RC3H1_MOUSE
ID RC3H1_MOUSE Reviewed; 1130 AA.
AC Q4VGL6; B2RS13; Q69Z31;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Roquin-1 {ECO:0000305};
DE Short=Roquin {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q5TC82};
DE AltName: Full=Protein Sanroque {ECO:0000303|PubMed:23583642};
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;
GN Name=Rc3h1 {ECO:0000312|MGI:MGI:2685397}; Synonyms=Gm551, Kiaa2025;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, MUTAGENESIS OF MET-199, IDENTIFICATION OF ROQ REGION, SANROQUE
RP MOUSE, AND MISCELLANEOUS.
RX PubMed=15917799; DOI=10.1038/nature03555;
RA Vinuesa C.G., Cook M.C., Angelucci C., Athanasopoulos V., Rui L.,
RA Hill K.M., Yu D., Domaschenz H., Whittle B., Lambe T., Roberts I.S.,
RA Copley R.R., Bell J.I., Cornall R.J., Goodnow C.C.;
RT "A RING-type ubiquitin ligase family member required to repress follicular
RT helper T cells and autoimmunity.";
RL Nature 435:452-458(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreatic islet;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [4]
RP FUNCTION.
RX PubMed=18172933; DOI=10.1038/nature06253;
RA Yu D., Tan A.H., Hu X., Athanasopoulos V., Simpson N., Silva D.G.,
RA Hutloff A., Giles K.M., Leedman P.J., Lam K.P., Goodnow C.C., Vinuesa C.G.;
RT "Roquin represses autoimmunity by limiting inducible T-cell co-stimulator
RT messenger RNA.";
RL Nature 450:299-303(2007).
RN [5]
RP ERRATUM OF PUBMED:18172933.
RA Yu D., Tan A.H., Hu X., Athanasopoulos V., Simpson N., Silva D.G.,
RA Hutloff A., Giles K.M., Leedman P.J., Lam K.P., Goodnow C.C., Vinuesa C.G.;
RL Nature 451:1022-1022(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1107 AND SER-1110, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-531; SER-535; SER-1107 AND
RP SER-1110, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Lung, Pancreas, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP FUNCTION, RNA-BINDING, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-14 AND
RP MET-199.
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 FUNCTION, INTERACTION WITH DDX6 AND EDC4, AND SUBCELLULAR LOCATION.
RX PubMed=20639877; DOI=10.1038/ni.1902;
RA Glasmacher E., Hoefig K.P., Vogel K.U., Rath N., Du L., Wolf C.,
RA Kremmer E., Wang X., Heissmeyer V.;
RT "Roquin binds inducible costimulator mRNA and effectors of mRNA decay to
RT induce microRNA-independent post-transcriptional repression.";
RL Nat. Immunol. 11:725-733(2010).
RN [10]
RP DISRUPTION PHENOTYPE.
RX PubMed=21844204; DOI=10.1084/jem.20110578;
RA Bertossi A., Aichinger M., Sansonetti P., Lech M., Neff F., Pal M.,
RA Wunderlich F.T., Anders H.J., Klein L., Schmidt-Supprian M.;
RT "Loss of Roquin induces early death and immune deregulation but not
RT autoimmunity.";
RL J. Exp. Med. 208:1749-1756(2011).
RN [11]
RP FUNCTION, INTERACTION WITH CCR4-NOT COMPLEX, AND MUTAGENESIS OF CYS-419.
RX PubMed=23663784; DOI=10.1016/j.cell.2013.04.016;
RA Leppek K., Schott J., Reitter S., Poetz F., Hammond M.C., Stoecklin G.;
RT "Roquin promotes constitutive mRNA decay via a conserved class of stem-loop
RT recognition motifs.";
RL Cell 153:869-881(2013).
RN [12]
RP FUNCTION, INTERACTION WITH EDC4, DISRUPTION PHENOTYPE, AND TISSUE
RP SPECIFICITY.
RX PubMed=23583643; DOI=10.1016/j.immuni.2012.12.004;
RA Vogel K.U., Edelmann S.L., Jeltsch K.M., Bertossi A., Heger K., Heinz G.A.,
RA Zoller J., Warth S.C., Hoefig K.P., Lohs C., Neff F., Kremmer E.,
RA Schick J., Repsilber D., Geerlof A., Blum H., Wurst W., Heikenwalder M.,
RA Schmidt-Supprian M., Heissmeyer V.;
RT "Roquin paralogs 1 and 2 redundantly repress the Icos and Ox40 costimulator
RT mRNAs and control follicular helper T cell differentiation.";
RL Immunity 38:655-668(2013).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, SANROQUE MOUSE, AND MISCELLANEOUS.
