RC3H2_HUMAN
ID RC3H2_HUMAN Reviewed; 1191 AA.
AC Q9HBD1; Q4VXB1; Q5JPD7; Q86ST6; Q8N3D6; Q96F27; Q9H5J2; Q9HBD2; Q9NWN9;
AC Q9NXE1;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2005, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Roquin-2;
DE EC=2.3.2.27 {ECO:0000269|PubMed:26249698};
DE AltName: Full=Membrane-associated nucleic acid-binding protein;
DE AltName: Full=RING finger and CCCH-type zinc finger domain-containing protein 2;
DE AltName: Full=RING finger protein 164;
DE AltName: Full=RING-type E3 ubiquitin transferase Roquin-2 {ECO:0000305};
GN Name=RC3H2; Synonyms=MNAB, RNF164;
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 [MRNA] (ISOFORM 1), NUCLEIC ACID-BINDING, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Monocyte;
RX PubMed=10938276; DOI=10.1074/jbc.m004461200;
RA Siess D.C., Vedder C.T., Merkens L.S., Tanaka T., Freed A.C., McCoy S.L.,
RA Heinrich M.C., Deffebach M.E., Bennett R.M., Hefeneider S.H.;
RT "A human gene coding for a membrane-associated nucleic acid-binding
RT protein.";
RL J. Biol. Chem. 275:33655-33662(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 509-1191.
RC TISSUE=Hepatoma;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 337-1191 (ISOFORM 4).
RC TISSUE=Lymph node, and Melanoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 42-1191 (ISOFORM 5).
RC TISSUE=Brain, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-549, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=20412057; DOI=10.1111/j.1742-4658.2010.07628.x;
RA Athanasopoulos V., Barker A., Yu D., Tan A.H., Srivastava M., Contreras N.,
RA Wang J., Lam K.P., Brown S.H., Goodnow C.C., Dixon N.E., Leedman P.J.,
RA Saint R., Vinuesa C.G.;
RT "The ROQUIN family of proteins localizes to stress granules via the ROQ
RT domain and binds target mRNAs.";
RL FEBS J. 277:2109-2127(2010).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-808, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [10]
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-983 AND SER-1119, 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 [12]
RP FUNCTION, INTERACTION WITH MAP3K5, AND MUTAGENESIS OF CYS-33.
RX PubMed=24448648; DOI=10.1126/scisignal.2004822;
RA Maruyama T., Araki T., Kawarazaki Y., Naguro I., Heynen S., Aza-Blanc P.,
RA Ronai Z., Matsuzawa A., Ichijo H.;
RT "Roquin-2 promotes ubiquitin-mediated degradation of ASK1 to regulate
RT stress responses.";
RL Sci. Signal. 7:RA8-RA8(2014).
RN [13]
RP FUNCTION.
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 [14]
RP FUNCTION.
RX PubMed=29186683; DOI=10.1016/j.celrep.2017.11.007;
RA Hirata Y., Katagiri K., Nagaoka K., Morishita T., Kudoh Y., Hatta T.,
RA Naguro I., Kano K., Udagawa T., Natsume T., Aoki J., Inada T., Noguchi T.,
RA Ichijo H., Matsuzawa A.;
RT "TRIM48 Promotes ASK1 Activation and Cell Death through Ubiquitination-
RT Dependent Degradation of the ASK1-Negative Regulator PRMT1.";
RL Cell Rep. 21:2447-2457(2017).
RN [15] {ECO:0007744|PDB:4ZLC, ECO:0007744|PDB:4ZLD}
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 171-325 IN COMPLEX WITH RNA, AND
RP RNA-BINDING.
RX PubMed=26249698; DOI=10.1107/s2053230x15011887;
RA Sakurai S., Ohto U., Shimizu T.;
RT "Structure of human Roquin-2 and its complex with constitutive-decay
RT element RNA.";
RL Acta Crystallogr. F 71:1048-1054(2015).
RN [16] {ECO:0007744|PDB:4Z30, ECO:0007744|PDB:4Z31}
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 87-404, MUTAGENESIS OF
RP 244-GLN--ARG-248 AND SER-323, FUNCTION, CATALYTIC ACTIVITY, PATHWAY,
RP ACTIVITY REGULATION, AND DOMAIN.
