ID RC3H1_HUMAN Reviewed; 1133 AA. AC Q5TC82; B3KVK1; Q5W180; Q5W181; Q8IVE6; Q8N9V1; DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot. DT 21-DEC-2004, sequence version 1. DT 27-MAR-2024, entry version 159. DE RecName: Full=Roquin-1 {ECO:0000305}; DE Short=Roquin {ECO:0000305}; DE EC=2.3.2.27 {ECO:0000269|PubMed:26489670}; DE AltName: Full=RING finger and C3H zinc finger protein 1; DE AltName: Full=RING finger and CCCH-type zinc finger domain-containing protein 1; DE AltName: Full=RING finger protein 198; GN Name=RC3H1 {ECO:0000312|HGNC:HGNC:29434}; Synonyms=KIAA2025, RNF198; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 589-1133 (ISOFORM 1). RC TISSUE=Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 25-1133 (ISOFORM 1), AND TISSUE RP SPECIFICITY. RC TISSUE=Brain; RA Nagase T., Kikuno R., Ohara O.; RT "The nucleotide sequence of a long cDNA clone isolated from human."; RL Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases. RN [4] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-535, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [5] RP REVIEW. RX PubMed=23550652; DOI=10.1111/imr.12056; RA Heissmeyer V., Vogel K.U.; RT "Molecular control of Tfh-cell differentiation by Roquin family proteins."; RL Immunol. Rev. 253:273-289(2013). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-535 AND SER-863, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-462, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [8] RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, INVOLVEMENT IN IMDYSHI, VARIANT RP IMDYSHI 688-ARG--GLU-1133 DEL, AND CHARACTERIZATION OF VARIANT IMDYSHI RP 688-ARG--GLU-1133 DEL. RX PubMed=31636267; DOI=10.1038/s41467-019-12704-6; RA Tavernier S.J., Athanasopoulos V., Verloo P., Behrens G., Staal J., RA Bogaert D.J., Naesens L., De Bruyne M., Van Gassen S., Parthoens E., RA Ellyard J., Cappello J., Morris L.X., Van Gorp H., Van Isterdael G., RA Saeys Y., Lamkanfi M., Schelstraete P., Dehoorne J., Bordon V., RA Van Coster R., Lambrecht B.N., Menten B., Beyaert R., Vinuesa C.G., RA Heissmeyer V., Dullaers M., Haerynck F.; RT "A human immune dysregulation syndrome characterized by severe RT hyperinflammation with a homozygous nonsense Roquin-1 mutation."; RL Nat. Commun. 10:4779-4779(2019). RN [9] {ECO:0007744|PDB:4ULW} RP X-RAY CRYSTALLOGRAPHY (1.91 ANGSTROMS) OF 177-328, RNA-BINDING, MUTAGENESIS RP OF 219-ARG-LYS-220 AND 259-LYS-ARG-260, AND SUBUNIT. RX PubMed=25504471; DOI=10.1038/ncomms6701; RA Schuetz A., Murakawa Y., Rosenbaum E., Landthaler M., Heinemann U.; RT "Roquin binding to target mRNAs involves a winged helix-turn-helix motif."; RL Nat. Commun. 5:5701-5701(2014). RN [10] {ECO:0007744|PDB:4QIK, ECO:0007744|PDB:4QIL} RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 88-407 IN COMPLEX WITH RNA, RP FUNCTION, RNA-BINDING, SUBUNIT, AND MUTAGENESIS OF 135-ARG-LYS-136; RP ARG-164; 239-LYS-THR-240; 247-GLN--ARG-251; 318-GLN-SER-319 AND RP 322-ASP-LYS-323. RX PubMed=25026078; DOI=10.1038/nsmb.2857; RA Tan D., Zhou M., Kiledjian M., Tong L.; RT "The ROQ domain of Roquin recognizes mRNA constitutive-decay element and RT double-stranded RNA."; RL Nat. Struct. Mol. Biol. 21:679-685(2014). RN [11] {ECO:0007744|PDB:3X1O} RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 145-344 IN COMPLEX WITH RNA, RP FUNCTION, RNA-BINDING, SUBUNIT, AND INTERACTION WITH AGO2. RX PubMed=25697406; DOI=10.1038/ncomms7253; RA Srivastava M., Duan G., Kershaw N.J., Athanasopoulos V., Yeo J.H., Ose T., RA Hu D., Brown S.H., Jergic S., Patel H.R., Pratama A., Richards S., RA Verma A., Jones E.Y., Heissmeyer V., Preiss T., Dixon N.E., Chong M.M., RA Babon J.J., Vinuesa C.G.; RT "Roquin binds microRNA-146a and Argonaute2 to regulate microRNA RT homeostasis."; RL Nat. Commun. 