Q9BV86 (NTM1A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
N-terminal Xaa-Pro-Lys N-methyltransferase 1
EC=2.1.1.244

Alternative name(s):
Alpha N-terminal protein methyltransferase 1A
Methyltransferase-like protein 11A
N-terminal RCC1 methyltransferase
X-Pro-Lys N-terminal protein methyltransferase 1A
Short name=NTM1A

Gene names

Name:	NTMT1
Synonyms:	C9orf32, METTL11A, NRMT
ORF Names:	AD-003

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	223 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Alpha-N-methyltransferase that methylates the N-terminus of target proteins containing the N-terminal motif [Ala/Pro/Ser]-Pro-Lys when the initiator Met is cleaved. Specifically catalyzes mono-, di- or tri-methylation of exposed alpha-amino group of Ala or Ser residue in the [Ala/Ser]-Pro-Lys motif and mono- or di-methylation of Pro in the Pro-Pro-Lys motif. Responsible for the N-terminal methylation of KLHL31, MYL2, MYL3, RB1, RCC1, RPL23A and SET. Required during mitosis for normal bipolar spindle formation and chromosome segregation via its action on RCC1. Ref.6 Ref.7
Catalytic activity	3 S-adenosyl-L-methionine + N-terminal-(A,S)PK-[protein] = 3 S-adenosyl-L-homocysteine + N-terminal-N,N,N-trimethyl-N-(A,S)PK-[protein]. 2 S-adenosyl-L-methionine + N-terminal-PPK-[protein] = 2 S-adenosyl-L-homocysteine + N-terminal-N,N-dimethyl-N-PPK-[protein].
Subcellular location	Nucleus. Note: Predominantly nuclear. Ref.7
Sequence similarities	Belongs to the methyltransferase superfamily. NTM1 family.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	S-adenosyl-L-methionine
Molecular function	Methyltransferase Transferase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	N-terminal peptidyl-alanine trimethylation Inferred from electronic annotation. Source: Compara N-terminal peptidyl-proline dimethylation Inferred from direct assay Ref.6Ref.7. Source: UniProtKB N-terminal peptidyl-serine dimethylation Inferred from direct assay Ref.7. Source: UniProtKB N-terminal peptidyl-serine trimethylation Inferred from direct assay Ref.7. Source: UniProtKB chromosome segregation Inferred from mutant phenotype Ref.7. Source: UniProtKB spindle organization Inferred from mutant phenotype Ref.7. Source: UniProtKB
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from direct assay Ref.7. Source: UniProtKB
Molecular_function	protein methyltransferase activity Inferred from direct assay Ref.6Ref.7. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DIS3	Q9Y2L1	1	EBI-373016,EBI-373539

Alternative products

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

Isoform 1 (identifier: Q9BV86-1)

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: Q9BV86-2)

The sequence of this isoform differs from the canonical sequence as follows:
     111-223: VRNYFCCGLQ...IYHVYSFALR → ATSPISTWPSSCGAARAASAPTASSSSKTTWPRRA

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.5

Chain

2 – 223

222

N-terminal Xaa-Pro-Lys N-methyltransferase 1

PRO_0000119288

Regions

Region

91 – 93

3

S-adenosyl-L-methionine binding

Region

119 – 120

2

S-adenosyl-L-methionine binding

Sites

Binding site

69

1

S-adenosyl-L-methionine; via carbonyl oxygen

Binding site

74

1

S-adenosyl-L-methionine

Binding site

135

1

S-adenosyl-L-methionine; via carbonyl oxygen

Amino acid modifications

Modified residue

2

1

N-acetylthreonine Ref.5

Natural variations

Alternative sequence

111 – 223

113

VRNYF…SFALR → ATSPISTWPSSCGAARAASA PTASSSSKTTWPRRA in isoform 2.

VSP_039886

Experimental info

Mutagenesis

167

1

D → A: Does not affect methyltransferase activity. Ref.7

Mutagenesis

168

1

N → A: Induces a strong decrease in methyltransferase activity. Ref.7

Mutagenesis

168

1

N → K: Loss of methyltransferase activity. Ref.7

Mutagenesis

177

1

D → A: Induces a slight decrease in methyltransferase activity. Ref.7

Mutagenesis

177

1

D → K: Induces a strong decrease in methyltransferase activity. Ref.7

Mutagenesis

180

1

D → A: Induces a decrease in methyltransferase activity. Ref.7

Mutagenesis

180

1

D → K: Induces a strong decrease in methyltransferase activity. Ref.7

Mutagenesis

182

1

S → A: Induces a slight decrease in methyltransferase activity. Ref.7

Mutagenesis

182

1

S → K: Induces a strong decrease in methyltransferase activity. Ref.7

Sequence conflict

25

1

P → L in BAF85021. Ref.2

Sequence conflict

39

1

S → SS in AAF14859. Ref.1

Sequence conflict

131

1

V → A in BAF83646. Ref.2

Secondary structure

1

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223

Helix Strand Turn

Details...

Helix

2 – 5

4

Helix

9 – 21

13

Helix

27 – 30

4

Turn

31 – 33

3

Helix

35 – 37

3

Helix

38 – 50

13

Helix

51 – 53

3

Beta strand

63 – 68

6

Turn

71 – 73

3

Helix

74 – 78

5

Turn

79 – 83

5

Beta strand

85 – 92

8

Helix

94 – 103

10

Helix

105 – 110

6

Beta strand

111 – 116

6

Helix

119 – 121

3

Beta strand

129 – 136

8

Helix

138 – 140

3

Helix

143 – 156

14

Beta strand

157 – 177

21

Turn

178 – 181

4

Beta strand

182 – 186

5

Helix

187 – 196

10

Beta strand

200 – 206

7

Beta strand

216 – 223

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 4A0EC492D9B52C49	FASTA	223	25,387
	10 20 30 40 50 60 MTSEVIEDEK QFYSKAKTYW KQIPPTVDGM LGGYGHISSI DINSSRKFLQ RFLREGPNKT 70 80 90 100 110 120 GTSCALDCGA GIGRITKRLL LPLFREVDMV DITEDFLVQA KTYLGEEGKR VRNYFCCGLQ 130 140 150 160 170 180 DFTPEPDSYD VIWIQWVIGH LTDQHLAEFL RRCKGSLRPN GIIVIKDNMA QEGVILDDVD 190 200 210 220 SSVCRDLDVV RRIICSAGLS LLAEERQENL PDEIYHVYSF ALR
	Isoform 2 [UniParc]. Checksum: 4D5E90507357F03B	FASTA	145	15,896
	10 20 30 40 50 60 MTSEVIEDEK QFYSKAKTYW KQIPPTVDGM LGGYGHISSI DINSSRKFLQ RFLREGPNKT 70 80 90 100 110 120 GTSCALDCGA GIGRITKRLL LPLFREVDMV DITEDFLVQA KTYLGEEGKR ATSPISTWPS 130 140 SCGAARAASA PTASSSSKTT WPRRA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning." Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M. , Zhou J., Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L. Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Adrenal gland.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Teratocarcinoma and Testis.
[3]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [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: Brain and Skin.
[5]	Bienvenut W.V. Submitted (OCT-2004) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-15 AND 79-85, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT THR-2, MASS SPECTROMETRY. Tissue: B-cell lymphoma.
[6]	"Identification of protein N-terminal methyltransferases in yeast and humans." Webb K.J., Lipson R.S., Al-Hadid Q., Whitelegge J.P., Clarke S.G. Biochemistry 49:5225-5235(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[7]	"NRMT is an alpha-N-methyltransferase that methylates RCC1 and retinoblastoma protein." Tooley C.E., Petkowski J.J., Muratore-Schroeder T.L., Balsbaugh J.L., Shabanowitz J., Sabat M., Minor W., Hunt D.F., Macara I.G. Nature 466:1125-1128(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, S-ADENOSYL-L-METHIONINE-BINDING, MUTAGENESIS OF ASP-167; ASN-168; ASP-177; ASP-180 AND SER-182.
[8]	"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].
[9]	"The crystal structure of human AD-003 protein in complex with S-adenosyl-L-homocysteine." Structural genomics consortium (SGC) Submitted (FEB-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 2-223 IN COMPLEX WITH S-ADENOSYL-L-HOMOCYSTEINE.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF110776 mRNA. Translation: AAF14859.1.
AK290957 mRNA. Translation: BAF83646.1.
AK292332 mRNA. Translation: BAF85021.1.
AK298840 mRNA. Translation: BAG60968.1.
AL590369 Genomic DNA. Translation: CAI14507.1.
AL590369 Genomic DNA. Translation: CAI14508.1.
BC001396 mRNA. Translation: AAH01396.1.
BC033234 mRNA. Translation: AAH33234.1.

IPI

IPI00515040.
IPI00549389.

RefSeq

NP_054783.2. NM_014064.2.

UniGene

Hs.741241.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2EX4	X-ray	1.75	A/B	2-223	[»]

ProteinModelPortal

Q9BV86.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31241N.

IntAct

Q9BV86. 2 interactions.

STRING

9606.ENSP00000361558.

PTM databases

PhosphoSite

Q9BV86.

Polymorphism databases

DMDM

74761281.

Proteomic databases

PaxDb

Q9BV86.

PRIDE

Q9BV86.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000372480; ENSP00000361558; ENSG00000148335.
ENST00000372481; ENSP00000361559; ENSG00000148335.
ENST00000372483; ENSP00000361561; ENSG00000148335.
ENST00000372486; ENSP00000361564; ENSG00000148335.

GeneID

28989.

KEGG

hsa:28989.

UCSC

uc004byd.1. human.
uc011mbs.1. human.

Organism-specific databases

CTD

28989.

GeneCards

GC09P132372.

H-InvDB

HIX0008452.

HGNC

HGNC:23373. NTMT1.

HPA

HPA020092.

MIM

613560. gene.

neXtProt

NX_Q9BV86.

PharmGKB

PA162395788.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG278169.

HOGENOM

HOG000161910.

HOVERGEN

HBG054992.

InParanoid

Q9BV86.

KO

K16219.

OMA

YHVYSLA.

OrthoDB

EOG4GTKDS.

PhylomeDB

Q9BV86.

Gene expression databases

Bgee

Q9BV86.

CleanEx

HS_METTL11A.

Genevestigator

Q9BV86.

GermOnline

ENSG00000148335. Homo sapiens.

Family and domain databases

InterPro

IPR008576. DUF858_MeTrfase_lik.
[Graphical view]

PANTHER

PTHR12753. PTHR12753. 1 hit.

Pfam

PF05891. Methyltransf_PK. 1 hit.
[Graphical view]

PIRSF

PIRSF016958. DUF858_MeTrfase_lik. 1 hit.

ProtoNet

Search...

Other

ChiTaRS

METTL11A. human.

EvolutionaryTrace

Q9BV86.

GenomeRNAi

28989.

NextBio

51905.

SOURCE

Search...

Entry information

Entry name

NTM1A_HUMAN

Accession

Primary (citable) accession number: Q9BV86
Secondary accession number(s): A8K4J2 , A8K8G7, Q5SZB9, Q9UI28

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 8, 2005
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 110 of the entry and version 3 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.