RX PubMed=23583642; DOI=10.1016/j.immuni.2013.01.011;
RA Pratama A., Ramiscal R.R., Silva D.G., Das S.K., Athanasopoulos V.,
RA Fitch J., Botelho N.K., Chang P.P., Hu X., Hogan J.J., Mana P., Bernal D.,
RA Korner H., Yu D., Goodnow C.C., Cook M.C., Vinuesa C.G.;
RT "Roquin-2 shares functions with its paralog Roquin-1 in the repression of
RT mRNAs controlling T follicular helper cells and systemic inflammation.";
RL Immunity 38:669-680(2013).
RN [14]
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 [15]
RP INTESTINAL INFLAMMATION IN SANROQUE MOUSE, AND MISCELLANEOUS.
RX PubMed=23451046; DOI=10.1371/journal.pone.0056436;
RA Schaefer J.S., Montufar-Solis D., Nakra N., Vigneswaran N., Klein J.R.;
RT "Small intestine inflammation in Roquin-mutant and Roquin-deficient mice.";
RL PLoS ONE 8:E56436-E56436(2013).
RN [16]
RP DISRUPTION PHENOTYPE, PROTEOLYTIC CLEAVAGE, MUTAGENESIS OF LYS-220;
RP LYS-239; ARG-260; ARG-488; ARG-510; ARG-560 AND ARG-579, AND FUNCTION.
RX PubMed=25282160; DOI=10.1038/ni.3008;
RA Jeltsch K.M., Hu D., Brenner S., Zoeller J., Heinz G.A., Nagel D.,
RA Vogel K.U., Rehage N., Warth S.C., Edelmann S.L., Gloury R., Martin N.,
RA Lohs C., Lech M., Stehklein J.E., Geerlof A., Kremmer E., Weber A.,
RA Anders H.J., Schmitz I., Schmidt-Supprian M., Fu M., Holtmann H.,
RA Krappmann D., Ruland J., Kallies A., Heikenwalder M., Heissmeyer V.;
RT "Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their
RT cooperatively repressed targets to promote T(H)17 differentiation.";
RL Nat. Immunol. 15:1079-1089(2014).
RN [17]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=26000482; DOI=10.1016/j.cell.2015.04.029;
RA Mino T., Murakawa Y., Fukao A., Vandenbon A., Wessels H.H., Ori D.,
RA Uehata T., Tartey S., Akira S., Suzuki Y., Vinuesa C.G., Ohler U.,
RA Standley D.M., Landthaler M., Fujiwara T., Takeuchi O.;
RT "Regnase-1 and Roquin regulate a common element in inflammatory mRNAs by
RT spatiotemporally distinct mechanisms.";
RL Cell 161:1058-1073(2015).
RN [18]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=29244194; DOI=10.1002/eji.201747109;
RA Hanieh H., Masuda K., Metwally H., Chalise J.P., Mohamed M., Nyati K.K.,
RA Standley D.M., Li S., Higa M., Zaman M.M., Kishimoto T.;
RT "Arid5a stabilizes OX40 mRNA in murine CD4+ T cells by recognizing a stem-
RT loop structure in its 3'UTR.";
RL Eur. J. Immunol. 48:593-604(2018).
RN [19]
RP MUTAGENESIS OF MET-199 AND ARG-687.
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 [20] {ECO:0007744|PDB:4QI0, ECO:0007744|PDB:4QI2}
RP X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) OF 147-326, RNA-BINDING, FUNCTION,
RP DOMAIN, AND MUTAGENESIS OF ARG-188; ARG-219; LYS-220; ARG-229; ARG-233;
RP SER-238; LYS-239; TYR-250; ARG-251; SER-253; LYS-259; ARG-260; SER-264;
RP SER-265; GLU-293 AND LYS-314.
RX PubMed=25026077; DOI=10.1038/nsmb.2855;
RA Schlundt A., Heinz G.A., Janowski R., Geerlof A., Stehle R., Heissmeyer V.,
RA Niessing D., Sattler M.;
RT "Structural basis for RNA recognition in roquin-mediated post-
RT transcriptional gene regulation.";
RL Nat. Struct. Mol. Biol. 21:671-678(2014).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 1-484 OF MUTATED AT MET-199 IN
RP COMPLEX WITH ZINC, FUNCTION, SANROQUE MOUSE, MISCELLANEOUS, MUTAGENESIS OF
RP MET-199, DOMAIN, 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 [22] {ECO:0007744|PDB:5F5F, ECO:0007744|PDB:5F5H}
RP X-RAY CRYSTALLOGRAPHY (2.23 ANGSTROMS) OF 147-326, FUNCTION, RNA-BINDING,
RP AND MUTAGENESIS OF MET-199; LYS-220; LYS-239; TYR-250; SER-253; LYS-259;
RP ARG-260 AND SER-265.
