Reviewed, UniProtKB/Swiss-Prot P50135 (HNMT_HUMAN)

Names and origin

Protein names

Recommended name:
    Histamine N-methyltransferase
      Short name=HMT
    EC=2.1.1.8

Gene names

Name:

HNMT

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

General annotation (Comments)

Function	Inactivates histamine by N-methylation. Plays an important role in degrading histamine and in regulating the airway response to histamine.
Catalytic activity	S-adenosyl-L-methionine + histamine = S-adenosyl-L-homocysteine + N(tau)-methylhistamine.
Subunit structure	Monomer.
Subcellular location	Cytoplasm.
Polymorphism	Variant Ile-105 has a reduced activity and seems to be linked with a predisposition to asthma.
Sequence similarities	Belongs to the methyltransferase superfamily. HNMT family.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	S-adenosyl-L-methionine
Molecular function	Methyltransferase Transferase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	respiratory gaseous exchange Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	histamine N-methyltransferase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 292

292

Histamine N-methyltransferase

PRO_0000084021

Sites

Binding site

28

1

Substrate

Binding site

60

1

S-adenosyl-L-methionine; via carbonyl oxygen

Binding site

89

1

S-adenosyl-L-methionine

Binding site

94

1

S-adenosyl-L-methionine

Binding site

120

1

S-adenosyl-L-methionine; via amide nitrogen

Binding site

142

1

S-adenosyl-L-methionine; via carbonyl oxygen

Binding site

283

1

Substrate

Amino acid modifications

Modified residue

3

1

Phosphoserine By similarity

Modified residue

10

1

Phosphoserine By similarity

Modified residue

18

1

Phosphoserine By similarity

Natural variations

Natural variant

105

1

T → I: dbSNP rs1801105. Ref.9 Ref.10

VAR_010252

Experimental info

Sequence conflict

199

1

I → V in BAA03752. Ref.1

Sequence conflict

234

1

N → D in AAH20677. Ref.6

Secondary structure

1

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292

Helix Strand Turn

Details...

