Descriptions

E3 ubiquitin-protein ligase ARIH1 is an E3 ubiquitin-protein ligase, which catalyzes ubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3, and acts as an atypical E3 ubiquitin-protein ligase by working together with cullin-RING ubiquitin ligase (CRL) complexes and initiating ubiquitination of CRL substrates. ARIH1 is autoinhibited by the ariadne domain, which masks the second RING-type zinc finger that contains the active site and inhibits the E3 activity. The inhibition is relieved upon binding to neddylated cullin-RING ubiquitin ligase complexes, which activate the E3 ligase activity of ARIH1.

Autoinhibitory domains (AIDs)

Target domain

276-347 (RING2 domain)

Relief mechanism

Partner binding

Assay

Deletion assay, Mutagenesis experiment, Structural analysis

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

11 structures for Q9Y4X5

Entry ID Method Resolution Chain Position Source
1WD2 NMR - A 336-394 PDB
2M9Y NMR - A 325-396 PDB
4KBL X-ray 330 A A/B 1-557 PDB
4KC9 X-ray 360 A A 1-557 PDB
5TTE X-ray 350 A B 1-557 PDB
5UDH X-ray 324 A A/B 90-557 PDB
7B5L EM 380 A H 1-557 PDB
7B5M EM 391 A H 1-557 PDB
7B5N EM 360 A H 1-557 PDB
7B5S EM 360 A H 1-557 PDB
AF-Q9Y4X5-F1 Predicted AlphaFoldDB

