P50135 (HNMT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [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	292 AA.
Sequence status	Complete.
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	Alternative splicing Polymorphism
Ligand	S-adenosyl-L-methionine
Molecular function	Methyltransferase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	brain development Inferred from electronic annotation. Source: Compara hyperosmotic response Inferred from electronic annotation. Source: Compara respiratory gaseous exchange Traceable author statement Ref.1. Source: ProtInc response to amine stimulus Inferred from electronic annotation. Source: Compara response to cocaine Inferred from electronic annotation. Source: Compara response to glucocorticoid stimulus Inferred from electronic annotation. Source: Compara response to interleukin-1 Inferred from electronic annotation. Source: Compara response to tumor cell Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA neuron projection Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay. Source: HPA
Molecular_function	histamine N-methyltransferase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P50135-1)

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: P50135-2)

Also known as: HNMT-S;

The sequence of this isoform differs from the canonical sequence as follows:
     64-292: GEIDLQILSK...NTLSFIVIEA → DCLIRGSSRV...PSFLVSFILF

Note: Has no histamine-methylating activity.

Isoform 3 (identifier: P50135-3)

The sequence of this isoform differs from the canonical sequence as follows:
     47-51: IGDTK → YQNCC
     52-292: Missing.

Note: No experimental confirmation available.

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

Alternative sequence

47 – 51

5

IGDTK → YQNCC in isoform 3.

VSP_043482

Alternative sequence

52 – 292

241

Missing in isoform 3.

VSP_043483

Alternative sequence

64 – 292

229

GEIDL…IVIEA → DCLIRGSSRVLKRNSCFILC STRQKDKPGMRIHDERSSEL PFGAARLESKSAFPSFLVSF ILF in isoform 2.

VSP_042027

Natural variant

105

1

T → I. Ref.13 Ref.14
Corresponds to variant rs1801105 [ dbSNP | Ensembl ].

VAR_010252

Experimental info

Sequence conflict

199

1

I → V in BAA03752. Ref.1

Sequence conflict

234

1

N → D in AAH20677. Ref.9

Secondary structure

1

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292

Helix Strand Turn

Details...

Helix

8 – 10

3

Helix

12 – 23

12

Helix

28 – 38

11

Helix

40 – 43

4

Turn

46 – 50

5

Beta strand

52 – 60

9

Helix

65 – 77

13

Beta strand

82 – 88

7

Helix

92 – 103

12

Beta strand

111 – 116

6

Helix

120 – 127

8

Beta strand

130 – 132

3

Beta strand

136 – 143

8

Helix

145 – 147

3

Helix

151 – 160

10

Beta strand

162 – 173

12

Beta strand

175 – 177

3

Helix

178 – 186

9

Helix

187 – 189

3

Helix

201 – 211

11

Beta strand

215 – 220

6

Beta strand

223 – 225

3

Helix

227 – 230

4

Helix

235 – 245

11

Helix

250 – 253

4

Helix

256 – 266

11

Turn

269 – 271

3

Beta strand

272 – 275

4

Beta strand

278 – 282

5

Beta strand

285 – 291

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 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
	Isoform 2 (HNMT-S) [UniParc]. Checksum: D3215E15F10E7EB3	FASTA	126	14,207
	10 20 30 40 50 60 MASSMRSLFS DHGKYVESFR RFLNHSTEHQ CMQEFMDKKL PGIIGRIGDT KSEIKILSIG 70 80 90 100 110 120 GGADCLIRGS SRVLKRNSCF ILCSTRQKDK PGMRIHDERS SELPFGAARL ESKSAFPSFL VSFILF
	Isoform 3 [UniParc]. Checksum: 722B5977BDD19382	FASTA	51	6,046
	10 20 30 40 50 MASSMRSLFS DHGKYVESFR RFLNHSTEHQ CMQEFMDKKL PGIIGRYQNC C