6:6253-6253(2015). RN [12] {ECO:0007744|PDB:4YWQ} RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 159-328, FUNCTION, DOMAIN, RP CATALYTIC ACTIVITY, AND PATHWAY. RX PubMed=26489670; DOI=10.1038/srep15660; RA Zhang Q., Fan L., Hou F., Dong A., Wang Y.X., Tong Y.; RT "New Insights into the RNA-Binding and E3 Ubiquitin Ligase Activities of RT Roquins."; RL Sci. Rep. 5:15660-15660(2015). CC -!- FUNCTION: Post-transcriptional repressor of mRNAs containing a CC conserved stem loop motif, called constitutive decay element (CDE), CC which is often located in the 3'-UTR, as in HMGXB3, ICOS, IER3, NFKBID, CC NFKBIZ, PPP1R10, TNF, TNFRSF4 and in many more mRNAs (PubMed:25026078, CC PubMed:31636267). Cleaves translationally inactive mRNAs harboring a CC stem-loop (SL), often located in their 3'-UTRs, during the early phase CC of inflammation in a helicase UPF1-independent manner (By similarity). CC Binds to CDE and promotes mRNA deadenylation and degradation. This CC process does not involve miRNAs (By similarity). In follicular helper T CC (Tfh) cells, represses of ICOS and TNFRSF4 expression, thus preventing CC spontaneous Tfh cell differentiation, germinal center B-cell CC differentiation in the absence of immunization and autoimmunity (By CC similarity). In resting or LPS-stimulated macrophages, controls CC inflammation by suppressing TNF expression (By similarity). Also CC recognizes CDE in its own mRNA and in that of paralogous RC3H2, CC possibly leading to feedback loop regulation (By similarity). CC Recognizes and binds mRNAs containing a hexaloop stem-loop motif, CC called alternative decay element (ADE) (By similarity). Together with CC ZC3H12A, destabilizes TNFRSF4/OX40 mRNA by binding to the conserved CC stem loop structure in its 3'UTR (By similarity). Able to interact with CC double-stranded RNA (dsRNA) (PubMed:25504471, PubMed:25026078). miRNA- CC binding protein that regulates microRNA homeostasis. Enhances DICER- CC mediated processing of pre-MIR146a but reduces mature MIR146a levels CC through an increase of 3' end uridylation. Both inhibits ICOS mRNA CC expression and they may act together to exert the suppression CC (PubMed:25697406, PubMed:31636267). Acts as a ubiquitin E3 ligase. CC Pairs with E2 enzymes UBE2A, UBE2B, UBE2D2, UBE2F, UBE2G1, UBE2G2 and CC UBE2L3 and produces polyubiquitin chains (PubMed:26489670). Shows the CC strongest activity when paired with UBE2N:UBE2V1 or UBE2N:UBE2V2 E2 CC complexes and generate both short and long polyubiquitin chains CC (PubMed:26489670). {ECO:0000250|UniProtKB:Q4VGL6, CC ECO:0000269|PubMed:25026078, ECO:0000269|PubMed:25504471, CC ECO:0000269|PubMed:25697406, ECO:0000269|PubMed:26489670, CC ECO:0000269|PubMed:31636267}. CC -!- CATALYTIC ACTIVITY: CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:26489670}; CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000269|PubMed:26489670}. CC -!