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P50135 (HNMT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Histamine N-methyltransferase

Short name=HMT
EC=2.1.1.8
Gene names
Name:HNMT
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length292 AA.
Sequence statusComplete.
Protein existenceEvidence 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 class I-like SAM-binding methyltransferase superfamily. HNMT family.

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 292292Histamine N-methyltransferase
PRO_0000084021

Sites

Binding site281Substrate
Binding site601S-adenosyl-L-methionine; via carbonyl oxygen
Binding site891S-adenosyl-L-methionine
Binding site941S-adenosyl-L-methionine
Binding site1201S-adenosyl-L-methionine; via amide nitrogen
Binding site1421S-adenosyl-L-methionine; via carbonyl oxygen
Binding site2831Substrate

Natural variations

Alternative sequence47 – 515IGDTK → YQNCC in isoform 3.
VSP_043482
Alternative sequence52 – 292241Missing in isoform 3.
VSP_043483
Alternative sequence64 – 292229GEIDL…IVIEA → DCLIRGSSRVLKRNSCFILC STRQKDKPGMRIHDERSSEL PFGAARLESKSAFPSFLVSF ILF in isoform 2.
VSP_042027
Natural variant1051T → I. Ref.13 Ref.14
Corresponds to variant rs1801105 [ dbSNP | Ensembl ].
VAR_010252

Experimental info

Sequence conflict1991I → V in BAA03752. Ref.1
Sequence conflict2341N → D in AAH20677. Ref.9

Secondary structure

.......................................................... 292
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 9CCADD1EE0CCB653

FASTA29233,295
        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 

« Hide

Isoform 2 (HNMT-S) [UniParc].

Checksum: D3215E15F10E7EB3
Show »

FASTA12614,207
Isoform 3 [UniParc].

Checksum: 722B5977BDD19382
Show »

FASTA516,046

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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 expand/collapse EMBL AC list , 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.
PIRG01409.
RefSeqNP_001019245.1. NM_001024074.2.
NP_001019246.1. NM_001024075.1.
NP_008826.1. NM_006895.2.
UniGeneHs.42151.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1ICZmodel-A1-249[»]
1JQDX-ray2.28A/B1-292[»]
1JQEX-ray1.91A/B1-292[»]
2AOTX-ray1.90A/B1-292[»]
2AOUX-ray2.30A/B1-292[»]
2AOVX-ray2.48A/B1-292[»]
2AOWX-ray2.97A/B1-292[»]
2AOXX-ray3.12A/B1-292[»]
ProteinModelPortalP50135.
SMRP50135. Positions 5-292.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109418. 5 interactions.
IntActP50135. 1 interaction.
MINTMINT-5001055.
STRING9606.ENSP00000280097.

Chemistry

BindingDBP50135.
ChEMBLCHEMBL2190.
DrugBankDB00613. Amodiaquine.
DB00667. Histamine Phosphate.
DB01103. Quinacrine.

PTM databases

PhosphoSiteP50135.

Polymorphism databases

DMDM1708272.

Proteomic databases

PaxDbP50135.
PeptideAtlasP50135.
PRIDEP50135.

Protocols and materials databases

DNASU3176.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000280096; ENSP00000280096; ENSG00000150540. [P50135-3]
ENST00000280097; ENSP00000280097; ENSG00000150540. [P50135-1]
ENST00000329366; ENSP00000333259; ENSG00000150540. [P50135-2]
ENST00000410115; ENSP00000386940; ENSG00000150540. [P50135-1]
ENST00000475675; ENSP00000419415; ENSG00000150540. [P50135-3]
GeneID3176.
KEGGhsa:3176.
UCSCuc002tvd.3. human. [P50135-3]
uc002tve.3. human. [P50135-2]
uc002tvf.3. human. [P50135-1]

Organism-specific databases

CTD3176.
GeneCardsGC02P138744.
HGNCHGNC:5028. HNMT.
HPAHPA035481.
MIM605238. gene.
neXtProtNX_P50135.
PharmGKBPA190.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG39680.
HOGENOMHOG000231790.
HOVERGENHBG051914.
InParanoidP50135.
KOK00546.
OMAMDISDCF.
OrthoDBEOG7Z69CQ.
PhylomeDBP50135.
TreeFamTF331080.

Enzyme and pathway databases

BioCycMetaCyc:HS07674-MONOMER.

Gene expression databases

BgeeP50135.
CleanExHS_HNMT.
GenevestigatorP50135.

Family and domain databases

InterProIPR016673. Histamine_N-methyltransferase.
[Graphical view]
PANTHERPTHR32330:SF0. PTHR32330:SF0. 1 hit.
PIRSFPIRSF016616. HHMT. 1 hit.
PROSITEPS51597. SAM_HNMT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP50135.
GenomeRNAi3176.
NextBio12602.
PROP50135.
SOURCESearch...

Entry information

Entry nameHNMT_HUMAN
AccessionPrimary (citable) accession number: P50135
Secondary accession number(s): B2R9J3 expand/collapse secondary AC list , Q546Z6, Q7Z7I2, Q8IU56, Q8WW98, Q9BRW6
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: March 19, 2014
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM