ARI1_HUMAN
ID ARI1_HUMAN Reviewed; 557 AA.
AC Q9Y4X5; B2R6U3; O76026; Q9H3T6; Q9UEN0; Q9UP39;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2002, sequence version 2.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=E3 ubiquitin-protein ligase ARIH1;
DE EC=2.3.2.31 {ECO:0000269|PubMed:15236971, ECO:0000269|PubMed:21532592, ECO:0000269|PubMed:27565346};
DE AltName: Full=H7-AP2 {ECO:0000303|PubMed:10521492};
DE AltName: Full=HHARI {ECO:0000303|PubMed:11278816};
DE AltName: Full=Monocyte protein 6 {ECO:0000303|Ref.10};
DE Short=MOP-6 {ECO:0000303|Ref.10};
DE AltName: Full=Protein ariadne-1 homolog {ECO:0000303|Ref.3};
DE Short=ARI-1 {ECO:0000303|Ref.3};
DE AltName: Full=UbcH7-binding protein {ECO:0000303|PubMed:11278816};
DE AltName: Full=UbcM4-interacting protein;
DE AltName: Full=Ubiquitin-conjugating enzyme E2-binding protein 1 {ECO:0000303|PubMed:10521492};
GN Name=ARIH1 {ECO:0000312|HGNC:HGNC:689};
GN Synonyms=ARI, MOP6 {ECO:0000303|Ref.10},
GN UBCH7BP {ECO:0000303|PubMed:11278816};
GN ORFNames=HUSSY-27 {ECO:0000303|PubMed:11124703};
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], AND TISSUE SPECIFICITY.
RC TISSUE=Fetal brain;
RX PubMed=10521492; DOI=10.1074/jbc.274.43.30963;
RA Moynihan T.P., Ardley H.C., Nuber U., Rose S.A., Jones P.F., Markham A.F.,
RA Scheffner M., Robinson P.A.;
RT "The ubiquitin-conjugating enzymes UbcH7 and UbcH8 interact with RING
RT finger/IBR motif-containing domains of HHARI and H7-AP1.";
RL J. Biol. Chem. 274:30963-30968(1999).
RN [2]
RP SEQUENCE REVISION TO 227.
RA Ardley H.C.;
RL Submitted (MAY-2002) to UniProtKB.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Trockenbacher A., Marksteiner R., Schneider R.;
RT "Human ariadne homolog.";
RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC 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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 95-557.
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 [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 298-557.
RC TISSUE=Brain;
RX PubMed=11124703;
RX DOI=10.1002/1097-0061(200101)18:1<69::aid-yea647>3.0.co;2-h;
RA Stanchi F., Bertocco E., Toppo S., Dioguardi R., Simionati B., Cannata N.,
RA Zimbello R., Lanfranchi G., Valle G.;
RT "Characterization of 16 novel human genes showing high similarity to yeast
RT sequences.";
RL Yeast 18:69-80(2001).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 377-557.
RC TISSUE=Monocyte;
RA Fujii Y., Takayama K., Ukai Y., Yoshimoto M.;
RT "Molecular and biological characterization of a new ring finger protein,
RT MOP-6 which is highly expressed in activated human monocytes.";
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP IDENTIFICATION.
RX PubMed=11124525; DOI=10.1159/000056780;
RA Tan N.G., Ardley H.C., Rose S.A., Leek J.P., Markham A.F., Robinson P.A.;
RT "Characterisation of the human and mouse orthologues of the Drosophila
RT ariadne gene.";
RL Cytogenet. Cell Genet. 90:242-245(2000).
RN [12]
RP INTERACTION WITH UBE2L3, MUTAGENESIS OF 187-GLN-ILE-188; ILE-188; CYS-208
RP AND TYR-258, AND SUBCELLULAR LOCATION.
RX PubMed=11278816; DOI=10.1074/jbc.m011028200;
RA Ardley H.C., Tan N.G.S., Rose S.A., Markham A.F., Robinson P.A.;
RT "Features of the parkin/ariadne-like ubiquitin ligase, HHARI, that regulate
RT its interaction with the ubiquitin-conjugating enzyme, Ubch7.";
RL J. Biol. Chem. 276:19640-19647(2001).
RN [13]
RP FUNCTION.
RX PubMed=14623119; DOI=10.1016/s0014-5793(03)01235-3;
RA Tan N.G., Ardley H.C., Scott G.B., Rose S.A., Markham A.F., Robinson P.A.;
RT "Human homologue of ariadne promotes the ubiquitylation of translation
RT initiation factor 4E homologous protein, 4EHP.";
RL FEBS Lett. 554:501-504(2003).
RN [14]
RP FUNCTION.
RX PubMed=17289916; DOI=10.1101/gad.1521607;
RA Okumura F., Zou W., Zhang D.E.;
RT "ISG15 modification of the eIF4E cognate 4EHP enhances cap structure-
RT binding activity of 4EHP.";
RL Genes Dev. 21:255-260(2007).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [16]
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 [17]
RP FUNCTION, CATALYTIC ACTIVITY, REACTION MECHANISM, INTERACTION WITH UBE2L3,
RP ACTIVE SITE, DOMAIN, AND MUTAGENESIS OF CYS-357.
RX PubMed=21532592; DOI=10.1038/nature09966;
RA Wenzel D.M., Lissounov A., Brzovic P.S., Klevit R.E.;
RT "UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT
RT hybrids.";
RL Nature 474:105-108(2011).