RX PubMed=27010430; DOI=10.1038/ncomms11032;
RA Janowski R., Heinz G.A., Schlundt A., Wommelsdorf N., Brenner S.,
RA Gruber A.R., Blank M., Buch T., Buhmann R., Zavolan M., Niessing D.,
RA Heissmeyer V., Sattler M.;
RT "Roquin recognizes a non-canonical hexaloop structure in the 3'-UTR of
RT Ox40.";
RL Nat. Commun. 7:11032-11032(2016).
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:23663784,
CC PubMed:25026077, PubMed:18172933). Cleaves translationally inactive
CC mRNAs harboring a stem-loop (SL), often located in their 3'-UTRs,
CC during the early phase of inflammation in a helicase UPF1-independent
CC manner (PubMed:26000482). Binds to CDE and promotes mRNA deadenylation
CC and degradation. This process does not involve miRNAs (PubMed:20412057,
CC PubMed:20639877). In follicular helper T (Tfh) cells, represses of ICOS
CC and TNFRSF4/Ox40 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 RC3H2,
CC possibly leading to feedback loop regulation (PubMed:23583642,
CC PubMed:23583643, PubMed:15917799). Inhibits cooperatively with ZC3H12A
CC the differentiation of helper T cells Th17 in lungs. They repress
CC target mRNA encoding the Th17 cell-promoting factors IL6, ICOS, REL,
CC IRF4, NFKBID and NFKBIZ. The cooperation requires RNA-binding by RC3H1
CC and the nuclease activity of ZC3H12A (PubMed:25282160). Recognizes and
CC binds mRNAs containing a hexaloop stem-loop motif, called alternative
CC decay element (ADE) (PubMed:27010430). Together with ZC3H12A,
CC destabilizes TNFRSF4/OX40 mRNA by binding to the conserved stem loop
CC structure in its 3'UTR (PubMed:29244194). Able to interact with double-
CC stranded RNA (By similarity). miRNA-binding protein that regulates
CC microRNA homeostasis. Enhances DICER-mediated processing of pre-MIR146a
CC but reduces mature MIR146a levels through an increase of 3' end
CC uridylation. Both inhibits ICOS mRNA expression and they may act
CC together to exert the suppression (PubMed:25697406). Acts as a
CC ubiquitin E3 ligase. Pairs with E2 enzymes UBE2A, UBE2B, UBE2D2, UBE2F,
CC UBE2G1, UBE2G2 and UBE2L3 and produces polyubiquitin chains. Shows the
CC strongest activity when paired with UBE2N:UBE2V1 or UBE2N:UBE2V2 E2
CC complexes and generate both short and long polyubiquitin chains (By
CC similarity). {ECO:0000250|UniProtKB:Q5TC82,
CC ECO:0000269|PubMed:15917799, ECO:0000269|PubMed:18172933,
CC ECO:0000269|PubMed:20412057, ECO:0000269|PubMed:20639877,
CC ECO:0000269|PubMed:23583642, ECO:0000269|PubMed:23583643,
CC ECO:0000269|PubMed:23663784, ECO:0000269|PubMed:25026077,
CC ECO:0000269|PubMed:25282160, ECO:0000269|PubMed:25697406,
CC ECO:0000269|PubMed:26000482, ECO:0000269|PubMed:27010430,
CC ECO:0000269|PubMed:29244194}.
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:0000250|UniProtKB:Q5TC82};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q5TC82}.
CC -!- SUBUNIT: Interacts with DDX6 and EDC4 (PubMed:20639877,
CC PubMed:23583643). Interacts with CCR4-NOT deadenylase complex
CC (PubMed:23663784). Interacts with RC3H1; the interaction is RNA
CC independent (PubMed:25697406). {ECO:0000269|PubMed:20639877,
CC ECO:0000269|PubMed:23583643, ECO:0000269|PubMed:23663784,
CC ECO:0000269|PubMed:25697406}.
