RNC_HUMAN
ID RNC_HUMAN Reviewed; 1374 AA.
AC Q9NRR4; E7EMP9; Q7Z5V2; Q86YH0; Q9NW73; Q9Y2V9; Q9Y4Y0;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2002, sequence version 2.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Ribonuclease 3;
DE EC=3.1.26.3 {ECO:0000269|PubMed:15565168, ECO:0000269|PubMed:15574589, ECO:0000269|PubMed:26027739, ECO:0000269|PubMed:26748718};
DE AltName: Full=Protein Drosha {ECO:0000303|PubMed:14508493};
DE AltName: Full=Ribonuclease III;
DE Short=RNase III;
DE AltName: Full=p241;
GN Name=DROSHA; Synonyms=RN3, RNASE3L, RNASEN;
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), FUNCTION, TISSUE SPECIFICITY, AND
RP SUBCELLULAR LOCATION.
RX PubMed=10948199; DOI=10.1074/jbc.m005494200;
RA Wu H., Xu H., Miraglia L.J., Crooke S.T.;
RT "Human RNase III is a 160-kDa protein involved in preribosomal RNA
RT processing.";
RL J. Biol. Chem. 275:36957-36965(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Cerebellum;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 166-613 (ISOFORM 2), AND INTERACTION WITH
RP SP1.
RC TISSUE=Colon;
RX PubMed=10976766; DOI=10.1023/a:1007177623283;
RA Gunther M., Laithier M., Brison O.;
RT "A set of proteins interacting with transcription factor Sp1 identified in
RT a two-hybrid screening.";
RL Mol. Cell. Biochem. 210:131-142(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 603-1374.
RC TISSUE=Embryo;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 653-1374 (ISOFORM 1).
RC TISSUE=Cervix, and Skin;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 706-1374.
RC TISSUE=Aorta;
RA Wei Y.J., Ding J.F., Xiong H., Zhou Y., Liew C.C.;
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP FUNCTION.
RX PubMed=14508493; DOI=10.1038/nature01957;
RA Lee Y., Ahn C., Han J., Choi H., Kim J., Yim J., Lee J., Provost P.,
RA Raadmark O., Kim S., Kim V.N.;
RT "The nuclear RNase III Drosha initiates microRNA processing.";
RL Nature 425:415-419(2003).
RN [9]
RP FUNCTION, AND INTERACTION WITH DGCR8.
RX PubMed=15589161; DOI=10.1016/j.cub.2004.11.001;
RA Landthaler M., Yalcin A., Tuschl T.;
RT "The human DiGeorge syndrome critical region gene 8 and its D. melanogaster
RT homolog are required for miRNA biogenesis.";
RL Curr. Biol. 14:2162-2167(2004).
RN [10]
RP FUNCTION, IDENTIFICATION IN THE MICROPROCESSOR COMPLEX, INTERACTION WITH
RP DGCR8, CATALYTIC ACTIVITY, COFACTOR, DOMAIN, AND MUTAGENESIS OF GLU-993;
RP GLU-1045; GLU-1171 AND GLU-1222.
RX PubMed=15574589; DOI=10.1101/gad.1262504;
RA Han J., Lee Y., Yeom K.-H., Kim Y.-K., Jin H., Kim V.N.;
RT "The Drosha-DGCR8 complex in primary microRNA processing.";
RL Genes Dev. 18:3016-3027(2004).
RN [11]
RP FUNCTION, AND IDENTIFICATION IN THE MICROPROCESSOR COMPLEX.
RX PubMed=15531877; DOI=10.1038/nature03120;
RA Gregory R.I., Yan K.-P., Amuthan G., Chendrimada T., Doratotaj B.,
RA Cooch N., Shiekhattar R.;
RT "The microprocessor complex mediates the genesis of microRNAs.";
RL Nature 432:235-240(2004).
RN [12]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15565168; DOI=10.1038/sj.emboj.7600491;
RA Zeng Y., Yi R., Cullen B.R.;
RT "Recognition and cleavage of primary microRNA precursors by the nuclear
RT processing enzyme Drosha.";
RL EMBO J. 24:138-148(2005).
RN [13]
RP FUNCTION, AND IDENTIFICATION IN THE MICROPROCESSOR COMPLEX.