RN [18]
RP SUBCELLULAR LOCATION.
RX PubMed=21590270; DOI=10.1007/s12031-011-9535-1;
RA Parelkar S.S., Cadena J.G., Kim C., Wang Z., Sugal R., Bentley B.,
RA Moral L., Ardley H.C., Schwartz L.M.;
RT "The parkin-like human homolog of Drosophila ariadne-1 (HHARI) can induce
RT aggresome formation in mammalian cells and is immunologically detectable in
RT Lewy bodies.";
RL J. Mol. Neurosci. 46:109-121(2012).
RN [19]
RP FUNCTION, INTERACTION WITH UBE2L3, INTERACTION WITH CULLIN-RING COMPLEXES,
RP ACTIVITY REGULATION, AND MUTAGENESIS OF HIS-205.
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 [20]
RP SUBCELLULAR LOCATION.
RX PubMed=23059369; DOI=10.1016/j.yexcr.2012.10.002;
RA Elmehdawi F., Wheway G., Szymanska K., Adams M., High A.S., Johnson C.A.,
RA Robinson P.A.;
RT "Human homolog of drosophila ariadne (HHARI) is a marker of cellular
RT proliferation associated with nuclear bodies.";
RL Exp. Cell Res. 319:161-172(2013).
RN [21]
RP FUNCTION, AND INDUCTION.
RX PubMed=25624349; DOI=10.1128/mcb.01152-14;
RA von Stechow L., Typas D., Carreras Puigvert J., Oort L., Siddappa R.,
RA Pines A., Vrieling H., van de Water B., Mullenders L.H., Danen E.H.;
RT "The E3 ubiquitin ligase ARIH1 protects against genotoxic stress by
RT initiating a 4EHP-mediated mRNA translation arrest.";
RL Mol. Cell. Biol. 35:1254-1268(2015).
RN [22]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH UBE2L3, INTERACTION WITH
RP CULLIN-RING COMPLEXES, ACTIVITY REGULATION, AND MUTAGENESIS OF VAL-123;
RP PHE-150; 156-LYS--PHE-158; ILE-188; 257-LYS-TYR-258; 265-SER--VAL-267;
RP 340-ASN-THR-341; 342-LYS-GLU-343; 531-ILE-GLU-352; ASN-358; HIS-359;
RP 378-PRO-TRP-379; 383-GLY--ALA-385; TRP-386; TYR-417; 420-ARG--ASN-423;
RP 430-PHE-GLU-431; TYR-476; GLU-492; ASN-493; GLN-495; GLU-499; GLU-503 AND
RP TYR-531.
RX PubMed=27565346; DOI=10.1016/j.cell.2016.07.027;
RA Scott D.C., Rhee D.Y., Duda D.M., Kelsall I.R., Olszewski J.L., Paulo J.A.,
RA de Jong A., Ovaa H., Alpi A.F., Harper J.W., Schulman B.A.;
RT "Two distinct types of E3 ligases work in unison to regulate substrate
RT ubiquitylation.";
RL Cell 166:1198-1214(2016).
RN [23]
RP FUNCTION, POSSIBLE INVOLVEMENT IN AORTIC ANEURYSM, AND VARIANTS GLN-15;
RP GLY-44 AND 171-ARG--ASP-557.
RX PubMed=29689197; DOI=10.1016/j.devcel.2018.03.020;
RG University of Washington Center for Mendelian Genomics;
RA Tan K.L., Haelterman N.A., Kwartler C.S., Regalado E.S., Lee P.T.,
RA Nagarkar-Jaiswal S., Guo D.C., Duraine L., Wangler M.F., Bamshad M.J.,
RA Nickerson D.A., Lin G., Milewicz D.M., Bellen H.J.;
RT "Ari-1 Regulates Myonuclear Organization Together with Parkin and Is
RT Associated with Aortic Aneurysms.";
RL Dev. Cell 45:226-244(2018).
RN [24]
RP STRUCTURE BY NMR OF 336-394 IN COMPLEX WITH ZINC, FUNCTION, CATALYTIC
RP ACTIVITY, AND MUTAGENESIS OF CYS-347; ILE-351; CYS-357; HIS-359; CYS-367;
RP PHE-371; CYS-372; TRP-373; TRP-379 AND TRP-386.
RX PubMed=15236971; DOI=10.1016/j.jmb.2004.05.035;
RA Capili A.D., Edghill E.L., Wu K., Borden K.L.;
RT "Structure of the C-terminal RING finger from a RING-IBR-RING/TRIAD motif
RT reveals a novel zinc-binding domain distinct from a RING.";
RL J. Mol. Biol. 340:1117-1129(2004).
RN [25]
RP STRUCTURE BY NMR OF 325-396 OF MUTANT CYS-357 IN COMPLEX WITH ZINC, AND
RP MUTAGENESIS OF CYS-357.
RX PubMed=24058416; DOI=10.1371/journal.pone.0074047;
RA Spratt D.E., Mercier P., Shaw G.S.;
RT "Structure of the HHARI catalytic domain shows glimpses of a HECT E3
RT ligase.";
RL PLoS ONE 8:E74047-E74047(2013).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (3.30 ANGSTROMS) IN COMPLEX WITH ZINC, ACTIVE SITE,
RP DOMAIN, ACTIVITY REGULATION, INTERACTION WITH UBE2L3, FUNCTION, AND
RP MUTAGENESIS OF ILE-188; PHE-416; 420-ARG--ASN-423; SER-427; 430-PHE-GLU-431
RP AND GLU-503.
