NEP1_HUMAN
ID NEP1_HUMAN Reviewed; 244 AA.
AC Q92979; O00675; O00726;
DT 10-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Ribosomal RNA small subunit methyltransferase NEP1 {ECO:0000305|PubMed:20047967};
DE EC=2.1.1.- {ECO:0000269|PubMed:20047967};
DE AltName: Full=18S rRNA (pseudouridine(1248)-N1)-methyltransferase {ECO:0000303|PubMed:20047967};
DE AltName: Full=18S rRNA Psi1248 methyltransferase {ECO:0000303|PubMed:20047967};
DE AltName: Full=Nucleolar protein EMG1 homolog {ECO:0000250|UniProtKB:Q06287};
DE AltName: Full=Protein C2f {ECO:0000303|PubMed:9074930};
DE AltName: Full=Ribosome biogenesis protein NEP1 {ECO:0000303|PubMed:20047967};
GN Name=EMG1 {ECO:0000303|PubMed:19463982};
GN Synonyms=C2F {ECO:0000303|PubMed:9074930};
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 [GENOMIC DNA / MRNA].
RX PubMed=9074930; DOI=10.1101/gr.7.3.268;
RA Ansari-Lari M.A., Shen Y., Muzny D.M., Lee W., Gibbs R.A.;
RT "Large-scale sequencing in human chromosome 12p13: experimental and
RT computational gene structure determination.";
RL Genome Res. 7:268-280(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [3]
RP PROTEIN SEQUENCE OF 2-11, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT
RP ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RA Bienvenut W.V.;
RL Submitted (OCT-2004) to UniProtKB.
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=11935223; DOI=10.1007/s00294-001-0269-4;
RA Eschrich D., Buchhaupt M., Koetter P., Entian K.-D.;
RT "Nep1p (Emg1p), a novel protein conserved in eukaryotes and archaea, is
RT involved in ribosome biogenesis.";
RL Curr. Genet. 40:326-338(2002).
RN [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=20047967; DOI=10.1093/nar/gkp1189;
RA Wurm J.P., Meyer B., Bahr U., Held M., Frolow O., Kotter P., Engels J.W.,
RA Heckel A., Karas M., Entian K.D., Wohnert J.;
RT "The ribosome assembly factor Nep1 responsible for Bowen-Conradi syndrome
RT is a pseudouridine-N1-specific methyltransferase.";
RL Nucleic Acids Res. 38:2387-2398(2010).
RN [6]
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 [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-5 AND SER-14, 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 [9]
RP VARIANT BWCNS GLY-86, AND CHARACTERIZATION OF VARIANT BWCNS GLY-86.
RX PubMed=19463982; DOI=10.1016/j.ajhg.2009.04.017;
RA Armistead J., Khatkar S., Meyer B., Mark B.L., Patel N., Coghlan G.,
RA Lamont R.E., Liu S., Wiechert J., Cattini P.A., Koetter P., Wrogemann K.,
RA Greenberg C.R., Entian K.-D., Zelinski T., Triggs-Raine B.;
RT "Mutation of a gene essential for ribosome biogenesis, EMG1, causes Bowen-
RT Conradi syndrome.";
RL Am. J. Hum. Genet. 84:728-739(2009).
CC -!- FUNCTION: S-adenosyl-L-methionine-dependent pseudouridine N(1)-
CC methyltransferase that methylates pseudouridine at position 1248
CC (Psi1248) in 18S rRNA. Involved the biosynthesis of the hypermodified
CC N1-methyl-N3-(3-amino-3-carboxypropyl) pseudouridine (m1acp3-Psi)
CC conserved in eukaryotic 18S rRNA. Is not able to methylate uridine at
CC this position (PubMed:20047967). Has also an essential role in 40S
CC ribosomal subunit biogenesis independent on its methyltransferase
CC activity, facilitating the incorporation of ribosomal protein S19
CC during the formation of pre-ribosomes (By similarity).
CC {ECO:0000250|UniProtKB:Q06287, ECO:0000269|PubMed:20047967}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=pseudouridine(1248) in human 18S rRNA + S-adenosyl-L-
CC methionine = H(+) + N(1)-methylpseudouridine(1248) in human 18S rRNA
CC + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:46712, Rhea:RHEA-
CC COMP:11638, Rhea:RHEA-COMP:11639, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:65314,
CC ChEBI:CHEBI:74890; Evidence={ECO:0000269|PubMed:20047967};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q06287}.
CC -!- INTERACTION:
CC Q92979; Q92979: EMG1; NbExp=3; IntAct=EBI-718638, EBI-718638;
CC Q92979; Q5TZK3: FAM74A6; NbExp=3; IntAct=EBI-718638, EBI-10247271;
CC Q92979; Q9H2F3: HSD3B7; NbExp=3; IntAct=EBI-718638, EBI-3918847;
CC Q92979; Q9H5H4: ZNF768; NbExp=3; IntAct=EBI-718638, EBI-1210580;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:11935223}.
