Reviewed, UniProtKB/Swiss-Prot P11086 (PNMT_HUMAN)

Names and origin

Protein names

Recommended name:
    Phenylethanolamine N-methyltransferase
      Short name=PNMTase
    EC=2.1.1.28
Alternative name(s):
    Noradrenaline N-methyltransferase

Gene names

Name:	PNMT
Synonyms:	PENT

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	282 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Converts noradrenaline to adrenaline.
Catalytic activity	S-adenosyl-L-methionine + phenylethanolamine = S-adenosyl-L-homocysteine + N-methylphenylethanolamine.
Pathway	Catecholamine biosynthesis; epinephrine biosynthesis; epinephrine from norepinephrine: step 1/1.
Sequence similarities	Belongs to the NNMT/PNMT/TEMT family.
biophysicochemical properties	Kinetic parameters: KM=99 µM for phenylethanolamine KM=3.4 µM for S-adenosyl-L-methionine

Ontologies

Keywords
Biological process	Catecholamine biosynthesis
Coding sequence diversity	Polymorphism
Ligand	S-adenosyl-L-methionine
Molecular function	Methyltransferase Transferase
Technical term	3D-structure
Gene Ontology (GO)
Biological process	catecholamine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	phenylethanolamine N-methyltransferase activity Ref.3 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 282

282

Phenylethanolamine N-methyltransferase

PRO_0000159709

Regions

Region

79 – 80

2

S-adenosyl-L-methionine binding

Region

158 – 159

2

S-adenosyl-L-methionine binding

Sites

Binding site

35

1

S-adenosyl-L-methionine

Binding site

40

1

S-adenosyl-L-methionine

Binding site

85

1

S-adenosyl-L-methionine

Binding site

101

1

S-adenosyl-L-methionine

Binding site

106

1

S-adenosyl-L-methionine

Binding site

181

1

S-adenosyl-L-methionine; via carbonyl oxygen

Binding site

219

1

Substrate

Natural variations

Natural variant

9

1

N → S: dbSNP rs11569781. Ref.9

VAR_029351

Natural variant

98

1

T → A Lower activity levels than wild-type. dbSNP rs36060376. Ref.9

VAR_036829

Natural variant

112

1

R → C: dbSNP rs34530498. Ref.9

VAR_036830

Natural variant

175

1

A → T: dbSNP rs34341496. Ref.9

VAR_036831

Natural variant

188

1

S → C: dbSNP rs5639.

VAR_037611

Natural variant

211

1

L → H: dbSNP rs5640.

VAR_037612

Natural variant

217

1

L → Q: dbSNP rs5641.

VAR_037613

Natural variant

254

1

R → H: dbSNP rs5642.

VAR_037614

Natural variant

276

1

W → R: dbSNP rs5643.

VAR_024547

Experimental info

Mutagenesis

35

1

Y → F: Strongly increases KM for substrate and S-adenosyl-L-methionine. Ref.6

Mutagenesis

185

1

E → A or Q: Strongly reduced enzyme activity. Increases affinity for S-adenosyl-L-methionine. Ref.6

Mutagenesis

185

1

E → D: Strongly reduced enzyme activity. Decreases affinity for substrate and S-adenosyl-L-methionine 3-fold. Ref.6

Mutagenesis

219

1

E → A: Reduced enzyme activity. Decreases affinity for substrate 6-fold. Decreases affinity for S-adenosyl-L-methionine 2-fold. Ref.6

Mutagenesis

267

1

D → A or N: Strongly reduced enzyme activity. Decreases affinity for substrate 200-fold. Decreases affinity for S-adenosyl-L-methionine 3-fold. Ref.6

Sequence conflict

169 – 170

2

SP → AQ in AAA60131. Ref.3

Secondary structure

1

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282

Helix Strand Turn

Details...