CC -!- INTERACTION:
CC Q4VGL6; Q8CJG0: Ago2; NbExp=2; IntAct=EBI-2366263, EBI-528299;
CC Q4VGL6; Q3UJB9: Edc4; NbExp=3; IntAct=EBI-2366263, EBI-2553526;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000269|PubMed:15917799,
CC ECO:0000269|PubMed:20412057, ECO:0000269|PubMed:20639877,
CC ECO:0000269|PubMed:23583642, ECO:0000269|PubMed:26000482}. Cytoplasmic
CC granule {ECO:0000269|PubMed:26000482}. Note=During stress, such as that
CC induced by arsenite treatment, localizes to cytosolic stress granules
CC (PubMed:26000482). Localization to stress granules, but not to P-
CC bodies, depends upon the RING-type zinc finger. ICOS repression may
CC correlate with the localization to P-bodies, not to stress granules
CC (PubMed:20639877). {ECO:0000269|PubMed:20639877,
CC ECO:0000269|PubMed:26000482}.
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest levels in lymph node
CC and thymus and slightly lesser amounts in brain, lung, and spleen (at
CC protein level) (PubMed:23583643). Very weak expression in heart,
CC muscle, and kidney (at protein level) (PubMed:23583643). Expressed in
CC CD4(+) helper T-cells (at protein level) (PubMed:29244194,
CC PubMed:15917799, PubMed:23583643). {ECO:0000269|PubMed:15917799,
CC ECO:0000269|PubMed:23583643, ECO:0000269|PubMed:29244194}.
CC -!- DOMAIN: The ROQ region is required for CDE RNA-binding
CC (PubMed:27010430, PubMed:25026077, PubMed:23663784). Has 2 separate
CC RNA-binding sites, one for CDE RNA and the other for dsRNA, both sites
CC are important for mRNA decay (By similarity). ADE RNA-binding involves
CC an extended binding surface on the ROQ region with a number of
CC additional residues compared with the CDE RNA (PubMed:27010430). It may
CC also be involved in localization to stress granules (PubMed:20412057,
CC PubMed:23583642). {ECO:0000250|UniProtKB:Q5TC82,
CC ECO:0000269|PubMed:20412057, ECO:0000269|PubMed:23583642,
CC ECO:0000269|PubMed:23663784, ECO:0000269|PubMed:25026077,
CC ECO:0000269|PubMed:27010430}.
CC -!- DOMAIN: The RING-type zinc finger may be required for proper
CC localization to stress granules, but not to P-bodies.
CC {ECO:0000269|PubMed:23583642}.
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:25697406}.
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:0000269|PubMed:25282160}.
CC -!- DISRUPTION PHENOTYPE: Mutant animals are born at Mendelian ratio, but
CC die within 6 hours after birth. They displayed a curly tail and
CC malformations of the caudal spinal column. Lethality can be rescued by
CC changing the genetic background from C57BL/6 to outbred CD1, which
CC allows about 4% of the animals to survive to adulthood. These animals
CC display enlarged spleens with a trend toward increased numbers of
CC eosinophils and monocytic/macrophage populations, dramatic and
CC selective expansion of CD8(+) effector-like T-cells. Splenic follicular
CC organization is normal, and the numbers of CD4(+) T-cell subtypes and
CC B-cells are not significantly altered. No spontaneous germinal center
CC formation, autoantibody production, nor autoimmune tissue damage.
CC Ablation of Rc3h1 gene in the T lineage leads to elevated ICOS levels
CC and expansion of effector CD8(+) T-cells, but not autoimmunity
CC (PubMed:21844204). Mice lacking both Rc3h1 and Rc3h2 genes in CD4(+) T-
CC cells develop lymphadenopathy and splenomegaly with increased spleen
CC weight and cellularity, already at young age. They show a prominent
CC lung pathology with a progressive reduction in the alveolar space
CC concomitant with inflammation. They show an average survival of 130
CC days. CD4(+) T-cells of these mutants show a pronounced bias toward
CC Th17 differentiation (PubMed:21844204, PubMed:23583643).
CC {ECO:0000269|PubMed:21844204, ECO:0000269|PubMed:23583643}.
CC -!- MISCELLANEOUS: Treatment of C57BL/6 males with ethylnitrosourea led to
CC the identification of the sanroque mouse strain. The causative mutation
CC in sanroque appears to be RC3H1 Arg-199. Homozygous sanroque mice
CC develop high titers of autoantibodies and display excessive numbers of
CC follicular helper T-cells and germinal centers with pattern of
CC pathology consistent with lupus (PubMed:15917799). Sanroque mice
CC reproducibly develop intestinal inflammation in the small intestine but
CC not the colon. Extensive cytokine dysregulation resulting in both over-
CC expression and under-expression of chemotactic cytokines occurs in the
CC ileum, the region most prone to the development of inflammation in
CC sanroque mice (PubMed:23451046). They show up-regulation of expression
CC of at least 15 miRNAs in T cells (PubMed:25697406). The lack of
CC compensation of RC3H1 defects by the RC3H2 paralog in sanroque mice may
CC be due to the fact that the mutated protein may retain its scaffolding
CC position within RNA granules, preventing RC3H2 to access mRNAs to be
CC regulated (PubMed:23583642). {ECO:0000269|PubMed:25697406,
CC ECO:0000305|PubMed:15917799, ECO:0000305|PubMed:23451046,
CC ECO:0000305|PubMed:23583642}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD32613.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY948287; AAY16368.1; -; mRNA.