CC -!- DISEASE: Bowen-Conradi syndrome (BWCNS) [MIM:211180]: A combination of
CC malformations characterized in newborns by low birth weight,
CC microcephaly, mild joint restriction, a prominent nose, micrognathia,
CC fifth finger clinodactyly, and 'rocker-bottom' feet. The syndrome is
CC transmitted as an autosomal recessive trait. The prognosis is poor,
CC with all infants dying within the first few months of life.
CC {ECO:0000269|PubMed:19463982}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the class IV-like SAM-binding methyltransferase
CC superfamily. RNA methyltransferase NEP1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB51325.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; U47924; AAB51325.1; ALT_INIT; Genomic_DNA.
DR EMBL; U72514; AAC51641.1; -; mRNA.
DR EMBL; BC055314; AAH55314.1; -; mRNA.
DR CCDS; CCDS73430.1; -.
DR RefSeq; NP_001306978.1; NM_001320049.1.
DR RefSeq; NP_006322.4; NM_006331.7.
DR PDB; 5FAI; X-ray; 1.80 A; A=14-244.
DR PDB; 7MQ8; EM; 3.60 A; SJ/SK=1-244.
DR PDB; 7MQ9; EM; 3.87 A; SJ/SK=1-244.
DR PDB; 7MQA; EM; 2.70 A; SJ/SK=1-244.
DR PDBsum; 5FAI; -.
DR PDBsum; 7MQ8; -.
DR PDBsum; 7MQ9; -.
DR PDBsum; 7MQA; -.
DR AlphaFoldDB; Q92979; -.
DR SMR; Q92979; -.
DR BioGRID; 115703; 93.
DR IntAct; Q92979; 29.
DR MINT; Q92979; -.
DR STRING; 9606.ENSP00000470560; -.
DR BindingDB; Q92979; -.
DR iPTMnet; Q92979; -.
DR PhosphoSitePlus; Q92979; -.
DR SwissPalm; Q92979; -.
DR BioMuta; EMG1; -.
DR DMDM; 20532172; -.
DR EPD; Q92979; -.
DR jPOST; Q92979; -.
DR MassIVE; Q92979; -.
DR MaxQB; Q92979; -.
DR PeptideAtlas; Q92979; -.
DR PRIDE; Q92979; -.
DR ProteomicsDB; 75641; -.
DR Antibodypedia; 6124; 191 antibodies from 24 providers.
DR DNASU; 10436; -.
DR Ensembl; ENST00000599672.6; ENSP00000470560.1; ENSG00000126749.16.
DR GeneID; 10436; -.
DR KEGG; hsa:10436; -.
DR MANE-Select; ENST00000599672.6; ENSP00000470560.1; NM_006331.8; NP_006322.4.
DR UCSC; uc031ysa.2; human.
DR CTD; 10436; -.
DR DisGeNET; 10436; -.
DR GeneCards; EMG1; -.
DR HGNC; HGNC:16912; EMG1.
DR HPA; ENSG00000126749; Low tissue specificity.
DR MalaCards; EMG1; -.
DR MIM; 211180; phenotype.
DR MIM; 611531; gene.
DR neXtProt; NX_Q92979; -.
DR OpenTargets; ENSG00000126749; -.
DR Orphanet; 1270; Bowen-Conradi syndrome.
DR PharmGKB; PA142671909; -.
DR VEuPathDB; HostDB:ENSG00000126749; -.
DR eggNOG; KOG3073; Eukaryota.
DR GeneTree; ENSGT00390000000305; -.
DR HOGENOM; CLU_055846_1_1_1; -.
DR InParanoid; Q92979; -.
DR OMA; QEQDWDA; -.
DR OrthoDB; 1266231at2759; -.
DR PhylomeDB; Q92979; -.
DR BRENDA; 2.1.1.257; 2681.
DR PathwayCommons; Q92979; -.
DR Reactome; R-HSA-6790901; rRNA modification in the nucleus and cytosol.
DR Reactome; R-HSA-6791226; Major pathway of rRNA processing in the nucleolus and cytosol.
DR SignaLink; Q92979; -.
DR BioGRID-ORCS; 10436; 43 hits in 236 CRISPR screens.
DR ChiTaRS; EMG1; human.
DR GeneWiki; EMG1; -.
DR GenomeRNAi; 10436; -.
DR Pharos; Q92979; Tbio.
DR PRO; PR:Q92979; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q92979; protein.
DR Bgee; ENSG00000126749; Expressed in islet of Langerhans and 194 other tissues.
DR ExpressionAtlas; Q92979; baseline and differential.
DR Genevisible; Q92979; HS.
DR GO; GO:0005694; C:chromosome; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032040; C:small-subunit processome; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0070037; F:rRNA (pseudouridine) methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0019843; F:rRNA binding; IBA:GO_Central.
DR GO; GO:0001824; P:blastocyst development; IEA:Ensembl.
DR GO; GO:0017126; P:nucleologenesis; IEA:Ensembl.
DR GO; GO:0042274; P:ribosomal small subunit biogenesis; ISS:UniProtKB.
DR GO; GO:0070475; P:rRNA base methylation; IBA:GO_Central.
DR GO; GO:0006364; P:rRNA processing; ISS:UniProtKB.
DR CDD; cd18088; Nep1-like; 1.