167 variants for Q9Y4X5

Variant ID(s) Position Change Description Diseaes Association Provenance
VAR_082646
CA273260089
rs1052050835
RCV001291053
15 E>Q probable disease-associated variant found in patient with an acute aortic dissection and ascending aortic aneurysm Aortic aneurysm [UniProt, ClinVar] Yes ClinGen
ClinVar
UniProt
TOPMed
dbSNP
rs2063786716
RCV001291431
44 E>G Aortic aneurysm [ClinVar] Yes ClinVar
dbSNP
RCV001291430
rs746505361
CA7645516
171 R>* Aortic aneurysm [ClinVar] Yes ClinGen
ClinVar
ExAC
dbSNP
gnomAD
rs751344394
CA7645402
7 Y>C No ClinGen
ExAC
TOPMed
gnomAD
CA393235936
rs1302485230
7 Y>H No ClinGen
TOPMed
rs1361234355
CA393235990
8 N>H No ClinGen
TOPMed
rs781240234
CA7645404
8 N>I No ClinGen
ExAC
TOPMed
gnomAD
rs1477796553
CA393236038
9 Y>C No ClinGen
TOPMed
CA393236051
rs1479803832
10 E>Q No ClinGen
gnomAD
rs1195230372
CA393236099
11 F>L No ClinGen
TOPMed
rs769816706
CA7645406
12 D>E No ClinGen
ExAC
TOPMed
gnomAD
rs1428522519
CA393236106
12 D>N No ClinGen
TOPMed
rs779981165
CA7645407
15 E>A No ClinGen
ExAC
gnomAD
rs779981165
CA393236205
15 E>G No ClinGen
ExAC
gnomAD
rs890255198
CA273260090
18 S>C No ClinGen
gnomAD
rs890255198
CA393236268
18 S>G No ClinGen
gnomAD
rs1321793234
CA393236299
19 E>K No ClinGen
gnomAD
rs868117311
CA273260091
21 D>E No ClinGen
Ensembl
CA7645411
rs768692029
22 S>G No ClinGen
ExAC
gnomAD
rs772456417
CA7645415
25 E>D No ClinGen
ExAC
gnomAD
rs1327083729
CA393236373
25 E>Q No ClinGen
TOPMed
CA7645416
rs773605993
28 E>D No ClinGen
ExAC
gnomAD
rs1348781230
CA393236418
28 E>G No ClinGen
gnomAD
CA7645418
rs761158526
29 D>E No ClinGen
ExAC
gnomAD
CA7645417
rs761158526
29 D>E No ClinGen
ExAC
gnomAD
CA7645419
rs752084483
30 E>K No ClinGen
ExAC
TOPMed
gnomAD
rs1490087109
CA393236491
32 D>E No ClinGen
gnomAD
CA393236505
rs1182181311
33 D>E No ClinGen
gnomAD
CA393236554
rs1253333685
36 D>E No ClinGen
gnomAD
CA7645421
rs763608232
37 D>G No ClinGen
ExAC
gnomAD
rs751293008
CA7645423
39 T>I No ClinGen
ExAC
gnomAD
CA7645422
rs751293008
39 T>N No ClinGen
ExAC
gnomAD
rs946176693
CA273260094
41 D>N No ClinGen
TOPMed
rs994449992
CA273260095
45 V>A No ClinGen
gnomAD
CA7645427
rs780042095
47 L>V No ClinGen
ExAC
TOPMed
gnomAD
rs1430641905
CA393236752
49 E>* No ClinGen
gnomAD
CA7645428
rs749268378
49 E>D No ClinGen
ExAC
gnomAD
CA393236754
rs1595845215
49 E>G No ClinGen
Ensembl
rs768801971
CA7645429
50 P>S No ClinGen
ExAC
gnomAD
CA273260096
rs1042181947
51 G>W No ClinGen
TOPMed
rs1312645720
CA393236805
53 G>S No ClinGen
gnomAD
rs1358544322
CA393236815
54 V>I No ClinGen
gnomAD
CA393236833
rs1239114198
55 G>A No ClinGen
TOPMed
gnomAD
CA393236840
rs1184730148
56 G>R No ClinGen
TOPMed
rs1000583730
CA273260097
57 E>Q No ClinGen
TOPMed
CA7645433
rs773561251
58 R>W No ClinGen
ExAC
gnomAD
rs1177781521
CA393236885
59 D>N No ClinGen
TOPMed
CA393236943
rs1426082091
64 G>R No ClinGen
gnomAD
rs777220733
CA7645436
66 T>M No ClinGen
ExAC
gnomAD
CA393236976
rs1450537917
69 G>D No ClinGen
TOPMed
gnomAD
rs1013967251
CA273260099
71 G>S No ClinGen
Ensembl
CA393236992
rs1264967111
72 S>C No ClinGen
TOPMed
CA393236999
rs774057607
73 A>P No ClinGen
