ID   ZCHC4_HUMAN             Reviewed;         513 AA.
AC   Q9H5U6; B2RXF6; B4DRD8; B7ZW20; Q5IW78; Q96AN7;
DT   31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT   24-JAN-2006, sequence version 3.
DT   27-MAR-2024, entry version 159.
DE   RecName: Full=rRNA N6-adenosine-methyltransferase ZCCHC4 {ECO:0000305};
DE            EC=2.1.1.- {ECO:0000269|PubMed:30531910, ECO:0000269|PubMed:31328227, ECO:0000269|PubMed:31799605};
DE   AltName: Full=Zinc finger CCHC domain-containing protein 4 {ECO:0000305};
GN   Name=ZCCHC4 {ECO:0000303|PubMed:30531910,
GN   ECO:0000312|HGNC:HGNC:22917};
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).
RC   TISSUE=Testis;
RA   Yue L., Zou X., Ci H., Li Y.;
RT   "Homo sapiens zinc finger, DHHC domain containing, similar to Mus musculus
RT   4930449I23Rik.";
RL   Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT HIS-396.
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT HIS-396.
RC   TISSUE=Lung, and Teratocarcinoma;
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), AND VARIANT
RP   HIS-396.
RC   TISSUE=Brain cortex, and Kidney;
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   [5]
RP   PRELIMINARY CHARACTERIZATION.
RX   PubMed=15225602; DOI=10.1016/j.febslet.2004.03.126;
RA   Albrecht M., Lengauer T.;
RT   "Novel Sm-like proteins with long C-terminal tails and associated
RT   methyltransferases.";
RL   FEBS Lett. 569:18-26(2004).
RN   [6]
RP   FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP   276-ASP--PHE-279.
RX   PubMed=30531910; DOI=10.1038/s41589-018-0184-3;
RA   Ma H., Wang X., Cai J., Dai Q., Natchiar S.K., Lv R., Chen K., Lu Z.,
RA   Chen H., Shi Y.G., Lan F., Fan J., Klaholz B.P., Pan T., Shi Y., He C.;
RT   "N6-methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA
RT   methylation.";
RL   Nat. Chem. Biol. 15:88-94(2019).
RN   [7]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=31328227; DOI=10.1093/nar/gkz619;
RA   van Tran N., Ernst F.G.M., Hawley B.R., Zorbas C., Ulryck N., Hackert P.,
RA   Bohnsack K.E., Bohnsack M.T., Jaffrey S.R., Graille M., Lafontaine D.L.J.;
RT   "The human 18S rRNA m6A methyltransferase METTL5 is stabilized by
RT   TRMT112.";
RL   Nucleic Acids Res. 47:7719-7733(2019).
RN   [8]
RP   FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH TRIP4;
RP   ASCC1; ASCC2; ASCC3; AHCYL1; AHCYL2 AND YTHDC2, AND MUTAGENESIS OF ASP-276.
RX   PubMed=31799605; DOI=10.1093/nar/gkz1147;
RA   Pinto R., Vaagboe C.B., Jakobsson M.E., Kim Y., Baltissen M.P.,
RA   O'Donohue M.F., Guzman U.H., Malecki J.M., Wu J., Kirpekar F., Olsen J.V.,
RA   Gleizes P.E., Vermeulen M., Leidel S.A., Slupphaug G., Falnes P.O.;
RT   "The human methyltransferase ZCCHC4 catalyses N6-methyladenosine
RT   modification of 28S ribosomal RNA.";
RL   Nucleic Acids Res. 48:830-846(2020).
RN   [9] {ECO:0007744|PDB:6UCA}
RP   X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 24-464 IN COMPLEX WITH
RP   S-ADENOSYL-L-METHIONINE AND ZINC, FUNCTION, CATALYTIC ACTIVITY, DOMAIN, AND
RP   MUTAGENESIS OF TYR-173; TYR-340; ASP-341; ASN-342; HIS-343 AND LEU-345.
RX   PubMed=31695039; DOI=10.1038/s41467-019-12923-x;
RA   Ren W., Lu J., Huang M., Gao L., Li D., Wang G.G., Song J.;
RT   "Structure and regulation of ZCCHC4 in m6A-methylation of 28S rRNA.";
RL   Nat. Commun. 10:5042-5042(2019).
