NTM1B_HUMAN
ID NTM1B_HUMAN Reviewed; 283 AA.
AC Q5VVY1; B2RXI0;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 24-NOV-2009, sequence version 2.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=N-terminal Xaa-Pro-Lys N-methyltransferase 2;
DE EC=2.1.1.299 {ECO:0000269|PubMed:24090352, ECO:0000269|PubMed:30417120};
DE AltName: Full=Alpha N-terminal protein methyltransferase 1B;
DE AltName: Full=Methyltransferase-like protein 11B;
DE AltName: Full=X-Pro-Lys N-terminal protein methyltransferase 1B;
DE Short=NTM1B;
GN Name=NTMT2 {ECO:0000312|HGNC:HGNC:31932};
GN Synonyms=C1orf184, METTL11B, NRMT2 {ECO:0000303|PubMed:24090352};
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=24090352; DOI=10.1042/bj20131163;
RA Petkowski J.J., Bonsignore L.A., Tooley J.G., Wilkey D.W., Merchant M.L.,
RA Macara I.G., Schaner Tooley C.E.;
RT "NRMT2 is an N-terminal monomethylase that primes for its homologue
RT NRMT1.";
RL Biochem. J. 456:453-462(2013).
RN [4] {ECO:0007744|PDB:5UBB, ECO:0007744|PDB:6DUB}
RP X-RAY CRYSTALLOGRAPHY (1.20 ANGSTROMS) OF 58-278 IN COMPLEX WITH PEPTIDE
RP SUBSTRATE AND S-ADENOSYL-L-METHIONINE, MUTAGENESIS OF ASN-89, FUNCTION, AND
RP CATALYTIC ACTIVITY.
RX PubMed=30417120; DOI=10.1038/s42003-018-0196-2;
RA Dong C., Dong G., Li L., Zhu L., Tempel W., Liu Y., Huang R., Min J.;
RT "An asparagine/glycine switch governs product specificity of human N-
RT terminal methyltransferase NTMT2.";
RL Commun. Biol. 1:183-183(2018).
CC -!- FUNCTION: Alpha N-methyltransferase that methylates the N-terminus of
CC target proteins containing the N-terminal motif [Ala/Pro/Ser]-Pro-Lys
CC when the initiator Met is cleaved. Specifically catalyzes
CC monomethylation of exposed alpha-amino group of Ala or Ser residue in
CC the [Ala/Ser]-Pro-Lys motif and Pro in the Pro-Pro-Lys motif
CC (PubMed:24090352, PubMed:30417120). Predominantly functions as a mono-
CC methyltransferase but is also able to di-/tri-methylate the GPKRIA
CC peptide and di-methylate the PPKRIA peptide (in vitro)
CC (PubMed:30417120). May activate NTMT1 by priming its substrates for
CC trimethylation (PubMed:24090352). {ECO:0000269|PubMed:24090352,
CC ECO:0000269|PubMed:30417120}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-terminal L-alanyl-L-prolyl-L-lysyl-[protein] + S-adenosyl-L-
CC methionine = H(+) + N-terminal N-methyl-L-alanyl-L-prolyl-L-lysyl-
CC [protein] + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:54096,
CC Rhea:RHEA-COMP:13785, Rhea:RHEA-COMP:13786, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:138057,
CC ChEBI:CHEBI:138058; EC=2.1.1.299;
CC Evidence={ECO:0000269|PubMed:24090352};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54097;
CC Evidence={ECO:0000305|PubMed:24090352};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-terminal L-prolyl-L-prolyl-L-lysyl-[protein] + S-adenosyl-L-
CC methionine = H(+) + N-terminal N-methyl-L-prolyl-L-prolyl-L-lysyl-
CC [protein] + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:54100,
CC Rhea:RHEA-COMP:13787, Rhea:RHEA-COMP:13788, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:138059,
CC ChEBI:CHEBI:138060; EC=2.1.1.299;
CC Evidence={ECO:0000269|PubMed:24090352};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54101;
CC Evidence={ECO:0000305|PubMed:24090352};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-terminal L-seryl-L-prolyl-L-lysyl-[protein] + S-adenosyl-L-
CC methionine = H(+) + N-terminal N-methyl-L-seryl-L-prolyl-L-lysyl-
CC [protein] + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:54104,
CC Rhea:RHEA-COMP:13789, Rhea:RHEA-COMP:13790, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:138061,
CC ChEBI:CHEBI:138062; EC=2.1.1.299;
CC Evidence={ECO:0000269|PubMed:24090352, ECO:0000269|PubMed:30417120};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54105;
CC Evidence={ECO:0000305|PubMed:24090352};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24090352}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. NTM1 family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AL445203; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC157860; AAI57861.1; -; mRNA.
