A2VEA3

SS
Gene name
ARIH1
Protein name
E3 ubiquitin-protein ligase ARIH1
Names
Protein ariadne-1 homolog, ARI-1, RING-type E3 ubiquitin transferase ARIH1
Species
Bos taurus (Bovine)
KEGG Pathway
bta:508410
EC number
2.3.2.31: Aminoacyltransferases
Protein Class

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)

406-555 (Ariadne domain) SS

Target domain

274-345 (RING2 domain)

Relief mechanism

Partner binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for A2VEA3

Entry ID Method Resolution Chain Position Source
AF-A2VEA3-F1 Predicted AlphaFoldDB

92 variants for A2VEA3

Variant ID(s) Position Change Description Diseaes Association Provenance
rs481876698 4 D>A No Ensembl
rs445583368 7 Y>* No Ensembl
rs464239680 9 Y>S No Ensembl
rs434445000 11 F>L No Ensembl
rs434445000 11 F>V No Ensembl
rs446689490 13 E>A No Ensembl
rs446689490 13 E>G No Ensembl
rs468353332 14 D>A No Ensembl
rs468353332 14 D>G No Ensembl
rs435518730 15 E>A No Ensembl
rs457225472 17 C>G No Ensembl
rs457225472 17 C>R No Ensembl
rs457225472 17 C>S No Ensembl
rs475706525 18 S>R No Ensembl
rs437191628 27 E>G No Ensembl
rs471095605 31 D>E No Ensembl
rs452451250 31 D>Y No Ensembl
rs459813144 32 D>A No Ensembl
rs459813144 32 D>V No Ensembl
rs441245962 32 D>Y No Ensembl
rs442126019 33 D>N No Ensembl
rs463898671 35 P>A No Ensembl
rs482538550 35 P>R No Ensembl
rs463898671 35 P>S No Ensembl
rs457716775 36 D>A No Ensembl
rs445611554 36 D>Y No Ensembl
rs479589051 39 N>I No Ensembl
rs446547729 41 D>A No Ensembl
rs468416601 45 V>G No Ensembl
rs480418158 46 E>G No Ensembl
rs136672001 52 L>R No Ensembl
rs450681722 54 V>G No Ensembl
rs469272957 57 E>V No Ensembl
rs452449870 59 D>E No Ensembl
rs433043203 59 D>G No Ensembl
rs464550062 66 T>R No Ensembl
rs474868905 67 G>A No Ensembl
rs453286172 67 G>C No Ensembl
rs442191168 68 G>D No Ensembl
rs457510249 73 A>V No Ensembl
rs476130359 75 G>R No Ensembl
rs457704022 77 G>R No Ensembl
rs479401690 78 G>R No Ensembl
rs478188600 86 G>C No Ensembl
rs464572964 87 G>C No Ensembl
rs468528822 90 G>R No Ensembl
rs137414194 93 Q>E No Ensembl
rs435632600 93 Q>L No Ensembl
rs132929646 96 D>V No Ensembl
rs457497760 96 D>Y No Ensembl
rs439937155 97 Y>* No Ensembl
rs451983249 98 R>H No Ensembl
rs473653192 99 Y>* No Ensembl
rs440048751 100 E>D No Ensembl
rs461715497 101 V>E No Ensembl
rs461715497 101 V>G No Ensembl
rs462766864 108 L>Q No Ensembl
rs720713380 108 L>V No Ensembl
rs478044529 117 E>A No Ensembl
rs478044529 117 E>G No Ensembl
rs444951927 121 V>D No Ensembl
rs441459765 142 K>R No Ensembl
rs459326741 143 L>R No Ensembl
rs481007744 248 T>I No Ensembl
rs463272351 260 I>T No Ensembl
rs478403170 266 E>A No Ensembl
rs450454339 392 E>D No Ensembl
rs477997170 394 D>A No Ensembl
rs469100663 394 D>Y No Ensembl
rs444812880 398 A>G No Ensembl
rs466432065 403 E>D No Ensembl
rs483197754 407 A>E No Ensembl
rs449987319 428 F>C No Ensembl
rs449185274 428 F>L No Ensembl
rs465225388 436 V>L No Ensembl
rs432617092 454 Q>* No Ensembl
rs454287955 460 V>G No Ensembl
rs466156147 461 D>H No Ensembl
rs436579163 476 F>L No Ensembl
rs455166752 479 Y>S No Ensembl
rs443344351 484 N>K No Ensembl
rs476293360 484 N>S No Ensembl
rs452100075 488 I>L No Ensembl
rs459654807 495 D>A No Ensembl
rs481471334 503 L>F No Ensembl
rs436732998 515 S>C No Ensembl
rs478926324 529 Y>* No Ensembl
rs449099624 534 R>L No Ensembl
rs467550463 543 E>* No Ensembl
rs482891546 552 Y>N No Ensembl
rs449945299 553 I>L No Ensembl
rs449945299 553 I>V No Ensembl