RX PubMed=16751099; DOI=10.1016/j.cell.2006.03.043;
RA Han J., Lee Y., Yeom K.-H., Nam J.-W., Heo I., Rhee J.-K., Sohn S.Y.,
RA Cho Y., Zhang B.-T., Kim V.N.;
RT "Molecular basis for the recognition of primary microRNAs by the Drosha-
RT DGCR8 complex.";
RL Cell 125:887-901(2006).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16906129; DOI=10.1038/sj.embor.7400783;
RA Pauley K.M., Eystathioy T., Jakymiw A., Hamel J.C., Fritzler M.J.,
RA Chan E.K.L.;
RT "Formation of GW bodies is a consequence of microRNA genesis.";
RL EMBO Rep. 7:904-910(2006).
RN [15]
RP FUNCTION.
RX PubMed=17159994; DOI=10.1038/nsmb1182;
RA Faller M., Matsunaga M., Yin S., Loo J.A., Guo F.;
RT "Heme is involved in microRNA processing.";
RL Nat. Struct. Mol. Biol. 14:23-29(2007).
RN [16]
RP INTERACTION WITH SNIP1.
RX PubMed=18632581; DOI=10.1073/pnas.0804218105;
RA Yu B., Bi L., Zheng B., Ji L., Chevalier D., Agarwal M., Ramachandran V.,
RA Li W., Lagrange T., Walker J.C., Chen X.;
RT "The FHA domain proteins DAWDLE in Arabidopsis and SNIP1 in humans act in
RT small RNA biogenesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10073-10078(2008).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP SUBCELLULAR LOCATION.
RX PubMed=22118463; DOI=10.1016/j.cell.2011.10.039;
RA Piskounova E., Polytarchou C., Thornton J.E., LaPierre R.J.,
RA Pothoulakis C., Hagan J.P., Iliopoulos D., Gregory R.I.;
RT "Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct
RT mechanisms.";
RL Cell 147:1066-1079(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-373, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-355 AND SER-373, 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 [21]
RP FUNCTION, SUBUNIT, CATALYTIC ACTIVITY, AND MUTAGENESIS OF GLU-1045 AND
RP GLU-1222.
RX PubMed=26027739; DOI=10.1016/j.cell.2015.05.010;
RA Nguyen T.A., Jo M.H., Choi Y.G., Park J., Kwon S.C., Hohng S., Kim V.N.,
RA Woo J.S.;
RT "Functional anatomy of the human microprocessor.";
RL Cell 161:1374-1387(2015).
RN [22]
RP INTERACTION WITH PUS10.
RX PubMed=31819270; DOI=10.1038/s41589-019-0420-5;
RA Song J., Zhuang Y., Zhu C., Meng H., Lu B., Xie B., Peng J., Li M., Yi C.;
RT "Differential roles of human PUS10 in miRNA processing and tRNA
RT pseudouridylation.";
RL Nat. Chem. Biol. 16:160-169(2020).
RN [23]
RP STRUCTURE BY NMR OF 1259-1337.
RX PubMed=20226070; DOI=10.1186/1758-907x-1-2;
RA Mueller G.A., Miller M.T., Derose E.F., Ghosh M., London R.E., Hall T.M.;
RT "Solution structure of the Drosha double-stranded RNA-binding domain.";
RL Silence 1:2-2(2010).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) OF 411-1365 OF MUTANT
RP GLN-1045/GLN-1222 IN COMPLEX WITH DGCR8 AND ZINC IONS, FUNCTION, CATALYTIC
RP ACTIVITY, INTERACTION WITH DGCR8, SUBUNIT, MUTAGENESIS OF CYS-536; CYS-538;
RP CYS-561; 622-ARG-PHE-623; CYS-676; 835-ARG-ARG-836; ARG-914; ARG-923;
RP TYR-927; 938-ARG--LYS-940; VAL-1077; LEU-1194 AND VAL-1243, AND REGION.
RX PubMed=26748718; DOI=10.1016/j.cell.2015.12.019;
RA Kwon S.C., Nguyen T.A., Choi Y.G., Jo M.H., Hohng S., Kim V.N., Woo J.S.;
RT "Structure of human DROSHA.";
RL Cell 164:81-90(2016).