CC   -!- FUNCTION: rRNA N6-methyltransferase that specifically methylates the
CC       adenine in position 4220 of 28S rRNA (PubMed:30531910, PubMed:31328227,
CC       PubMed:31799605, PubMed:31695039). N6-methylation of adenine(4220) in
CC       28S rRNA is required for translation (PubMed:30531910,
CC       PubMed:31799605). {ECO:0000269|PubMed:30531910,
CC       ECO:0000269|PubMed:31328227, ECO:0000269|PubMed:31695039,
CC       ECO:0000269|PubMed:31799605}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=adenosine(4220) in 28S rRNA + S-adenosyl-L-methionine = H(+) +
CC         N(6)-methyladenosine(4220) in 28S rRNA + S-adenosyl-L-homocysteine;
CC         Xref=Rhea:RHEA:58724, Rhea:RHEA-COMP:16142, Rhea:RHEA-COMP:16143,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC         ChEBI:CHEBI:74411, ChEBI:CHEBI:74449;
CC         Evidence={ECO:0000269|PubMed:30531910, ECO:0000269|PubMed:31328227,
CC         ECO:0000269|PubMed:31695039, ECO:0000269|PubMed:31799605};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58725;
CC         Evidence={ECO:0000269|PubMed:30531910, ECO:0000269|PubMed:31328227,
CC         ECO:0000269|PubMed:31695039, ECO:0000269|PubMed:31799605};
CC   -!- SUBUNIT: Interacts with components of the ASC-1 complex TRIP4, ASCC1,
CC       ASCC2 and ASCC3 (PubMed:31799605). Interact with AHCYL1 and AHCYL2
CC       (PubMed:31799605). Interact with YTHDC2 (PubMed:31799605).
CC       {ECO:0000269|PubMed:31799605}.
CC   -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:30531910,
CC       ECO:0000269|PubMed:31799605}. Cytoplasm {ECO:0000269|PubMed:30531910}.
CC       Note=Accumulates in the nucleolus, where ribosome biogenesis takes
CC       place. {ECO:0000269|PubMed:30531910}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q9H5U6-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9H5U6-2; Sequence=VSP_043359;
CC       Name=3;
CC         IsoId=Q9H5U6-3; Sequence=VSP_043360;
CC   -!- DOMAIN: The regulatory loop blocks the catalytic center by bridging the
CC       methyltransferase domain and the C-terminal CCHC-type zinc finger,
CC       resulting in an autoinhibitory conformation.
CC       {ECO:0000269|PubMed:31695039}.
CC   -!- SIMILARITY: Belongs to the ZCCHC4 family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH16914.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=BAB15524.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AY629351; AAV41218.1; -; mRNA.
DR   EMBL; CH471069; EAW92837.1; -; Genomic_DNA.
DR   EMBL; AK299211; BAG61250.1; -; mRNA.
DR   EMBL; AK026677; BAB15524.1; ALT_INIT; mRNA.
DR   EMBL; BC016914; AAH16914.1; ALT_INIT; mRNA.
DR   EMBL; BC157834; AAI57835.1; -; mRNA.
DR   EMBL; BC171821; AAI71821.1; -; mRNA.
DR   CCDS; CCDS43218.1; -. [Q9H5U6-1]
DR   RefSeq; NP_079212.2; NM_024936.2. [Q9H5U6-1]
DR   PDB; 6UCA; X-ray; 3.10 A; A/B/C/D/E/F=24-464.
DR   PDBsum; 6UCA; -.
DR   AlphaFoldDB; Q9H5U6; -.
DR   SMR; Q9H5U6; -.
DR   BioGRID; 118838; 7.
DR   IntAct; Q9H5U6; 1.
DR   STRING; 9606.ENSP00000303468; -.
DR   iPTMnet; Q9H5U6; -.
DR   PhosphoSitePlus; Q9H5U6; -.
DR   BioMuta; ZCCHC4; -.
DR   DMDM; 85700439; -.
DR   EPD; Q9H5U6; -.
DR   jPOST; Q9H5U6; -.
DR   MassIVE; Q9H5U6; -.
DR   MaxQB; Q9H5U6; -.
DR   PaxDb; 9606-ENSP00000303468; -.
DR   PeptideAtlas; Q9H5U6; -.