Helix

13 – 23

11

Helix

28 – 38

11

Helix

40 – 43

4

Turn

44 – 50

7

Beta strand

52 – 60

9

Helix

65 – 77

13

Beta strand

82 – 88

7

Helix

92 – 104

13

Beta strand

111 – 116

6

Helix

120 – 129

10

Beta strand

130 – 132

3

Beta strand

136 – 143

8

Helix

145 – 147

3

Helix

151 – 160

10

Beta strand

162 – 173

12

Helix

178 – 186

9

Helix

187 – 189

3

Helix

201 – 211

11

Beta strand

215 – 220

6

Beta strand

223 – 225

3

Helix

227 – 229

3

Beta strand

230 – 233

4

Helix

235 – 245

11

Helix

250 – 253

4

Helix

256 – 265

10

Turn

269 – 271

3

Beta strand

272 – 275

4

Beta strand

278 – 282

5

Beta strand

285 – 291

7

Sequences

	Sequence		Length	Mass (Da)
	P50135-1 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 9CCADD1EE0CCB653	FASTA	292	33,295
	10 20 30 40 50 60 MASSMRSLFS DHGKYVESFR RFLNHSTEHQ CMQEFMDKKL PGIIGRIGDT KSEIKILSIG 70 80 90 100 110 120 GGAGEIDLQI LSKVQAQYPG VCINNEVVEP SAEQIAKYKE LVAKTSNLEN VKFAWHKETS 130 140 150 160 170 180 SEYQSRMLEK KELQKWDFIH MIQMLYYVKD IPATLKFFHS LLGTNAKMLI IVVSGSSGWD 190 200 210 220 230 240 KLWKKYGSRF PQDDLCQYIT SDDLTQMLDN LGLKYECYDL LSTMDISDCF IDGNENGDLL 250 260 270 280 290 WDFLTETCNF NATAPPDLRA ELGKDLQEPE FSAKKEGKVL FNNTLSFIVI EA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure and function of human histamine N-methyltransferase: critical enzyme in histamine metabolism in airway." Yamauchi K., Sekizawa K., Suzuki H., Nakazawa H., Ohkawara Y., Katayose D., Ohtsu H., Tamura G., Shibahara S., Takemura M. Am. J. Physiol. 267:L342-L349(1994) [PubMed: 7943261] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Kidney.
[2]	"Human histamine N-methyltransferase pharmacogenetics: cloning and expression of kidney cDNA." Girard B., Otterness D.M., Wood T.C., Honchel R., Wieben E.D., Weinshilboum R.M. Mol. Pharmacol. 45:461-468(1994) [PubMed: 8145732] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Kidney.
[3]	"Human histamine N-methyltransferase gene: structural characterization and chromosomal location." Aksoy S., Raftogianis R., Weinshilboum R.M. Biochem. Biophys. Res. Commun. 219:548-554(1996) [PubMed: 8605025] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Further characterization of the histamine N-methyltransferase gene: a new mRNA species and several 3'-UTR Variants from human brain." Barnes W.G., Grinde E., Crawford D.R., Herrick-Davis K., Hough L.B. Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[5]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: Liver.
[7]	"Homo sapiens histamine N-methyltransferase (HNMT) gene, consensus of Coriell PDR 90." Thomae B., Wieben E., Eckloff B., Weinshilboum R.M. Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-221.
[8]	"Two polymorphic forms of human histamine methyltransferase: structural, thermal, and kinetic comparisons." Horton J.R., Sawada K., Nishibori M., Zhang X., Cheng X. Structure 9:837-849(2001) [PubMed: 11566133] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH SUBSTRATES AND INHIBITOR.
[9]	"Human histamine N-methyltransferase pharmacogenetics: common genetic polymorphisms that alter activity." Preuss C.V., Wood T.C., Szumlanski C.L., Raftogianis R.B., Otterness D.M., Girard B., Scott M.C., Weinshilboum R.M. Mol. Pharmacol. 53:708-717(1998) [PubMed: 9547362] [Abstract] Cited for: VARIANT ILE-105.
[10]	"Histamine N-methyltransferase pharmacogenetics: association of a common functional polymorphism with asthma." Yan L., Galinsky R.E., Bernstein J.A., Liggett S.B., Weinshilboum R.M. Pharmacogenetics 10:261-266(2000) [PubMed: 10803682] [Abstract] Cited for: VARIANT ILE-105.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

D16224 mRNA. Translation: BAA03752.1.
U08092 mRNA. Translation: AAA17423.1.
U44111 , U44106, U44107, U44108, U44109, U44110 Genomic DNA. Translation: AAB18137.1.
AF523358 mRNA. Translation: AAN33016.1.
AF523359 mRNA. Translation: AAN33017.1.
AF523360 mRNA. Translation: AAN33018.1.
AC093674 Genomic DNA. Translation: AAY24212.1.
BC020677 mRNA. Translation: AAH20677.1.
AF467014 , AF467009, AF467010, AF467011, AF467012, AF467013 Genomic DNA. Translation: AAP42155.1.

IPI

IPI00030023.

PIR

G01409.

RefSeq

NP_008826.1.

UniGene

Hs.42151

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ICZ	model	-	A	1-249	[»]
1JQD	X-ray	2.28	A/B	1-292	[»]
1JQE	X-ray	1.91	A/B	1-292	[»]
2AOT	X-ray	1.90	A	1-292	[»]
			B	1-292	[»]
2AOU	X-ray	2.30	A	1-292	[»]
			B	1-292	[»]
2AOV	X-ray	2.48	A/B	1-292	[»]
2AOW	X-ray	2.97	A/B	1-292	[»]
2AOX	X-ray	3.12	A/B	1-292	[»]

ModBase

Search...

PTM databases

PhosphoSite

P50135.

Proteomic databases

PeptideAtlas

P50135.

PRIDE

P50135.

Genome annotation databases

Ensembl

ENSG00000150540. Homo sapiens. [Contig view]

GeneID

3176.

Organism-specific databases

GeneCards

GC02P138438.

H-InvDB

HIX0002483.

HGNC

HGNC:5028. HNMT.

MIM

605238. gene.

PharmGKB

PA190.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P50135.

HOVERGEN

P50135.

OMA

P50135. YDLLSTM.

Enzyme and pathway databases

BRENDA

2.1.1.8. 247.

Gene expression databases

ArrayExpress

P50135.

Bgee

P50135.

CleanEx

HS_HNMT.

GermOnline

ENSG00000150540. Homo sapiens.

Family and domain databases

InterPro

IPR016673. Histamine_N-methyltransferase.
[Graphical view]

PIRSF

PIRSF016616. HHMT. 1 hit.

ProtoNet

Search...

Other Resources

DrugBank

DB00613. Amodiaquine.
DB00667. Histamine Phosphate.
DB01103. Quinacrine.

NextBio

12602.

SOURCE

Search...

Entry information

Entry name

HNMT_HUMAN

Accession

Primary (citable) accession number: P50135
Secondary accession number(s): Q546Z6, Q7Z7I2, Q8WW98

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	June 16, 2009
This is version 83 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)