Rc3h1
entrez
381305
canonical
uniprot
Q4VGL6
canonical
ensembl
ENSMUSG00000040423
resolver
ensp
ENSMUSP00000124871
resolver
enst
ENSMUST00000161609
resolver
genesymbol
Rc3h1
resolver
genesymbol_syn
Gm551
resolver
genesymbol_syn
Kiaa2025
resolver
uniprot
B2RS13
resolver
uniprot
Q69Z31
resolver
uniprot_entry
RC3H1_MOUSE
resolver
uniprot_sec
B2RS13
resolver
uniprot_sec
Q69Z31
resolver
amino_acid_sequence
MPVQAPQWTDFLSCPICTQTFDETIRKPISLGCGHTVCKMCLNKLHRKACPFDQTTINTDIELLPVNSALLQLVGAQIPEQQPITLCSGVEDTKHYEEAKKCVEELALYLKPLSSARGVGLNSTTQSVLSRPMQRKLVTLVHCQLVEEEGRIRAMRAARSLGERTVTELILQHQNPQQLSSNLWAAVRARGCQFLGPAMQEEALKLVLLALEDGSALSRKVLVLFVVQRLEPRFPQASKTSIGHVVQLLYRASCFKVTKRDEDSSLMQLKEEFRTYEALRREHDSQIVQIAMEAGLRIAPDQWSSLLYGDQSHKSHMQSIIDKLQTPASFAQSVQELTIALQRTGDPANLNRLRPHLELLANIDPSPDAPPPTWEQLENGLVAVRTVVHGLVDYIQNHSKKGADQQQPPQHSKYKTYMCRDMKQRGGCPRGASCTFAHSQEELEKFRKMNKRLVPRRPLSASLGQLNEVGLPSAPILSDESAVDLSNRKPPALPNGIASSGSTVTQLIPRGTDPSFDSSLKPVKLDHLSSSAPGSPPDLLESAPKSISALPVNPHPVPPRGPTDLPPMPVTKPIQMVPRGSQLYPAQQADVYYQDPRGSAPAFETAPYQQGMYYTPPPCVSRFVRPPPSAPEPGPPYLDHYSPYLQDRVINSQYGTQPQQYPPMYPAHYDGRRVYPAQSYTREEMFRESPIPIDIPSAAVPSYVPESRERYQQVEGYYPVAPHPAQIRPSYPRDPPYSRLPPPQPHPSLDELHRRRKEIMAQLEERKVISPPPFAPSPTLPPAFHPEEFLDEDLKVAGKYKANDYSQYSPWSCDTIGSYIGTKDAKPKDVVAAGSVEMMNVESKGTREQRLDLQRRAVETSDDDLIPFGDRPTVSRFGAISRTSKTLYQGAGPLQAIAPQGAPTKSINISDYSAYGAHGGWGDSPYSPHANIPPQGHFIEREKMSMAEVASHGKPLLSAEREQLRLELQQLNHQISQQTQLRGLEAVSNRLVLQREVNTLASQPQPPQLPPKWPGMISSEQLSLELHQVEREIGKRTRELSMENQCSVDMKSKLGTSKQAENGQPEPQNKIRTEDLTLTFSDVPNGSALTQENLSLLSNKTSSLNLSEDSEGGGDNNDSQRSGVVSNSAP
uniprot
proteins
ec_number
2.3.2.27
uniprot
proteins
function
FUNCTION: Post-transcriptional repressor of mRNAs containing a conserved stem loop motif, called constitutive decay element (CDE), which is often located in the 3'-UTR, as in HMGXB3, ICOS, IER3, NFKBID, NFKBIZ, PPP1R10, TNF, TNFRSF4 and in many more mRNAs (PubMed:18172933, PubMed:23663784, PubMed:25026077). Cleaves translationally inactive mRNAs harboring a stem-loop (SL), often located in their 3'-UTRs, during the early phase of inflammation in a helicase UPF1-independent manner (PubMed:26000482). Binds to CDE and promotes mRNA deadenylation and degradation. This process does not involve miRNAs (PubMed:20412057, PubMed:20639877). In follicular helper T (Tfh) cells, represses of ICOS and TNFRSF4/Ox40 expression, thus preventing spontaneous Tfh cell differentiation, germinal center B-cell differentiation in the absence of immunization and autoimmunity. In resting or LPS-stimulated macrophages, controls inflammation by suppressing TNF expression. Also recognizes CDE in its own mRNA and in that of paralogous RC3H2, possibly leading to feedback loop regulation (PubMed:15917799, PubMed:23583642, PubMed:23583643). Inhibits cooperatively with ZC3H12A the differentiation of helper T cells Th17 in lungs. They repress target mRNA encoding the Th17 cell-promoting factors IL6, ICOS, REL, IRF4, NFKBID and NFKBIZ. The cooperation requires RNA-binding by RC3H1 and the nuclease activity of ZC3H12A (PubMed:25282160). Recognizes and binds mRNAs containing a hexaloop stem-loop motif, called alternative decay element (ADE) (PubMed:27010430). Together with ZC3H12A, destabilizes TNFRSF4/OX40 mRNA by binding to the conserved stem loop structure in its 3'UTR (PubMed:29244194). Able to interact with double-stranded RNA (By similarity). miRNA-binding protein that regulates microRNA