DR   ProteomicsDB; 80928; -. [Q9H5U6-1]
DR   ProteomicsDB; 80929; -. [Q9H5U6-2]
DR   ProteomicsDB; 80930; -. [Q9H5U6-3]
DR   Pumba; Q9H5U6; -.
DR   Antibodypedia; 23199; 91 antibodies from 14 providers.
DR   DNASU; 29063; -.
DR   Ensembl; ENST00000302874.9; ENSP00000303468.4; ENSG00000168228.16. [Q9H5U6-1]
DR   Ensembl; ENST00000507760.5; ENSP00000422115.1; ENSG00000168228.16. [Q9H5U6-2]
DR   GeneID; 29063; -.
DR   KEGG; hsa:29063; -.
DR   MANE-Select; ENST00000302874.9; ENSP00000303468.4; NM_024936.3; NP_079212.2.
DR   UCSC; uc003grl.5; human. [Q9H5U6-1]
DR   AGR; HGNC:22917; -.
DR   CTD; 29063; -.
DR   DisGeNET; 29063; -.
DR   GeneCards; ZCCHC4; -.
DR   HGNC; HGNC:22917; ZCCHC4.
DR   HPA; ENSG00000168228; Low tissue specificity.
DR   MIM; 611792; gene.
DR   neXtProt; NX_Q9H5U6; -.
DR   OpenTargets; ENSG00000168228; -.
DR   PharmGKB; PA134950003; -.
DR   VEuPathDB; HostDB:ENSG00000168228; -.
DR   eggNOG; KOG4399; Eukaryota.
DR   GeneTree; ENSGT00390000012556; -.
DR   HOGENOM; CLU_034589_0_0_1; -.
DR   InParanoid; Q9H5U6; -.
DR   OMA; MCNNHFF; -.
DR   OrthoDB; 3425157at2759; -.
DR   PhylomeDB; Q9H5U6; -.
DR   TreeFam; TF313872; -.
DR   PathwayCommons; Q9H5U6; -.
DR   SignaLink; Q9H5U6; -.
DR   BioGRID-ORCS; 29063; 12 hits in 1155 CRISPR screens.
DR   ChiTaRS; ZCCHC4; human.
DR   GenomeRNAi; 29063; -.
DR   Pharos; Q9H5U6; Tbio.
DR   PRO; PR:Q9H5U6; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; Q9H5U6; Protein.
DR   Bgee; ENSG00000168228; Expressed in primordial germ cell in gonad and 109 other cell types or tissues.
DR   ExpressionAtlas; Q9H5U6; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR   GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR   GO; GO:0008988; F:rRNA (adenine-N6-)-methyltransferase activity; IDA:UniProtKB.
DR   GO; GO:1904047; F:S-adenosyl-L-methionine binding; IDA:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR   GO; GO:0045727; P:positive regulation of translation; IDA:UniProtKB.
DR   GO; GO:0031167; P:rRNA methylation; IDA:UniProtKB.
DR   InterPro; IPR002052; DNA_methylase_N6_adenine_CS.
DR   InterPro; IPR041370; Mlase_EEF1AKMT1/ZCCHC4.
DR   InterPro; IPR039846; ZCCHC4.
DR   InterPro; IPR010666; Znf_GRF.
DR   PANTHER; PTHR13493:SF3; RRNA N6-ADENOSINE-METHYLTRANSFERASE ZCCHC4; 1.
DR   PANTHER; PTHR13493; ZINC FINGER CCHC DOMAIN-CONTAINING; 1.
DR   Pfam; PF10237; N6-adenineMlase; 1.
DR   Pfam; PF06839; zf-GRF; 1.
DR   PROSITE; PS50216; DHHC; 1.
DR   PROSITE; PS00092; N6_MTASE; 1.
DR   PROSITE; PS51999; ZF_GRF; 1.
DR   Genevisible; Q9H5U6; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cytoplasm; Metal-binding;
KW   Methyltransferase; Nucleus; Reference proteome; S-adenosyl-L-methionine;
KW   Transferase; Zinc; Zinc-finger.