DR Gene3D; 3.40.1280.10; -; 1.
DR InterPro; IPR029028; Alpha/beta_knot_MTases.
DR InterPro; IPR005304; Rbsml_bgen_MeTrfase_EMG1/NEP1.
DR InterPro; IPR029026; tRNA_m1G_MTases_N.
DR PANTHER; PTHR12636; PTHR12636; 1.
DR Pfam; PF03587; EMG1; 1.
DR SUPFAM; SSF75217; SSF75217; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Direct protein sequencing; Disease variant;
KW Methyltransferase; Nucleus; Phosphoprotein; Reference proteome;
KW Ribosome biogenesis; RNA-binding; rRNA processing; rRNA-binding;
KW S-adenosyl-L-methionine; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.3, ECO:0007744|PubMed:22814378"
FT CHAIN 2..244
FT /note="Ribosomal RNA small subunit methyltransferase NEP1"
FT /id="PRO_0000158606"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 176
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q06287"
FT BINDING 201
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q06287"
FT BINDING 206
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q06287"
FT BINDING 219..224
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q06287"
FT SITE 84
FT /note="Interaction with substrate rRNA"
FT /evidence="ECO:0000250|UniProtKB:Q06287"
FT SITE 86
FT /note="Stabilizes Arg-84"
FT /evidence="ECO:0000250|UniProtKB:Q06287"
FT SITE 125
FT /note="Interaction with substrate rRNA"
FT /evidence="ECO:0000250|UniProtKB:Q06287"
FT SITE 128
FT /note="Interaction with substrate rRNA"
FT /evidence="ECO:0000250|UniProtKB:Q06287"
FT SITE 132
FT /note="Interaction with substrate rRNA"
FT /evidence="ECO:0000250|UniProtKB:Q06287"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.3, ECO:0007744|PubMed:22814378"
FT MOD_RES 5
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 34
FT /note="A -> G (in dbSNP:rs11064480)"
FT /id="VAR_050237"
FT VARIANT 86
FT /note="D -> G (in BWCNS; studies in fibroblasts show a
FT dramatically reduced level of EMG1 protein in a BWCNS-
FT affected patient compared to normal fibroblasts although
FT patient fibroblasts do not have complete EMG1 deficiency;
FT the mutation increases dimerization of EMG1 subunits
FT suggesting that aggregation of EMG1 leads to reduced levels
FT of the protein; dbSNP:rs74435397)"
FT /evidence="ECO:0000269|PubMed:19463982"
FT /id="VAR_062480"
FT STRAND 42..50
FT /evidence="ECO:0007829|PDB:5FAI"
FT STRAND 54..57
FT /evidence="ECO:0007829|PDB:5FAI"
FT STRAND 60..63
FT /evidence="ECO:0007829|PDB:5FAI"
FT TURN 66..68
FT /evidence="ECO:0007829|PDB:5FAI"
FT HELIX 75..77
FT /evidence="ECO:0007829|PDB:5FAI"
FT HELIX 80..82
FT /evidence="ECO:0007829|PDB:5FAI"
FT HELIX 85..97
FT /evidence="ECO:0007829|PDB:5FAI"
FT HELIX 99..102
FT /evidence="ECO:0007829|PDB:5FAI"
FT STRAND 106..112
FT /evidence="ECO:0007829|PDB:5FAI"
FT STRAND 117..120
FT /evidence="ECO:0007829|PDB:5FAI"
FT HELIX 130..143
FT /evidence="ECO:0007829|PDB:5FAI"
FT STRAND 144..147
FT /evidence="ECO:0007829|PDB:5FAI"
FT STRAND 154..159
FT /evidence="ECO:0007829|PDB:5FAI"
FT HELIX 163..166
FT /evidence="ECO:0007829|PDB:5FAI"
FT STRAND 172..176
FT /evidence="ECO:0007829|PDB:5FAI"
FT STRAND 181..183
FT /evidence="ECO:0007829|PDB:5FAI"
FT HELIX 186..189
FT /evidence="ECO:0007829|PDB:5FAI"
FT STRAND 192..201
FT /evidence="ECO:0007829|PDB:5FAI"
FT STRAND 203..205
FT /evidence="ECO:0007829|PDB:5FAI"
FT STRAND 214..218
FT /evidence="ECO:0007829|PDB:5FAI"
FT HELIX 226..241
FT /evidence="ECO:0007829|PDB:5FAI"
SQ SEQUENCE 244 AA; 26720 MW; 922F6CF49B4EFD11 CRC64;
MAAPSDGFKP RERSGGEQAQ DWDALPPKRP RLGAGNKIGG RRLIVVLEGA SLETVKVGKT
YELLNCDKHK SILLKNGRDP GEARPDITHQ SLLMLMDSPL NRAGLLQVYI HTQKNVLIEV
NPQTRIPRTF DRFCGLMVQL LHKLSVRAAD GPQKLLKVIK NPVSDHFPVG CMKVGTSFSI
PVVSDVRELV PSSDPIVFVV GAFAHGKVSV EYTEKMVSIS NYPLSAALTC AKLTTAFEEV
WGVI