- SUBUNIT: Able to homodimerize (PubMed:25504471, PubMed:25026078, CC PubMed:25697406). Interacts with DDX6 and EDC4 (By similarity). CC Interacts with CCR4-NOT deadenylase complex (PubMed:31636267). CC Interacts with RC3H1; the interaction is RNA independent CC (PubMed:25697406). {ECO:0000250|UniProtKB:Q4VGL6, CC ECO:0000269|PubMed:25026078, ECO:0000269|PubMed:25504471, CC ECO:0000269|PubMed:25697406, ECO:0000269|PubMed:31636267}. CC -!- INTERACTION: CC Q5TC82; Q66GS9: CEP135; NbExp=4; IntAct=EBI-7958436, EBI-1046993; CC -!- SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000269|PubMed:31636267}. CC Cytoplasmic granule {ECO:0000250|UniProtKB:Q4VGL6}. Note=During stress, CC such as that induced by arsenite treatment, localizes to cytosolic CC stress granules (By similarity). Localization to stress granules, but CC not to P-bodies, depends upon the RING-type zinc finger (By CC similarity). ICOS repression may correlate with the localization to P- CC bodies, not to stress granules (By similarity). CC {ECO:0000250|UniProtKB:Q4VGL6}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q5TC82-1; Sequence=Displayed; CC Name=2; CC IsoId=Q5TC82-2; Sequence=VSP_015015, VSP_015016; CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed at higher level in CC cerebellum, spleen, ovary and liver. {ECO:0000269|Ref.3}. CC -!- DOMAIN: The RING-type zinc finger is required for proper localization CC to stress granules, but not to P-bodies. CC {ECO:0000250|UniProtKB:Q4VGL6}. CC -!- DOMAIN: The ROQ region is required for CDE RNA-binding CC (PubMed:25504471, PubMed:25026078). Has 2 separate RNA-binding sites, CC one for CDE RNA and the other for dsRNA, both sites are important for CC mRNA decay (PubMed:25026078). ADE RNA-binding involves an extended CC binding surface on the ROQ region with a number of additional residues CC compared with the CDE RNA (By similarity). It may also be involved in CC localization to stress granules (By similarity). CC {ECO:0000250|UniProtKB:Q4VGL6, ECO:0000269|PubMed:25026078, CC ECO:0000269|PubMed:25504471}. CC -!- DOMAIN: HEPN (higher eukaryotes and prokaryotes nucleotide-binding) are CC observed in both N- and C-terminal sides of ROQ domain with 3D CC structure even if they are poredcted on the basis of sequence. CC {ECO:0000269|PubMed:26489670}. CC -!- PTM: Proteolytically cleaved after Arg-510 and Arg-579 by MALT1 in CC activated CD4(+) T cells; cleavage at Arg-510 and Arg-579 is critical CC for promoting RC3H1 degradation in response to T-cell receptor (TCR) CC stimulation, and hence is necessary for prolonging the stability of a CC set of mRNAs controlling Th17 cell differentiation. CC {ECO:0000250|UniProtKB:Q4VGL6}. CC -!- DISEASE: Immune dysregulation and systemic hyperinflammation syndrome CC (IMDYSHI) [MIM:618998]: An autosomal recessive disorder characterized CC by systemic hyperinflammation in the absence of an infectious agent or CC autoimmune trigger. Features include lymphadenopathy, CC hepatosplenomegaly, recurrent fever, and laboratory evidence of immune CC dysregulation with abnormal immune cell populations and increased serum CC levels of inflammatory cytokines. {ECO:0000269|PubMed:31636267}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SEQUENCE CAUTION: CC Sequence=BAC04186.