METL9_HUMAN
ID METL9_HUMAN Reviewed; 318 AA.
AC Q9H1A3; Q8NBT8; Q9BWJ7; Q9H1A2; Q9Y390;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Protein-L-histidine N-pros-methyltransferase {ECO:0000305};
DE EC=2.1.1.- {ECO:0000269|PubMed:33563959, ECO:0000269|PubMed:34562450};
DE AltName: Full=DORA reverse strand protein {ECO:0000303|PubMed:11132146};
DE Short=DREV {ECO:0000303|PubMed:11132146};
DE Short=DREV1 {ECO:0000303|PubMed:11132146};
DE AltName: Full=Methyltransferase-like protein 9 {ECO:0000303|PubMed:33563959};
DE Short=hMETTL9 {ECO:0000303|PubMed:33563959};
DE Flags: Precursor;
GN Name=METTL9 {ECO:0000303|PubMed:33563959, ECO:0000312|HGNC:HGNC:24586};
GN Synonyms=DREV {ECO:0000303|PubMed:11132146};
GN ORFNames=CGI-81 {ECO:0000303|PubMed:10810093};
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] (ISOFORMS 1 AND 2).
RX PubMed=11132146; DOI=10.1007/s002510000259;
RA Bates E.E.M., Kissenpfennig A., Peronne C., Mattei M.-G., Fossiez F.,
RA Malissen B., Lebecque S.;
RT "The mouse and human IGSF6 (DORA) genes map to the inflammatory bowel
RT disease 1 locus and are embedded in an intron of a gene of unknown
RT function.";
RL Immunogenetics 52:112-120(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Eye;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 27-318 (ISOFORM 2).
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=34562450; DOI=10.1016/j.jbc.2021.101230;
RA Daitoku H., Someya M., Kako K., Hayashi T., Tajima T., Haruki H.,
RA Sekiguchi N., Uetake T., Akimoto Y., Fukamizu A.;
RT "siRNA screening identifies METTL9 as a histidine Npi-methyltransferase
RT that targets the proinflammatory protein S100A9.";
RL J. Biol. Chem. 297:101230-101230(2021).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP GLU-174.
RX PubMed=33563959; DOI=10.1038/s41467-020-20670-7;
RA Davydova E., Shimazu T., Schuhmacher M.K., Jakobsson M.E.,
RA Willemen H.L.D.M., Liu T., Moen A., Ho A.Y.Y., Malecki J., Schroer L.,
RA Pinto R., Suzuki T., Groensberg I.A., Sohtome Y., Akakabe M., Weirich S.,
RA Kikuchi M., Olsen J.V., Dohmae N., Umehara T., Sodeoka M., Siino V.,
RA McDonough M.A., Eijkelkamp N., Schofield C.J., Jeltsch A., Shinkai Y.,
RA Falnes P.O.;
RT "The methyltransferase METTL9 mediates pervasive 1-methylhistidine
RT modification in mammalian proteomes.";
RL Nat. Commun. 12:891-891(2021).
CC -!- FUNCTION: Protein-histidine N-methyltransferase that specifically
CC catalyzes 1-methylhistidine (pros-methylhistidine) methylation of
CC target proteins (PubMed:33563959, PubMed:34562450). Mediates
CC methylation of proteins with a His-x-His (HxH) motif (where 'x' is
CC preferably a small amino acid) (PubMed:33563959). Catalyzes methylation
CC of target proteins such as S100A9, NDUFB3, SLC39A5, SLC39A7, ARMC6 and
CC DNAJB12; 1-methylhistidine modification may affect the binding of zinc
CC and other metals to its target proteins (PubMed:33563959,
CC PubMed:34562450). Constitutes the main methyltransferase for the 1-
CC methylhistidine modification in cell (PubMed:33563959).
CC {ECO:0000269|PubMed:33563959, ECO:0000269|PubMed:34562450}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-histidyl-[protein] + S-adenosyl-L-methionine = H(+) +
CC N(pros)-methyl-L-histidyl-[protein] + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:67076, Rhea:RHEA-COMP:9745, Rhea:RHEA-COMP:17184,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29979, ChEBI:CHEBI:43903,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789;
CC Evidence={ECO:0000269|PubMed:33563959, ECO:0000269|PubMed:34562450};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67077;
CC Evidence={ECO:0000269|PubMed:33563959, ECO:0000269|PubMed:34562450};
CC -!- INTERACTION:
CC Q9H1A3; Q9HB07: MYG1; NbExp=3; IntAct=EBI-2804879, EBI-709754;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000269|PubMed:34562450, ECO:0000305|PubMed:33563959}.
CC Mitochondrion {ECO:0000305|PubMed:33563959}. Note=Colocalizes with
CC membranous compartments such as the endoplasmic reticulum and
CC mitochondria. {ECO:0000269|PubMed:33563959}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H1A3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H1A3-2; Sequence=VSP_030997;
CC -!- SIMILARITY: Belongs to the METTL9 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD34076.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AJ278578; CAC20438.1; -; mRNA.
DR EMBL; AJ278577; CAC20437.1; -; mRNA.
DR EMBL; AJ278581; CAC20439.1; -; Genomic_DNA.
DR EMBL; AK075237; BAC11490.1; -; mRNA.
DR EMBL; AK074529; BAC11042.1; -; mRNA.
DR EMBL; AK075022; BAC11356.1; -; mRNA.
DR EMBL; CH878403; EAW50517.1; -; Genomic_DNA.
DR EMBL; CH878403; EAW50518.1; -; Genomic_DNA.
DR EMBL; BC000195; AAH00195.2; -; mRNA.