CC -!- FUNCTION: Ribonuclease III double-stranded (ds) RNA-specific
CC endoribonuclease that is involved in the initial step of microRNA
CC (miRNA) biogenesis. Component of the microprocessor complex that is
CC required to process primary miRNA transcripts (pri-miRNAs) to release
CC precursor miRNA (pre-miRNA) in the nucleus. Within the microprocessor
CC complex, DROSHA cleaves the 3' and 5' strands of a stem-loop in pri-
CC miRNAs (processing center 11 bp from the dsRNA-ssRNA junction) to
CC release hairpin-shaped pre-miRNAs that are subsequently cut by the
CC cytoplasmic DICER to generate mature miRNAs. Involved also in pre-rRNA
CC processing. Cleaves double-strand RNA and does not cleave single-strand
CC RNA. Involved in the formation of GW bodies.
CC {ECO:0000269|PubMed:10948199, ECO:0000269|PubMed:14508493,
CC ECO:0000269|PubMed:15531877, ECO:0000269|PubMed:15565168,
CC ECO:0000269|PubMed:15574589, ECO:0000269|PubMed:15589161,
CC ECO:0000269|PubMed:16751099, ECO:0000269|PubMed:16906129,
CC ECO:0000269|PubMed:17159994, ECO:0000269|PubMed:26027739,
CC ECO:0000269|PubMed:26748718}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Endonucleolytic cleavage to 5'-phosphomonoester.; EC=3.1.26.3;
CC Evidence={ECO:0000269|PubMed:15565168, ECO:0000269|PubMed:15574589,
CC ECO:0000269|PubMed:26027739, ECO:0000269|PubMed:26748718};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000305|PubMed:15574589};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000305|PubMed:15574589};
CC Note=Each RNase III domain binds at least one Mg(2+) or Mn(2+) ion.
CC {ECO:0000305};
CC -!- SUBUNIT: Component of the microprocessor complex, or pri-miRNA
CC processing protein complex, which is composed of DROSHA and DGCR8
CC (PubMed:15589161, PubMed:15574589, PubMed:15531877, PubMed:16751099,
CC PubMed:26027739, PubMed:26748718). The microprocessor complex is a
CC heterotrimer; each of the two DROSHA RNase III domains binds one DGCR8
CC (via C-terminal region) (PubMed:26027739, PubMed:26748718). Interacts
CC with SP1 and SNIP1 (PubMed:10976766, PubMed:18632581). Interacts with
CC SRRT/ARS2 (By similarity). Interacts with CPSF3 and ISY1; this
CC interaction is in an RNA dependent manner (By similarity). Interacts
CC with PUS10; interaction promotes pri-miRNAs processing
CC (PubMed:31819270). {ECO:0000250|UniProtKB:Q5HZJ0,
CC ECO:0000269|PubMed:10976766, ECO:0000269|PubMed:15531877,
CC ECO:0000269|PubMed:15574589, ECO:0000269|PubMed:15589161,
CC ECO:0000269|PubMed:16751099, ECO:0000269|PubMed:18632581,
CC ECO:0000269|PubMed:26027739, ECO:0000269|PubMed:26748718,
CC ECO:0000269|PubMed:31819270}.
CC -!- INTERACTION:
CC Q9NRR4; P17844: DDX5; NbExp=6; IntAct=EBI-528367, EBI-351962;
CC Q9NRR4; Q8WYQ5: DGCR8; NbExp=13; IntAct=EBI-528367, EBI-528411;
CC Q9NRR4; P35637: FUS; NbExp=2; IntAct=EBI-528367, EBI-400434;
CC Q9NRR4; Q15797: SMAD1; NbExp=3; IntAct=EBI-528367, EBI-1567153;
CC Q9NRR4; P04637: TP53; NbExp=5; IntAct=EBI-528367, EBI-366083;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10948199,
CC ECO:0000269|PubMed:16906129, ECO:0000269|PubMed:22118463}. Nucleus,
CC nucleolus {ECO:0000269|PubMed:10948199}. Note=A fraction is
CC translocated to the nucleolus during the S phase of the cell cycle.
CC Localized in GW bodies (GWBs), also known as P-bodies.
CC {ECO:0000269|PubMed:10948199, ECO:0000269|PubMed:22118463}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9NRR4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NRR4-2; Sequence=VSP_005777;
CC Name=3;
CC IsoId=Q9NRR4-3; Sequence=VSP_012450, VSP_012451, VSP_012452,
CC VSP_012453;
CC Name=4;
CC IsoId=Q9NRR4-4; Sequence=VSP_012450, VSP_012451;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:10948199}.
