Q86U44 (MTA70_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
N6-adenosine-methyltransferase 70 kDa subunit
Short name=MT-A70
EC=2.1.1.62

Alternative name(s):
Methyltransferase-like protein 3

Gene names

Name:	METTL3
Synonyms:	MTA70

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	580 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	N6-methyltransferase that methylates adenosine residues of some mRNAs. N6-methyladenosine (m6A), which is present at internal sites of some mRNAs, may play a role in the efficiency of mRNA splicing, transport or translation. Ref.1
Catalytic activity	S-adenosyl-L-methionine + m7G(5')pppAm = S-adenosyl-L-homocysteine + m7G(5')pppm6Am.
Subcellular location	Nucleus speckle. Note: Colocalizes with speckles in interphase nuclei. Suggesting that it may be associated with nuclear pre-mRNA splicing components. Ref.1
Tissue specificity	Widely expressed at low level. Expressed in spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocytes. Ref.1
Sequence similarities	Belongs to the MT-A70-like family.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	RNA-binding S-adenosyl-L-methionine
Molecular function	Methyltransferase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	gene expression Traceable author statement. Source: Reactome
Cellular_component	nuclear speck Inferred from electronic annotation. Source: UniProtKB-SubCell nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW mRNA (2'-O-methyladenosine-N6-)-methyltransferase activity Inferred from mutant phenotype Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q86U44-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q86U44-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-284: Missing.
     486-505: GVKGNPQGFNQGLDCDVIVA → SSSGAQFNRWSTKKNHLISY
     506-580: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 580	580	N6-adenosine-methyltransferase 70 kDa subunit		PRO_0000207630
Amino acid modifications
	Modified residue	43	1	Phosphoserine Ref.5 Ref.7 Ref.9
	Modified residue	219	1	Phosphoserine Ref.7
	Modified residue	243	1	Phosphoserine Ref.7
Natural variations
	Alternative sequence	1 – 284	284	Missing in isoform 2.		VSP_007864
	Alternative sequence	486 – 505	20	GVKGN…DVIVA → SSSGAQFNRWSTKKNHLISY in isoform 2.		VSP_007865
	Alternative sequence	506 – 580	75	Missing in isoform 2.		VSP_007866
Experimental info
	Sequence conflict	251	1	N → I in AAB71850. Ref.1
	Sequence conflict	263 – 264	2	KF → I in AAB71850. Ref.1
	Sequence conflict	382	1	D → V in AAB71850. Ref.1
	Sequence conflict	568	1	R → K in AAH52244. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 25, 2003. Version 2. Checksum: 63A7F10195A3C6AC	FASTA	580	64,474
	10 20 30 40 50 60 MSDTWSSIQA HKKQLDSLRE RLQRRRKQDS GHLDLRNPEA ALSPTFRSDS PVPTAPTSGG 70 80 90 100 110 120 PKPSTASAVP ELATDPELEK KLLHHLSDLA LTLPTDAVSI CLAISTPDAP ATQDGVESLL 130 140 150 160 170 180 QKFAAQELIE VKRGLLQDDA HPTLVTYADH SKLSAMMGAV AEKKGPGEVA GTVTGQKRRA 190 200 210 220 230 240 EQDSTTVAAF ASSLVSGLNS SASEPAKEPA KKSRKHAASD VDLEIESLLN QQSTKEQQSK 250 260 270 280 290 300 KVSQEILELL NTTTAKEQSI VEKFRSRGRA QVQEFCDYGT KEECMKASDA DRPCRKLHFR 310 320 330 340 350 360 RIINKHTDES LGDCSFLNTC FHMDTCKYVH YEIDACMDSE APGSKDHTPS QELALTQSVG 370 380 390 400 410 420 GDSSADRLFP PQWICCDIRY LDVSILGKFA VVMADPPWDI HMELPYGTLT DDEMRRLNIP 430 440 450 460 470 480 VLQDDGFLFL WVTGRAMELG RECLNLWGYE RVDEIIWVKT NQLQRIIRTG RTGHWLNHGK 490 500 510 520 530 540 EHCLVGVKGN PQGFNQGLDC DVIVAEVRST SHKPDEIYGM IERLSPGTRK IELFGRPHNV 550 560 570 580 QPNWITLGNQ LDGIHLLDPD VVARFKQRYP DGIISKPKNL
	Isoform 2 [UniParc]. Checksum: D95A9087F7B99439	FASTA	221	25,479
	10 20 30 40 50 60 MKASDADRPC RKLHFRRIIN KHTDESLGDC SFLNTCFHMD TCKYVHYEID ACMDSEAPGS 70 80 90 100 110 120 KDHTPSQELA LTQSVGGDSS ADRLFPPQWI CCDIRYLDVS ILGKFAVVMA DPPWDIHMEL 130 140 150 160 170 180 PYGTLTDDEM RRLNIPVLQD DGFLFLWVTG RAMELGRECL NLWGYERVDE IIWVKTNQLQ 190 200 210 220 RIIRTGRTGH WLNHGKEHCL VSSSGAQFNR WSTKKNHLIS Y