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK093501; BAC04186.1; ALT_INIT; mRNA. DR EMBL; AK122948; BAG53813.1; -; mRNA. DR EMBL; AL121983; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL136170; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AB095945; BAC23121.1; -; mRNA. DR CCDS; CCDS30940.1; -. [Q5TC82-1] DR CCDS; CCDS72987.1; -. [Q5TC82-2] DR RefSeq; NP_001287779.1; NM_001300850.1. DR RefSeq; NP_001287780.1; NM_001300851.1. [Q5TC82-2] DR RefSeq; NP_001287781.1; NM_001300852.1. DR RefSeq; NP_742068.1; NM_172071.3. [Q5TC82-1] DR PDB; 3X1O; X-ray; 2.20 A; A/B=145-344. DR PDB; 4QIK; X-ray; 1.90 A; A/B=88-407. DR PDB; 4QIL; X-ray; 2.90 A; A/B=88-407. DR PDB; 4ULW; X-ray; 1.91 A; A/B=177-328. DR PDB; 4YWQ; X-ray; 1.70 A; A/B=159-328. DR PDBsum; 3X1O; -. DR PDBsum; 4QIK; -. DR PDBsum; 4QIL; -. DR PDBsum; 4ULW; -. DR PDBsum; 4YWQ; -. DR AlphaFoldDB; Q5TC82; -. DR BMRB; Q5TC82; -. DR SMR; Q5TC82; -. DR BioGRID; 127186; 677. DR CORUM; Q5TC82; -. DR IntAct; Q5TC82; 8. DR MINT; Q5TC82; -. DR STRING; 9606.ENSP00000356669; -. DR GlyGen; Q5TC82; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q5TC82; -. DR PhosphoSitePlus; Q5TC82; -. DR BioMuta; RC3H1; -. DR DMDM; 73621450; -. DR EPD; Q5TC82; -. DR jPOST; Q5TC82; -. DR MassIVE; Q5TC82; -. DR MaxQB; Q5TC82; -. DR PaxDb; 9606-ENSP00000356669; -. DR PeptideAtlas; Q5TC82; -. DR ProteomicsDB; 64943; -. [Q5TC82-1] DR ProteomicsDB; 64944; -. [Q5TC82-2] DR Pumba; Q5TC82; -. DR Antibodypedia; 34400; 154 antibodies from 22 providers. DR DNASU; 149041; -. DR Ensembl; ENST00000258349.8; ENSP00000258349.4; ENSG00000135870.12. [Q5TC82-1] DR Ensembl; ENST00000367694.2; ENSP00000356667.2; ENSG00000135870.12. [Q5TC82-2] DR Ensembl; ENST00000367696.7; ENSP00000356669.2; ENSG00000135870.12. [Q5TC82-1] DR GeneID; 149041; -. DR KEGG; hsa:149041; -. DR MANE-Select; ENST00000367696.7; ENSP00000356669.2; NM_172071.4; NP_742068.1. DR UCSC; uc001gju.5; human. [Q5TC82-1] DR AGR; HGNC:29434; -. DR CTD; 149041; -. DR DisGeNET; 149041; -. DR GeneCards; RC3H1; -. DR HGNC; HGNC:29434; RC3H1. DR HPA; ENSG00000135870; Low tissue specificity. DR MalaCards; RC3H1; -. DR MIM; 609424; gene. DR MIM; 618998; phenotype. DR neXtProt; NX_Q5TC82; -. DR OpenTargets; ENSG00000135870; -. DR PharmGKB; PA142671090; -. DR VEuPathDB; HostDB:ENSG00000135870; -. DR eggNOG; KOG3161; Eukaryota. DR GeneTree; ENSGT00940000157143; -. DR HOGENOM; CLU_004948_0_0_1; -. DR InParanoid; Q5TC82; -. DR OMA; WGSSPYS; -. DR OrthoDB; 2909513at2759; -. DR PhylomeDB; Q5TC82; -. DR TreeFam; TF317698; -. DR PathwayCommons; Q5TC82; -. DR SignaLink; Q5TC82; -. DR SIGNOR; Q5TC82; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 149041; 44 hits in 1196 CRISPR screens. DR ChiTaRS; RC3H1; human. DR GenomeRNAi; 149041; -. DR Pharos; Q5TC82; Tbio. DR PRO; PR:Q5TC82; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q5TC82; Protein. DR Bgee; ENSG00000135870; Expressed in tibialis anterior and 195 other cell types or tissues. DR GO; GO:0010494; C:cytoplasmic stress granule; ISS:BHF-UCL. DR GO; GO:0000932; C:P-body; IMP:UniProtKB. DR GO; GO:1905762; F:CCR4-NOT complex binding; IMP:UniProtKB. DR GO; GO:0003725; F:double-stranded RNA binding; IDA:UniProtKB. DR GO; GO:0035198; F:miRNA binding; ISS:UniProtKB. DR GO; GO:0003730; F:mRNA 3'-UTR binding; ISS:BHF-UCL. DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0035613; F:RNA stem-loop binding; IDA:UniProtKB. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB. DR GO; GO:0061158; P:3'-UTR-mediated mRNA destabilization; ISS:UniProtKB. DR GO; GO:0001782; P:B cell homeostasis; IEA:Ensembl. DR GO; GO:0071347; P:cellular response to interleukin-1; ISS:UniProtKB. DR GO; GO:0048535; P:lymph node development; IEA:Ensembl. DR GO; GO:0046007; P:negative regulation of activated T cell proliferation; ISS:BHF-UCL. DR GO; GO:0030889; P:negative regulation of B cell proliferation; ISS:BHF-UCL. DR GO; GO:0002635; P:negative regulation of germinal center formation; ISS:BHF-UCL. DR GO; GO:2000320; P:negative regulation of T-helper 17 cell differentiation; ISS:UniProtKB. DR GO; GO:0045623; P:negative regulation of T-helper cell differentiation; ISS:BHF-UCL. DR GO; GO:0000956; P:nuclear-transcribed mRNA catabolic process; IDA:UniProtKB. DR GO; GO:0000288; P:nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; IBA:GO_Central. DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; ISS:UniProtKB. DR GO; GO:0033962; P:P-body assembly; ISS:BHF-UCL. DR GO; GO:1901224; P:positive regulation of non-canonical NF-kappaB signal transduction; IEA:Ensembl. DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; ISS:BHF-UCL. DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB. DR GO; GO:0002634; P:regulation of germinal center formation; ISS:BHF-UCL. DR GO; GO:2000628; P:regulation of miRNA metabolic process; ISS:UniProtKB. DR GO; GO:0043488; P:regulation of mRNA stability; ISS:BHF-UCL. DR GO; GO:1900151; P:regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; IMP:UniProtKB. DR GO; GO:0050856; P:regulation of T cell receptor signaling pathway; ISS:BHF-UCL. DR GO; GO:0048536; P:spleen development; IEA:Ensembl. DR GO; GO:0043029; P:T cell homeostasis; IEA:Ensembl. DR GO; GO:0042098; P:T cell proliferation; IEA:Ensembl. DR GO; GO:0050852; P:T cell receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0061470; P:T follicular helper cell differentiation; IEA:Ensembl. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central. DR CDD; cd16781; mRING-HC-C3HC3D_Roquin1; 1. DR Gene3D; 1.20.120.1790; -; 1. DR Gene3D; 4.10.1000.10; Zinc finger, CCCH-type; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR041523; ROQ_II. DR InterPro; IPR048575; Roquin_1_2-like_ROQ. DR InterPro; IPR000571; Znf_CCCH. DR InterPro; IPR036855; Znf_CCCH_sf. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR InterPro; IPR017907; Znf_RING_CS. DR PANTHER; PTHR13139; RING FINGER AND CCCH-TYPE ZINC FINGER DOMAIN-CONTAINING PROTEIN; 1. DR PANTHER; PTHR13139:SF6; ROQUIN-1; 1. DR Pfam; PF18386; ROQ_II; 1. DR Pfam; PF21206; Roquin_1_2-like_ROQ; 1. DR Pfam; PF14634; zf-RING_5; 1. DR SMART; SM00184; RING; 1. DR SMART; SM00356; ZnF_C3H1; 1. DR SUPFAM; SSF90229; CCCH zinc finger; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR PROSITE; PS50103; ZF_C3H1; 1. DR PROSITE; PS00518; ZF_RING_1; 1. DR PROSITE; PS50089; ZF_RING_2; 1. DR Genevisible; Q5TC82; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Disease variant; KW Metal-binding; Phosphoprotein; Reference proteome; Repeat; RNA-binding; KW Transferase; Zinc; Zinc-finger. FT CHAIN 