Full text data of ARIH1
ARIH1
(ARI, MOP6, UBCH7BP)
[Confidence: low (only semi-automatic identification from reviews)]
E3 ubiquitin-protein ligase ARIH1; 6.3.2.- (H7-AP2; HHARI; Monocyte protein 6; MOP-6; Protein ariadne-1 homolog; ARI-1; UbcH7-binding protein; UbcM4-interacting protein; Ubiquitin-conjugating enzyme E2-binding protein 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
E3 ubiquitin-protein ligase ARIH1; 6.3.2.- (H7-AP2; HHARI; Monocyte protein 6; MOP-6; Protein ariadne-1 homolog; ARI-1; UbcH7-binding protein; UbcM4-interacting protein; Ubiquitin-conjugating enzyme E2-binding protein 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9Y4X5
ID ARI1_HUMAN Reviewed; 557 AA.
AC Q9Y4X5; B2R6U3; O76026; Q9H3T6; Q9UEN0; Q9UP39;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 10-MAY-2002, sequence version 2.
DT 22-JAN-2014, entry version 127.
DE RecName: Full=E3 ubiquitin-protein ligase ARIH1;
DE EC=6.3.2.-;
DE AltName: Full=H7-AP2;
DE AltName: Full=HHARI;
DE AltName: Full=Monocyte protein 6;
DE Short=MOP-6;
DE AltName: Full=Protein ariadne-1 homolog;
DE Short=ARI-1;
DE AltName: Full=UbcH7-binding protein;
DE AltName: Full=UbcM4-interacting protein;
DE AltName: Full=Ubiquitin-conjugating enzyme E2-binding protein 1;
GN Name=ARIH1; Synonyms=ARI, MOP6, UBCH7BP; ORFNames=HUSSY-27;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Markham A.F., 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G.,
RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A.,
RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W.,
RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X.,
RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K.,
RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S.,
RA Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human
RT chromosome 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 95-557.
RX PubMed=10880484;
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
RT defines 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>3.3.CO;2-8;
RA Stanchi F., Bertocco E., Toppo S., Dioguardi R., Simionati B.,
RA Cannata N., Zimbello R., Lanfranchi G., Valle G.;
RT "Characterization of 16 novel human genes showing high similarity to
RT yeast 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
RT protein, MOP-6 which is highly expressed in activated human
RT monocytes.";
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP IDENTIFICATION.
RX PubMed=11124525;
RA Tan N.G., Ardley H.C., Rose S.A., Leek J.P., Markham A.F.,
RA 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;
RP CYS-208 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
RT regulate its interaction with the ubiquitin-conjugating enzyme,
RT 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.,
RA 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.,
RA Walther T.C., 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.,
RA Buerckstuemmer T., 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, REACTION MECHANISM, INTERACTION WITH UBE2L3, AND MUTAGENESIS
RP 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 STRUCTURE BY NMR OF 336-394 IN COMPLEX WITH ZINC, DOMAIN RING-TYPE 2
RP ZINC FINGER, FUNCTION, AND MUTAGENESIS OF CYS-347; ILE-351; CYS-357;
RP HIS-359; CYS-367; 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
RT motif reveals a novel zinc-binding domain distinct from a RING.";
RL J. Mol. Biol. 340:1117-1129(2004).
CC -!- FUNCTION: E3 ubiquitin-protein ligase, which catalyzes
CC polyubiquitination of target proteins together with ubiquitin-
CC conjugating enzyme E2 UBE2L3. May play a role in protein
CC translation by mediating polyubiquitination of EIF4E2, leading to
CC its subsequent degradation. Acts as the ligase involved in
CC ISGylation of EIF4E2.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with UBE2L3.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Note=Mainly cytoplasmic.
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- DOMAIN: The RING-type 2 zinc finger is atypical: it only binds 1
CC zinc ion instead of 2 and uses a different hydrophobic network
CC compared to classical RING-types.