CC -!- DOMAIN: The 2 RNase III domains form an intramolecular dimer where the
CC domain 1 cuts the 3'strand while the domain 2 cleaves the 5'strand of
CC pri-miRNAs, independently of each other. {ECO:0000269|PubMed:15574589}.
CC -!- SIMILARITY: Belongs to the ribonuclease III family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD29637.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAA91511.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=The dark side of RNA - Issue
CC 87 of October 2007;
CC URL="https://web.expasy.org/spotlight/back_issues/087";
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DR EMBL; AF189011; AAF80558.1; -; mRNA.
DR EMBL; BX647724; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC008768; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC022417; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC106802; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AJ242976; CAB45133.1; -; mRNA.
DR EMBL; AK001121; BAA91511.1; ALT_INIT; mRNA.
DR EMBL; BC041162; AAH41162.1; -; mRNA.
DR EMBL; BC054003; AAH54003.1; -; mRNA.
DR EMBL; AF116910; AAD29637.1; ALT_FRAME; mRNA.
DR CCDS; CCDS47194.1; -. [Q9NRR4-4]
DR CCDS; CCDS47195.1; -. [Q9NRR4-1]
DR RefSeq; NP_001093882.1; NM_001100412.1. [Q9NRR4-4]
DR RefSeq; NP_037367.3; NM_013235.4. [Q9NRR4-1]
DR RefSeq; XP_005248348.1; XM_005248291.3.
DR RefSeq; XP_005248351.1; XM_005248294.3. [Q9NRR4-2]
DR PDB; 2KHX; NMR; -; A=1259-1337.
DR PDB; 2NA2; NMR; -; A=1259-1337.
DR PDB; 5B16; X-ray; 3.20 A; A=411-458, A=522-711, A=850-1365.
DR PDB; 6LXD; EM; 3.90 A; A=391-1374.
DR PDB; 6LXE; EM; 4.20 A; A=391-1374.
DR PDB; 6V5B; EM; 3.70 A; A=353-1365.
DR PDB; 6V5C; EM; 4.40 A; A=353-1365.
DR PDBsum; 2KHX; -.
DR PDBsum; 2NA2; -.
DR PDBsum; 5B16; -.
DR PDBsum; 6LXD; -.
DR PDBsum; 6LXE; -.
DR PDBsum; 6V5B; -.
DR PDBsum; 6V5C; -.
DR AlphaFoldDB; Q9NRR4; -.
DR BMRB; Q9NRR4; -.
DR SMR; Q9NRR4; -.
DR BioGRID; 118870; 69.
DR ComplexPortal; CPX-3080; Microprocessor complex.
DR CORUM; Q9NRR4; -.
DR DIP; DIP-33300N; -.
DR IntAct; Q9NRR4; 35.
DR MINT; Q9NRR4; -.
DR STRING; 9606.ENSP00000425979; -.
DR iPTMnet; Q9NRR4; -.
DR PhosphoSitePlus; Q9NRR4; -.
DR BioMuta; DROSHA; -.
DR DMDM; 20139357; -.
DR EPD; Q9NRR4; -.
DR jPOST; Q9NRR4; -.
DR MassIVE; Q9NRR4; -.
DR MaxQB; Q9NRR4; -.
DR PaxDb; Q9NRR4; -.
DR PeptideAtlas; Q9NRR4; -.
DR PRIDE; Q9NRR4; -.
DR ProteomicsDB; 16990; -.
DR ProteomicsDB; 82409; -. [Q9NRR4-1]
DR ProteomicsDB; 82410; -. [Q9NRR4-2]
DR ProteomicsDB; 82411; -. [Q9NRR4-3]
DR Antibodypedia; 22652; 291 antibodies from 37 providers.
DR DNASU; 29102; -.
DR Ensembl; ENST00000344624.8; ENSP00000339845.3; ENSG00000113360.17. [Q9NRR4-1]
DR Ensembl; ENST00000511367.6; ENSP00000425979.2; ENSG00000113360.17. [Q9NRR4-1]
DR Ensembl; ENST00000513349.5; ENSP00000424161.1; ENSG00000113360.17. [Q9NRR4-4]
DR GeneID; 29102; -.