1..1133 FT /note="Roquin-1" FT /id="PRO_0000055965" FT ZN_FING 14..54 FT /note="RING-type; degenerate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175" FT ZN_FING 413..441 FT /note="C3H1-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723" FT REGION 89..173 FT /note="HEPN-N" FT /evidence="ECO:0000269|PubMed:26489670" FT REGION 174..326 FT /note="ROQ" FT /evidence="ECO:0000269|PubMed:25504471, FT ECO:0000269|PubMed:26489670" FT REGION 327..396 FT /note="HEPN-C" FT /evidence="ECO:0000269|PubMed:26489670" FT REGION 505..543 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1000..1019 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1058..1078 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1094..1133 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 14 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q4VGL6" FT BINDING 17 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q4VGL6" FT BINDING 33 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q4VGL6" FT BINDING 35 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q4VGL6" FT BINDING 38 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q4VGL6" FT BINDING 50 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q4VGL6" FT BINDING 53 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q4VGL6" FT SITE 510 FT /note="Cleavage; by MALT1" FT /evidence="ECO:0000250|UniProtKB:Q4VGL6" FT SITE 579 FT /note="Cleavage; by MALT1" FT /evidence="ECO:0000250|UniProtKB:Q4VGL6" FT MOD_RES 462 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 531 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q4VGL6" FT MOD_RES 535 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 863 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1110 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q4VGL6" FT VAR_SEQ 988..996 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_015015" FT VAR_SEQ 1084 FT /note="S -> SS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_015016" FT VARIANT 688..1133 FT /note="Missing (in IMDYSHI; decreased protein abundance; FT loss of localization to P-bodies; decreased interaction FT with CCR4-NOT deadenylase complex; loss of function in FT regulation of deadenylation-dependent decapping of FT nuclear-transcribed mRNA; failed to regulate the production FT of inflammatory cytokines)" FT /evidence="ECO:0000269|PubMed:31636267" FT /id="VAR_084832" FT MUTAGEN 135..136 FT /note="RK->EE: No effect on CDERNA-binding but abolishes FT dsRNA binding; when associated with E-164 or A-322-323-A." FT /evidence="ECO:0000269|PubMed:25026078" FT MUTAGEN 164 FT /note="R->E: No effect on CDERNA-binding but abolishes FT dsRNA binding; when associated with 135-E-E-136." FT /evidence="ECO:0000269|PubMed:25026078" FT MUTAGEN 219..220 FT /note="RK->AA: Strongly decreases binding to RNA containing FT CDE stem-loop motifs. Abolishes binding to RNA containing FT CDE stem-loop motifs and dsRNA; when associated with FT 259-A-A-260." FT /evidence="ECO:0000269|PubMed:25504471" FT MUTAGEN 239..240 FT /note="KT->EA: Abolishes CDERNA-binding but no effect on FT dsRNA binding." FT /evidence="ECO:0000269|PubMed:25026078" FT MUTAGEN 247..251 FT /note="QLLYR->ALLAE: Abolishes CDERNA-binding but no effect FT on dsRNA binding." FT /evidence="ECO:0000269|PubMed:25026078" FT MUTAGEN 