CC -!- MISCELLANEOUS: Members of the RBR family are atypical E3 ligases.
CC They interact with the E2 conjugating enzyme UBE2L3 and function
CC like HECT-type E3 enzymes: they bind E2s via the first RING
CC domain, but require an obligate trans-thiolation step during the
CC ubiquitin transfer, requiring a conserved cysteine residue in the
CC second RING domain (PubMed:21532592).
CC -!- SIMILARITY: Belongs to the RBR family. Ariadne subfamily.
CC -!- SIMILARITY: Contains 1 IBR-type zinc finger.
CC -!- SIMILARITY: Contains 2 RING-type zinc fingers.
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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 RefSeq; NP_005735.2; NM_005744.3.
DR UniGene; Hs.268787; -.
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 PDBsum; 1WD2; -.
DR PDBsum; 2M9Y; -.
DR PDBsum; 4KBL; -.
DR PDBsum; 4KC9; -.
DR ProteinModelPortal; Q9Y4X5; -.
DR SMR; Q9Y4X5; 101-553.
DR DIP; DIP-53626N; -.
DR IntAct; Q9Y4X5; 2.
DR MINT; MINT-3086735; -.
DR STRING; 9606.ENSP00000369217; -.
DR PhosphoSite; Q9Y4X5; -.
DR DMDM; 20532376; -.
DR PaxDb; Q9Y4X5; -.
DR PeptideAtlas; Q9Y4X5; -.
DR PRIDE; Q9Y4X5; -.
DR Ensembl; ENST00000379887; ENSP00000369217; ENSG00000166233.
DR GeneID; 25820; -.
DR KEGG; hsa:25820; -.
DR UCSC; uc002aut.4; human.
DR CTD; 25820; -.
DR GeneCards; GC15P072766; -.
DR H-InvDB; HIX0012409; -.
DR HGNC; HGNC:689; ARIH1.
DR HPA; HPA003295; -.
DR MIM; 605624; gene.
DR neXtProt; NX_Q9Y4X5; -.
DR PharmGKB; PA24982; -.
DR eggNOG; NOG327249; -.
DR HOGENOM; HOG000216612; -.
DR HOVERGEN; HBG018737; -.
DR InParanoid; Q9Y4X5; -.
DR KO; K11968; -.
DR OMA; PYEVEFK; -.
DR OrthoDB; EOG7NKKJX; -.
DR PhylomeDB; Q9Y4X5; -.
DR Reactome; REACT_6900; Immune System.
DR UniPathway; UPA00143; -.
DR ChiTaRS; ARIH1; human.
DR EvolutionaryTrace; Q9Y4X5; -.
DR GeneWiki; ARIH1; -.
DR GenomeRNAi; 25820; -.
DR NextBio; 47071; -.
DR PRO; PR:Q9Y4X5; -.
DR ArrayExpress; Q9Y4X5; -.
DR Bgee; Q9Y4X5; -.
DR CleanEx; HS_ARIH1; -.
DR Genevestigator; Q9Y4X5; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000151; C:ubiquitin ligase complex; TAS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; TAS:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR002867; Znf_C6HC.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF01485; IBR; 2.
DR SMART; SM00647; IBR; 2.
DR SMART; SM00184; RING; 2.
DR PROSITE; PS00518; ZF_RING_1; FALSE_NEG.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Coiled coil; Complete proteome; Cytoplasm; Ligase;
KW Metal-binding; Reference proteome; Repeat; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT CHAIN 1 557 E3 ubiquitin-protein ligase ARIH1.
FT /FTId=PRO_0000055752.
FT ZN_FING 186 236 RING-type 1; atypical.
FT ZN_FING 256 317 IBR-type.
FT ZN_FING 344 375 RING-type 2.
FT REGION 186 254 Interaction with UBE2L3.
FT COILED 433 449 Potential.
FT COMPBIAS 10 38 Asp/Glu-rich (acidic).