Helix

17 – 21

5

Helix

23 – 27

5

Helix

32 – 40

9

Turn

42 – 45

4

Helix

53 – 66

14

Beta strand

73 – 79

7

Helix

85 – 87

3

Turn

88 – 90

3

Helix

91 – 93

3

Beta strand

95 – 100

6

Helix

104 – 114

11

Helix

124 – 134

11

Helix

140 – 150

11

Beta strand

151 – 155

5

Beta strand

161 – 163

3

Beta strand

173 – 182

10

Helix

184 – 187

4

Helix

191 – 202

12

Beta strand

205 – 218

14

Beta strand

221 – 225

5

Beta strand

227 – 230

4

Helix

236 – 245

10

Beta strand

248 – 257

10

Helix

260 – 262

3

Beta strand

271 – 279

9

Sequences

	Sequence		Length	Mass (Da)
	P11086-1 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: 56F3A9981D9ABF4C	FASTA	282	30,855
	10 20 30 40 50 60 MSGADRSPNA GAAPDSAPGQ AAVASAYQRF EPRAYLRNNY APPRGDLCNP NGVGPWKLRC 70 80 90 100 110 120 LAQTFATGEV SGRTLIDIGS GPTVYQLLSA CSHFEDITMT DFLEVNRQEL GRWLQEEPGA 130 140 150 160 170 180 FNWSMYSQHA CLIEGKGECW QDKERQLRAR VKRVLPIDVH QPQPLGAGSP APLPADALVS 190 200 210 220 230 240 AFCLEAVSPD LASFQRALDH ITTLLRPGGH LLLIGALEES WYLAGEARLT VVPVSEEEVR 250 260 270 280 EALVRSGYKV RDLRTYIMPA HLQTGVDDVK GVFFAWAQKV GL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of cDNA and chromosomal assignment of the gene for human phenylethanolamine N-methyltransferase, the enzyme for epinephrine biosynthesis." Kaneda N., Ichinose H., Kobayashi K., Oka K., Kishi F., Nakazawa A., Kurosawa Y., Fujita K., Nagatsu T. J. Biol. Chem. 263:7672-7677(1988) [PubMed: 3372503] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Structure of human phenylethanolamine N-methyltransferase gene: existence of two types of mRNA with different transcription initiation sites." Sasaoka T., Kaneda N., Kurosawa Y., Fujita K., Nagatsu T. Neurochem. Int. 15:555-565(1989) Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[3]	"Transgenic mice express the human phenylethanolamine N-methyltransferase gene in adrenal medulla and retina." Baetge E.E., Behringer R.R., Messing A., Brinster R.L., Palmiter R.D. Proc. Natl. Acad. Sci. U.S.A. 85:3648-3652(1988) [PubMed: 2835776] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain, Lung and Testis.
[5]	"Getting the adrenaline going: crystal structure of the adrenaline-synthesizing enzyme PNMT." Martin J.L., Begun J., McLeish M.J., Caine J.M., Grunewald G.L. Structure 9:977-985(2001) [PubMed: 11591352] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH S-ADENOSYL-L-HOMOCYSTEINE AND SYNTHETIC INHIBITOR.
[6]	"Mode of binding of methyl acceptor substrates to the adrenaline-synthesizing enzyme phenylethanolamine N-methyltransferase: implications for catalysis." Gee C.L., Tyndall J.D.A., Grunewald G.L., Wu Q., McLeish M.J., Martin J.L. Biochemistry 44:16875-16885(2005) [PubMed: 16363801] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEXES WITH SUBSTRATE ANALOGS AND S-ADENOSYL-L-HOMOCYSTEINE, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF TYR-35; GLU-185; GLU-219 AND ASP-267.
[7]	"Comparison of the binding of 3-fluoromethyl-7-sulfonyl-1,2,3,4-tetrahydroisoquinolines with their isosteric sulfonamides to the active site of phenylethanolamine N-methyltransferase." Grunewald G.L., Seim M.R., Regier R.C., Martin J.L., Gee C.L., Drinkwater N., Criscione K.R. J. Med. Chem. 49:5424-5433(2006) [PubMed: 16942016] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH SYNTHETIC INHIBITOR.
[8]	"Enzyme adaptation to inhibitor binding: a cryptic binding site in phenylethanolamine N-methyltransferase." Gee C.L., Drinkwater N., Tyndall J.D.A., Grunewald G.L., Wu Q., McLeish M.J., Martin J.L. J. Med. Chem. 50:4845-4853(2007) [PubMed: 17845018] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEXES WITH SYNTHETIC INHIBITOR.
[9]	"Human phenylethanolamine N-methyltransferase pharmacogenomics: gene re-sequencing and functional genomics." Ji Y., Salavaggione O.E., Wang L., Adjei A.A., Eckloff B., Wieben E.D., Weinshilboum R.M. J. Neurochem. 95:1766-1776(2005) [PubMed: 16277617] [Abstract] Cited for: VARIANTS SER-9; ALA-98; CYS-112 AND THR-175, CHARACTERIZATION OF VARIANT ALA-98.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

J03727 mRNA. Translation: AAA60130.1.
X52730 Genomic DNA. Translation: CAA36944.1.
J03280 Genomic DNA. Translation: AAA60131.1.
BC037246 mRNA. Translation: AAH37246.1.

IPI

IPI00003466.

PIR

A28171.

RefSeq

NP_002677.1.

UniGene

Hs.1892

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HNN	X-ray	2.40	A/B	1-282	[»]
1N7I	X-ray	2.80	A/B	1-282	[»]
1N7J	X-ray	2.70	A/B	1-282	[»]
1YZ3	X-ray	2.40	A/B	1-282	[»]
2AN3	X-ray	2.20	A/B	1-282	[»]
2AN4	X-ray	2.20	A/B	1-282	[»]
2AN5	X-ray	2.50	A/B	1-282	[»]
2G70	X-ray	2.40	A/B	1-282	[»]
2G71	X-ray	2.20	A/B	1-282	[»]
2G72	X-ray	2.00	A/B	1-282	[»]
2G8N	X-ray	2.15	A/B	1-282	[»]
2OBF	X-ray	2.30	A/B	1-282	[»]
2ONY	X-ray	2.60	A/B	1-282	[»]
2ONZ	X-ray	2.80	A/B	1-282	[»]
2OPB	X-ray	2.80	A/B	1-282	[»]

ModBase

Search...

Proteomic databases

PRIDE

P11086.

Genome annotation databases

Ensembl

ENSG00000141744. Homo sapiens. [Contig view]

GeneID

5409.

KEGG

hsa:5409.

Organism-specific databases

GeneCards

GC17P035078.

H-InvDB

HIX0027187.

HGNC

HGNC:9160. PNMT.

HPA

CAB017029.

MIM

171190. gene.

PharmGKB

PA274.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P11086.

HOVERGEN

P11086.

OMA

P11086. ALEESWY.

Enzyme and pathway databases

BRENDA

2.1.1.28. 247.

Gene expression databases

Bgee

P11086.

CleanEx

HS_PNMT.

GermOnline

ENSG00000141744. Homo sapiens.

Family and domain databases

InterPro

IPR000940. NNMT_TEMT_trans.
[Graphical view]

PANTHER

PTHR10867. NNMT_TEMT_trans. 1 hit.

Pfam

PF01234. NNMT_PNMT_TEMT. 1 hit.
[Graphical view]

PIRSF

PIRSF000384. PNMTase. 1 hit.

PROSITE

PS01100. NNMT_PNMT_TEMT. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

20943.

SOURCE

Search...

Entry information

Entry name

PNMT_HUMAN

Accession

Primary (citable) accession number: P11086

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	June 16, 2009
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)