DR KEGG; hsa:29102; -.
DR MANE-Select; ENST00000344624.8; ENSP00000339845.3; NM_001382508.1; NP_001369437.1.
DR UCSC; uc003jhg.3; human. [Q9NRR4-1]
DR CTD; 29102; -.
DR DisGeNET; 29102; -.
DR GeneCards; DROSHA; -.
DR HGNC; HGNC:17904; DROSHA.
DR HPA; ENSG00000113360; Low tissue specificity.
DR MIM; 608828; gene.
DR neXtProt; NX_Q9NRR4; -.
DR OpenTargets; ENSG00000113360; -.
DR PharmGKB; PA142671060; -.
DR VEuPathDB; HostDB:ENSG00000113360; -.
DR eggNOG; KOG1817; Eukaryota.
DR GeneTree; ENSGT00730000111052; -.
DR HOGENOM; CLU_004383_0_0_1; -.
DR InParanoid; Q9NRR4; -.
DR OMA; CSNFCEK; -.
DR OrthoDB; 935825at2759; -.
DR PhylomeDB; Q9NRR4; -.
DR TreeFam; TF314734; -.
DR BRENDA; 3.1.26.3; 2681.
DR PathwayCommons; Q9NRR4; -.
DR Reactome; R-HSA-203927; MicroRNA (miRNA) biogenesis.
DR SignaLink; Q9NRR4; -.
DR SIGNOR; Q9NRR4; -.
DR BioGRID-ORCS; 29102; 303 hits in 1081 CRISPR screens.
DR ChiTaRS; DROSHA; human.
DR EvolutionaryTrace; Q9NRR4; -.
DR GeneWiki; RNASEN; -.
DR GenomeRNAi; 29102; -.
DR Pharos; Q9NRR4; Tbio.
DR PRO; PR:Q9NRR4; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9NRR4; protein.
DR Bgee; ENSG00000113360; Expressed in endothelial cell and 192 other tissues.
DR ExpressionAtlas; Q9NRR4; baseline and differential.
DR Genevisible; Q9NRR4; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070877; C:microprocessor complex; IDA:BHF-UCL.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0017151; F:DEAD/H-box RNA helicase binding; IPI:BHF-UCL.
DR GO; GO:0003725; F:double-stranded RNA binding; IBA:GO_Central.
DR GO; GO:0001530; F:lipopolysaccharide binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070878; F:primary miRNA binding; IDA:ARUK-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL.
DR GO; GO:0070412; F:R-SMAD binding; IPI:BHF-UCL.
DR GO; GO:0004525; F:ribonuclease III activity; IDA:WormBase.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0046332; F:SMAD binding; IPI:BHF-UCL.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IDA:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB.
DR GO; GO:0010586; P:miRNA metabolic process; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0031054; P:pre-miRNA processing; IEA:Ensembl.
DR GO; GO:0031053; P:primary miRNA processing; IDA:WormBase.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0050727; P:regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:2000628; P:regulation of miRNA metabolic process; IEA:Ensembl.
DR GO; GO:0045589; P:regulation of regulatory T cell differentiation; IEA:Ensembl.
DR GO; GO:0006396; P:RNA processing; IBA:GO_Central.
DR GO; GO:0006364; P:rRNA processing; IEA:InterPro.
DR CDD; cd19877; DSRM_RNAse_III_meta_like; 1.
DR CDD; cd00593; RIBOc; 2.
DR DisProt; DP02463; -.
DR Gene3D; 1.10.1520.10; -; 2.
DR HAMAP; MF_00104; RNase_III; 1.
DR InterPro; IPR014720; dsRBD_dom.
DR InterPro; IPR011907; RNase_III.
DR InterPro; IPR000999; RNase_III_dom.
DR InterPro; IPR044442; RNAse_III_DSRM__animal.
DR InterPro; IPR036389; RNase_III_sf.
DR PANTHER; PTHR11207; PTHR11207; 1.
DR Pfam; PF00035; dsrm; 1.
DR Pfam; PF14622; Ribonucleas_3_3; 1.
DR Pfam; PF00636; Ribonuclease_3; 1.
DR SMART; SM00358; DSRM; 1.
DR SMART; SM00535; RIBOc; 2.