FT COMPBIAS 51 92 Gly-rich.
FT METAL 344 344 Zinc.
FT METAL 347 347 Zinc.
FT METAL 362 362 Zinc.
FT METAL 367 367 Zinc.
FT MUTAGEN 187 188 QI->HV: No loss of interaction with
FT UBE2L3.
FT MUTAGEN 188 188 I->A: Loss of interaction with UBE2L3.
FT MUTAGEN 208 208 C->A,H: Loss of interaction with UBE2L3.
FT MUTAGEN 258 258 Y->A: No loss of interaction with UBE2L3.
FT MUTAGEN 347 347 C->A: Impairs zinc-binding and folding.
FT Abolishes E3 ubiquitin-protein ligase
FT activity.
FT MUTAGEN 351 351 I->A: Disrupts the hydrophobic network.
FT Abolishes E3 ubiquitin-protein ligase
FT activity.
FT MUTAGEN 357 357 C->A,S: Does not affect zinc binding and
FT folding. Abolishes ability to transfer
FT ubiquitin and E3 ubiquitin-protein ligase
FT activity.
FT MUTAGEN 359 359 H->A: Does not affect zinc binding,
FT folding. Does not impair E3 ubiquitin-
FT protein ligase activity.
FT MUTAGEN 367 367 C->A: Impairs zinc-binding and folding.
FT Abolishes E3 ubiquitin-protein ligase
FT activity.
FT MUTAGEN 371 371 F->A: Disrupts the hydrophobic network.
FT Abolishes E3 ubiquitin-protein ligase
FT activity.
FT MUTAGEN 372 372 C->A: Impairs E3 ubiquitin-protein ligase
FT activity.
FT MUTAGEN 373 373 W->A: Abolishes E3 ubiquitin-protein
FT ligase activity.
FT MUTAGEN 379 379 W->A: Does not affect E3 ubiquitin-
FT protein ligase activity.
FT MUTAGEN 386 386 W->A: Does not affect E3 ubiquitin-
FT protein ligase activity.
FT CONFLICT 122 122 E -> D (in Ref. 3; AAD28088).
FT CONFLICT 227 227 Q -> H (in Ref. 1; CAB45870).
FT CONFLICT 237 237 D -> N (in Ref. 8; CAA10274).
FT CONFLICT 303 303 F -> S (in Ref. 9; CAA08817).
FT CONFLICT 309 316 ENWHDPVK -> AIGMILFQ (in Ref. 9;
FT CAA08817).
FT CONFLICT 322 322 K -> T (in Ref. 9; CAA08817).
FT STRAND 101 104
FT HELIX 106 119
FT TURN 120 124
FT HELIX 128 137
FT TURN 138 140
FT HELIX 142 151
FT TURN 187 189
FT HELIX 209 219
FT STRAND 220 224
FT STRAND 234 236
FT HELIX 242 248
FT HELIX 254 269
FT STRAND 271 275
FT STRAND 284 289
FT STRAND 294 296
FT STRAND 298 300
FT STRAND 302 304
FT TURN 305 307
FT HELIX 317 326
FT STRAND 340 343
FT TURN 345 347
FT STRAND 350 352
FT STRAND 358 361
FT HELIX 366 368
FT STRAND 370 372
FT TURN 373 375
FT STRAND 378 381
FT STRAND 384 386
FT HELIX 409 432
FT HELIX 434 440
FT TURN 453 455
FT HELIX 458 480
FT HELIX 486 510
FT TURN 511 515
FT TURN 518 520
FT HELIX 521 549
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
//
ID ARI1_HUMAN Reviewed; 557 AA.
AC Q9Y4X5; B2R6U3; O76026; Q9H3T6; Q9UEN0; Q9UP39;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 10-MAY-2002, sequence version 2.
DT 22-JAN-2014, entry version 127.