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 and in many more mRNAs. Binds to CDE and promotes
CC mRNA deadenylation and degradation. This process does not involve
CC miRNAs. In follicular helper T (Tfh) cells, represses of ICOS and
CC TNFRSF4 expression, thus preventing spontaneous Tfh cell
CC differentiation, germinal center B-cell differentiation in the absence
CC of immunization and autoimmunity. In resting or LPS-stimulated
CC macrophages, controls inflammation by suppressing TNF expression. Also
CC recognizes CDE in its own mRNA and in that of paralogous RC3H1,
CC possibly leading to feedback loop regulation (By similarity). 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). Acts as a ubiquitin E3 ligase. Pairs with E2 enzymes
CC UBE2B, UBE2D2, UBE2E2, UBE2E3, UBE2G2, UBE2K and UBE2Q2 and produces
CC polyubiquitin chains (PubMed:26489670). Shows the strongest activity
CC when paired with UBE2N:UBE2V1 or UBE2N:UBE2V2 E2 complexes and generate
CC both short and long polyubiquitin chains (PubMed:26489670). Involved in
CC the ubiquitination of MAP3K5 (PubMed:24448648, PubMed:26489670,
CC PubMed:29186683). Able to interact with double-stranded RNA (dsRNA)
CC (PubMed:26489670). {ECO:0000250|UniProtKB:P0C090,
CC ECO:0000269|PubMed:24448648, ECO:0000269|PubMed:26489670,
CC ECO:0000269|PubMed:29186683}.
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 ECO:0000303|PubMed:24448648};
CC -!- ACTIVITY REGULATION: Binding to dsRNA, but not CDE RNA, crosstalks with
CC the E3 ubiquitin ligase activity and may inhibit ubiquitination.
CC {ECO:0000269|PubMed:26489670}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:24448648, ECO:0000269|PubMed:26489670}.
CC -!- SUBUNIT: Interacts with EDC4. Interacts with CCR4-NOT deadenylase
CC complex (By similarity). Interacts with MAP3K5; the interaction is
CC probably stimulus-dependent (PubMed:24448648).
CC {ECO:0000250|UniProtKB:P0C090, ECO:0000269|PubMed:24448648}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000250}. Note=During
CC stress, such as that induced by arsenite, localizes to cytosolic stress
CC granules. Localization to stress granules, but not to P-bodies, depends
CC upon the RING-type zinc finger. {ECO:0000269|PubMed:20412057}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1;
CC IsoId=Q9HBD1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9HBD1-2; Sequence=VSP_015021, VSP_015022;
CC Name=3;
CC IsoId=Q9HBD1-3; Sequence=VSP_015020, VSP_015023;
CC Name=4;
CC IsoId=Q9HBD1-4; Sequence=VSP_015024;
CC Name=5;
CC IsoId=Q9HBD1-5; Sequence=VSP_015018, VSP_015019;
CC Name=6;
CC IsoId=Q9HBD1-6; Sequence=VSP_015017, VSP_015024;
CC -!- TISSUE SPECIFICITY: Expressed in spleen, testis, ovary and small
CC intestine. {ECO:0000269|PubMed:10938276}.
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. Has 2 separate
CC RNA-binding sites, one for CDE RNA and the other for dsRNA
CC (PubMed:26249698). It may also be involved in localization to stress
CC granules (By similarity). {ECO:0000250|UniProtKB:Q4VGL6,
CC ECO:0000269|PubMed:26249698}.
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-509 and Arg-585 by MALT1 in
CC activated CD4(+) T cells; cleavage at Arg-509 and Arg-585 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:P0C090}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91340.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB15634.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF255303; AAG00432.1; -; mRNA.
DR EMBL; AF255304; AAG00433.1; -; mRNA.
DR EMBL; AK000308; BAA91073.1; -; mRNA.
DR EMBL; AK000720; BAA91340.1; ALT_INIT; mRNA.
DR EMBL; AK027042; BAB15634.1; ALT_INIT; mRNA.
DR EMBL; AL833177; CAI46182.1; -; mRNA.
DR EMBL; AL834431; CAD39091.1; -; mRNA.
DR EMBL; AC007066; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL359512; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471090; EAW87547.1; -; Genomic_DNA.
DR EMBL; BC011688; AAH11688.2; -; mRNA.
DR EMBL; BC044642; AAH44642.1; -; mRNA.
DR CCDS; CCDS43874.1; -. [Q9HBD1-1]
DR CCDS; CCDS48014.1; -. [Q9HBD1-4]
DR CCDS; CCDS87685.1; -. [Q9HBD1-3]
DR RefSeq; NP_001094058.1; NM_001100588.1. [Q9HBD1-1]
DR RefSeq; NP_061323.2; NM_018835.2. [Q9HBD1-4]
DR PDB; 4Z30; X-ray; 2.71 A; A=86-404.