FT   CHAIN           1..513
FT                   /note="rRNA N6-adenosine-methyltransferase ZCCHC4"
FT                   /id="PRO_0000150952"
FT   DOMAIN          395..447
FT                   /note="DHHC"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00067"
FT   ZN_FING         40..82
FT                   /note="GRF-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01343"
FT   ZN_FING         443..460
FT                   /note="CCHC-type"
FT   REGION          337..357
FT                   /note="Regulatory loop"
FT                   /evidence="ECO:0000269|PubMed:31695039"
FT   REGION          466..513
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         40
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01343,
FT                   ECO:0000269|PubMed:31695039, ECO:0007744|PDB:6UCA"
FT   BINDING         42
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01343,
FT                   ECO:0000269|PubMed:31695039, ECO:0007744|PDB:6UCA"
FT   BINDING         64
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01343,
FT                   ECO:0000269|PubMed:31695039, ECO:0007744|PDB:6UCA"
FT   BINDING         73
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01343,
FT                   ECO:0000269|PubMed:31695039, ECO:0007744|PDB:6UCA"
FT   BINDING         125
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:31695039,
FT                   ECO:0007744|PDB:6UCA"
FT   BINDING         128
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:31695039,
FT                   ECO:0007744|PDB:6UCA"
FT   BINDING         140
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:31695039,
FT                   ECO:0007744|PDB:6UCA"
FT   BINDING         143
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:31695039,
FT                   ECO:0007744|PDB:6UCA"
FT   BINDING         172..175
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000269|PubMed:31695039,
FT                   ECO:0007744|PDB:6UCA"
FT   BINDING         202
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000269|PubMed:31695039,
FT                   ECO:0007744|PDB:6UCA"
FT   BINDING         225
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000269|PubMed:31695039,
FT                   ECO:0007744|PDB:6UCA"
FT   BINDING         243..244
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000269|PubMed:31695039,
FT                   ECO:0007744|PDB:6UCA"
FT   BINDING         276
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000269|PubMed:31695039,
FT                   ECO:0007744|PDB:6UCA"
FT   BINDING         380
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000269|PubMed:31695039,
FT                   ECO:0007744|PDB:6UCA"
FT   BINDING         383
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000269|PubMed:31695039,
FT                   ECO:0007744|PDB:6UCA"
FT   BINDING         393
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000269|PubMed:31695039,
FT                   ECO:0007744|PDB:6UCA"
FT   BINDING         394
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000269|PubMed:31695039,
FT                   ECO:0007744|PDB:6UCA"
FT   BINDING         397
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000269|PubMed:31695039,
FT                   ECO:0007744|PDB:6UCA"
FT   BINDING         400
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000269|PubMed:31695039,
FT                   ECO:0007744|PDB:6UCA"
FT   BINDING         410
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000269|PubMed:31695039,
FT                   ECO:0007744|PDB:6UCA"
FT   BINDING         411
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000269|PubMed:31695039,
FT                   ECO:0007744|PDB:6UCA"
FT   BINDING         414
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000269|PubMed:31695039,
FT                   ECO:0007744|PDB:6UCA"
FT   BINDING         417
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000269|PubMed:31695039,
FT                   ECO:0007744|PDB:6UCA"
FT   BINDING         424
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000269|PubMed:31695039,
FT                   ECO:0007744|PDB:6UCA"
FT   BINDING         425
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000269|PubMed:31695039,
FT                   ECO:0007744|PDB:6UCA"
FT   BINDING         428
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000269|PubMed:31695039,
FT                   ECO:0007744|PDB:6UCA"
FT   BINDING         431
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000269|PubMed:31695039,
FT                   ECO:0007744|PDB:6UCA"
FT   BINDING         436
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000269|PubMed:31695039,
FT                   ECO:0007744|PDB:6UCA"
FT   BINDING         438
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000269|PubMed:31695039,
FT                   ECO:0007744|PDB:6UCA"
FT   VAR_SEQ         230..513
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_043359"
FT   VAR_SEQ         470..472
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_043360"
FT   VARIANT         382
FT                   /note="P -> L (in dbSNP:rs3752873)"
FT                   /id="VAR_053751"
FT   VARIANT         396
FT                   /note="L -> H (in dbSNP:rs315675)"
FT                   /evidence="ECO:0000269|PubMed:14702039,
FT                   ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2"
FT                   /id="VAR_024925"
FT   MUTAGEN         173
FT                   /note="Y->A: Abolished rRNA methyltransferase activity."