DR EMBL; AF151839; AAD34076.1; ALT_INIT; mRNA.
DR CCDS; CCDS10598.2; -. [Q9H1A3-1]
DR CCDS; CCDS45440.1; -. [Q9H1A3-2]
DR RefSeq; NP_001070648.1; NM_001077180.2. [Q9H1A3-2]
DR RefSeq; NP_001275588.1; NM_001288659.1.
DR RefSeq; NP_001275589.1; NM_001288660.1.
DR RefSeq; NP_057109.3; NM_016025.4. [Q9H1A3-1]
DR AlphaFoldDB; Q9H1A3; -.
DR SMR; Q9H1A3; -.
DR BioGRID; 119297; 93.
DR IntAct; Q9H1A3; 18.
DR MINT; Q9H1A3; -.
DR STRING; 9606.ENSP00000350874; -.
DR GlyGen; Q9H1A3; 1 site.
DR iPTMnet; Q9H1A3; -.
DR PhosphoSitePlus; Q9H1A3; -.
DR BioMuta; METTL9; -.
DR DMDM; 74718034; -.
DR EPD; Q9H1A3; -.
DR jPOST; Q9H1A3; -.
DR MassIVE; Q9H1A3; -.
DR MaxQB; Q9H1A3; -.
DR PaxDb; Q9H1A3; -.
DR PeptideAtlas; Q9H1A3; -.
DR PRIDE; Q9H1A3; -.
DR ProteomicsDB; 80382; -. [Q9H1A3-1]
DR ProteomicsDB; 80383; -. [Q9H1A3-2]
DR Antibodypedia; 25721; 26 antibodies from 12 providers.
DR DNASU; 51108; -.
DR Ensembl; ENST00000358154.8; ENSP00000350874.3; ENSG00000197006.15. [Q9H1A3-1]
DR Ensembl; ENST00000396014.8; ENSP00000379335.4; ENSG00000197006.15. [Q9H1A3-2]
DR Ensembl; ENST00000638803.2; ENSP00000491526.2; ENSG00000284548.3.
DR GeneID; 51108; -.
DR KEGG; hsa:51108; -.
DR MANE-Select; ENST00000358154.8; ENSP00000350874.3; NM_016025.5; NP_057109.3.
DR UCSC; uc002dje.4; human. [Q9H1A3-1]
DR CTD; 51108; -.
DR DisGeNET; 51108; -.
DR GeneCards; METTL9; -.
DR HGNC; HGNC:24586; METTL9.
DR HPA; ENSG00000197006; Low tissue specificity.
DR MIM; 609388; gene.
DR neXtProt; NX_Q9H1A3; -.
DR OpenTargets; ENSG00000197006; -.
DR PharmGKB; PA145148428; -.
DR VEuPathDB; HostDB:ENSG00000197006; -.
DR eggNOG; KOG3987; Eukaryota.
DR GeneTree; ENSGT00390000013648; -.
DR InParanoid; Q9H1A3; -.
DR OMA; PYMHYVE; -.
DR OrthoDB; 899076at2759; -.
DR PhylomeDB; Q9H1A3; -.
DR TreeFam; TF314187; -.
DR PathwayCommons; Q9H1A3; -.
DR SignaLink; Q9H1A3; -.
DR BioGRID-ORCS; 51108; 15 hits in 1076 CRISPR screens.
DR ChiTaRS; METTL9; human.
DR GenomeRNAi; 51108; -.
DR Pharos; Q9H1A3; Tdark.
DR PRO; PR:Q9H1A3; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9H1A3; protein.
DR Bgee; ENSG00000197006; Expressed in secondary oocyte and 206 other tissues.
DR ExpressionAtlas; Q9H1A3; baseline and differential.
DR Genevisible; Q9H1A3; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0106370; F:protein-L-histidine N-pros-methyltransferase activity; IDA:UniProtKB.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR007884; METL9.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR12890; PTHR12890; 1.
DR Pfam; PF05219; DREV; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Glycoprotein;
KW Methyltransferase; Mitochondrion; Reference proteome; Signal; Transferase.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..318
FT /note="Protein-L-histidine N-pros-methyltransferase"
FT /id="PRO_0000317490"
FT CARBOHYD 35
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 251
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10810093,
FT ECO:0000303|PubMed:11132146, ECO:0000303|PubMed:14702039"
FT /id="VSP_030997"
FT MUTAGEN 174
FT /note="E->A: Abolished protein-L-histidine N-pros-
FT methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:33563959"
FT CONFLICT 43..44
FT /note="PA -> RS (in Ref. 5; AAD34076)"
FT /evidence="ECO:0000305"
FT CONFLICT 57
FT /note="Y -> C (in Ref. 2; BAC11490)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 318 AA; 36536 MW; 81DEF9CC78342229 CRC64;
MRLLAGWLCL SLASVWLARR MWTLRSPLTR SLYVNMTSGP GGPAAAAGGR KENHQWYVCN
REKLCESLQA VFVQSYLDQG TQIFLNNSIE KSGWLFIQLY HSFVSSVFSL FMSRTSINGL
LGRGSMFVFS PDQFQRLLKI NPDWKTHRLL DLGAGDGEVT KIMSPHFEEI YATELSETMI
WQLQKKKYRV LGINEWQNTG FQYDVISCLN LLDRCDQPLT LLKDIRSVLE PTRGRVILAL
VLPFHPYVEN VGGKWEKPSE ILEIKGQNWE EQVNSLPEVF RKAGFVIEAF TRLPYLCEGD
MYNDYYVLDD AVFVLKPV