DR SUPFAM; SSF69065; SSF69065; 2.
DR PROSITE; PS50137; DS_RBD; 1.
DR PROSITE; PS00517; RNASE_3_1; 2.
DR PROSITE; PS50142; RNASE_3_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Endonuclease; Hydrolase; Magnesium;
KW Manganese; Metal-binding; Nuclease; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Ribosome biogenesis; RNA-binding;
KW RNA-mediated gene silencing.
FT CHAIN 1..1374
FT /note="Ribonuclease 3"
FT /id="PRO_0000180468"
FT DOMAIN 876..1056
FT /note="RNase III 1"
FT DOMAIN 1107..1233
FT /note="RNase III 2"
FT DOMAIN 1260..1334
FT /note="DRBM"
FT REGION 1..95
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 130..406
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 390..1365
FT /note="Necessary for interaction with DGCR8 and pri-miRNA
FT processing activity"
FT /evidence="ECO:0000269|PubMed:26027739,
FT ECO:0000269|PubMed:26748718"
FT REGION 452..497
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 69..95
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 130..164
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 177..204
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 217..315
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 353..395
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 452..478
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 479..493
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 536
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:26748718"
FT BINDING 538
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:26748718"
FT BINDING 549
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:26748718"
FT BINDING 561
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26748718"
FT BINDING 609
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26748718"
FT BINDING 676
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26748718"
FT BINDING 680
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26748718"
FT BINDING 969
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O67082"
FT BINDING 1026
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:26748718"
FT BINDING 1042
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O67082"
FT BINDING 1045
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O67082,
FT ECO:0000305|PubMed:15574589"
FT BINDING 1147
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O67082"
FT BINDING 1219
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O67082"
FT BINDING 1222
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O67082,
FT ECO:0000305|PubMed:15574589"
FT SITE 1215
FT /note="Important for activity"
FT /evidence="ECO:0000250"
FT MOD_RES 355
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 373
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 285..353
FT /note="RERERERHRHRDNRRSPSLERSYKKEYKRSGRSYGLSVVPEPAGCTPELPGE
FT IIKNTDSWAPPLEIVNH -> S (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10976766"
FT /id="VSP_005777"
FT VAR_SEQ 316..352
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_012450"
FT VAR_SEQ 353
FT /note="H -> S (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_012451"
FT VAR_SEQ 1198..1229
FT /note="EYAITNDKTKRPVALRTKTLADLLESFIAALY -> VWSIYLLSNCDCCLLR
FT PSLVFLQTMNEVCSLK (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_012452"
FT VAR_SEQ 1230..1374
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_012453"
FT VARIANT 67
FT /note="P -> T (in dbSNP:rs35342496)"
FT /id="VAR_051866"
FT VARIANT 321
FT /note="S -> L (in dbSNP:rs55656741)"
FT /id="VAR_061778"
FT MUTAGEN 536
FT /note="C->A: Impairs protein folding and stability; when
FT associated with A-538."
FT /evidence="ECO:0000269|PubMed:26748718"
FT MUTAGEN 538
FT /note="C->A: Impairs protein folding and stability; when
FT associated with A-536."
FT /evidence="ECO:0000269|PubMed:26748718"
FT MUTAGEN 561
FT /note="C->A: Impairs protein folding and stability."
FT /evidence="ECO:0000269|PubMed:26748718"
FT MUTAGEN 622..623
FT /note="RF->AA: Abolishes RNase activity."
FT /evidence="ECO:0000269|PubMed:26748718"
FT MUTAGEN 676
FT /note="C->A: Impairs protein folding and stability."
FT /evidence="ECO:0000269|PubMed:26748718"
FT MUTAGEN 835..836
FT /note="RR->AA: Abolishes RNase activity."
FT /evidence="ECO:0000269|PubMed:26748718"
FT MUTAGEN 914
FT /note="R->M: Impairs RNase activity."
FT /evidence="ECO:0000269|PubMed:26748718"
FT MUTAGEN 923
FT /note="R->A: Abolishes RNase activity; when associated with
FT A-927."
FT /evidence="ECO:0000269|PubMed:26748718"
FT MUTAGEN 927
FT /note="Y->A: Abolishes RNase activity; when associated with
FT A-923."