DR EMBL; BC171858; AAI71858.1; -; mRNA.
DR CCDS; CCDS44275.1; -.
DR RefSeq; NP_001129579.1; NM_001136107.1.
DR PDB; 5UBB; X-ray; 2.00 A; A=58-278.
DR PDB; 6DUB; X-ray; 1.20 A; A/B=58-278.
DR PDB; 6KDR; X-ray; 2.11 A; A/B=61-283.
DR PDB; 6KDS; X-ray; 1.84 A; A=61-283.
DR PDBsum; 5UBB; -.
DR PDBsum; 6DUB; -.
DR PDBsum; 6KDR; -.
DR PDBsum; 6KDS; -.
DR AlphaFoldDB; Q5VVY1; -.
DR SMR; Q5VVY1; -.
DR STRING; 9606.ENSP00000408058; -.
DR BindingDB; Q5VVY1; -.
DR ChEMBL; CHEMBL4630834; -.
DR iPTMnet; Q5VVY1; -.
DR PhosphoSitePlus; Q5VVY1; -.
DR BioMuta; METTL11B; -.
DR DMDM; 269849617; -.
DR PaxDb; Q5VVY1; -.
DR PeptideAtlas; Q5VVY1; -.
DR PRIDE; Q5VVY1; -.
DR Antibodypedia; 34370; 73 antibodies from 16 providers.
DR DNASU; 149281; -.
DR Ensembl; ENST00000439373.3; ENSP00000408058.3; ENSG00000203740.4.
DR GeneID; 149281; -.
DR KEGG; hsa:149281; -.
DR MANE-Select; ENST00000439373.3; ENSP00000408058.3; NM_001136107.2; NP_001129579.1.
DR UCSC; uc009wvv.2; human.
DR CTD; 149281; -.
DR GeneCards; METTL11B; -.
DR HGNC; HGNC:31932; NTMT2.
DR HPA; ENSG00000203740; Group enriched (heart muscle, skeletal muscle).
DR neXtProt; NX_Q5VVY1; -.
DR OpenTargets; ENSG00000203740; -.
DR VEuPathDB; HostDB:ENSG00000203740; -.
DR eggNOG; KOG3178; Eukaryota.
DR GeneTree; ENSGT00390000008371; -.
DR HOGENOM; CLU_055356_3_0_1; -.
DR InParanoid; Q5VVY1; -.
DR OMA; RKYDVIW; -.
DR OrthoDB; 1528533at2759; -.
DR PhylomeDB; Q5VVY1; -.
DR TreeFam; TF314174; -.
DR BRENDA; 2.1.1.299; 2681.
DR PathwayCommons; Q5VVY1; -.
DR BioGRID-ORCS; 149281; 5 hits in 1066 CRISPR screens.
DR ChiTaRS; METTL11B; human.
DR GenomeRNAi; 149281; -.
DR Pharos; Q5VVY1; Tdark.
DR PRO; PR:Q5VVY1; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q5VVY1; protein.
DR Bgee; ENSG00000203740; Expressed in apex of heart and 18 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0008168; F:methyltransferase activity; IBA:GO_Central.
DR GO; GO:0071885; F:N-terminal protein N-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0006480; P:N-terminal protein amino acid methylation; IDA:UniProtKB.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR008576; MeTrfase_NTM1.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR12753; PTHR12753; 1.