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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). 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] [Europe PMC] [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] (ISOFORM 1). Tissue: Brain.
[5]	"Characterization of a new mRNA species from the human histamine N-methyltransferase gene." Barnes W.G., Grinde E., Crawford D.R., Herrick-Davis K., Hough L.B. Genomics 83:168-171(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING. Tissue: Brain.
[6]	"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] (ISOFORM 1). Tissue: Cerebellum.
[7]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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] (ISOFORMS 1 AND 3). Tissue: Liver and Prostate.
[10]	"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.
[11]	"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].
[12]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH SUBSTRATES AND INHIBITOR.
[13]	"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] [Europe PMC] [Abstract] Cited for: VARIANT ILE-105.
[14]	"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] [Europe PMC] [Abstract] Cited for: VARIANT ILE-105.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.
AF523356 mRNA. Translation: AAN33014.1.
AF523357 mRNA. Translation: AAN33015.1.
AK313804 mRNA. Translation: BAG36540.1.
AC093674 Genomic DNA. Translation: AAY24212.1.
CH471058 Genomic DNA. Translation: EAX11612.1.
CH471058 Genomic DNA. Translation: EAX11613.1.
CH471058 Genomic DNA. Translation: EAX11614.1.
BC005907 mRNA. Translation: AAH05907.1.
BC020677 mRNA. Translation: AAH20677.1.
AH012839 Genomic DNA. Translation: AAP42155.1.

IPI

IPI00029307.
IPI00030023.

PIR

G01409.

RefSeq

NP_001019245.1. NM_001024074.2.
NP_001019246.1. NM_001024075.1.
NP_008826.1. NM_006895.2.

UniGene

Hs.42151.

3D structure databases

PDBe
RCSB PDB
PDBj

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/B	1-292	[»]
2AOU	X-ray	2.30	A/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	[»]

ProteinModelPortal

P50135.

ModBase

Search...

Protein-protein interaction databases

IntAct

P50135. 1 interaction.

STRING

9606.ENSP00000280097.

PTM databases

PhosphoSite

P50135.

Polymorphism databases

DMDM

1708272.

Proteomic databases

PaxDb

P50135.

PeptideAtlas

P50135.

PRIDE

P50135.

Protocols and materials databases

DNASU

3176.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000280096; ENSP00000280096; ENSG00000150540.
ENST00000280097; ENSP00000280097; ENSG00000150540.
ENST00000329366; ENSP00000333259; ENSG00000150540.
ENST00000410115; ENSP00000386940; ENSG00000150540.
ENST00000475675; ENSP00000419415; ENSG00000150540.

GeneID

3176.

KEGG

hsa:3176.

UCSC

uc002tvf.3. human.

Organism-specific databases

CTD

3176.

GeneCards

GC02P138744.

HGNC

HGNC:5028. HNMT.

HPA

HPA035481.

MIM

605238. gene.

neXtProt

NX_P50135.

PharmGKB

PA190.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG39680.

HOGENOM

HOG000231790.

HOVERGEN

HBG051914.

InParanoid

P50135.

KO

K00546.

OMA

WKKYGSR.

OrthoDB

EOG4NCMDJ.

PhylomeDB

P50135.

Enzyme and pathway databases

BioCyc

MetaCyc:HS07674-MONOMER.

Gene expression databases

Bgee

P50135.

CleanEx

HS_HNMT.

Genevestigator

P50135.

GermOnline

ENSG00000150540. Homo sapiens.

Family and domain databases

InterPro

IPR016673. Histamine_N-methyltransferase.
[Graphical view]

PANTHER

PTHR32330. PTHR32330. 1 hit.

PIRSF

PIRSF016616. HHMT. 1 hit.

ProtoNet

Search...

Other

BindingDB

P50135.

ChEMBL

CHEMBL2190.

DrugBank

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

EvolutionaryTrace

P50135.

GenomeRNAi

3176.

NextBio

12602.

SOURCE

Search...

Entry information

Entry name

HNMT_HUMAN

Accession

Primary (citable) accession number: P50135
Secondary accession number(s): B2R9J3 , Q546Z6, Q7Z7I2, Q8IU56, Q8WW98, Q9BRW6

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 121 of the entry and version 1 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.