DR EMBL; AK173335; BAD32613.1; ALT_INIT; mRNA.
DR EMBL; BC138663; AAI38664.1; -; mRNA.
DR CCDS; CCDS15410.1; -.
DR RefSeq; NP_001020123.1; NM_001024952.2.
DR PDB; 4QI0; X-ray; 1.94 A; A/B=147-326.
DR PDB; 4QI2; X-ray; 3.00 A; A/B/C/D=147-326.
DR PDB; 4TXA; X-ray; 2.75 A; A=1-484.
DR PDB; 5F5F; X-ray; 3.00 A; A/C/E/G=171-360.
DR PDB; 5F5H; X-ray; 2.23 A; A/B=147-326.
DR PDB; 6TQA; X-ray; 2.40 A; A/B/C/D=147-326.
DR PDB; 6TQB; X-ray; 1.60 A; A=147-326.
DR PDBsum; 4QI0; -.
DR PDBsum; 4QI2; -.
DR PDBsum; 4TXA; -.
DR PDBsum; 5F5F; -.
DR PDBsum; 5F5H; -.
DR PDBsum; 6TQA; -.
DR PDBsum; 6TQB; -.
DR AlphaFoldDB; Q4VGL6; -.
DR BMRB; Q4VGL6; -.
DR SASBDB; Q4VGL6; -.
DR SMR; Q4VGL6; -.
DR BioGRID; 237867; 7.
DR IntAct; Q4VGL6; 54.
DR MINT; Q4VGL6; -.
DR STRING; 10090.ENSMUSP00000124871; -.
DR iPTMnet; Q4VGL6; -.
DR PhosphoSitePlus; Q4VGL6; -.
DR EPD; Q4VGL6; -.
DR jPOST; Q4VGL6; -.
DR MaxQB; Q4VGL6; -.
DR PaxDb; Q4VGL6; -.
DR PRIDE; Q4VGL6; -.
DR ProteomicsDB; 253186; -.
DR Antibodypedia; 34400; 146 antibodies from 22 providers.
DR DNASU; 381305; -.
DR Ensembl; ENSMUST00000161609; ENSMUSP00000124871; ENSMUSG00000040423.
DR GeneID; 381305; -.
DR KEGG; mmu:381305; -.
DR UCSC; uc007del.2; mouse.
DR CTD; 149041; -.
DR MGI; MGI:2685397; Rc3h1.
DR VEuPathDB; HostDB:ENSMUSG00000040423; -.
DR eggNOG; KOG3161; Eukaryota.
DR GeneTree; ENSGT00940000157143; -.
DR HOGENOM; CLU_004948_0_0_1; -.
DR InParanoid; Q4VGL6; -.
DR OMA; YGTHSGW; -.
DR OrthoDB; 1009668at2759; -.
DR PhylomeDB; Q4VGL6; -.
DR TreeFam; TF317698; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 381305; 6 hits in 73 CRISPR screens.
DR ChiTaRS; Rc3h1; mouse.
DR PRO; PR:Q4VGL6; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q4VGL6; protein.
DR Bgee; ENSMUSG00000040423; Expressed in manus and 217 other tissues.
DR ExpressionAtlas; Q4VGL6; baseline and differential.
DR Genevisible; Q4VGL6; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB.
DR GO; GO:0000932; C:P-body; IDA:UniProtKB.
DR GO; GO:1905762; F:CCR4-NOT complex binding; ISO:MGI.
DR GO; GO:0003725; F:double-stranded RNA binding; ISS:UniProtKB.
DR GO; GO:0035198; F:miRNA binding; IDA:UniProtKB.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; IDA:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; IDA:MGI.
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; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0061158; P:3'-UTR-mediated mRNA destabilization; IDA:UniProtKB.
DR GO; GO:0001782; P:B cell homeostasis; IGI:MGI.
DR GO; GO:0071347; P:cellular response to interleukin-1; IDA:UniProtKB.