FT                   /evidence="ECO:0000269|PubMed:31695039"
FT   MUTAGEN         276..279
FT                   /note="DPPF->AAAA: Loss of methyltransferase activity."
FT                   /evidence="ECO:0000269|PubMed:30531910"
FT   MUTAGEN         276
FT                   /note="D->A: Loss of methyltransferase activity."
FT                   /evidence="ECO:0000269|PubMed:31799605"
FT   MUTAGEN         340
FT                   /note="Y->A: Strongly impaired rRNA methyltransferase
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:31695039"
FT   MUTAGEN         341
FT                   /note="D->A: Increased rRNA methylation."
FT                   /evidence="ECO:0000269|PubMed:31695039"
FT   MUTAGEN         342
FT                   /note="N->A: Strongly impaired rRNA methyltransferase
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:31695039"
FT   MUTAGEN         343
FT                   /note="H->A: Decreased S-adenosyl-L-methionine-binding."
FT                   /evidence="ECO:0000269|PubMed:31695039"
FT   MUTAGEN         343
FT                   /note="H->A: Strongly impaired rRNA methyltransferase
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:31695039"
FT   MUTAGEN         345
FT                   /note="L->A: Increased rRNA methylation."
FT                   /evidence="ECO:0000269|PubMed:31695039"
FT   CONFLICT        348
FT                   /note="H -> R (in Ref. 3; BAG61250)"
FT                   /evidence="ECO:0000305"
FT   STRAND          46..50
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   TURN            53..55
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   STRAND          60..63
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   TURN            70..72
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   STRAND          77..80
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   HELIX           85..97
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   HELIX           104..114
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   HELIX           119..121
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   STRAND          123..125
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   TURN            126..129
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   STRAND          130..132
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   HELIX           134..140
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   HELIX           151..154
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   HELIX           157..159
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   TURN            167..170
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   HELIX           177..190
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   STRAND          193..199
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   HELIX           201..212
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   STRAND          220..226
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   HELIX           228..232
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   TURN            236..238
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   STRAND          239..243
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   TURN            244..247
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   HELIX           253..264
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   HELIX           265..268
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   STRAND          270..275
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   STRAND          279..281
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   HELIX           284..298
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   STRAND          312..317
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   HELIX           318..320
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   HELIX           321..327
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   STRAND          340..342
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   STRAND          350..352
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   STRAND          358..364
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   HELIX           366..368
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   HELIX           373..375
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   STRAND          376..380
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   TURN            381..384
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   STRAND          385..388
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   TURN            395..398
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   STRAND          404..406
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   STRAND          409..411
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   TURN            412..415
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   STRAND          416..418
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   TURN            426..428
FT                   /evidence="ECO:0007829|PDB:6UCA"
FT   STRAND          430..432
FT                   /evidence="ECO:0007829|PDB:6UCA"
SQ   SEQUENCE   513 AA;  59010 MW;  D74690827DC935F4 CRC64;
     MAASRNGFEA VEAEGSAGCR GSSGMEVVLP LDPAVPAPLC PHGPTLLFVK VTQGKEETRR
     FYACSACRDR KDCNFFQWED EKLSGARLAA REAHNRRCQP PLSRTQCVER YLKFIELPLT
     QRKFCQTCQQ LLLPDDWGQH SEHQVLGNVS ITQLRRPSQL LYPLENKKTN AQYLFADRSC
     QFLVDLLSAL GFRRVLCVGT PRLHELIKLT ASGDKKSNIK SLLLDIDFRY SQFYMEDSFC
     HYNMFNHHFF DGKTALEVCR AFLQEDKGEG IIMVTDPPFG GLVEPLAITF KKLIAMWKEG
     QSQDDSHKEL PIFWIFPYFF ESRICQFFPS FQMLDYQVDY DNHALYKHGK TGRKQSPVRI
     FTNIPPNKII LPTEEGYRFC SPCQRYVSLE NQHCELCNSC TSKDGRKWNH CFLCKKCVKP
     SWIHCSICNH CAVPDHSCEG PKHGCFICGE LDHKRSTCPN IATSKRANKA VRKQKQRKSN
     KMKMETTKGQ SMNHTSATRR KKRRERAHQY LGS
//