyGen; O95376; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O95376; -. DR PhosphoSitePlus; O95376; -. DR SwissPalm; O95376; -. DR BioMuta; ARIH2; -. DR EPD; O95376; -. DR jPOST; O95376; -. DR MassIVE; O95376; -. DR MaxQB; O95376; -. DR PaxDb; 9606-ENSP00000348769; -. DR PeptideAtlas; O95376; -. DR ProteomicsDB; 50829; -. DR Pumba; O95376; -. DR Antibodypedia; 13411; 405 antibodies from 36 providers. DR DNASU; 10425; -. DR Ensembl; ENST00000356401.9; ENSP00000348769.4; ENSG00000177479.20. DR Ensembl; ENST00000449376.5; ENSP00000403222.1; ENSG00000177479.20. DR GeneID; 10425; -. DR KEGG; hsa:10425; -. DR MANE-Select; ENST00000356401.9; ENSP00000348769.4; NM_006321.4; NP_006312.1. DR AGR; HGNC:690; -. DR CTD; 10425; -. DR DisGeNET; 10425; -. DR GeneCards; ARIH2; -. DR HGNC; HGNC:690; ARIH2. DR HPA; ENSG00000177479; Low tissue specificity. DR MIM; 605615; gene. DR neXtProt; NX_O95376; -. DR OpenTargets; ENSG00000177479; -. DR PharmGKB; PA24983; -. DR VEuPathDB; HostDB:ENSG00000177479; -. DR eggNOG; KOG1812; Eukaryota. DR GeneTree; ENSGT00940000154875; -. DR HOGENOM; CLU_009823_0_1_1; -. DR InParanoid; O95376; -. DR OMA; ICKVCHT; -. DR OrthoDB; 3084186at2759; -. DR PhylomeDB; O95376; -. DR TreeFam; TF300805; -. DR BRENDA; 2.3.2.31; 2681. DR PathwayCommons; O95376; -. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; O95376; -. DR SIGNOR; O95376; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 10425; 56 hits in 1209 CRISPR screens. DR ChiTaRS; ARIH2; human. DR GeneWiki; ARIH2; -. DR GenomeRNAi; 10425; -. DR Pharos; O95376; Tbio. DR PRO; PR:O95376; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; O95376; Protein. DR Bgee; ENSG00000177479; Expressed in apex of heart and 206 other cell types or tissues. DR ExpressionAtlas; O95376; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0000151; C:ubiquitin ligase complex; IBA:GO_Central. DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; IPI:UniProtKB. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; TAS:ProtInc. DR GO; GO:0048588; P:developmental cell growth; IDA:UniProtKB. DR GO; GO:0071425; P:hematopoietic stem cell proliferation; IDA:UniProtKB. DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central. DR GO; GO:1903955; P:positive regulation of protein targeting to mitochondrion; HMP:ParkinsonsUK-UCL. DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB. DR GO; GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB. DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB. DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB. DR CDD; cd20344; BRcat_RBR_TRIAD1; 1. DR CDD; cd20360; Rcat_RBR_TRIAD1; 1. DR CDD; cd16773; RING-HC_RBR_TRIAD1; 1. DR Gene3D; 1.20.120.1750; -; 1. DR Gene3D; 2.20.25.20; -; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR045840; Ariadne. DR InterPro; IPR047555; BRcat_RBR_TRIAD1. DR InterPro; IPR031127; E3_UB_ligase_RBR. DR InterPro; IPR002867; IBR_dom. DR InterPro; IPR047556; Rcat_RBR_TRIAD1. 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:SF210; E3 UBIQUITIN-PROTEIN LIGASE ARIH2; 1. DR PANTHER; PTHR11685; RBR FAMILY RING FINGER AND IBR DOMAIN-CONTAINING; 1. DR Pfam; PF19422; Ariadne; 1. DR Pfam; PF01485; IBR; 2. DR SMART; SM00647; IBR; 2. DR SMART; SM00184; RING; 2. DR SUPFAM; SSF57850; RING/U-box; 3. DR PROSITE; PS51873; TRIAD; 1. DR PROSITE; PS00518; ZF_RING_1; 1. DR PROSITE; PS50089; ZF_RING_2; 2. DR Genevisible; O95376; HS. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasm; Metal-binding; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; Transferase; Ubl conjugation; KW Ubl conjugation pathway; Zinc; Zinc-finger. FT CHAIN 1..493 FT /note="E3 ubiquitin-protein ligase ARIH2" FT /id="PRO_0000055755" FT ZN_FING 139..188 FT /note="RING-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT ZN_FING 208..270 FT /note="IBR-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT ZN_FING 297..326 FT /note="RING-type 2; atypical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT REGION 1..38 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 65..112 FT /note="UBA-like" FT /evidence="ECO:0000250|UniProtKB:Q9Y4X5" FT REGION 135..344 FT /note="TRIAD supradomain" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT REGION 359..493 FT /note="Ariadne domain" FT /evidence="ECO:0000250|UniProtKB:Q9Y4X5" FT COMPBIAS 15..36 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 310 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221, FT ECO:0000305|PubMed:24076655" FT BINDING 139 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 142 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 156 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 158 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 161 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 164 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 183 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 188 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 228 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 233 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 249 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 252 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 257 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 260 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 265 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 270 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 297 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 300 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 315 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 318 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 323 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 326 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 333 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 340 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT MOD_RES 353 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332, FT ECO:0007744|PubMed:23186163" FT VARIANT 24 FT /note="E -> K (in dbSNP:rs11507)" FT /id="VAR_054105" FT VARIANT 29 FT /note="E -> D (in dbSNP:rs34221642)" FT /id="VAR_054106" FT MUTAGEN 84..86 FT /note="LKV->AKA: Reduced interaction with neddylated CUL5; FT when associated with A-100." FT /evidence="ECO:0000269|PubMed:24076655" FT MUTAGEN 100 FT /note="W->A: Reduced interaction with neddylated CUL5; when FT associated with 84-A--A-86." FT /evidence="ECO:0000269|PubMed:24076655" FT MUTAGEN 158 FT /note="H->A: Loss of effect in myelopoiesis. Abolishes FT