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase." Bokar J.A., Shambaugh M.E., Polayes D., Matera A.G., Rottman F.M. RNA 3:1233-1247(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), PROTEIN SEQUENCE OF 48-56; 134-149 AND 509-522, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]	"Full-length cDNA libraries and normalization." Li W.B., Gruber C., Jessee J., Polayes D. Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Placenta.
[3]	"The DNA sequence and analysis of human chromosome 14." Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J. Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lung and Pancreas.
[5]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-43, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[6]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Embryonic kidney.
[7]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-43; SER-219 AND SER-243, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[9]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-43, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF014837 Genomic DNA. Translation: AAB71850.1. AF283991 Genomic DNA. Translation: AAG13956.1. AE000658 Genomic DNA. No translation available. BX247964 mRNA. Translation: CAD62303.1. BC003031 mRNA. Translation: AAH03031.1. BC001650 mRNA. Translation: AAH01650.1. BC052244 mRNA. Translation: AAH52244.1.
IPI	IPI00009755. IPI00328636.
RefSeq	NP_062826.2. NM_019852.3.
UniGene	Hs.168799.
3D structure databases
ProteinModelPortal	Q86U44.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000298717.
PTM databases
PhosphoSite	Q86U44.
Polymorphism databases
DMDM	33301371.
Proteomic databases
PaxDb	Q86U44.
PeptideAtlas	Q86U44.
PRIDE	Q86U44.
Protocols and materials databases
DNASU	56339.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000298717; ENSP00000298717; ENSG00000165819.
GeneID	56339.
KEGG	hsa:56339.
UCSC	uc001wbb.3. human.
Organism-specific databases
CTD	56339.
GeneCards	GC14M021966.
HGNC	HGNC:17563. METTL3.
HPA	HPA001299.
MIM	612472. gene.
neXtProt	NX_Q86U44.
PharmGKB	PA134955499.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG4725.
HOGENOM	HOG000012669.
HOVERGEN	HBG052521.
InParanoid	Q86U44.
KO	K05925.
OMA	TKKSRKH.
OrthoDB	EOG4JQ3XC.
PhylomeDB	Q86U44.
Enzyme and pathway databases
Reactome	REACT_1675. mRNA Processing. REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	Q86U44.
Bgee	Q86U44.
CleanEx	HS_METTL3.
Genevestigator	Q86U44.
GermOnline	ENSG00000165819. Homo sapiens.
Family and domain databases
InterPro	IPR025848. MT-A70. IPR007757. MT-A70-like. [Graphical view]
Pfam	PF05063. MT-A70. 1 hit. [Graphical view]
PROSITE	PS51143. MT_A70. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	56339.
NextBio	61981.
SOURCE	Search...

Entry information

Entry name

MTA70_HUMAN

Accession

Primary (citable) accession number: Q86U44
Secondary accession number(s): O14736, Q86V05, Q9HB32

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 25, 2003
Last sequence update:	July 25, 2003
Last modified:	April 3, 2013
This is version 90 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.