DR PDB; 4Z31; X-ray; 2.50 A; A/B=87-404.
DR PDB; 4ZLC; X-ray; 2.70 A; A/B/C/D=171-325.
DR PDB; 4ZLD; X-ray; 1.60 A; A=171-325.
DR PDBsum; 4Z30; -.
DR PDBsum; 4Z31; -.
DR PDBsum; 4ZLC; -.
DR PDBsum; 4ZLD; -.
DR AlphaFoldDB; Q9HBD1; -.
DR SMR; Q9HBD1; -.
DR BioGRID; 120029; 661.
DR IntAct; Q9HBD1; 15.
DR MINT; Q9HBD1; -.
DR STRING; 9606.ENSP00000362774; -.
DR GlyGen; Q9HBD1; 7 sites, 1 O-linked glycan (7 sites).
DR iPTMnet; Q9HBD1; -.
DR PhosphoSitePlus; Q9HBD1; -.
DR BioMuta; RC3H2; -.
DR DMDM; 73621223; -.
DR EPD; Q9HBD1; -.
DR jPOST; Q9HBD1; -.
DR MassIVE; Q9HBD1; -.
DR MaxQB; Q9HBD1; -.
DR PaxDb; Q9HBD1; -.
DR PeptideAtlas; Q9HBD1; -.
DR PRIDE; Q9HBD1; -.
DR ProteomicsDB; 81522; -. [Q9HBD1-1]
DR ProteomicsDB; 81523; -. [Q9HBD1-2]
DR ProteomicsDB; 81524; -. [Q9HBD1-3]
DR ProteomicsDB; 81525; -. [Q9HBD1-4]
DR ProteomicsDB; 81526; -. [Q9HBD1-5]
DR ProteomicsDB; 81527; -. [Q9HBD1-6]
DR TopDownProteomics; Q9HBD1-3; -. [Q9HBD1-3]
DR Antibodypedia; 30358; 63 antibodies from 15 providers.
DR DNASU; 54542; -.
DR Ensembl; ENST00000357244.7; ENSP00000349783.2; ENSG00000056586.16. [Q9HBD1-1]
DR Ensembl; ENST00000373670.5; ENSP00000362774.1; ENSG00000056586.16. [Q9HBD1-1]
DR Ensembl; ENST00000423239.6; ENSP00000411767.1; ENSG00000056586.16. [Q9HBD1-4]
DR Ensembl; ENST00000471874.2; ENSP00000474148.1; ENSG00000056586.16. [Q9HBD1-5]
DR Ensembl; ENST00000498479.5; ENSP00000474709.1; ENSG00000056586.16. [Q9HBD1-2]
DR GeneID; 54542; -.
DR KEGG; hsa:54542; -.
DR MANE-Select; ENST00000357244.7; ENSP00000349783.2; NM_001100588.3; NP_001094058.1.
DR UCSC; uc004bnb.2; human. [Q9HBD1-1]
DR CTD; 54542; -.
DR GeneCards; RC3H2; -.
DR HGNC; HGNC:21461; RC3H2.
DR HPA; ENSG00000056586; Low tissue specificity.
DR MIM; 615231; gene.
DR neXtProt; NX_Q9HBD1; -.
DR OpenTargets; ENSG00000056586; -.
DR PharmGKB; PA162400905; -.
DR VEuPathDB; HostDB:ENSG00000056586; -.
DR eggNOG; KOG3161; Eukaryota.
DR GeneTree; ENSGT00940000157685; -.
DR HOGENOM; CLU_011007_0_0_1; -.
DR InParanoid; Q9HBD1; -.
DR OMA; GTEHVEN; -.
DR PhylomeDB; Q9HBD1; -.
DR TreeFam; TF317698; -.
DR PathwayCommons; Q9HBD1; -.
DR SignaLink; Q9HBD1; -.
DR SIGNOR; Q9HBD1; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 54542; 12 hits in 1119 CRISPR screens.
DR ChiTaRS; RC3H2; human.
DR GenomeRNAi; 54542; -.
DR Pharos; Q9HBD1; Tbio.
DR PRO; PR:Q9HBD1; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q9HBD1; protein.
DR Bgee; ENSG00000056586; Expressed in cerebellar vermis and 203 other tissues.
DR ExpressionAtlas; Q9HBD1; baseline and differential.