No associated diseases with A2VEA3

7 regional properties for A2VEA3

Type Name Position InterPro Accession
domain Protein kinase domain 284 - 537 IPR000719
domain SH2 domain 160 - 259 IPR000980
domain Serine-threonine/tyrosine-protein kinase, catalytic domain 284 - 533 IPR001245
domain SH3 domain 95 - 156 IPR001452
active_site Tyrosine-protein kinase, active site 400 - 412 IPR008266
binding_site Protein kinase, ATP binding site 290 - 312 IPR017441
domain Tyrosine-protein kinase, catalytic domain 284 - 536 IPR020635

Functions

Description
EC Number 2.3.2.31 Aminoacyltransferases
Subcellular Localization
  • Cytoplasm
  • Nucleus
  • Nucleus, Cajal body
  • Mainly cytoplasmic
  • Present in Lewy body
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

10 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.
Cul2-RING ubiquitin ligase complex A ubiquitin ligase complex in which a cullin from the Cul2 subfamily and a RING domain protein form the catalytic core; substrate specificity is conferred by an elongin-BC adaptor and a SOCS/BC box protein.
Cul3-RING ubiquitin ligase complex A ubiquitin ligase complex in which a cullin from the Cul3 subfamily and a RING domain protein form the catalytic core; substrate specificity is conferred by a BTB-domain-containing protein.
Cul4A-RING E3 ubiquitin ligase complex A ubiquitin ligase complex in which a cullin from the Cul4A subfamily and a RING domain protein form the catalytic core; substrate specificity is conferred by an adaptor protein.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
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.
SCF ubiquitin ligase complex A ubiquitin ligase complex in which a cullin from the Cul1 subfamily and a RING domain protein form the catalytic core; substrate specificity is conferred by a Skp1 adaptor and an F-box protein. SCF complexes are involved in targeting proteins for degradation by the proteasome. The best characterized complexes are those from yeast and mammals (with core subunits named Cdc53/Cul1, Rbx1/Hrt1/Roc1).
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.

5 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-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.

11 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
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
Q9Y4X5 ARIH1 E3 ubiquitin-protein ligase ARIH1 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 DDDEPDDDNL DLGEVELVEP GLGVGGERDG
70 80 90 100 110 120
LLCGETGGGG GSALGPGGGG GGGGGGGGPG HEQEEDYRYE VLTAEQILQH MVECIREVNE
130 140 150 160 170 180
VIQNPATITR ILLSHFNWDK EKLMERYFDG NLEKLFAECH VINPSKKSRT RQMNTRSSAQ
190 200 210 220 230 240
DMPCQICYLN YPNSYFTGLE CGHKFCMQCW SEYLTTKIME EGMGQTISCP AHGCDILVDD
250 260 270 280 290 300
NTVMRLITDS KVKLKYQHLI TNSFVECNRL LKWCPAPDCH HVVKVQYPDA KPVRCKCGRQ
310 320 330 340 350 360
FCFNCGENWH DPVKCKWLKK WIKKCDDDSE TSNWIAANTK ECPKCHVTIE KDGGCNHMVC
370 380 390 400 410 420
RNQNCKAEFC WVCLGPWEPH GSAWYNCNRY NEDDAKAARD AQERSRAALQ RYLFYCNRYM
430 440 450 460 470 480
NHMQSLRFEH KLYAQVKQKM EEMQQHNMSW IEVQFLKKAV DVLCQCRATL MYTYVFAFYL
490 500 510 520 530 540
KKNNQSIIFE NNQADLENAT EVLSGYLERD ISQDSLQDIK QKVQDKYRYC ESRRRVLLQH
550
VHEGYEKDLW EYIED