homeostasis. Enhances DICER-mediated processing of pre-MIR146a but reduces mature MIR146a levels through an increase of 3' end uridylation. Both inhibits ICOS mRNA expression and they may act together to exert the suppression (PubMed:25697406). Acts as a ubiquitin E3 ligase. Pairs with E2 enzymes UBE2A, UBE2B, UBE2D2, UBE2F, UBE2G1, UBE2G2 and UBE2L3 and produces polyubiquitin chains. Shows the strongest activity when paired with UBE2N:UBE2V1 or UBE2N:UBE2V2 E2 complexes and generate both short and long polyubiquitin chains (By similarity). {ECO:0000250|UniProtKB:Q5TC82, ECO:0000269|PubMed:15917799, ECO:0000269|PubMed:18172933, ECO:0000269|PubMed:20412057, ECO:0000269|PubMed:20639877, ECO:0000269|PubMed:23583642, ECO:0000269|PubMed:23583643, ECO:0000269|PubMed:23663784, ECO:0000269|PubMed:25026077, ECO:0000269|PubMed:25282160, ECO:0000269|PubMed:25697406, ECO:0000269|PubMed:26000482, ECO:0000269|PubMed:27010430, ECO:0000269|PubMed:29244194}.
uniprot
proteins
mass_dalton
125378
uniprot
proteins
mutagenesis
MUTAGEN 14; /note="C->A: No effect on localization to stress granules."; /evidence="ECO:0000269|PubMed:20412057"; MUTAGEN 188; /note="R->A: No effect on CDERNA-binding."; /evidence="ECO:0000269|PubMed:25026077"; MUTAGEN 199; /note="M->R: In sanroque; partial loss of ICOS regulation, no effect on localization to stress granules, no effect on RNA-binding."; /evidence="ECO:0000269|PubMed:15917799, ECO:0000269|PubMed:20412057, ECO:0000269|PubMed:25697406, ECO:0000269|PubMed:27010430, ECO:0000269|PubMed:31636267"; MUTAGEN 219; /note="R->A: No effect on CDERNA-binding."; /evidence="ECO:0000269|PubMed:25026077"; MUTAGEN 220; /note="K->A: Strongly decreases CDE and ADERNA-binding. Increases target-mRNA expression. Increases ICOS surface expression; when associated with A-239 and A-260."; /evidence="ECO:0000269|PubMed:25026077, ECO:0000269|PubMed:25282160, ECO:0000269|PubMed:27010430"; MUTAGEN 229; /note="R->A: No effect on CDERNA-binding."; /evidence="ECO:0000269|PubMed:25026077, ECO:0000269|PubMed:27010430"; MUTAGEN 233; /note="R->A: No effect on CDERNA-binding."; /evidence="ECO:0000269|PubMed:25026077"; MUTAGEN 238; /note="S->A: Decreases CDERNA-binding."; /evidence="ECO:0000269|PubMed:25026077"; MUTAGEN 239; /note="K->A: Strongly decreases CDE and ADERNA-binding. Increases target-mRNA expression. Abolishes CDERNA-binding and highly increases target-mRNA expression; when associated with A-260. Increases target-mRNA expression. Increases ICOS surface expression; when associated with A-220 and A-260."; /evidence="ECO:0000269|PubMed:25026077, ECO:0000269|PubMed:25282160, ECO:0000269|PubMed:27010430"; MUTAGEN 250; /note="Y->A: Decreases CDERNA-binding. Increases target-mRNA expression."; /evidence="ECO:0000269|PubMed:25026077, ECO:0000269|PubMed:27010430"; MUTAGEN 251; /note="R->A: No effect on CDERNA-binding."; /evidence="ECO:0000269|PubMed:25026077"; MUTAGEN 253; /note="S->A: Slightly decreases CDE and ADERNA-binding."; /evidence="ECO:0000269|PubMed:25026077, ECO:0000269|PubMed:27010430"; MUTAGEN 259; /note="K->A: Strongly decreases CDE and ADERNA-binding."; /evidence="ECO:0000269|PubMed:25026077, ECO:0000269|PubMed:27010430"; MUTAGEN 260; /note="R->A: Strongly decreases CDE and ADERNA-binding. Increases target-mRNA expression. Abolishes CDERNA-binding and highly increases target-mRNA expression; when associated with A-239. Increases target-mRNA