RX PubMed=23707686; DOI=10.1016/j.str.2013.04.019;
RA Duda D.M., Olszewski J.L., Schuermann J.P., Kurinov I., Miller D.J.,
RA Nourse A., Alpi A.F., Schulman B.A.;
RT "Structure of HHARI, a RING-IBR-RING ubiquitin ligase: autoinhibition of an
RT Ariadne-family E3 and insights into ligation mechanism.";
RL Structure 21:1030-1041(2013).
CC -!- FUNCTION: E3 ubiquitin-protein ligase, which catalyzes ubiquitination
CC of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3
CC (PubMed:15236971, PubMed:21532592, PubMed:24076655, PubMed:27565346,
CC PubMed:23707686). Acts as an atypical E3 ubiquitin-protein ligase by
CC working together with cullin-RING ubiquitin ligase (CRL) complexes and
CC initiating ubiquitination of CRL substrates: associates with CRL
CC complexes and specifically mediates addition of the first ubiquitin on
CC CRLs targets (PubMed:27565346). The initial ubiquitin is then elongated
CC by CDC34/UBE2R1 and UBE2R2 (PubMed:27565346). E3 ubiquitin-protein
CC ligase activity is activated upon binding to neddylated cullin-RING
CC ubiquitin ligase complexes (PubMed:24076655, PubMed:27565346). Plays a
CC role in protein translation in response to DNA damage by mediating
CC ubiquitination of EIF4E2, the consequences of EIF4E2 ubiquitination are
CC however unclear (PubMed:25624349). According to a report, EIF4E2
CC ubiquitination leads to promote EIF4E2 cap-binding and protein
CC translation arrest (PubMed:25624349). According to another report
CC EIF4E2 ubiquitination leads to its subsequent degradation
CC (PubMed:14623119). Acts as the ligase involved in ISGylation of EIF4E2
CC (PubMed:17289916). In vitro, controls the degradation of the LINC
CC (LInker of Nucleoskeleton and Cytoskeleton) complex member SUN2 and may
CC therefore have a role in the formation and localization of the LINC
CC complex, and as a consequence, nuclear subcellular localization and
CC nuclear morphology (PubMed:29689197). {ECO:0000269|PubMed:14623119,
CC ECO:0000269|PubMed:15236971, ECO:0000269|PubMed:17289916,
CC ECO:0000269|PubMed:21532592, ECO:0000269|PubMed:23707686,
CC ECO:0000269|PubMed:24076655, ECO:0000269|PubMed:25624349,
CC ECO:0000269|PubMed:27565346, ECO:0000269|PubMed:29689197}.
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:15236971,
CC ECO:0000269|PubMed:21532592, ECO:0000269|PubMed:27565346};
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 (PubMed:23707686). 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 PubMed:27565346). {ECO:0000269|PubMed:23707686,
CC ECO:0000269|PubMed:24076655, ECO:0000269|PubMed:27565346}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts (via the first RING-type zinc finger) with UBE2L3
CC (PubMed:11278816, PubMed:21532592, PubMed:24076655, PubMed:23707686).
CC Associates with cullin-RING ubiquitin ligase (CRL) complexes containing
CC CUL1, CUL2 and CUL3 (PubMed:24076655, PubMed:27565346). Interacts with
CC neddylated CUL1 (PubMed:24076655, PubMed:27565346). Interacts with
CC neddylated CUL2 (PubMed:24076655, PubMed:27565346). Interacts with
CC neddylated CUL3 (PubMed:24076655, PubMed:27565346). Interacts with
CC neddylated CUL4A (PubMed:24076655). {ECO:0000269|PubMed:11278816,
CC ECO:0000269|PubMed:21532592, ECO:0000269|PubMed:23707686,
CC ECO:0000269|PubMed:24076655, ECO:0000269|PubMed:27565346}.
CC -!- INTERACTION:
CC Q9Y4X5; Q13616: CUL1; NbExp=8; IntAct=EBI-2514233, EBI-359390;
CC Q9Y4X5; P68036: UBE2L3; NbExp=6; IntAct=EBI-2514233, EBI-711173;
CC Q9Y4X5; P68036-1: UBE2L3; NbExp=3; IntAct=EBI-2514233, EBI-15556257;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11278816,
CC ECO:0000269|PubMed:21590270, ECO:0000269|PubMed:23059369}. Nucleus
CC {ECO:0000269|PubMed:23059369}. Nucleus, Cajal body
CC {ECO:0000269|PubMed:23059369}. Note=Mainly cytoplasmic
CC (PubMed:11278816). Present in Lewy body (PubMed:21590270).
CC {ECO:0000269|PubMed:11278816, ECO:0000269|PubMed:21590270}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:10521492}.
CC -!- INDUCTION: Up-regulated following DNA damage (PubMed:25624349).
CC {ECO:0000269|PubMed:25624349}.
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 (PubMed:21532592, PubMed:23707686). The active
CC site probably forms a thioester intermediate with ubiquitin taken from
CC the active-site cysteine of the E2 before ultimately transferring it to
CC a Lys residue on the substrate (PubMed:21532592, PubMed:23707686).
CC {ECO:0000269|PubMed:21532592, ECO:0000269|PubMed:23707686}.
CC -!- DOMAIN: The Ariadne domain inhibits activity by masking the second
CC RING-type zinc finger that contains the active site (PubMed:23707686).