DE RecName: Full=E3 ubiquitin-protein ligase ARIH1;
DE EC=6.3.2.-;
DE AltName: Full=H7-AP2;
DE AltName: Full=HHARI;
DE AltName: Full=Monocyte protein 6;
DE Short=MOP-6;
DE AltName: Full=Protein ariadne-1 homolog;
DE Short=ARI-1;
DE AltName: Full=UbcH7-binding protein;
DE AltName: Full=UbcM4-interacting protein;
DE AltName: Full=Ubiquitin-conjugating enzyme E2-binding protein 1;
GN Name=ARIH1; Synonyms=ARI, MOP6, UBCH7BP; ORFNames=HUSSY-27;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Markham A.F., 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G.,
RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A.,
RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W.,
RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X.,
RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K.,
RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S.,
RA Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human
RT chromosome 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 95-557.
RX PubMed=10880484;
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
RT defines 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>3.3.CO;2-8;
RA Stanchi F., Bertocco E., Toppo S., Dioguardi R., Simionati B.,
RA Cannata N., Zimbello R., Lanfranchi G., Valle G.;
RT "Characterization of 16 novel human genes showing high similarity to
RT yeast 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
RT protein, MOP-6 which is highly expressed in activated human
RT monocytes.";
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP IDENTIFICATION.
RX PubMed=11124525;
RA Tan N.G., Ardley H.C., Rose S.A., Leek J.P., Markham A.F.,
RA 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;
RP CYS-208 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
RT regulate its interaction with the ubiquitin-conjugating enzyme,
RT 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.,
RA 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.,
RA Walther T.C., 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.,
RA Buerckstuemmer T., 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, REACTION MECHANISM, INTERACTION WITH UBE2L3, AND MUTAGENESIS
RP 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 STRUCTURE BY NMR OF 336-394 IN COMPLEX WITH ZINC, DOMAIN RING-TYPE 2
RP ZINC FINGER, FUNCTION, AND MUTAGENESIS OF CYS-347; ILE-351; CYS-357;
RP HIS-359; CYS-367; 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
RT motif reveals a novel zinc-binding domain distinct from a RING.";
RL J. Mol. Biol. 340:1117-1129(2004).
CC -!- FUNCTION: E3 ubiquitin-protein ligase, which catalyzes
CC polyubiquitination of target proteins together with ubiquitin-
CC conjugating enzyme E2 UBE2L3. May play a role in protein
CC translation by mediating polyubiquitination of EIF4E2, leading to
CC its subsequent degradation. Acts as the ligase involved in
CC ISGylation of EIF4E2.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with UBE2L3.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Note=Mainly cytoplasmic.
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- DOMAIN: The RING-type 2 zinc finger is atypical: it only binds 1
CC zinc ion instead of 2 and uses a different hydrophobic network
CC compared to classical RING-types.
CC -!- MISCELLANEOUS: Members of the RBR family are atypical E3 ligases.
CC They interact with the E2 conjugating enzyme UBE2L3 and function
CC like HECT-type E3 enzymes: they bind E2s via the first RING
CC domain, but require an obligate trans-thiolation step during the
CC ubiquitin transfer, requiring a conserved cysteine residue in the
CC second RING domain (PubMed:21532592).
CC -!- SIMILARITY: Belongs to the RBR family. Ariadne subfamily.
CC -!- SIMILARITY: Contains 1 IBR-type zinc finger.
CC -!- SIMILARITY: Contains 2 RING-type zinc fingers.
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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 RefSeq; NP_005735.2; NM_005744.3.
DR UniGene; Hs.268787; -.
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 PDBsum; 1WD2; -.
DR PDBsum; 2M9Y; -.
DR PDBsum; 4KBL; -.
DR PDBsum; 4KC9; -.
DR ProteinModelPortal; Q9Y4X5; -.
DR SMR; Q9Y4X5; 101-553.
DR DIP; DIP-53626N; -.
DR IntAct; Q9Y4X5; 2.
DR MINT; MINT-3086735; -.
DR STRING; 9606.ENSP00000369217; -.