ExAC
gnomAD
CA7645439
rs774057607
73 A>S No ClinGen
ExAC
gnomAD
rs1303516615
CA393237004
74 L>V No ClinGen
TOPMed
gnomAD
CA7645442
rs559502830
76 P>L No ClinGen
1000Genomes
TOPMed
gnomAD
rs767341707
CA7645441
76 P>T No ClinGen
ExAC
gnomAD
rs1228917143
CA393237018
77 G>S No ClinGen
gnomAD
rs755947974
CA7645446
78 G>S No ClinGen
ExAC
gnomAD
CA393237049
rs1199225308
82 G>R No ClinGen
TOPMed
gnomAD
CA393237048
rs1199225308
82 G>S No ClinGen
TOPMed
gnomAD
CA393237056
rs1465600303
83 G>C No ClinGen
gnomAD
rs12902861
CA273260104
84 G>C No ClinGen
Ensembl
rs753843976
CA7645456
85 G>D No ClinGen
ExAC
gnomAD
CA273260105
rs967532979
86 G>V No ClinGen
TOPMed
gnomAD
rs1417513681
CA393237078
87 G>D No ClinGen
TOPMed
rs1297238945
CA393237076
87 G>R No ClinGen
TOPMed
CA273260106
rs977706882
88 G>S No ClinGen
Ensembl
rs1379429183
CA393237087
89 G>S No ClinGen
TOPMed
gnomAD
RCV002056684
RCV000455671
rs375614248
90 G>missing No ClinVar
dbSNP
CA393237100
rs1375923364
91 P>S No ClinGen
TOPMed
rs1464648760
CA393237106
92 G>W No ClinGen
gnomAD
rs1405301183
CA393237114
93 H>R No ClinGen
gnomAD
rs1481483194
CA393237120
94 E>Q No ClinGen
TOPMed
CA273260108
rs957384868
95 Q>H No ClinGen
TOPMed
gnomAD
rs1359687603
CA393237167
100 R>C No ClinGen
gnomAD
CA7645461
rs368784844
100 R>H No ClinGen
ESP
ExAC
TOPMed
gnomAD
rs1206162417
CA393237174
101 Y>C No ClinGen
TOPMed
rs921251553
CA273260109
102 E>K No ClinGen
gnomAD
CA273260110
rs12903022
107 E>D No ClinGen
Ensembl
rs1210904578
CA393237232
110 L>V No ClinGen
gnomAD
CA393237253
rs1191965773
113 M>L No ClinGen
gnomAD
CA273260112
rs867712471
118 R>L No ClinGen
Ensembl
CA7645467
rs746369007
121 N>K No ClinGen
ExAC
gnomAD
CA7645469
rs770477644
122 E>D No ClinGen
ExAC
TOPMed
gnomAD
rs771736875
CA7645492
130 I>L No ClinGen
ExAC
TOPMed
gnomAD
CA393242616
rs771736875
130 I>V No ClinGen
ExAC
TOPMed
gnomAD
CA393242655
rs1297406432
136 S>G No ClinGen
TOPMed
rs147408829
CA273265289
139 N>S No ClinGen
ESP
TOPMed
gnomAD
rs1243956076
CA393235448
154 L>V No ClinGen
gnomAD
rs933413352
CA273268323
162 H>R No ClinGen
TOPMed
rs769334669
CA7645515
167 S>N No ClinGen
ExAC
TOPMed
gnomAD
rs769334669
CA7645514
167 S>T No ClinGen
ExAC
TOPMed
gnomAD
CA7645517
rs770559164
171 R>Q No ClinGen
ExAC
gnomAD
rs148941976
CA7645518
173 R>C No ClinGen
1000Genomes
ExAC
gnomAD
rs969696237
CA273268324
173 R>H No ClinGen
gnomAD
CA393235841
rs979829613
174 Q>H No ClinGen
Ensembl
rs1251423210
CA393235886
176 N>S No ClinGen
TOPMed
CA7645519
rs759288383
177 T>A No ClinGen
ExAC
gnomAD
CA7645521
rs775316269
180 S>T No ClinGen
ExAC
TOPMed
gnomAD
CA7645523
rs764009252
183 D>N No ClinGen
ExAC
gnomAD
rs1000868639
CA273268326
191 L>V No ClinGen
TOPMed
CA273268327
rs779405166
192 N>K No ClinGen
TOPMed
CA393236276
rs1345775312
196 S>L No ClinGen
gnomAD
CA7645537
rs769496771
197 Y>C No ClinGen
ExAC
gnomAD
rs1295878502
CA393237641
198 F>L No ClinGen
gnomAD
CA393237676
rs1345038178
202 E>Q No ClinGen
gnomAD
CA273269551
rs961904194
209 M>L No ClinGen
TOPMed
gnomAD
rs961904194
CA273269550
209 M>V No ClinGen
TOPMed
gnomAD
CA393237876
rs1228878159
213 S>N No ClinGen
gnomAD
rs1286785152