FT /evidence="ECO:0000269|PubMed:26748718"
FT MUTAGEN 938..940
FT /note="RKK->QQQ: Abolishes RNase activity."
FT /evidence="ECO:0000269|PubMed:26748718"
FT MUTAGEN 993
FT /note="E->A,Q: No effect on pri-miRNA processing activity."
FT /evidence="ECO:0000269|PubMed:15574589"
FT MUTAGEN 1045
FT /note="E->Q: Impairs pri-miRNA processing activity.
FT Abolishes cleavage of the 3' strand. Abolishes enzyme
FT activity; when associated with Q-1222."
FT /evidence="ECO:0000269|PubMed:15574589,
FT ECO:0000269|PubMed:26027739"
FT MUTAGEN 1077
FT /note="V->E: Loss of one DGCR8 interaction site; no effect
FT on the second DGCR8 interaction site."
FT /evidence="ECO:0000269|PubMed:26748718"
FT MUTAGEN 1171
FT /note="E->A,Q: No effect on pri-miRNA processing activity."
FT /evidence="ECO:0000269|PubMed:15574589"
FT MUTAGEN 1194
FT /note="L->R: Abolishes interaction with DGCR8."
FT /evidence="ECO:0000269|PubMed:26748718"
FT MUTAGEN 1222
FT /note="E->Q: Impairs pri-miRNA processing activity.
FT Abolishes cleavage of the 5' strand. Abolishes enzyme
FT activity; when associated with Q-1045."
FT /evidence="ECO:0000269|PubMed:15574589,
FT ECO:0000269|PubMed:26027739"
FT MUTAGEN 1243
FT /note="V->D: Abolishes interaction with DGCR8."
FT /evidence="ECO:0000269|PubMed:26748718"
FT CONFLICT 166..174
FT /note="YQYPPGYSH -> RERERTSLE (in Ref. 4; CAB45133)"
FT /evidence="ECO:0000305"
FT CONFLICT 612
FT /note="L -> P (in Ref. 4; CAB45133)"
FT /evidence="ECO:0000305"
FT CONFLICT 1020
FT /note="R -> P (in Ref. 1; AAF80558)"
FT /evidence="ECO:0000305"
FT CONFLICT 1230
FT /note="I -> T (in Ref. 1; AAF80558)"
FT /evidence="ECO:0000305"
FT CONFLICT 1272
FT /note="L -> R (in Ref. 2; BX647724)"
FT /evidence="ECO:0000305"
FT STRAND 413..415
FT /evidence="ECO:0007829|PDB:5B16"
FT STRAND 420..423
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 441..451
FT /evidence="ECO:0007829|PDB:5B16"
FT TURN 455..457
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 506..510
FT /evidence="ECO:0007829|PDB:5B16"
FT STRAND 531..535
FT /evidence="ECO:0007829|PDB:5B16"
FT TURN 547..550
FT /evidence="ECO:0007829|PDB:5B16"
FT STRAND 563..565
FT /evidence="ECO:0007829|PDB:5B16"
FT TURN 568..570
FT /evidence="ECO:0007829|PDB:5B16"
FT STRAND 572..580
FT /evidence="ECO:0007829|PDB:5B16"
FT STRAND 582..584
FT /evidence="ECO:0007829|PDB:5B16"
FT STRAND 591..593
FT /evidence="ECO:0007829|PDB:5B16"
FT STRAND 595..610
FT /evidence="ECO:0007829|PDB:5B16"
FT STRAND 618..632
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 642..652
FT /evidence="ECO:0007829|PDB:5B16"
FT TURN 653..656
FT /evidence="ECO:0007829|PDB:5B16"
FT STRAND 678..686
FT /evidence="ECO:0007829|PDB:5B16"
FT STRAND 694..696
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 699..708
FT /evidence="ECO:0007829|PDB:5B16"
FT STRAND 737..743
FT /evidence="ECO:0007829|PDB:5B16"
FT STRAND 751..754
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 856..860
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 863..875
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 876..878
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 880..883
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 890..897
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 910..919
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 966..986