DR PhosphoSite; Q9Y4X5; -.
DR DMDM; 20532376; -.
DR PaxDb; Q9Y4X5; -.
DR PeptideAtlas; Q9Y4X5; -.
DR PRIDE; Q9Y4X5; -.
DR Ensembl; ENST00000379887; ENSP00000369217; ENSG00000166233.
DR GeneID; 25820; -.
DR KEGG; hsa:25820; -.
DR UCSC; uc002aut.4; human.
DR CTD; 25820; -.
DR GeneCards; GC15P072766; -.
DR H-InvDB; HIX0012409; -.
DR HGNC; HGNC:689; ARIH1.
DR HPA; HPA003295; -.
DR MIM; 605624; gene.
DR neXtProt; NX_Q9Y4X5; -.
DR PharmGKB; PA24982; -.
DR eggNOG; NOG327249; -.
DR HOGENOM; HOG000216612; -.
DR HOVERGEN; HBG018737; -.
DR InParanoid; Q9Y4X5; -.
DR KO; K11968; -.
DR OMA; PYEVEFK; -.
DR OrthoDB; EOG7NKKJX; -.
DR PhylomeDB; Q9Y4X5; -.
DR Reactome; REACT_6900; Immune System.
DR UniPathway; UPA00143; -.
DR ChiTaRS; ARIH1; human.
DR EvolutionaryTrace; Q9Y4X5; -.
DR GeneWiki; ARIH1; -.
DR GenomeRNAi; 25820; -.
DR NextBio; 47071; -.
DR PRO; PR:Q9Y4X5; -.
DR ArrayExpress; Q9Y4X5; -.
DR Bgee; Q9Y4X5; -.
DR CleanEx; HS_ARIH1; -.
DR Genevestigator; Q9Y4X5; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000151; C:ubiquitin ligase complex; TAS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; TAS:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR002867; Znf_C6HC.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF01485; IBR; 2.
DR SMART; SM00647; IBR; 2.
DR SMART; SM00184; RING; 2.
DR PROSITE; PS00518; ZF_RING_1; FALSE_NEG.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Coiled coil; Complete proteome; Cytoplasm; Ligase;
KW Metal-binding; Reference proteome; Repeat; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT CHAIN 1 557 E3 ubiquitin-protein ligase ARIH1.
FT /FTId=PRO_0000055752.
FT ZN_FING 186 236 RING-type 1; atypical.
FT ZN_FING 256 317 IBR-type.
FT ZN_FING 344 375 RING-type 2.
FT REGION 186 254 Interaction with UBE2L3.
FT COILED 433 449 Potential.
FT COMPBIAS 10 38 Asp/Glu-rich (acidic).
FT COMPBIAS 51 92 Gly-rich.
FT METAL 344 344 Zinc.
FT METAL 347 347 Zinc.
FT METAL 362 362 Zinc.
FT METAL 367 367 Zinc.
FT MUTAGEN 187 188 QI->HV: No loss of interaction with
FT UBE2L3.
FT MUTAGEN 188 188 I->A: Loss of interaction with UBE2L3.
FT MUTAGEN 208 208 C->A,H: Loss of interaction with UBE2L3.
FT MUTAGEN 258 258 Y->A: No loss of interaction with UBE2L3.
FT MUTAGEN 347 347 C->A: Impairs zinc-binding and folding.
FT Abolishes E3 ubiquitin-protein ligase
FT activity.
FT MUTAGEN 351 351 I->A: Disrupts the hydrophobic network.
FT Abolishes E3 ubiquitin-protein ligase
FT activity.
FT MUTAGEN 357 357 C->A,S: Does not affect zinc binding and
FT folding. Abolishes ability to transfer
FT ubiquitin and E3 ubiquitin-protein ligase
FT activity.
FT MUTAGEN 359 359 H->A: Does not affect zinc binding,
FT folding. Does not impair E3 ubiquitin-
FT protein ligase activity.
