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};
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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 Genevisible; O95376; HS.
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.
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
//
