RC3H1_HUMAN
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 03-AUG-2022, entry version 150.
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 -!- 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};
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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; 666.
DR CORUM; Q5TC82; -.
DR IntAct; Q5TC82; 7.
DR MINT; Q5TC82; -.
DR STRING; 9606.ENSP00000356669; -.
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; Q5TC82; -.
DR PeptideAtlas; Q5TC82; -.
DR PRIDE; Q5TC82; -.
DR ProteomicsDB; 64943; -. [Q5TC82-1]
DR ProteomicsDB; 64944; -. [Q5TC82-2]
DR Antibodypedia; 34400; 146 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 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; YGTHSGW; -.
DR OrthoDB; 1009668at2759; -.
DR PhylomeDB; Q5TC82; -.
DR TreeFam; TF317698; -.
DR PathwayCommons; Q5TC82; -.
DR SignaLink; Q5TC82; -.
DR SIGNOR; Q5TC82; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 149041; 36 hits in 1120 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 193 other tissues.
DR Genevisible; Q5TC82; HS.
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; ISS:UniProtKB.
DR GO; GO:0033962; P:P-body assembly; ISS:BHF-UCL.
DR GO; GO:0061014; P:positive regulation of mRNA catabolic process; ISS:UniProtKB.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; 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 Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR032671; RC3H1.
DR InterPro; IPR041523; ROQ_II.
DR InterPro; IPR027370; Znf-RING_LisH.
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:SF6; PTHR13139:SF6; 1.
DR Pfam; PF18386; ROQ_II; 1.
DR Pfam; PF13445; zf-RING_UBOX; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00356; ZnF_C3H1; 1.
DR SUPFAM; SSF90229; SSF90229; 1.
DR PROSITE; PS50103; ZF_C3H1; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
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 nuclear-
FT transcribed mRNA; failed to regulate the production of
FT inflammatory cytokines)"
FT /evidence="ECO:0000269|PubMed:31636267"
FT /id="VAR_084832"
FT MUTAGEN 135..136
FT /note="RK->EE: No effect on CDE RNA-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 CDE RNA-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 259-A-
FT A-260."
FT /evidence="ECO:0000269|PubMed:25504471"
FT MUTAGEN 239..240
FT /note="KT->EA: Abolishes CDE RNA-binding but no effect on
FT dsRNA binding."
FT /evidence="ECO:0000269|PubMed:25026078"
FT MUTAGEN 247..251
FT /note="QLLYR->ALLAE: Abolishes CDE RNA-binding but no
FT effect 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 219-A-
FT 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 CDE RNA-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