DR Genevisible; Q9HBD1; HS.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0000932; C:P-body; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0003725; F:double-stranded RNA binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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; IDA:UniProtKB.
DR GO; GO:0001782; P:B cell homeostasis; IEA:Ensembl.
DR GO; GO:0060173; P:limb development; IEA:Ensembl.
DR GO; GO:0048286; P:lung alveolus development; IEA:Ensembl.
DR GO; GO:0048535; P:lymph node development; IEA:Ensembl.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:2000320; P:negative regulation of T-helper 17 cell differentiation; ISS:UniProtKB.
DR GO; GO:0000288; P:nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; IBA:GO_Central.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:2000628; P:regulation of miRNA metabolic process; ISS:UniProtKB.
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; IPR032670; RC3H2.
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:SF2; PTHR13139:SF2; 1.
DR Pfam; PF18386; ROQ_II; 1.
DR Pfam; PF00642; zf-CCCH; 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; Metal-binding;
KW Phosphoprotein; Reference proteome; Repressor; RNA-binding; Transferase;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..1191
FT /note="Roquin-2"
FT /id="PRO_0000055968"
FT ZN_FING 14..54
FT /note="RING-type; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 410..438
FT /note="C3H1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT REGION 91..170
FT /note="HEPN-N"
FT /evidence="ECO:0000269|PubMed:26489670"
FT REGION 171..325
FT /note="ROQ"
FT /evidence="ECO:0000269|PubMed:26249698"
FT REGION 326..396
FT /note="HEPN-C"
FT /evidence="ECO:0000269|PubMed:26489670"
FT REGION 528..576
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 644..680
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 534..576
FT /note="Polar residues"
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 509
FT /note="Cleavage; by MALT1"
FT /evidence="ECO:0000250|UniProtKB:Q4VGL6"
FT SITE 585
FT /note="Cleavage; by MALT1"
FT /evidence="ECO:0000250|UniProtKB:Q4VGL6"
FT MOD_RES 549
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 808
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 983
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1119
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..195
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_015017"
FT VAR_SEQ 195..218
FT /note="AMQEEALKLVLLALEDGSALSRKV -> GKIGYYLTFFISYWGLRMPISGAR
FT (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015018"
FT VAR_SEQ 219..1191
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015019"
FT VAR_SEQ 443..506
FT /note="YRLRNKKINATVRTFPLLNKVGVNNTVTTTAGNVISVIGSTETTGKIVPSTN
FT GISNAENSVSQL -> CNPRGLYLHCCLLSSVASLGTVHNELYKQQHCDREKISVCAVK
FT RAETCFSSQFFSPLEEPREED (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015020"
FT VAR_SEQ 454..478
FT /note="VRTFPLLNKVGVNNTVTTTAGNVIS -> EVLKQQGKLFQVQTEFQMQKTVF
FT PS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_015021"
FT VAR_SEQ 479..1191
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_015022"
FT VAR_SEQ 507..1191
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015023"
FT VAR_SEQ 1040..1191
FT /note="LQSDYTEDATDTKPDRDIELELSALDTDEPDGQSEPIEEILDIQLGISSQND
FT QLLNGMAVENGHPVQQHQKEPPKQKKQSLGEDHVILEEQKTILPVTSCFSQPLPVSISN
FT ASCLPITTSVSAGNLILKTHVMSEDKNDFLKPVANGKMVNS -> VKKLNLSASCLMYL
FT FSAAASWLYHY (in isoform 4 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_015024"
FT MUTAGEN 33
FT /note="C->S: Loss of activity. Loss of MAP3K5
FT ubiquitination."
FT /evidence="ECO:0000269|PubMed:24448648"
FT MUTAGEN 244..248
FT /note="QLLYR->ALLAA: Abolishes binding to CDE RNA but not
FT dsRNA."
FT /evidence="ECO:0000269|PubMed:26489670"
FT MUTAGEN 323
FT /note="S->E: Decreases dsRNA-binding."