CC {ECO:0000269|PubMed:23707686}.
CC -!- DISEASE: Note=Defects in ARIH1 have been found in several individuals
CC with thoracic aortic aneurysms and cerebrovascular disease.
CC {ECO:0000269|PubMed:29689197}.
CC -!- SIMILARITY: Belongs to the RBR family. Ariadne subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: The RING-type 2 zinc finger was initially reported to only
CC bind 1 zinc ion instead of 2 compared to classical RING-types
CC (PubMed:15236971). But it was later shown that it is not the case and
CC binds 2 zinc ions (PubMed:24058416, PubMed:23707686).
CC {ECO:0000269|PubMed:15236971, ECO:0000269|PubMed:23707686,
CC ECO:0000269|PubMed:24058416}.
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DR EMBL; AJ243190; CAB45870.1; -; mRNA.
DR EMBL; AF072832; AAD28088.1; -; mRNA.
DR EMBL; AK312715; BAG35590.1; -; mRNA.
DR EMBL; AC079322; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC100827; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471082; EAW77907.1; -; Genomic_DNA.
DR EMBL; BC051877; AAH51877.1; -; mRNA.
DR EMBL; AJ130976; CAA10274.1; -; mRNA.
DR EMBL; AJ009771; CAA08817.1; -; mRNA.
DR EMBL; AB014774; BAB19786.1; -; mRNA.
DR CCDS; CCDS10244.1; -.
DR RefSeq; NP_005735.2; NM_005744.3.
DR PDB; 1WD2; NMR; -; A=336-394.
DR PDB; 2M9Y; NMR; -; A=325-396.
DR PDB; 4KBL; X-ray; 3.30 A; A/B=1-557.
DR PDB; 4KC9; X-ray; 3.60 A; A=1-557.
DR PDB; 5TTE; X-ray; 3.50 A; B=1-557.
DR PDB; 5UDH; X-ray; 3.24 A; A/B=90-557.
DR PDB; 7B5L; EM; 3.80 A; H=1-557.
DR PDB; 7B5M; EM; 3.91 A; H=1-557.
DR PDB; 7B5N; EM; 3.60 A; H=1-557.
DR PDB; 7B5S; EM; 3.60 A; H=1-557.
DR PDBsum; 1WD2; -.
DR PDBsum; 2M9Y; -.
DR PDBsum; 4KBL; -.
DR PDBsum; 4KC9; -.
DR PDBsum; 5TTE; -.
DR PDBsum; 5UDH; -.
DR PDBsum; 7B5L; -.
DR PDBsum; 7B5M; -.
DR PDBsum; 7B5N; -.
DR PDBsum; 7B5S; -.
DR AlphaFoldDB; Q9Y4X5; -.
DR SMR; Q9Y4X5; -.
DR BioGRID; 117348; 242.
DR DIP; DIP-53626N; -.
DR IntAct; Q9Y4X5; 81.
DR MINT; Q9Y4X5; -.
DR STRING; 9606.ENSP00000369217; -.
DR GlyGen; Q9Y4X5; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y4X5; -.
DR MetOSite; Q9Y4X5; -.
DR PhosphoSitePlus; Q9Y4X5; -.
DR BioMuta; ARIH1; -.
DR DMDM; 20532376; -.
DR EPD; Q9Y4X5; -.
DR jPOST; Q9Y4X5; -.
DR MassIVE; Q9Y4X5; -.
DR MaxQB; Q9Y4X5; -.
DR PaxDb; Q9Y4X5; -.
DR PeptideAtlas; Q9Y4X5; -.
DR PRIDE; Q9Y4X5; -.
DR ProteomicsDB; 86264; -.
DR Antibodypedia; 1143; 105 antibodies from 29 providers.
DR DNASU; 25820; -.
DR Ensembl; ENST00000379887.9; ENSP00000369217.4; ENSG00000166233.15.
DR GeneID; 25820; -.
DR KEGG; hsa:25820; -.
DR MANE-Select; ENST00000379887.9; ENSP00000369217.4; NM_005744.5; NP_005735.2.
DR UCSC; uc002aut.5; human.
DR CTD; 25820; -.
DR DisGeNET; 25820; -.
DR GeneCards; ARIH1; -.
DR HGNC; HGNC:689; ARIH1.
DR HPA; ENSG00000166233; Tissue enhanced (skeletal muscle, testis).
DR MIM; 605624; gene.
DR neXtProt; NX_Q9Y4X5; -.
DR OpenTargets; ENSG00000166233; -.
DR PharmGKB; PA24982; -.
DR VEuPathDB; HostDB:ENSG00000166233; -.
DR eggNOG; KOG1815; Eukaryota.
DR GeneTree; ENSGT00940000155744; -.
DR HOGENOM; CLU_009823_4_2_1; -.
DR InParanoid; Q9Y4X5; -.
DR OMA; CAAHACD; -.
DR OrthoDB; 469819at2759; -.
DR PhylomeDB; Q9Y4X5; -.
DR TreeFam; TF300805; -.
DR BRENDA; 2.3.2.27; 2681.
DR BRENDA; 2.3.2.31; 2681.
DR PathwayCommons; Q9Y4X5; -.
DR Reactome; R-HSA-1169408; ISG15 antiviral mechanism.
DR SignaLink; Q9Y4X5; -.
DR SIGNOR; Q9Y4X5; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 25820; 771 hits in 1123 CRISPR screens.