FT MUTAGEN 367 367 C->A: Impairs zinc-binding and folding.
FT Abolishes E3 ubiquitin-protein ligase
FT activity.
FT MUTAGEN 371 371 F->A: Disrupts the hydrophobic network.
FT Abolishes E3 ubiquitin-protein ligase
FT activity.
FT MUTAGEN 372 372 C->A: Impairs E3 ubiquitin-protein ligase
FT activity.
FT MUTAGEN 373 373 W->A: Abolishes E3 ubiquitin-protein
FT ligase activity.
FT MUTAGEN 379 379 W->A: Does not affect E3 ubiquitin-
FT protein ligase activity.
FT MUTAGEN 386 386 W->A: Does not affect E3 ubiquitin-
FT protein ligase activity.
FT CONFLICT 122 122 E -> D (in Ref. 3; AAD28088).
FT CONFLICT 227 227 Q -> H (in Ref. 1; CAB45870).
FT CONFLICT 237 237 D -> N (in Ref. 8; CAA10274).
FT CONFLICT 303 303 F -> S (in Ref. 9; CAA08817).
FT CONFLICT 309 316 ENWHDPVK -> AIGMILFQ (in Ref. 9;
FT CAA08817).
FT CONFLICT 322 322 K -> T (in Ref. 9; CAA08817).
FT STRAND 101 104
FT HELIX 106 119
FT TURN 120 124
FT HELIX 128 137
FT TURN 138 140
FT HELIX 142 151
FT TURN 187 189
FT HELIX 209 219
FT STRAND 220 224
FT STRAND 234 236
FT HELIX 242 248
FT HELIX 254 269
FT STRAND 271 275
FT STRAND 284 289
FT STRAND 294 296
FT STRAND 298 300
FT STRAND 302 304
FT TURN 305 307
FT HELIX 317 326
FT STRAND 340 343
FT TURN 345 347
FT STRAND 350 352
FT STRAND 358 361
FT HELIX 366 368
FT STRAND 370 372
FT TURN 373 375
FT STRAND 378 381
FT STRAND 384 386
FT HELIX 409 432
FT HELIX 434 440
FT TURN 453 455
FT HELIX 458 480
FT HELIX 486 510
FT TURN 511 515
FT TURN 518 520
FT HELIX 521 549
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
//
MIM
605624
*RECORD*
*FIELD* NO
605624
*FIELD* TI
*605624 ARIADNE, DROSOPHILA, HOMOLOG OF, 1; ARIH1
;;ARI;;
UBCH7-BINDING PROTEIN; UBCH7BP
read more*FIELD* TX
Proteins are targeted for ubiquitination in a 3-step process. The first
step involves the activation of ubiquitin (191339) through a
ubiquitin-activating enzyme, or E1 (e.g., UBE1; 314370). Ubiquitin is
then transferred to a ubiquitin-conjugating enzyme, or E2 (e.g., UBE2A;
312180). The E2, either alone or in conjunction with a ubiquitin-protein
ligase, or E3 (e.g., UBE3A; 601623), catalyzes the final attachment of
ubiquitin to the target protein. The ubiquitylated protein is then
recognized and degraded by the 26S proteasome (see PSMD11; 604449).
Using the yeast 2-hybrid system to isolate proteins interacting with the
E2 UBCH7 (UBE2L3; 603721), followed by screening a fetal brain cDNA
library, Moynihan et al. (1999) obtained a cDNA encoding ARIH1, which
they termed HHARI (human homolog of Drosophila ariadne). Sequence
analysis predicted that the 557-amino acid protein, 72% identical to the
Drosophila ariadne protein, contains a highly acidic domain and a
poly(gly) tract in its N terminus, followed by 3 cys/his-rich motifs (2
RING fingers and an IBR, or 'in between RING fingers' domain) in its
central region. Northern blot analysis detected ubiquitous expression of
2.2-, 2.7-, and 6.5-kb transcripts. The smallest transcript was weakly
expressed except in testis, where it was predominant. Binding analysis
showed that ARIH1, through a RING finger and its IBR motif, associates
with at least the C-terminal 54 residues of UBCH7, as well as with UBCH8
(UBE2L6; 603890). ARIH1 did not associate with UBCH1 or UBCH5 (UBE2D1;
602961).