DR Pfam; PF05891; Methyltransf_PK; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Methyltransferase; Nucleus; Reference proteome;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..283
FT /note="N-terminal Xaa-Pro-Lys N-methyltransferase 2"
FT /id="PRO_0000271077"
FT BINDING 124
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:30417120,
FT ECO:0007744|PDB:5UBB"
FT BINDING 129
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:30417120,
FT ECO:0007744|PDB:5UBB"
FT BINDING 146
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:30417120,
FT ECO:0007744|PDB:5UBB"
FT BINDING 174..175
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:30417120,
FT ECO:0007744|PDB:5UBB"
FT BINDING 190
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:30417120"
FT BINDING 195
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:30417120,
FT ECO:0007744|PDB:5UBB"
FT VARIANT 72
FT /note="A -> G (in dbSNP:rs12073565)"
FT /id="VAR_060621"
FT VARIANT 150
FT /note="S -> P (in dbSNP:rs6427235)"
FT /id="VAR_029859"
FT VARIANT 247
FT /note="S -> R (in dbSNP:rs12735494)"
FT /id="VAR_060622"
FT MUTAGEN 89
FT /note="N->G: Increases methylation activity. Higher
FT affinity for mono-methylated peptide than wild-type."
FT /evidence="ECO:0000269|PubMed:30417120"
FT TURN 59..62
FT /evidence="ECO:0007829|PDB:6DUB"
FT HELIX 64..76
FT /evidence="ECO:0007829|PDB:6DUB"
FT HELIX 83..86
FT /evidence="ECO:0007829|PDB:6DUB"
FT TURN 87..89
FT /evidence="ECO:0007829|PDB:6DUB"
FT HELIX 91..93
FT /evidence="ECO:0007829|PDB:6DUB"
FT HELIX 94..105
FT /evidence="ECO:0007829|PDB:6DUB"
FT TURN 106..108
FT /evidence="ECO:0007829|PDB:6DUB"
FT STRAND 109..111
FT /evidence="ECO:0007829|PDB:6DUB"
FT STRAND 117..123
FT /evidence="ECO:0007829|PDB:6DUB"
FT TURN 126..128
FT /evidence="ECO:0007829|PDB:6DUB"
FT HELIX 129..133
FT /evidence="ECO:0007829|PDB:6DUB"
FT TURN 134..138
FT /evidence="ECO:0007829|PDB:6DUB"
FT STRAND 139..147
FT /evidence="ECO:0007829|PDB:6DUB"
FT HELIX 149..158
FT /evidence="ECO:0007829|PDB:6DUB"
FT HELIX 160..165
FT /evidence="ECO:0007829|PDB:6DUB"
FT STRAND 166..171
FT /evidence="ECO:0007829|PDB:6DUB"
FT HELIX 174..176
FT /evidence="ECO:0007829|PDB:6DUB"
FT STRAND 184..191
FT /evidence="ECO:0007829|PDB:6DUB"
FT HELIX 193..195
FT /evidence="ECO:0007829|PDB:6DUB"
FT HELIX 198..210
FT /evidence="ECO:0007829|PDB:6DUB"
FT STRAND 212..232
FT /evidence="ECO:0007829|PDB:6DUB"
FT TURN 233..236
FT /evidence="ECO:0007829|PDB:6DUB"
FT STRAND 237..241
FT /evidence="ECO:0007829|PDB:6DUB"
FT HELIX 242..251
FT /evidence="ECO:0007829|PDB:6DUB"
FT STRAND 256..261
FT /evidence="ECO:0007829|PDB:6DUB"
FT STRAND 272..277
FT /evidence="ECO:0007829|PDB:6DUB"
SQ SEQUENCE 283 AA; 32400 MW; F1FEAB7391A229C4 CRC64;
MAHRGAHFAF RSRWQKTDDE LCRHSMSFIL HKAIRNDFFQ SYLYLLEKIP LVKLYALTSQ
VINGEMQFYA RAKLFYQEVP ATEEGMMGNF IELSSPDIQA SQKFLRKFVG GPGRAGTDCA
LDCGSGIGRV SKHVLLPVFN SVELVDMMES FLLEAQNYLQ VKGDKVESYH CYSLQEFTPP
FRRYDVIWIQ WVSGHLTDKD LLAFLSRCRD GLKENGIIIL KDNVAREGCI LDLSDSSVTR
DMDILRSLIR KSGLVVLGQE KQDGFPEQCI PVWMFALHSD RHS