DR ChiTaRS; ARIH1; human.
DR EvolutionaryTrace; Q9Y4X5; -.
DR GeneWiki; ARIH1; -.
DR GenomeRNAi; 25820; -.
DR Pharos; Q9Y4X5; Tbio.
DR PRO; PR:Q9Y4X5; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q9Y4X5; protein.
DR Bgee; ENSG00000166233; Expressed in secondary oocyte and 210 other tissues.
DR ExpressionAtlas; Q9Y4X5; baseline and differential.
DR Genevisible; Q9Y4X5; HS.
DR GO; GO:0015030; C:Cajal body; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0097413; C:Lewy body; IDA:UniProtKB.
DR GO; GO:0016604; C:nuclear body; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
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:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0019787; F:ubiquitin-like protein transferase activity; TAS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR045840; Ariadne.
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 PANTHER; PTHR11685; PTHR11685; 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; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Disease variant; Metal-binding;
KW Nucleus; Reference proteome; Repeat; Transferase; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT CHAIN 1..557
FT /note="E3 ubiquitin-protein ligase ARIH1"
FT /id="PRO_0000055752"
FT ZN_FING 186..236
FT /note="RING-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT ZN_FING 256..317
FT /note="IBR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT ZN_FING 344..375
FT /note="RING-type 2; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT REGION 1..95
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 105..153
FT /note="UBA-like"
FT /evidence="ECO:0000305|PubMed:23707686"
FT REGION 182..393
FT /note="TRIAD supradomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT REGION 408..557
FT /note="Ariadne domain"
FT /evidence="ECO:0000305|PubMed:23707686"
FT COMPBIAS 1..44
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 357
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:21532592, ECO:0000269|PubMed:23707686"
FT BINDING 186
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23707686, ECO:0007744|PDB:4KBL,
FT ECO:0007744|PDB:4KC9"
FT BINDING 189
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23707686, ECO:0007744|PDB:4KBL,
FT ECO:0007744|PDB:4KC9"
FT BINDING 203
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23707686, ECO:0007744|PDB:4KBL,
FT ECO:0007744|PDB:4KC9"
FT BINDING 205
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23707686, ECO:0007744|PDB:4KBL,
FT ECO:0007744|PDB:4KC9"
FT BINDING 208
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23707686, ECO:0007744|PDB:4KBL,
FT ECO:0007744|PDB:4KC9"
FT BINDING 211
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23707686, ECO:0007744|PDB:4KBL,
FT ECO:0007744|PDB:4KC9"
FT BINDING 231
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23707686, ECO:0007744|PDB:4KBL,
FT ECO:0007744|PDB:4KC9"
FT BINDING 236
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23707686, ECO:0007744|PDB:4KBL,
FT ECO:0007744|PDB:4KC9"
FT BINDING 276
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23707686, ECO:0007744|PDB:4KBL,
FT ECO:0007744|PDB:4KC9"
FT BINDING 281
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23707686, ECO:0007744|PDB:4KBL,
FT ECO:0007744|PDB:4KC9"
FT BINDING 297
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23707686, ECO:0007744|PDB:4KBL,
FT ECO:0007744|PDB:4KC9"
FT BINDING 299
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23707686, ECO:0007744|PDB:4KBL,
FT ECO:0007744|PDB:4KC9"
FT BINDING 304
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23707686, ECO:0007744|PDB:4KBL,
FT ECO:0007744|PDB:4KC9"
FT BINDING 307
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23707686, ECO:0007744|PDB:4KBL,
FT ECO:0007744|PDB:4KC9"
FT BINDING 312
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23707686, ECO:0007744|PDB:4KBL,
FT ECO:0007744|PDB:4KC9"
FT BINDING 317
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23707686, ECO:0007744|PDB:4KBL,
FT ECO:0007744|PDB:4KC9"
FT BINDING 344
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:15236971, ECO:0000269|PubMed:23707686,
FT ECO:0000269|PubMed:24058416, ECO:0007744|PDB:1WD2,
FT ECO:0007744|PDB:2M9Y, ECO:0007744|PDB:4KBL,
FT ECO:0007744|PDB:4KC9"
FT BINDING 347
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:15236971, ECO:0000269|PubMed:23707686,
FT ECO:0000269|PubMed:24058416, ECO:0007744|PDB:1WD2,
FT ECO:0007744|PDB:2M9Y, ECO:0007744|PDB:4KBL,
FT ECO:0007744|PDB:4KC9"
FT BINDING 362
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:15236971, ECO:0000269|PubMed:23707686,
FT ECO:0000269|PubMed:24058416, ECO:0007744|PDB:1WD2,
FT ECO:0007744|PDB:2M9Y, ECO:0007744|PDB:4KBL,
FT ECO:0007744|PDB:4KC9"
FT BINDING 367
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:15236971, ECO:0000269|PubMed:23707686,
FT ECO:0000269|PubMed:24058416, ECO:0007744|PDB:1WD2,
FT ECO:0007744|PDB:2M9Y, ECO:0007744|PDB:4KBL,
FT ECO:0007744|PDB:4KC9"
FT BINDING 372
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23707686, ECO:0000269|PubMed:24058416,
FT ECO:0007744|PDB:2M9Y, ECO:0007744|PDB:4KBL,
FT ECO:0007744|PDB:4KC9"
FT BINDING 375
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23707686, ECO:0000269|PubMed:24058416,
FT ECO:0007744|PDB:2M9Y, ECO:0007744|PDB:4KBL,
FT ECO:0007744|PDB:4KC9"
FT BINDING 382
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23707686, ECO:0000269|PubMed:24058416,
FT ECO:0007744|PDB:2M9Y, ECO:0007744|PDB:4KBL,
FT ECO:0007744|PDB:4KC9"
FT BINDING 389
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23707686, ECO:0000269|PubMed:24058416,
FT ECO:0007744|PDB:2M9Y, ECO:0007744|PDB:4KBL,
FT ECO:0007744|PDB:4KC9"
FT MOD_RES 142
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1K5"
FT VARIANT 15
FT /note="E -> Q (probable disease-associated variant found in
FT patient with an acute aortic dissection and ascending
FT aortic aneurysm; dbSNP:rs1052050835)"
FT /evidence="ECO:0000269|PubMed:29689197"
FT /id="VAR_082646"
FT VARIANT 44
FT /note="E -> G (probable disease-associated variant found in
FT patient with basilar tip artery aneurysm and distal left
FT internal carotid artery aneurysm)"
FT /evidence="ECO:0000269|PubMed:29689197"
FT /id="VAR_082647"
FT VARIANT 171..557
FT /note="Missing (probable disease-associated variant found
FT in patient with fusiform aneurysm of the aortic root and
FT ascending aorta)"
FT /evidence="ECO:0000269|PubMed:29689197"
FT /id="VAR_082648"
FT MUTAGEN 123
FT /note="V->A: Strongly decreased ability to initiate
FT ubiquitination of cullin-RING complexes."