Using radiation hybrid analysis, Moynihan et al. (1999) mapped the ARIH1
gene to 15q. Tan et al. (2000) mapped the ARIH1 gene to 15q24 using
FISH. By genomic sequence analysis, they determined that ARIH1, as well
as its 98% identical mouse homolog, contains 14 exons.
Wenzel et al. (2011) showed that, unlike many ubiquitin-conjugating
enzymes (E2s) that transfer ubiquitin with RINGs, UBCH7 (603721) lacks
intrinsic ubiquitin ligase (E3)-independent reactivity with lysine,
explaining its preference for HECTs. Despite lacking lysine reactivity,
UBCH7 exhibits activity with the RING-in-between-RING (RBR) family of
E3s that includes parkin (602544) and HHARI. Found in all eukaryotes,
RBRs regulate processes such as translation and immune signaling. RBRs
contain a canonical C3HC4-type RING, followed by 2 conserved
cys/his-rich zinc-binding domains, in-between-RING (IBR) and RING2
domains, which together define this E3 family. Wenzel et al. (2011)
showed that RBRs function like RING/HECT hybrids: they bind E2s via a
RING domain, but transfer ubiquitin through an obligate thioester-linked
ubiquitin, requiring a conserved cysteine residue in RING2. Wenzel et
al. (2011) concluded that their results defined the functional cadre of
E3s for UBCH7, an E2 involved in cell proliferation and immune function,
and indicated a novel mechanism for an entire class of E3s.
*FIELD* RF
1. Moynihan, T. P.; Ardley, H. C.; Nuber, U.; Rose, S. A.; Jones,
P. F.; Markham, A. F.; Scheffner, M.; Robinson, P. A.: The ubiquitin-conjugating
enzymes UbcH7 and UbcH8 interact with RING finger/IBR motif-containing
domains of HHARI and H7-AP1. J. Biol. Chem. 274: 30963-30968, 1999.
2. Tan, N. G. S.; Ardley, H. C.; Rose, S. A.; Leek, J. P.; Markham,
A. F.; Robinson, P. A.: Characterisation of the human and mouse orthologues
of the Drosophila ariadne gene. Cytogenet. Cell Genet. 90: 242-245,
2000.
3. Wenzel, D. M.; Lissounov, A.; Brzovic, P. S.; Klevit, R. E.: UBCH7
reactivity profile reveals parkin and HHARI to be RING/HECT hybrids. Nature 474:
105-108, 2011.
*FIELD* CN
Ada Hamosh - updated: 6/22/2011
*FIELD* CD
Paul J. Converse: 2/8/2001
*FIELD* ED
alopez: 06/23/2011
terry: 6/22/2011
wwang: 12/17/2008
carol: 5/12/2004
mgross: 2/8/2001
*RECORD*
*FIELD* NO
605624
*FIELD* TI
*605624 ARIADNE, DROSOPHILA, HOMOLOG OF, 1; ARIH1
;;ARI;;
UBCH7-BINDING PROTEIN; UBCH7BP
read more*FIELD* TX
Proteins are targeted for ubiquitination in a 3-step process. The first
step involves the activation of ubiquitin (191339) through a
ubiquitin-activating enzyme, or E1 (e.g., UBE1; 314370). Ubiquitin is
then transferred to a ubiquitin-conjugating enzyme, or E2 (e.g., UBE2A;
312180). The E2, either alone or in conjunction with a ubiquitin-protein
ligase, or E3 (e.g., UBE3A; 601623), catalyzes the final attachment of
ubiquitin to the target protein. The ubiquitylated protein is then
recognized and degraded by the 26S proteasome (see PSMD11; 604449).