CA393238218
229 I>T No ClinGen
TOPMed
CA393238283
rs1343881622
234 H>N No ClinGen
TOPMed
CA7645560
rs748015574
235 G>D No ClinGen
ExAC
gnomAD
CA393238472
rs1181805525
246 M>V No ClinGen
TOPMed
gnomAD
CA7645576
rs754711191
247 R>C No ClinGen
ExAC
TOPMed
CA7645577
rs778561142
247 R>H No ClinGen
ExAC
TOPMed
gnomAD
rs147551270
CA7645578
251 D>E No ClinGen
ESP
ExAC
TOPMed
gnomAD
rs1392004426
CA393239750
251 D>N No ClinGen
TOPMed
rs1461577237
CA393239907
262 I>V No ClinGen
gnomAD
CA393240186
rs1405057056
270 N>S No ClinGen
gnomAD
rs1454157851
CA393240191
271 R>Q No ClinGen
gnomAD
rs778633164
CA7645597
272 L>R No ClinGen
ExAC
gnomAD
rs149030231
CA273270415
280 D>G No ClinGen
ESP
rs1218416217
CA393240249
280 D>H No ClinGen
TOPMed
rs758299803
CA7645599
283 H>Q No ClinGen
ExAC
gnomAD
rs777749802
CA7645600
288 Q>H No ClinGen
ExAC
gnomAD
CA393240354
rs1271592185
288 Q>R No ClinGen
TOPMed
CA393240410
rs1339411218
292 A>T No ClinGen
TOPMed
rs781125737
CA7645603
294 P>A No ClinGen
ExAC
gnomAD
CA393240576
rs1332093999
294 P>L No ClinGen
TOPMed
rs1259128502
COSM1374415
CA393240585
296 R>C large_intestine [Cosmic] No ClinGen
cosmic curated
TOPMed
gnomAD
rs1259128502
CA393240584
296 R>G No ClinGen
TOPMed
gnomAD
rs769846251
CA7645605
296 R>H No ClinGen
ExAC
TOPMed
gnomAD
rs769846251
CA7645606
296 R>L No ClinGen
ExAC
TOPMed
gnomAD
CA393240607
rs1463886403
299 C>S No ClinGen
TOPMed
rs1417583080
CA393240617
301 R>C No ClinGen
TOPMed
rs1188543265
CA393240620
301 R>H No ClinGen
TOPMed
rs1320295436
CA393240801
321 K>N No ClinGen
TOPMed
CA7645640
rs757137026
326 K>T No ClinGen
ExAC
CA393240891
rs1595871915
333 T>P No ClinGen
Ensembl
rs750348642
CA7645642
335 N>S No ClinGen
ExAC
TOPMed
gnomAD
rs192253156
CA273271038
357 C>Y No ClinGen
1000Genomes
rs969550607
CA273271039
365 Q>* No ClinGen
Ensembl
rs573902027
CA7645661
370 E>D No ClinGen
1000Genomes
ExAC
gnomAD
rs1284449604
CA393241194
373 W>R No ClinGen
gnomAD
CA7645686
rs753804913
391 R>H No ClinGen
ExAC
gnomAD
CA7645687
rs759517486
399 A>V No ClinGen
ExAC
gnomAD
CA7645734
rs762126728
406 R>L No ClinGen
ExAC
gnomAD
CA393241459
rs762126728
406 R>Q No ClinGen
ExAC
gnomAD
CA7645735
rs767859277
409 A>E No ClinGen
ExAC
gnomAD
rs753701203
CA7645738
420 R>H No ClinGen
ExAC
gnomAD
rs777142325
CA7645741
443 E>G No ClinGen
ExAC
CA273272166
rs113869196
459 K>R No ClinGen
Ensembl
CA7645747
rs779944062
483 K>R No ClinGen
ExAC
gnomAD
rs768710024
CA7645749
484 K>N No ClinGen
ExAC
gnomAD
rs1203862513
CA393242169
503 E>K No ClinGen
gnomAD
CA7645776
rs753167225
521 I>V No ClinGen
ExAC
gnomAD
rs1447655771
CA393242349
528 K>M No ClinGen
gnomAD
COSM382806
CA393242415
rs1276382860
535 R>L lung [Cosmic] No ClinGen
cosmic curated
gnomAD
rs770168604
CA7645801
538 V>G No ClinGen
ExAC
gnomAD
rs1370979485
CA393242436
539 L>S No ClinGen
TOPMed
rs1218251335
CA393242453
541 Q>H No ClinGen
gnomAD
rs1213846918
CA393242474
544 H>L No ClinGen
TOPMed
gnomAD
rs1213846918
CA393242472
544 H>R No ClinGen
TOPMed
gnomAD
CA393242495
rs1348294540
547 Y>C No ClinGen
TOPMed
rs1245309692
CA393242551
554 Y>* No ClinGen
gnomAD
CA393242570
rs1477923543
557 D>Y No ClinGen
gnomAD