FT /evidence="ECO:0000269|PubMed:27565346"
FT MUTAGEN 150
FT /note="F->A: Strongly decreased ability to initiate
FT ubiquitination of cullin-RING complexes."
FT /evidence="ECO:0000269|PubMed:27565346"
FT MUTAGEN 156..158
FT /note="KLF->AAA: Strongly decreased ability to initiate
FT ubiquitination of cullin-RING complexes."
FT /evidence="ECO:0000269|PubMed:27565346"
FT MUTAGEN 187..188
FT /note="QI->HV: No loss of interaction with UBE2L3."
FT /evidence="ECO:0000269|PubMed:11278816"
FT MUTAGEN 188
FT /note="I->A: Loss of interaction with UBE2L3. Decreased E3
FT ligase activity. Strongly decreased ability to initiate
FT ubiquitination of cullin-RING complexes."
FT /evidence="ECO:0000269|PubMed:11278816,
FT ECO:0000269|PubMed:23707686, ECO:0000269|PubMed:27565346"
FT MUTAGEN 205
FT /note="H->A: Impaired interaction with UBE2L3 without
FT affecting interaction with neddylated cullin-RING
FT complexes."
FT /evidence="ECO:0000269|PubMed:24076655"
FT MUTAGEN 208
FT /note="C->A,H: Loss of interaction with UBE2L3."
FT /evidence="ECO:0000269|PubMed:11278816"
FT MUTAGEN 257..258
FT /note="KY->AAA: Strongly decreased ability to initiate
FT ubiquitination of cullin-RING complexes."
FT /evidence="ECO:0000269|PubMed:27565346"
FT MUTAGEN 258
FT /note="Y->A: No loss of interaction with UBE2L3."
FT /evidence="ECO:0000269|PubMed:11278816"
FT MUTAGEN 265..267
FT /note="SFV->AAA: Strongly decreased ability to initiate
FT ubiquitination of cullin-RING complexes."
FT /evidence="ECO:0000269|PubMed:27565346"
FT MUTAGEN 340..341
FT /note="NT->AA: Strongly decreased ability to initiate
FT ubiquitination of cullin-RING complexes."
FT /evidence="ECO:0000269|PubMed:27565346"
FT MUTAGEN 342..343
FT /note="KE->AA: Strongly decreased ability to initiate
FT ubiquitination of cullin-RING complexes."
FT /evidence="ECO:0000269|PubMed:27565346"
FT MUTAGEN 347
FT /note="C->A: Impairs zinc-binding and folding. Abolishes E3
FT ubiquitin-protein ligase activity."
FT /evidence="ECO:0000269|PubMed:15236971"
FT MUTAGEN 351..352
FT /note="IE->AA: Strongly decreased ability to initiate
FT ubiquitination of cullin-RING complexes."
FT /evidence="ECO:0000269|PubMed:27565346"
FT MUTAGEN 351
FT /note="I->A: Disrupts the hydrophobic network. Abolishes E3
FT ubiquitin-protein ligase activity."
FT /evidence="ECO:0000269|PubMed:15236971"
FT MUTAGEN 357
FT /note="C->A,S: Does not affect zinc binding and folding.
FT Abolishes ability to transfer ubiquitin and E3 ubiquitin-
FT protein ligase activity."
FT /evidence="ECO:0000269|PubMed:15236971,
FT ECO:0000269|PubMed:21532592, ECO:0000269|PubMed:24058416,
FT ECO:0000269|PubMed:24076655"
FT MUTAGEN 358
FT /note="N->A: Defects in ligation."
FT /evidence="ECO:0000269|PubMed:27565346"
FT MUTAGEN 359
FT /note="H->A: Defects in ligation. Does not affect zinc
FT binding, folding. Does not impair E3 ubiquitin-protein
FT ligase activity."
FT /evidence="ECO:0000269|PubMed:15236971,
FT ECO:0000269|PubMed:27565346"
FT MUTAGEN 367
FT /note="C->A: Impairs zinc-binding and folding. Abolishes E3
FT ubiquitin-protein ligase activity."