Using the yeast 2-hybrid system to isolate proteins interacting with the
E2 UBCH7 (UBE2L3; 603721), followed by screening a fetal brain cDNA
library, Moynihan et al. (1999) obtained a cDNA encoding ARIH1, which
they termed HHARI (human homolog of Drosophila ariadne). Sequence
analysis predicted that the 557-amino acid protein, 72% identical to the
Drosophila ariadne protein, contains a highly acidic domain and a
poly(gly) tract in its N terminus, followed by 3 cys/his-rich motifs (2
RING fingers and an IBR, or 'in between RING fingers' domain) in its
central region. Northern blot analysis detected ubiquitous expression of
2.2-, 2.7-, and 6.5-kb transcripts. The smallest transcript was weakly
expressed except in testis, where it was predominant. Binding analysis
showed that ARIH1, through a RING finger and its IBR motif, associates
with at least the C-terminal 54 residues of UBCH7, as well as with UBCH8
(UBE2L6; 603890). ARIH1 did not associate with UBCH1 or UBCH5 (UBE2D1;
602961).
Using radiation hybrid analysis, Moynihan et al. (1999) mapped the ARIH1
gene to 15q. Tan et al. (2000) mapped the ARIH1 gene to 15q24 using
FISH. By genomic sequence analysis, they determined that ARIH1, as well
as its 98% identical mouse homolog, contains 14 exons.
Wenzel et al. (2011) showed that, unlike many ubiquitin-conjugating
enzymes (E2s) that transfer ubiquitin with RINGs, UBCH7 (603721) lacks
intrinsic ubiquitin ligase (E3)-independent reactivity with lysine,
explaining its preference for HECTs. Despite lacking lysine reactivity,
UBCH7 exhibits activity with the RING-in-between-RING (RBR) family of
E3s that includes parkin (602544) and HHARI. Found in all eukaryotes,
RBRs regulate processes such as translation and immune signaling. RBRs
contain a canonical C3HC4-type RING, followed by 2 conserved
cys/his-rich zinc-binding domains, in-between-RING (IBR) and RING2
domains, which together define this E3 family. Wenzel et al. (2011)
showed that RBRs function like RING/HECT hybrids: they bind E2s via a
RING domain, but transfer ubiquitin through an obligate thioester-linked
ubiquitin, requiring a conserved cysteine residue in RING2. Wenzel et
al. (2011) concluded that their results defined the functional cadre of
E3s for UBCH7, an E2 involved in cell proliferation and immune function,
and indicated a novel mechanism for an entire class of E3s.
*FIELD* RF
1. Moynihan, T. P.; Ardley, H. C.; Nuber, U.; Rose, S. A.; Jones,
P. F.; Markham, A. F.; Scheffner, M.; Robinson, P. A.: The ubiquitin-conjugating
enzymes UbcH7 and UbcH8 interact with RING finger/IBR motif-containing
domains of HHARI and H7-AP1. J. Biol. Chem. 274: 30963-30968, 1999.
2. Tan, N. G. S.; Ardley, H. C.; Rose, S. A.; Leek, J. P.; Markham,
A. F.; Robinson, P. A.: Characterisation of the human and mouse orthologues
of the Drosophila ariadne gene. Cytogenet. Cell Genet. 90: 242-245,
2000.
3. Wenzel, D. M.; Lissounov, A.; Brzovic, P. S.; Klevit, R. E.: UBCH7
reactivity profile reveals parkin and HHARI to be RING/HECT hybrids. Nature 474:
105-108, 2011.
*FIELD* CN
Ada Hamosh - updated: 6/22/2011
*FIELD* CD
Paul J. Converse: 2/8/2001
*FIELD* ED
alopez: 06/23/2011
terry: 6/22/2011
wwang: 12/17/2008
carol: 5/12/2004
mgross: 2/8/2001