DR GO; GO:0048535; P:lymph node development; IGI:MGI.
DR GO; GO:0046007; P:negative regulation of activated T cell proliferation; IMP:BHF-UCL.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; IMP:BHF-UCL.
DR GO; GO:0002635; P:negative regulation of germinal center formation; IMP:BHF-UCL.
DR GO; GO:2000320; P:negative regulation of T-helper 17 cell differentiation; IMP:UniProtKB.
DR GO; GO:0045623; P:negative regulation of T-helper cell differentiation; IMP:MGI.
DR GO; GO:0000956; P:nuclear-transcribed mRNA catabolic process; IMP:BHF-UCL.
DR GO; GO:0000288; P:nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; IMP:UniProtKB.
DR GO; GO:0033962; P:P-body assembly; IMP:BHF-UCL.
DR GO; GO:0061014; P:positive regulation of mRNA catabolic process; IDA:UniProtKB.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IDA:MGI.
DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; IDA:MGI.
DR GO; GO:0000209; P:protein polyubiquitination; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IDA:MGI.
DR GO; GO:0002634; P:regulation of germinal center formation; IMP:BHF-UCL.
DR GO; GO:2000628; P:regulation of miRNA metabolic process; IMP:UniProtKB.
DR GO; GO:0043488; P:regulation of mRNA stability; IMP:BHF-UCL.
DR GO; GO:1900151; P:regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; ISO:MGI.
DR GO; GO:0050856; P:regulation of T cell receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0048536; P:spleen development; IGI:MGI.
DR GO; GO:0043029; P:T cell homeostasis; IGI:MGI.
DR GO; GO:0042098; P:T cell proliferation; IGI:MGI.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0061470; P:T follicular helper cell differentiation; IGI:MGI.
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; Cytoplasm; Metal-binding; Phosphoprotein; Reference proteome;
KW Repeat; Repressor; RNA-binding; Transferase; Zinc; Zinc-finger.
FT CHAIN 1..1130
FT /note="Roquin-1"
FT /id="PRO_0000055966"
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 128..176
FT /note="HEPN-N"
FT /evidence="ECO:0000269|PubMed:25697406"
FT REGION 177..326
FT /note="ROQ"
FT /evidence="ECO:0000269|PubMed:25026077"
FT REGION 327..399
FT /note="HEPN-C"
FT /evidence="ECO:0000269|PubMed:25697406"
FT REGION 493..567
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 722..750
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1100..1130
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 496..513
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 551..567
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 725..747
FT /note="Pro 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:0000269|PubMed:25697406,
FT ECO:0007744|PDB:4TXA"
FT BINDING 17
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:25697406,
FT ECO:0007744|PDB:4TXA"
FT BINDING 33
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25697406,
FT ECO:0007744|PDB:4TXA"
FT BINDING 35
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25697406,
FT ECO:0007744|PDB:4TXA"
FT BINDING 38
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:25697406,
FT ECO:0007744|PDB:4TXA"
FT BINDING 50
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25697406,
FT ECO:0007744|PDB:4TXA"
FT BINDING 53
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25697406,
FT ECO:0007744|PDB:4TXA"
FT SITE 510
FT /note="Cleavage; by MALT1"
FT /evidence="ECO:0000269|PubMed:25282160"
FT SITE 579
FT /note="Cleavage; by MALT1"
FT /evidence="ECO:0000269|PubMed:25282160"
FT MOD_RES 462
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5TC82"
FT MOD_RES 531
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 535
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 861
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5TC82"
FT MOD_RES 1107
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 1110
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MUTAGEN 14
FT /note="C->A: No effect on localization to stress granules."
FT /evidence="ECO:0000269|PubMed:20412057"
FT MUTAGEN 188
FT /note="R->A: No effect on CDE RNA-binding."
FT /evidence="ECO:0000269|PubMed:25026077"
FT MUTAGEN 199
FT /note="M->R: In sanroque; partial loss of ICOS regulation,
FT no effect on localization to stress granules, no effect on
FT RNA-binding."
FT /evidence="ECO:0000269|PubMed:15917799,
FT ECO:0000269|PubMed:20412057, ECO:0000269|PubMed:25697406,
FT ECO:0000269|PubMed:27010430, ECO:0000269|PubMed:31636267"
FT MUTAGEN 219
FT /note="R->A: No effect on CDE RNA-binding."
FT /evidence="ECO:0000269|PubMed:25026077"
FT MUTAGEN 220
FT /note="K->A: Strongly decreases CDE and ADE RNA-binding.