interaction with UBE2L3." FT /evidence="ECO:0000269|PubMed:16118314, FT ECO:0000269|PubMed:24076655" FT MUTAGEN 161 FT /note="C->A: Loss of effect in myelopoiesis." FT /evidence="ECO:0000269|PubMed:16118314" FT MUTAGEN 257 FT /note="C->A: Does not affect interaction with UBE2L3." FT /evidence="ECO:0000269|PubMed:24076655" FT MUTAGEN 300 FT /note="C->A: Does not affect interaction with UBE2L3." FT /evidence="ECO:0000269|PubMed:24076655" FT MUTAGEN 310 FT /note="C->A: Abolishes E3 ubiquitin-protein ligase FT activity." FT /evidence="ECO:0000269|PubMed:24076655" FT CONFLICT 280..281 FT /note="CA -> LQ (in Ref. 2; CAA10276)" FT /evidence="ECO:0000305" FT HELIX 42..45 FT /evidence="ECO:0007829|PDB:7ONI" FT STRAND 61..65 FT /evidence="ECO:0007829|PDB:7OD1" FT HELIX 66..84 FT /evidence="ECO:0007829|PDB:7OD1" FT HELIX 88..97 FT /evidence="ECO:0007829|PDB:7OD1" FT TURN 98..100 FT /evidence="ECO:0007829|PDB:7OD1" FT HELIX 102..111 FT /evidence="ECO:0007829|PDB:7OD1" FT HELIX 113..119 FT /evidence="ECO:0007829|PDB:7OD1" FT TURN 140..142 FT /evidence="ECO:0007829|PDB:7OD1" FT HELIX 162..174 FT /evidence="ECO:0007829|PDB:7OD1" FT HELIX 194..197 FT /evidence="ECO:0007829|PDB:7OD1" FT HELIX 198..200 FT /evidence="ECO:0007829|PDB:7OD1" FT HELIX 204..221 FT /evidence="ECO:0007829|PDB:7OD1" FT STRAND 225..227 FT /evidence="ECO:0007829|PDB:7OD1" FT STRAND 230..232 FT /evidence="ECO:0007829|PDB:7ONI" FT STRAND 235..241 FT /evidence="ECO:0007829|PDB:7OD1" FT STRAND 246..248 FT /evidence="ECO:0007829|PDB:7OD1" FT TURN 250..252 FT /evidence="ECO:0007829|PDB:7OD1" FT STRAND 255..257 FT /evidence="ECO:0007829|PDB:7OD1" FT TURN 258..260 FT /evidence="ECO:0007829|PDB:7OD1" FT STRAND 261..263 FT /evidence="ECO:0007829|PDB:7OD1" FT HELIX 270..282 FT /evidence="ECO:0007829|PDB:7OD1" FT HELIX 284..287 FT /evidence="ECO:0007829|PDB:7OD1" FT STRAND 293..296 FT /evidence="ECO:0007829|PDB:7OD1" FT TURN 298..300 FT /evidence="ECO:0007829|PDB:7OD1" FT STRAND 303..305 FT /evidence="ECO:0007829|PDB:7OD1" FT STRAND 311..314 FT /evidence="ECO:0007829|PDB:7OD1" FT TURN 316..318 FT /evidence="ECO:0007829|PDB:7OD1" FT STRAND 321..323 FT /evidence="ECO:0007829|PDB:7OD1" FT TURN 324..326 FT /evidence="ECO:0007829|PDB:7OD1" FT HELIX 330..332 FT /evidence="ECO:0007829|PDB:7OD1" FT STRAND 333..335 FT /evidence="ECO:0007829|PDB:7OD1" FT HELIX 354..398 FT /evidence="ECO:0007829|PDB:7OD1" FT STRAND 399..402 FT /evidence="ECO:0007829|PDB:7ONI" FT HELIX 404..432 FT /evidence="ECO:0007829|PDB:7OD1" FT HELIX 438..462 FT /evidence="ECO:0007829|PDB:7OD1" FT HELIX 464..466 FT /evidence="ECO:0007829|PDB:7OD1" FT HELIX 469..490 FT /evidence="ECO:0007829|PDB:7OD1" SQ SEQUENCE 493 AA; 57819 MW; 30AFFDD327B51013 CRC64; MSVDMNSQGS DSNEEDYDPN CEEEEEEEED DPGDIEDYYV GVASDVEQQG ADAFDPEEYQ FTCLTYKESE GALNEHMTSL ASVLKVSHSV AKLILVNFHW QVSEILDRYK SNSAQLLVEA RVQPNPSKHV PTSHPPHHCA VCMQFVRKEN LLSLACQHQF CRSCWEQHCS VLVKDGVGVG VSCMAQDCPL RTPEDFVFPL LPNEELREKY RRYLFRDYVE SHYQLQLCPG ADCPMVIRVQ EPRARRVQCN RCNEVFCFKC RQMYHAPTDC ATIRKWLTKC ADDSETANYI SAHTKDCPKC NICIEKNGGC NHMQCSKCKH DFCWMCLGDW KTHGSEYYEC SRYKENPDIV NQSQQAQARE ALKKYLFYFE RWENHNKSLQ LEAQTYQRIH EKIQERVMNN LGTWIDWQYL QNAAKLLAKC RYTLQYTYPY AYYMESGPRK KLFEYQQAQL EAEIENLSWK VERADSYDRG DLENQMHIAE QRRRTLLKDF HDT //