1 associated diseases with Q9Y4X5

Without disease ID

6 regional properties for Q9Y4X5

Type Name Position InterPro Accession
domain Zinc finger, RING-type 186 - 234 IPR001841-1
domain Zinc finger, RING-type 276 - 347 IPR001841-2
domain IBR domain 256 - 317 IPR002867-1
domain IBR domain 325 - 389 IPR002867-2
domain TRIAD supradomain 182 - 393 IPR044066
domain Ariadne domain 403 - 524 IPR045840

Functions

Description
EC Number 2.3.2.31 Aminoacyltransferases
Subcellular Localization
  • Cytoplasm
  • Nucleus
  • Nucleus, Cajal body
  • Mainly cytoplasmic (PubMed:11278816)
  • Present in Lewy body (PubMed:21590270)
PANTHER Family PTHR11685 RBR FAMILY RING FINGER AND IBR DOMAIN-CONTAINING
PANTHER Subfamily PTHR11685:SF212 E3 UBIQUITIN-PROTEIN LIGASE ARIH1
PANTHER Protein Class ubiquitin-protein ligase
protein modifying enzyme
PANTHER Pathway Category No pathway information available

7 GO annotations of cellular component

Name Definition
Cajal body A class of nuclear body, first seen after silver staining by Ramon y Cajal in 1903, enriched in small nuclear ribonucleoproteins, and certain general RNA polymerase II transcription factors; ultrastructurally, they appear as a tangle of coiled, electron-dense threads roughly 0.5 micrometers in diameter; involved in aspects of snRNP biogenesis; the protein coilin serves as a marker for Cajal bodies. Some argue that Cajal bodies are the sites for preassembly of transcriptosomes, unitary particles involved in transcription and processing of RNA.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
Lewy body Cytoplasmic, spherical inclusion commonly found in damaged neurons, and composed of abnormally phosphorylated, neurofilament proteins aggregated with ubiquitin and alpha-synuclein.
nuclear body Extra-nucleolar nuclear domains usually visualized by confocal microscopy and fluorescent antibodies to specific proteins.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
ubiquitin ligase complex A protein complex that includes a ubiquitin-protein ligase and enables ubiquitin protein ligase activity. The complex also contains other proteins that may confer substrate specificity on the complex.

6 GO annotations of molecular function

Name Definition
ubiquitin conjugating enzyme binding Binding to a ubiquitin conjugating enzyme, any of the E2 proteins.
ubiquitin protein ligase activity Catalysis of the transfer of ubiquitin to a substrate protein via the reaction X-ubiquitin + S -> X + S-ubiquitin, where X is either an E2 or E3 enzyme, the X-ubiquitin linkage is a thioester bond, and the S-ubiquitin linkage is an amide bond: an isopeptide bond between the C-terminal glycine of ubiquitin and the epsilon-amino group of lysine residues in the substrate or, in the linear extension of ubiquitin chains, a peptide bond the between the C-terminal glycine and N-terminal methionine of ubiquitin residues.
ubiquitin protein ligase binding Binding to a ubiquitin protein ligase enzyme, any of the E3 proteins.
ubiquitin-like protein transferase activity Catalysis of the transfer of a ubiquitin-like from one protein to another via the reaction X-ULP + Y --> Y-ULP + X, where both X-ULP and Y-ULP are covalent linkages. ULP represents a ubiquitin-like protein.
ubiquitin-protein transferase activity Catalysis of the transfer of ubiquitin from one protein to another via the reaction X-Ub + Y --> Y-Ub + X, where both X-Ub and Y-Ub are covalent linkages.
zinc ion binding Binding to a zinc ion (Zn).