FT Increases target-mRNA expression. Increases ICOS surface
FT expression; when associated with A-239 and A-260."
FT /evidence="ECO:0000269|PubMed:25026077,
FT ECO:0000269|PubMed:25282160, ECO:0000269|PubMed:27010430"
FT MUTAGEN 229
FT /note="R->A: No effect on CDE RNA-binding."
FT /evidence="ECO:0000269|PubMed:25026077,
FT ECO:0000269|PubMed:27010430"
FT MUTAGEN 233
FT /note="R->A: No effect on CDE RNA-binding."
FT /evidence="ECO:0000269|PubMed:25026077"
FT MUTAGEN 238
FT /note="S->A: Decreases CDE RNA-binding."
FT /evidence="ECO:0000269|PubMed:25026077"
FT MUTAGEN 239
FT /note="K->A: Strongly decresases CDE and ADE RNA-binding.
FT Increases target-mRNA expression. Abolishes CDE RNA-binding
FT and highly increases target-mRNA expression; when
FT associated with A-260. Increases target-mRNA expression.
FT Increases ICOS surface expression; when associated with A-
FT 220 and A-260."
FT /evidence="ECO:0000269|PubMed:25026077,
FT ECO:0000269|PubMed:25282160, ECO:0000269|PubMed:27010430"
FT MUTAGEN 250
FT /note="Y->A: Decreases CDE RNA-binding. Increases target-
FT mRNA expression."
FT /evidence="ECO:0000269|PubMed:25026077,
FT ECO:0000269|PubMed:27010430"
FT MUTAGEN 251
FT /note="R->A: No effect on CDE RNA-binding."
FT /evidence="ECO:0000269|PubMed:25026077"
FT MUTAGEN 253
FT /note="S->A: Slightly decresases CDE and ADE RNA-binding."
FT /evidence="ECO:0000269|PubMed:25026077,
FT ECO:0000269|PubMed:27010430"
FT MUTAGEN 259
FT /note="K->A: Strongly decresases CDE and ADE RNA-binding."
FT /evidence="ECO:0000269|PubMed:25026077,
FT ECO:0000269|PubMed:27010430"
FT MUTAGEN 260
FT /note="R->A: Strongly decresases CDE and ADE RNA-binding.
FT Increases target-mRNA expression. Abolishes CDE RNA-binding
FT and highly increases target-mRNA expression; when
FT associated with A-239. Increases target-mRNA expression.
FT Increases ICOS surface expression; when associated with A-
FT 220 and A-239."
FT /evidence="ECO:0000269|PubMed:25026077,
FT ECO:0000269|PubMed:25282160, ECO:0000269|PubMed:27010430"
FT MUTAGEN 264
FT /note="S->A: Decreases CDE RNA-binding."
FT /evidence="ECO:0000269|PubMed:25026077"
FT MUTAGEN 265
FT /note="S->Y: Decresases CDE and ADE RNA-binding."
FT /evidence="ECO:0000269|PubMed:25026077,
FT ECO:0000269|PubMed:27010430"
FT MUTAGEN 293
FT /note="E->A: No effect on CDE RNA-binding."
FT /evidence="ECO:0000269|PubMed:25026077"
FT MUTAGEN 314
FT /note="K->A: No effect on CDE RNA-binding."
FT /evidence="ECO:0000269|PubMed:25026077"
FT MUTAGEN 419
FT /note="C->R: No effect on RNA-binding."
FT /evidence="ECO:0000269|PubMed:23663784"
FT MUTAGEN 434
FT /note="C->R: No effect on localization to stress granules,
FT reduces RNA-binding."
FT MUTAGEN 488
FT /note="R->G: No effect on cleavage."
FT /evidence="ECO:0000269|PubMed:25282160"
FT MUTAGEN 510
FT /note="R->G: Abolishes the formation of a preferential
FT cleavage product. Abolishes protein cleavage; when
FT associated with G-579."
FT /evidence="ECO:0000269|PubMed:25282160"
FT MUTAGEN 560
FT /note="R->G: No effect on cleavage."
FT /evidence="ECO:0000269|PubMed:25282160"
FT MUTAGEN 579
FT /note="R->G: Abolishes the formation of an alternative
FT cleavage product. Abolishes protein cleavage; when
FT associated with G-510."
FT /evidence="ECO:0000269|PubMed:25282160"
FT MUTAGEN 687..1130
FT /note="Missing: Failed to reduce poly(A) tailed ICOS mRNA.
FT Failed to regulate the production of inflammatory
FT cytokines."