259..260 FT /note="KR->AA: Strongly decreases binding to RNA containing FT CDE stem-loop motifs. Abolishes binding to RNA containing FT CDE stem-loop motifs and dsRNA; when associated with FT 219-A-A-220." FT /evidence="ECO:0000269|PubMed:25504471" FT MUTAGEN 318..319 FT /note="QS->AA: Slightly reduces stem-loop RNA and dsRNA FT binding." FT /evidence="ECO:0000269|PubMed:25026078" FT MUTAGEN 322..323 FT /note="DK->AA: No effect on CDERNA-binding but abolishes FT dsRNA binding; when associated with 135-E-E-136." FT /evidence="ECO:0000269|PubMed:25026078" FT CONFLICT 986 FT /note="L -> P (in Ref. 1; BAC04186)" FT /evidence="ECO:0000305" FT HELIX 92..108 FT /evidence="ECO:0007829|PDB:4QIK" FT TURN 112..115 FT /evidence="ECO:0007829|PDB:4QIK" FT STRAND 119..121 FT /evidence="ECO:0007829|PDB:4QIK" FT HELIX 122..124 FT /evidence="ECO:0007829|PDB:4QIK" FT STRAND 127..129 FT /evidence="ECO:0007829|PDB:4QIK" FT HELIX 131..142 FT /evidence="ECO:0007829|PDB:4QIK" FT HELIX 148..173 FT /evidence="ECO:0007829|PDB:4QIK" FT TURN 176..178 FT /evidence="ECO:0007829|PDB:4QIK" FT HELIX 179..189 FT /evidence="ECO:0007829|PDB:4YWQ" FT HELIX 197..211 FT /evidence="ECO:0007829|PDB:4YWQ" FT STRAND 216..218 FT /evidence="ECO:0007829|PDB:4YWQ" FT HELIX 219..233 FT /evidence="ECO:0007829|PDB:4YWQ" FT HELIX 239..251 FT /evidence="ECO:0007829|PDB:4YWQ" FT STRAND 255..258 FT /evidence="ECO:0007829|PDB:4YWQ" FT STRAND 266..269 FT /evidence="ECO:0007829|PDB:4YWQ" FT HELIX 271..273 FT /evidence="ECO:0007829|PDB:4YWQ" FT HELIX 276..293 FT /evidence="ECO:0007829|PDB:4YWQ" FT HELIX 300..308 FT /evidence="ECO:0007829|PDB:4YWQ" FT STRAND 309..312 FT /evidence="ECO:0007829|PDB:4YWQ" FT HELIX 314..325 FT /evidence="ECO:0007829|PDB:4YWQ" FT HELIX 329..342 FT /evidence="ECO:0007829|PDB:4QIK" FT TURN 343..345 FT /evidence="ECO:0007829|PDB:4QIK" FT HELIX 350..353 FT /evidence="ECO:0007829|PDB:4QIK" FT HELIX 354..361 FT /evidence="ECO:0007829|PDB:4QIK" FT HELIX 374..397 FT /evidence="ECO:0007829|PDB:4QIK" SQ SEQUENCE 1133 AA; 125736 MW; E307838DF80A7099 CRC64; MPVQAPQWTD FLSCPICTQT FDETIRKPIS LGCGHTVCKM CLNKLHRKAC PFDQTTINTD IELLPVNSAL LQLVGAQVPE QQPITLCSGV EDTKHYEEAK KCVEELALYL KPLSSARGVG LNSTTQSVLS RPMQRKLVTL VHCQLVEEEG RIRAMRAARS LGERTVTELI LQHQNPQQLS SNLWAAVRAR GCQFLGPAMQ EEALKLVLLA LEDGSALSRK VLVLFVVQRL EPRFPQASKT SIGHVVQLLY RASCFKVTKR DEDSSLMQLK EEFRTYEALR REHDSQIVQI AMEAGLRIAP DQWSSLLYGD QSHKSHMQSI IDKLQTPASF AQSVQELTIA LQRTGDPANL NRLRPHLELL ANIDPSPDAP PPTWEQLENG LVAVRTVVHG LVDYIQNHSK KGADQQQPPQ HSKYKTYMCR DMKQRGGCPR GASCTFAHSQ EELEKFRKMN KRLVPRRPLS ASLGQLNEVG LPSAAILPDE GAVDLPSRKP PALPNGIVST GNTVTQLIPR GTDPSYDSSL KPGKIDHLSS SAPGSPPDLL ESVPKSISAL PVNPHSIPPR GPADLPPMPV TKPLQMVPRG SQLYPAQQTD VYYQDPRGAA PPFEPAPYQQ GMYYTPPPQC VSRFVRPPPS APEPAPPYLD HYPPYLQERV VNSQYGTQPQ QYPPIYPSHY DGRRVYPAPS YTREEIFRES PIPIEIPPAA VPSYVPESRE RYQQIESYYP VAPHPTQIRP SYLREPPYSR LPPPPQPHPS LDELHRRRKE IMAQLEERKV ISPPPFAPSP TLPPTFHPEE FLDEDLKVAG KYKGNDYSQY SPWSCDTIGS YIGTKDAKPK DVVAAGSVEM MNVESKGMRD QRLDLQRRAA ETSDDDLIPF GDRPTVSRFG AISRTSKTIY QGAGPMQAMA PQGAPTKSIN ISDYSPYGTH GGWGASPYSP HQNIPSQGHF SERERISMSE VASHGKPLPS AEREQLRLEL QQLNHQISQQ TQLRGLEAVS NRLVLQREAN TLAGQSQPPP PPPPKWPGMI SSEQLSLELH QVEREIGKRT RELSMENQCS LDMKSKLNTS KQAENGQPEP QNKVPAEDLT LTFSDVPNGS ALTQENISLL SNKTSSLNLS EDPEGGGDNN DSQRSGVTPS SAP //