FT /evidence="ECO:0000269|PubMed:15236971"
FT MUTAGEN 371
FT /note="F->A: Disrupts the hydrophobic network. Abolishes E3
FT ubiquitin-protein ligase activity."
FT /evidence="ECO:0000269|PubMed:15236971"
FT MUTAGEN 372
FT /note="C->A: Impairs E3 ubiquitin-protein ligase activity."
FT /evidence="ECO:0000269|PubMed:15236971"
FT MUTAGEN 373
FT /note="W->A: Abolishes E3 ubiquitin-protein ligase
FT activity."
FT /evidence="ECO:0000269|PubMed:15236971"
FT MUTAGEN 378..379
FT /note="PW->AA: Defects in ligation."
FT /evidence="ECO:0000269|PubMed:27565346"
FT MUTAGEN 379
FT /note="W->A: Does not affect E3 ubiquitin-protein ligase
FT activity."
FT /evidence="ECO:0000269|PubMed:15236971"
FT MUTAGEN 383..385
FT /note="GSA->AAD: Defects in ligation."
FT /evidence="ECO:0000269|PubMed:27565346"
FT MUTAGEN 386
FT /note="W->A: Does not affect E3 ubiquitin-protein ligase
FT activity. Strongly decreased ability to initiate
FT ubiquitination of cullin-RING complexes."
FT /evidence="ECO:0000269|PubMed:15236971,
FT ECO:0000269|PubMed:27565346"
FT MUTAGEN 416
FT /note="F->A: Slightly relieves autoinhibition of the E3
FT ligase activity by the ariadne domain."
FT /evidence="ECO:0000269|PubMed:23707686"
FT MUTAGEN 417
FT /note="Y->A: Hyperactive 'open' mutant that displays
FT enhanced E3 ubiquitin-protein ligase activity."
FT /evidence="ECO:0000269|PubMed:27565346"
FT MUTAGEN 420..423
FT /note="RYMN->AYMA: Slightly relieves autoinhibition of the
FT E3 ligase activity by the ariadne domain. Hyperactive
FT 'open' mutant that displays enhanced E3 ubiquitin-protein
FT ligase activity; when associated with A-503."
FT /evidence="ECO:0000269|PubMed:23707686,
FT ECO:0000269|PubMed:27565346"
FT MUTAGEN 427
FT /note="S->A: Slightly relieves autoinhibition of the E3
FT ligase activity by the ariadne domain."
FT /evidence="ECO:0000269|PubMed:23707686"
FT MUTAGEN 430..431
FT /note="FE->AA: Relieves autoinhibition of the E3 ligase
FT activity by the ariadne domain; when associated with A-503.
FT Hyperactive 'open' mutant that displays enhanced E3
FT ubiquitin-protein ligase activity; when associated with A-
FT 503."
FT /evidence="ECO:0000269|PubMed:23707686,
FT ECO:0000269|PubMed:24076655, ECO:0000269|PubMed:27565346"
FT MUTAGEN 476
FT /note="Y->A: Hyperactive 'open' mutant that displays
FT enhanced E3 ubiquitin-protein ligase activity."
FT /evidence="ECO:0000269|PubMed:27565346"
FT MUTAGEN 492
FT /note="E->A: Hyperactive 'open' mutant that displays
FT enhanced E3 ubiquitin-protein ligase activity."
FT /evidence="ECO:0000269|PubMed:27565346"
FT MUTAGEN 493
FT /note="N->A: Hyperactive 'open' mutant that displays
FT enhanced E3 ubiquitin-protein ligase activity."
FT /evidence="ECO:0000269|PubMed:27565346"
FT MUTAGEN 495
FT /note="Q->A: Hyperactive 'open' mutant that displays
FT enhanced E3 ubiquitin-protein ligase activity."
FT /evidence="ECO:0000269|PubMed:27565346"
FT MUTAGEN 499
FT /note="E->A: Hyperactive 'open' mutant that displays
FT enhanced E3 ubiquitin-protein ligase activity."
FT /evidence="ECO:0000269|PubMed:27565346"
FT MUTAGEN 503
FT /note="E->A: Relieves autoinhibition of the E3 ligase
FT activity by the ariadne domain; when associated with 430-A-
FT A-431. Hyperactive 'open' mutant that displays enhanced E3
FT ubiquitin-protein ligase activity; when associated with
FT 430-A-A-431. Hyperactive 'open' mutant that displays
FT enhanced E3 ubiquitin-protein ligase activity; when
FT associated with 420-A--A-423."
FT /evidence="ECO:0000269|PubMed:23707686,
FT ECO:0000269|PubMed:24076655, ECO:0000269|PubMed:27565346"
FT MUTAGEN 531
FT /note="Y->A: Strongly decreased ability to initiate
FT ubiquitination of cullin-RING complexes."