FT /evidence="ECO:0000269|PubMed:31636267"
FT TURN 15..17
FT /evidence="ECO:0007829|PDB:4TXA"
FT STRAND 23..26
FT /evidence="ECO:0007829|PDB:4TXA"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:4TXA"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:4TXA"
FT HELIX 39..45
FT /evidence="ECO:0007829|PDB:4TXA"
FT STRAND 47..49
FT /evidence="ECO:0007829|PDB:4TXA"
FT TURN 51..53
FT /evidence="ECO:0007829|PDB:4TXA"
FT TURN 60..63
FT /evidence="ECO:0007829|PDB:4TXA"
FT HELIX 68..71
FT /evidence="ECO:0007829|PDB:4TXA"
FT TURN 72..74
FT /evidence="ECO:0007829|PDB:4TXA"
FT HELIX 90..107
FT /evidence="ECO:0007829|PDB:4TXA"
FT HELIX 108..110
FT /evidence="ECO:0007829|PDB:4TXA"
FT HELIX 131..141
FT /evidence="ECO:0007829|PDB:4TXA"
FT HELIX 148..170
FT /evidence="ECO:0007829|PDB:4TXA"
FT HELIX 176..189
FT /evidence="ECO:0007829|PDB:6TQB"
FT HELIX 197..211
FT /evidence="ECO:0007829|PDB:6TQB"
FT STRAND 216..218
FT /evidence="ECO:0007829|PDB:4QI0"
FT HELIX 219..230
FT /evidence="ECO:0007829|PDB:6TQB"
FT TURN 231..233
FT /evidence="ECO:0007829|PDB:6TQB"
FT HELIX 239..251
FT /evidence="ECO:0007829|PDB:6TQB"
FT STRAND 255..260
FT /evidence="ECO:0007829|PDB:6TQB"
FT STRAND 263..269
FT /evidence="ECO:0007829|PDB:6TQB"
FT HELIX 271..273
FT /evidence="ECO:0007829|PDB:6TQB"
FT HELIX 276..293
FT /evidence="ECO:0007829|PDB:6TQB"
FT HELIX 300..308
FT /evidence="ECO:0007829|PDB:6TQB"
FT STRAND 309..313
FT /evidence="ECO:0007829|PDB:6TQB"
FT HELIX 314..324
FT /evidence="ECO:0007829|PDB:6TQB"
FT HELIX 329..343
FT /evidence="ECO:0007829|PDB:4TXA"
FT HELIX 350..353
FT /evidence="ECO:0007829|PDB:4TXA"
FT HELIX 354..361
FT /evidence="ECO:0007829|PDB:4TXA"
FT HELIX 374..397
FT /evidence="ECO:0007829|PDB:4TXA"
SQ SEQUENCE 1130 AA; 125378 MW; 5B750E5D28FC86F2 CRC64;
MPVQAPQWTD FLSCPICTQT FDETIRKPIS LGCGHTVCKM CLNKLHRKAC PFDQTTINTD
IELLPVNSAL LQLVGAQIPE 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 LPSAPILSDE
SAVDLSNRKP PALPNGIASS GSTVTQLIPR GTDPSFDSSL KPVKLDHLSS SAPGSPPDLL
ESAPKSISAL PVNPHPVPPR GPTDLPPMPV TKPIQMVPRG SQLYPAQQAD VYYQDPRGSA
PAFETAPYQQ GMYYTPPPCV SRFVRPPPSA PEPGPPYLDH YSPYLQDRVI NSQYGTQPQQ
YPPMYPAHYD GRRVYPAQSY TREEMFRESP IPIDIPSAAV PSYVPESRER YQQVEGYYPV
APHPAQIRPS YPRDPPYSRL PPPQPHPSLD ELHRRRKEIM AQLEERKVIS PPPFAPSPTL
PPAFHPEEFL DEDLKVAGKY KANDYSQYSP WSCDTIGSYI GTKDAKPKDV VAAGSVEMMN
VESKGTREQR LDLQRRAVET SDDDLIPFGD RPTVSRFGAI SRTSKTLYQG AGPLQAIAPQ
GAPTKSINIS DYSAYGAHGG WGDSPYSPHA NIPPQGHFIE REKMSMAEVA SHGKPLLSAE
REQLRLELQQ LNHQISQQTQ LRGLEAVSNR LVLQREVNTL ASQPQPPQLP PKWPGMISSE
QLSLELHQVE REIGKRTREL SMENQCSVDM KSKLGTSKQA ENGQPEPQNK IRTEDLTLTF
SDVPNGSALT QENLSLLSNK TSSLNLSEDS EGGGDNNDSQ RSGVVSNSAP