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 993..1004
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 1006..1013
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 1014..1016
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 1018..1021
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 1033..1054
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 1057..1068
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 1072..1079
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 1085..1088
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 1095..1098
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 1104..1114
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 1121..1127
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 1144..1164
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 1171..1181
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 1184..1194
FT /evidence="ECO:0007829|PDB:5B16"
FT STRAND 1203..1205
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 1214..1231
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 1234..1244
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 1246..1248
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 1249..1254
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 1261..1269
FT /evidence="ECO:0007829|PDB:5B16"
FT STRAND 1275..1277
FT /evidence="ECO:0007829|PDB:2KHX"
FT STRAND 1283..1291
FT /evidence="ECO:0007829|PDB:5B16"
FT STRAND 1292..1294
FT /evidence="ECO:0007829|PDB:2KHX"
FT STRAND 1297..1304
FT /evidence="ECO:0007829|PDB:5B16"
FT STRAND 1307..1316
FT /evidence="ECO:0007829|PDB:5B16"
FT HELIX 1317..1330
FT /evidence="ECO:0007829|PDB:5B16"
SQ SEQUENCE 1374 AA; 159316 MW; ED6FDEA09F3B8092 CRC64;
MMQGNTCHRM SFHPGRGCPR GRGGHGARPS APSFRPQNLR LLHPQQPPVQ YQYEPPSAPS
TTFSNSPAPN FLPPRPDFVP FPPPMPPSAQ GPLPPCPIRP PFPNHQMRHP FPVPPCFPPM
PPPMPCPNNP PVPGAPPGQG TFPFMMPPPS MPHPPPPPVM PQQVNYQYPP GYSHHNFPPP
SFNSFQNNPS SFLPSANNSS SPHFRHLPPY PLPKAPSERR SPERLKHYDD HRHRDHSHGR
GERHRSLDRR ERGRSPDRRR QDSRYRSDYD RGRTPSRHRS YERSRERERE RHRHRDNRRS
PSLERSYKKE YKRSGRSYGL SVVPEPAGCT PELPGEIIKN TDSWAPPLEI VNHRSPSREK
KRARWEEEKD RWSDNQSSGK DKNYTSIKEK EPEETMPDKN EEEEEELLKP VWIRCTHSEN
YYSSDPMDQV GDSTVVGTSR LRDLYDKFEE ELGSRQEKAK AARPPWEPPK TKLDEDLESS
SESECESDED STCSSSSDSE VFDVIAEIKR KKAHPDRLHD ELWYNDPGQM NDGPLCKCSA
KARRTGIRHS IYPGEEAIKP CRPMTNNAGR LFHYRITVSP PTNFLTDRPT VIEYDDHEYI
FEGFSMFAHA PLTNIPLCKV IRFNIDYTIH FIEEMMPENF CVKGLELFSL FLFRDILELY
DWNLKGPLFE DSPPCCPRFH FMPRFVRFLP DGGKEVLSMH QILLYLLRCS KALVPEEEIA
NMLQWEELEW QKYAEECKGM IVTNPGTKPS SVRIDQLDRE QFNPDVITFP IIVHFGIRPA
QLSYAGDPQY QKLWKSYVKL RHLLANSPKV KQTDKQKLAQ REEALQKIRQ KNTMRREVTV
ELSSQGFWKT GIRSDVCQHA MMLPVLTHHI RYHQCLMHLD KLIGYTFQDR CLLQLAMTHP
SHHLNFGMNP DHARNSLSNC GIRQPKYGDR KVHHMHMRKK GINTLINIMS RLGQDDPTPS
RINHNERLEF LGDAVVEFLT SVHLYYLFPS LEEGGLATYR TAIVQNQHLA MLAKKLELDR
FMLYAHGPDL CRESDLRHAM ANCFEALIGA VYLEGSLEEA KQLFGRLLFN DPDLREVWLN
YPLHPLQLQE PNTDRQLIET SPVLQKLTEF EEAIGVIFTH VRLLARAFTL RTVGFNHLTL
GHNQRMEFLG DSIMQLVATE YLFIHFPDHH EGHLTLLRSS LVNNRTQAKV AEELGMQEYA
ITNDKTKRPV ALRTKTLADL LESFIAALYI DKDLEYVHTF MNVCFFPRLK EFILNQDWND
PKSQLQQCCL TLRTEGKEPD IPLYKTLQTV GPSHARTYTV AVYFKGERIG CGKGPSIQQA
EMGAAMDALE KYNFPQMAHQ KRFIERKYRQ ELKEMRWERE HQEREPDETE DIKK