4 GO annotations of biological process

Name Definition
positive regulation of proteasomal ubiquitin-dependent protein catabolic process Any process that activates or increases the frequency, rate or extent of the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, and mediated by the proteasome.
protein polyubiquitination Addition of multiple ubiquitin groups to a protein, forming a ubiquitin chain.
protein ubiquitination The process in which one or more ubiquitin groups are added to a protein.
ubiquitin-dependent protein catabolic process The chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of a ubiquitin group, or multiple ubiquitin groups, to the protein.

12 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
A2VEA3 ARIH1 E3 ubiquitin-protein ligase ARIH1 Bos taurus (Bovine) SS
Q94981 ari-1 E3 ubiquitin-protein ligase ariadne-1 Drosophila melanogaster (Fruit fly) SS
O76924 ari-2 Potential E3 ubiquitin-protein ligase ariadne-2 Drosophila melanogaster (Fruit fly) SS
O60260 PRKN E3 ubiquitin-protein ligase parkin Homo sapiens (Human) EV
O95376 ARIH2 E3 ubiquitin-protein ligase ARIH2 Homo sapiens (Human) EV
Q9Z1K5 Arih1 E3 ubiquitin-protein ligase ARIH1 Mus musculus (Mouse) SS
Q9Z1K6 Arih2 E3 ubiquitin-protein ligase ARIH2 Mus musculus (Mouse) SS
O01965 ari-1.1 E3 ubiquitin-protein ligase ari-1.1 Caenorhabditis elegans SS
Q22431 ari-2 Potential E3 ubiquitin-protein ligase ariadne-2 Caenorhabditis elegans SS
B1H1E4 arih1 E3 ubiquitin-protein ligase arih1 Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) SS
Q6NW85 arih1l E3 ubiquitin-protein ligase arih1l Danio rerio (Zebrafish) (Brachydanio rerio) SS
Q6PFJ9 arih1 E3 ubiquitin-protein ligase arih1 Danio rerio (Zebrafish) (Brachydanio rerio) SS
10 20 30 40 50 60
MDSDEGYNYE FDEDEECSEE DSGAEEEEDE DDDEPDDDTL DLGEVELVEP GLGVGGERDG
70 80 90 100 110 120
LLCGETGGGG GSALGPGGGG GGGGGGGGGG PGHEQEEDYR YEVLTAEQIL QHMVECIREV
130 140 150 160 170 180
NEVIQNPATI TRILLSHFNW DKEKLMERYF DGNLEKLFAE CHVINPSKKS RTRQMNTRSS
190 200 210 220 230 240
AQDMPCQICY LNYPNSYFTG LECGHKFCMQ CWSEYLTTKI MEEGMGQTIS CPAHGCDILV
250 260 270 280 290 300
DDNTVMRLIT DSKVKLKYQH LITNSFVECN RLLKWCPAPD CHHVVKVQYP DAKPVRCKCG
310 320 330 340 350 360
RQFCFNCGEN WHDPVKCKWL KKWIKKCDDD SETSNWIAAN TKECPKCHVT IEKDGGCNHM
370 380 390 400 410 420
VCRNQNCKAE FCWVCLGPWE PHGSAWYNCN RYNEDDAKAA RDAQERSRAA LQRYLFYCNR
430 440 450 460 470 480
YMNHMQSLRF EHKLYAQVKQ KMEEMQQHNM SWIEVQFLKK AVDVLCQCRA TLMYTYVFAF
490 500 510 520 530 540
YLKKNNQSII FENNQADLEN ATEVLSGYLE RDISQDSLQD IKQKVQDKYR YCESRRRVLL
550
QHVHEGYEKD LWEYIED