Protein: Roquin-2 (EC 2.3.2.27) (Membrane-associated nucleic acid-binding protein) (RING finger and CCCH-type zinc finger domain-containing protein 2) (RING-type E3 ubiquitin transferase Roquin-2) (P0C090)
Organism: Mus musculus (Mouse)
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 and in many more mRNAs. Binds to CDE and promotes mRNA deadenylation and degradation. This process does not involve miRNAs. In follicular helper T (Tfh) cells, represses of ICOS and TNFRSF4 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 RC3H1, possibly leading to feedback loop regulation. 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. 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. Acts as a ubiquitin E3 ligase. Pairs with E2 enzymes UBE2B, UBE2D2, UBE2E2, UBE2E3, UBE2G2, UBE2K and UBE2Q2 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. Involved in the ubiquitination of MAP3K5 (By similarity). Able to interact with double-stranded RNA (dsRNA).
Subcellular location: Cytoplasm, P-body {ECO:0000269|PubMed:23583642}. Note=During stress, such as that induced by arsenite, localizes to cytosolic stress granules. Localization to stress granules, but not to P-bodies, depends upon the RING-type zinc finger.
Interaction partners:
- CCR4-NOT transcription complex subunit 1
- Roquin-1
- Deubiquitinase MYSM1
- Endoribonuclease ZC3H12A
Sequence:
MPVQAAQWTEFLSCPICYNEFDENVHKPISLGCSHTVCKTCLNKLHRKACPFDQTAINTDIDVLPVNFALLQLVGAQVPDHQSIKLSNLGENKHYEVAKKCVEDLALYLKPLSGGKGVASLNQSALSRPMQRKLVTLVNCQLVEEEGRVRAMRAARSLGERTVTELILQHQNPQQLSANLWAAVRARGCQFLGPAMQEEALKLVLLALEDGSALSRKVLVLFVVQRLEPRFPQASKTSIGHVVQLLYRASCFKVTKRDEDSSLMQLKEEFRSYEALRREHDAQIVHIAMEAGLRISPEQWSSLLYGDLAHKSHMQSIIDKLQSPESFAKSVQELTIVLQRTGDPANLNRLRPHLELLANIDPNPDAVSPTWEQLENAMVAVKTVVHGLVDFIQNYSRKGHETPQPQPNSKYKTSMCRDLRQQGGCPRGTNCTFAHSQEELEKYRLRNKKMSATVRTFPLLNKVGVNSTVTTTAGNVISVIGSTETTGKIVASTNGISNTESSVSQLIPRGTDSAVRTLETVKKVGKVGTNAQNAGPSAESVSENKIGSPPKTPVSNAAATSAGPSNFGTELNSLPPKSSPFLTRVPVYPQHSESIQYFQDPRTQIPFEVPQYPQTGYYPPPPTVPAGVTPCVPRFVRSSNVPESSLPPASMPYADHYSTFSPRDRMNSSPYQPPPPQQYGPVPPVPSGMYAPVYDSRRIWRPAMYQRDDIIRSNSLPPMDVMHSSVYQTSLRERYNSLDGYYSVACQPPNDPRTTVPLPREPCGHLKTSCEEQLRRKPDQWTQYHTQKTPVSSTLPVATQSPTPPSPLFSVDFRSDFSESVSGAKFEEDHLSHYSPWSCGTIGSCINAIDSEPKDVIANSNAVLMDLDSGDVKRRVHLFEAQRRTKEEDPIIPFSDGPIISKWGAISRSSRTGYHTTDPVQATASQGSATKPISVSDYVPYVNAVDSRWSSYGNDATSSAHYIERDRFIVTDLSGHRKHSSTGDLLSIELQQAKSNSLLLQREANALAMQQKWNSLDEGRHLTLNLLSKEIELRNGENDYTEDTVDTKPDRDIELELSALDTDEPDGQSEQIEEILDIQLGISSQNDQLLNGTAVENGHPAQQHQKDPGKPKRQSLGEDHVILEEQKPILPVTSCFSQPRPMSISSASCLPITTSVSVGNLILKTHVMSEDKNDFLKPIANGKMVNS