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 and ARIH2 are 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 or ARIH2.

Autoinhibitory domains (AIDs)

Target domain

299-339 (RING2 domain)

Relief mechanism

Partner binding

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for Q9Z1K6

Entry ID Method Resolution Chain Position Source
AF-Q9Z1K6-F1 Predicted AlphaFoldDB

2 variants for Q9Z1K6

Variant ID(s) Position Change Description Diseaes Association Provenance
rs46596494 42 A>V No Ensembl
rs235516447 386 E>Q No Ensembl

No associated diseases with Q9Z1K6

8 regional properties for Q9Z1K6

Type Name Position InterPro Accession
domain Zinc finger, RING-type 138 - 189 IPR001841-1
domain Zinc finger, RING-type 299 - 339 IPR001841-2
domain IBR domain 207 - 269 IPR002867-1
domain IBR domain 277 - 339 IPR002867-2
domain TRIAD supradomain 134 - 343 IPR044066
domain Ariadne domain 352 - 469 IPR045840
domain E3 ubiquitin-protein ligase ARIH2, BRcat domain 216 - 287 IPR047555
domain E3 ubiquitin-protein ligase TRIAD1, Rcat domain 291 - 346 IPR047556

Functions

Description
EC Number 2.3.2.31 Aminoacyltransferases
Subcellular Localization
  • Nucleus
  • Cytoplasm
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

5 GO annotations of cellular component

Name Definition
Cul5-RING ubiquitin ligase complex A ubiquitin ligase complex in which a cullin from the Cul5 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.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
nucleoplasm That part of the nuclear content other than the chromosomes or the nucleolus.
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.

4 GO annotations of molecular function

Name Definition
metal ion binding Binding to a metal ion.
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 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.

8 GO annotations of biological process

Name Definition
developmental cell growth The growth of a cell, where growth contributes to the progression of the cell over time from one condition to another.
hematopoietic stem cell proliferation The expansion of a hematopoietic stem cell population by cell division. A hematopoietic stem cell is a stem cell from which all cells of the lymphoid and myeloid lineages develop.
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 K48-linked ubiquitination A protein ubiquitination process in which a polymer of ubiquitin, formed by linkages between lysine residues at position 48 of the ubiquitin monomers, is added to a protein. K48-linked ubiquitination targets the substrate protein for degradation.
protein K63-linked ubiquitination A protein ubiquitination process in which a polymer of ubiquitin, formed by linkages between lysine residues at position 63 of the ubiquitin monomers, is added to a protein. K63-linked ubiquitination does not target the substrate protein for degradation, but is involved in several pathways, notably as a signal to promote error-free DNA postreplication repair.
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.

13 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
A2VEA3 ARIH1 E3 ubiquitin-protein ligase ARIH1 Bos taurus (Bovine) SS
O76924 ari-2 Potential E3 ubiquitin-protein ligase ariadne-2 Drosophila melanogaster (Fruit fly) SS
Q94981 ari-1 E3 ubiquitin-protein ligase ariadne-1 Drosophila melanogaster (Fruit fly) SS
Q9NWF9 RNF216 E3 ubiquitin-protein ligase RNF216 Homo sapiens (Human) PR
O95376 ARIH2 E3 ubiquitin-protein ligase ARIH2 Homo sapiens (Human) EV
Q9Y4X5 ARIH1 E3 ubiquitin-protein ligase ARIH1 Homo sapiens (Human) EV
Q9WVS6 Prkn E3 ubiquitin-protein ligase parkin Mus musculus (Mouse) EV SS
Q9Z1K5 Arih1 E3 ubiquitin-protein ligase ARIH1 Mus musculus (Mouse) SS
Q22431 ari-2 Potential E3 ubiquitin-protein ligase ariadne-2 Caenorhabditis elegans SS
O01965 ari-1.1 E3 ubiquitin-protein ligase ari-1.1 Caenorhabditis elegans SS
B1H1E4 arih1 E3 ubiquitin-protein ligase arih1 Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) SS
Q6PFJ9 arih1 E3 ubiquitin-protein ligase arih1 Danio rerio (Zebrafish) (Brachydanio rerio) SS
Q6NW85 arih1l E3 ubiquitin-protein ligase arih1l Danio rerio (Zebrafish) (Brachydanio rerio) SS
10 20 30 40 50 60
MSVDMNSQGS DSNEEDYDPN CEEEEEEEED PGDIEDYYVG VASDVEQQGA DAFDPEEYQF
70 80 90 100 110 120
TCLTYKESEG ALHEHMTSLA SVLKVSHSVA KLILVNFHWQ VSEILDRYRS NSAQLLVEAR
130 140 150 160 170 180
VQPNPSKHVP TAHPPHHCAV CMQFVRKENL LSLACQHQFC RSCWEQHCSV LVKDGVGVGI
190 200 210 220 230 240
SCMAQDCPLR TPEDFVFPLL PNEELRDKYR RYLFRDYVES HFQLQLCPGA DCPMVIRVQE
250 260 270 280 290 300
PRARRVQCNR CSEVFCFKCR QMYHAPTDCA TIRKWLTKCA DDSETANYIS AHTKDCPKCN
310 320 330 340 350 360
ICIEKNGGCN HMQCSKCKHD FCWMCLGDWK THGSEYYECS RYKENPDIVN QSQQAQAREA
370 380 390 400 410 420
LKKYLFYFER WENHNKSLQL EAQTYERIHE KIQERVMNNL GTWIDWQYLQ NAAKLLAKCR
430 440 450 460 470 480
YTLQYTYPYA YYMESGPRKK LFEYQQAQLE AEIENLSWKV ERADSYDRGD LENQMHIAEQ
490
RRRTLLKDFH DT