FT /evidence="ECO:0000269|PubMed:27565346"
FT CONFLICT 122
FT /note="E -> D (in Ref. 3; AAD28088)"
FT /evidence="ECO:0000305"
FT CONFLICT 227
FT /note="Q -> H (in Ref. 1; CAB45870)"
FT /evidence="ECO:0000305"
FT CONFLICT 237
FT /note="D -> N (in Ref. 8; CAA10274)"
FT /evidence="ECO:0000305"
FT CONFLICT 303
FT /note="F -> S (in Ref. 9; CAA08817)"
FT /evidence="ECO:0000305"
FT CONFLICT 309..316
FT /note="ENWHDPVK -> AIGMILFQ (in Ref. 9; CAA08817)"
FT /evidence="ECO:0000305"
FT CONFLICT 322
FT /note="K -> T (in Ref. 9; CAA08817)"
FT /evidence="ECO:0000305"
FT STRAND 101..105
FT /evidence="ECO:0007829|PDB:5UDH"
FT HELIX 106..124
FT /evidence="ECO:0007829|PDB:5UDH"
FT HELIX 128..137
FT /evidence="ECO:0007829|PDB:5UDH"
FT TURN 138..140
FT /evidence="ECO:0007829|PDB:5UDH"
FT HELIX 142..149
FT /evidence="ECO:0007829|PDB:5UDH"
FT HELIX 154..161
FT /evidence="ECO:0007829|PDB:5UDH"
FT TURN 187..189
FT /evidence="ECO:0007829|PDB:5UDH"
FT HELIX 195..197
FT /evidence="ECO:0007829|PDB:5UDH"
FT STRAND 198..200
FT /evidence="ECO:0007829|PDB:5UDH"
FT STRAND 206..208
FT /evidence="ECO:0007829|PDB:5UDH"
FT HELIX 209..219
FT /evidence="ECO:0007829|PDB:5UDH"
FT STRAND 220..224
FT /evidence="ECO:0007829|PDB:4KBL"
FT STRAND 232..235
FT /evidence="ECO:0007829|PDB:5UDH"
FT HELIX 242..248
FT /evidence="ECO:0007829|PDB:5UDH"
FT HELIX 252..268
FT /evidence="ECO:0007829|PDB:5UDH"
FT STRAND 273..275
FT /evidence="ECO:0007829|PDB:5UDH"
FT STRAND 283..289
FT /evidence="ECO:0007829|PDB:5UDH"
FT STRAND 294..296
FT /evidence="ECO:0007829|PDB:5UDH"
FT STRAND 298..300
FT /evidence="ECO:0007829|PDB:5UDH"
FT STRAND 302..304
FT /evidence="ECO:0007829|PDB:5UDH"
FT TURN 305..307
FT /evidence="ECO:0007829|PDB:5UDH"
FT HELIX 317..325
FT /evidence="ECO:0007829|PDB:5UDH"
FT TURN 326..328
FT /evidence="ECO:0007829|PDB:5UDH"
FT TURN 331..333
FT /evidence="ECO:0007829|PDB:2M9Y"
FT HELIX 337..340
FT /evidence="ECO:0007829|PDB:2M9Y"
FT STRAND 341..343
FT /evidence="ECO:0007829|PDB:5UDH"
FT TURN 345..347
FT /evidence="ECO:0007829|PDB:5UDH"
FT STRAND 350..352
FT /evidence="ECO:0007829|PDB:5UDH"
FT STRAND 359..361
FT /evidence="ECO:0007829|PDB:5UDH"
FT STRAND 364..366
FT /evidence="ECO:0007829|PDB:5UDH"
FT STRAND 370..372
FT /evidence="ECO:0007829|PDB:5UDH"
FT TURN 373..375
FT /evidence="ECO:0007829|PDB:5UDH"
FT STRAND 378..386
FT /evidence="ECO:0007829|PDB:5UDH"
FT HELIX 411..432
FT /evidence="ECO:0007829|PDB:5UDH"
FT HELIX 434..444
FT /evidence="ECO:0007829|PDB:5UDH"
FT HELIX 452..480
FT /evidence="ECO:0007829|PDB:5UDH"
FT HELIX 486..510
FT /evidence="ECO:0007829|PDB:5UDH"
FT TURN 511..515
FT /evidence="ECO:0007829|PDB:5UDH"
FT STRAND 518..520
FT /evidence="ECO:0007829|PDB:5UDH"
FT HELIX 521..548
FT /evidence="ECO:0007829|PDB:5UDH"
SQ SEQUENCE 557 AA; 64118 MW; DFFF8965DAB41DC8 CRC64;
MDSDEGYNYE FDEDEECSEE DSGAEEEEDE DDDEPDDDTL DLGEVELVEP GLGVGGERDG
LLCGETGGGG GSALGPGGGG GGGGGGGGGG PGHEQEEDYR YEVLTAEQIL QHMVECIREV
NEVIQNPATI TRILLSHFNW DKEKLMERYF DGNLEKLFAE CHVINPSKKS RTRQMNTRSS
AQDMPCQICY LNYPNSYFTG LECGHKFCMQ CWSEYLTTKI MEEGMGQTIS CPAHGCDILV
DDNTVMRLIT DSKVKLKYQH LITNSFVECN RLLKWCPAPD CHHVVKVQYP DAKPVRCKCG
RQFCFNCGEN WHDPVKCKWL KKWIKKCDDD SETSNWIAAN TKECPKCHVT IEKDGGCNHM
VCRNQNCKAE FCWVCLGPWE PHGSAWYNCN RYNEDDAKAA RDAQERSRAA LQRYLFYCNR
YMNHMQSLRF EHKLYAQVKQ KMEEMQQHNM SWIEVQFLKK AVDVLCQCRA TLMYTYVFAF
YLKKNNQSII FENNQADLEN ATEVLSGYLE RDISQDSLQD IKQKVQDKYR YCESRRRVLL
QHVHEGYEKD LWEYIED