FT /evidence="ECO:0000269|PubMed:26489670"
FT CONFLICT 650
FT /note="A -> G (in Ref. 2; BAA91073)"
FT /evidence="ECO:0000305"
FT HELIX 93..106
FT /evidence="ECO:0007829|PDB:4Z31"
FT HELIX 107..109
FT /evidence="ECO:0007829|PDB:4Z31"
FT HELIX 128..138
FT /evidence="ECO:0007829|PDB:4Z31"
FT HELIX 145..169
FT /evidence="ECO:0007829|PDB:4Z31"
FT HELIX 173..186
FT /evidence="ECO:0007829|PDB:4ZLD"
FT HELIX 194..208
FT /evidence="ECO:0007829|PDB:4ZLD"
FT HELIX 216..227
FT /evidence="ECO:0007829|PDB:4ZLD"
FT TURN 228..230
FT /evidence="ECO:0007829|PDB:4ZLD"
FT HELIX 236..248
FT /evidence="ECO:0007829|PDB:4ZLD"
FT STRAND 252..257
FT /evidence="ECO:0007829|PDB:4ZLD"
FT STRAND 260..266
FT /evidence="ECO:0007829|PDB:4ZLD"
FT HELIX 268..270
FT /evidence="ECO:0007829|PDB:4ZLD"
FT HELIX 273..290
FT /evidence="ECO:0007829|PDB:4ZLD"
FT HELIX 297..305
FT /evidence="ECO:0007829|PDB:4ZLD"
FT STRAND 306..308
FT /evidence="ECO:0007829|PDB:4ZLD"
FT HELIX 311..320
FT /evidence="ECO:0007829|PDB:4ZLD"
FT HELIX 326..341
FT /evidence="ECO:0007829|PDB:4Z31"
FT HELIX 347..350
FT /evidence="ECO:0007829|PDB:4Z31"
FT HELIX 351..358
FT /evidence="ECO:0007829|PDB:4Z31"
FT HELIX 371..394
FT /evidence="ECO:0007829|PDB:4Z31"
SQ SEQUENCE 1191 AA; 131669 MW; 93633D8D83DC7409 CRC64;
MPVQAAQWTE FLSCPICYNE FDENVHKPIS LGCSHTVCKT CLNKLHRKAC PFDQTAINTD
IDVLPVNFAL LQLVGAQVPD HQSIKLSNLG ENKHYEVAKK CVEDLALYLK PLSGGKGVAS
LNQSALSRPM QRKLVTLVNC QLVEEEGRVR AMRAARSLGE RTVTELILQH QNPQQLSANL
WAAVRARGCQ FLGPAMQEEA LKLVLLALED GSALSRKVLV LFVVQRLEPR FPQASKTSIG
HVVQLLYRAS CFKVTKRDED SSLMQLKEEF RSYEALRREH DAQIVHIAME AGLRISPEQW
SSLLYGDLAH KSHMQSIIDK LQSPESFAKS VQELTIVLQR TGDPANLNRL RPHLELLANI
DPNPDAVSPT WEQLENAMVA VKTVVHGLVD FIQNYSRKGH ETPQPQPNSK YKTSMCRDLR
QQGGCPRGTN CTFAHSQEEL EKYRLRNKKI NATVRTFPLL NKVGVNNTVT TTAGNVISVI
GSTETTGKIV PSTNGISNAE NSVSQLISRS TDSTLRALET VKKVGKVGAN GQNAAGPSAD
SVTENKIGSP PKTPVSNVAA TSAGPSNVGT ELNSVPQKSS PFLTRVPVYP PHSENIQYFQ
DPRTQIPFEV PQYPQTGYYP PPPTVPAGVA PCVPRFVRSN NVPESSLPPA SMPYADHYST
FSPRDRMNSS PYQPPPPQPY GPVPPVPSGM YAPVYDSRRI WRPPMYQRDD IIRSNSLPPM
DVMHSSVYQT SLRERYNSLD GYYSVACQPP SEPRTTVPLP REPCGHLKTS CEEQIRRKPD
QWAQYHTQKA PLVSSTLPVA TQSPTPPSPL FSVDFRADFS ESVSGTKFEE DHLSHYSPWS
CGTIGSCINA IDSEPKDVIA NSNAVLMDLD SGDVKRRVHL FETQRRTKEE DPIIPFSDGP
IISKWGAISR SSRTGYHTTD PVQATASQGS ATKPISVSDY VPYVNAVDSR WSSYGNEATS
SAHYVERDRF IVTDLSGHRK HSSTGDLLSL ELQQAKSNSL LLQREANALA MQQKWNSLDE
GRHLTLNLLS KEIELRNGEL QSDYTEDATD TKPDRDIELE LSALDTDEPD GQSEPIEEIL
DIQLGISSQN DQLLNGMAVE NGHPVQQHQK EPPKQKKQSL GEDHVILEEQ KTILPVTSCF
SQPLPVSISN ASCLPITTSV SAGNLILKTH VMSEDKNDFL KPVANGKMVN S