expression. Increases ICOS surface expression; when associated with A-220 and A-239."; /evidence="ECO:0000269|PubMed:25026077, ECO:0000269|PubMed:25282160, ECO:0000269|PubMed:27010430"; MUTAGEN 264; /note="S->A: Decreases CDERNA-binding."; /evidence="ECO:0000269|PubMed:25026077"; MUTAGEN 265; /note="S->Y: Decreases CDE and ADERNA-binding."; /evidence="ECO:0000269|PubMed:25026077, ECO:0000269|PubMed:27010430"; MUTAGEN 293; /note="E->A: No effect on CDERNA-binding."; /evidence="ECO:0000269|PubMed:25026077"; MUTAGEN 314; /note="K->A: No effect on CDERNA-binding."; /evidence="ECO:0000269|PubMed:25026077"; MUTAGEN 419; /note="C->R: No effect on RNA-binding."; /evidence="ECO:0000269|PubMed:23663784"; MUTAGEN 434; /note="C->R: No effect on localization to stress granules, reduces RNA-binding."; MUTAGEN 488; /note="R->G: No effect on cleavage."; /evidence="ECO:0000269|PubMed:25282160"; MUTAGEN 510; /note="R->G: Abolishes the formation of a preferential cleavage product. Abolishes protein cleavage; when associated with G-579."; /evidence="ECO:0000269|PubMed:25282160"; MUTAGEN 560; /note="R->G: No effect on cleavage."; /evidence="ECO:0000269|PubMed:25282160"; MUTAGEN 579; /note="R->G: Abolishes the formation of an alternative cleavage product. Abolishes protein cleavage; when associated with G-510."; /evidence="ECO:0000269|PubMed:25282160"; MUTAGEN 687..1130; /note="Missing: Failed to reduce poly(A) tailed ICOS mRNA. Failed to regulate the production of inflammatory cytokines."; /evidence="ECO:0000269|PubMed:31636267
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000250|UniProtKB:Q5TC82}.
uniprot
proteins
post_translational_modification
PTM: Proteolytically cleaved after Arg-510 and Arg-579 by MALT1 in activated CD4(+) T cells; cleavage at Arg-510 and Arg-579 is critical for promoting RC3H1 degradation in response to T-cell receptor (TCR) stimulation, and hence is necessary for prolonging the stability of a set of mRNAs controlling Th17 cell differentiation. {ECO:0000269|PubMed:25282160}.
uniprot
proteins
pubmed
15368895
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15917799
uniprot
proteins
pubmed
17242355
uniprot
proteins
pubmed
18172933
uniprot
proteins
pubmed
20412057
uniprot
proteins
pubmed
20639877
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21844204
uniprot
proteins
pubmed
23451046
uniprot
proteins
pubmed
23550652
uniprot
proteins
pubmed
23583642
uniprot
proteins
pubmed
23583643
uniprot
proteins
pubmed
23663784
uniprot
proteins
pubmed
25026077
uniprot
proteins
pubmed
25282160
uniprot
proteins
pubmed
25697406
uniprot
proteins
pubmed
26000482
uniprot
proteins
pubmed
27010430
uniprot
proteins
pubmed
29244194
uniprot
proteins
pubmed
31636267
uniprot
proteins
sequence_length
1130
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000269|PubMed:15917799, ECO:0000269|PubMed:20412057, ECO:0000269|PubMed:20639877, ECO:0000269|PubMed:23583642, ECO:0000269|PubMed:26000482}. Cytoplasmic granule {ECO:0000269|PubMed:26000482}. Note=During stress, such as that induced by arsenite treatment, localizes to cytosolic stress granules (PubMed:26000482). Localization to stress granules, but not to P-bodies, depends upon the RING-type zinc finger. ICOS repression may correlate with the localization to P-bodies, not to stress granules (PubMed:20639877). {ECO:0000269|PubMed:20639877, ECO:0000269|PubMed:26000482}.
uniprot
proteins