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Reviewed, UniProtKB/Swiss-Prot P50135 (HNMT_HUMAN)

Last modified June 16, 2009. Version 83. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Histamine N-methyltransferase
      Short name=HMT
    EC=2.1.1.8
Gene names
Name: HNMT
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length292 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
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 methyltransferase superfamily. HNMT family.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   LigandS-adenosyl-L-methionine
   Molecular functionMethyltransferase
Transferase
   PTMPhosphoprotein
   Technical term3D-structure
Gene Ontology (GO)
   Biological processrespiratory gaseous exchange Ref.1

Traceable author statement. Source: ProtInc

   Cellular componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular functionhistamine N-methyltransferase activity

Inferred from electronic annotation. Source: EC

Complete GO annotation...

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

Amino acid modifications

Modified residue31Phosphoserine By similarity
Modified residue101Phosphoserine By similarity
Modified residue181Phosphoserine By similarity

Natural variations

Natural variant1051T → I: dbSNP rs1801105. Ref.9 Ref.10
VAR_010252

Experimental info

Sequence conflict1991I → V in BAA03752. Ref.1
Sequence conflict2341N → D in AAH20677. Ref.6

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
P50135-1 [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

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: 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. 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: 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

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.
AC093674 Genomic DNA. Translation: AAY24212.1.
BC020677 mRNA. Translation: AAH20677.1.
AF467014 expand/collapse EMBL AC list , AF467009, AF467010, AF467011, AF467012, AF467013 Genomic DNA. Translation: AAP42155.1.
IPIIPI00030023.
PIRG01409.
RefSeqNP_008826.1.
UniGeneHs.42151

3D structure databases

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

PTM databases

PhosphoSiteP50135.

Proteomic databases

PeptideAtlasP50135.
PRIDEP50135.

Genome annotation databases

EnsemblENSG00000150540. Homo sapiens. [Contig view]
GeneID3176.

Organism-specific databases

GeneCardsGC02P138438.
H-InvDBHIX0002483.
HGNCHGNC:5028. HNMT.
MIM605238. gene.
PharmGKBPA190.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP50135.
HOVERGENP50135.
OMAP50135. YDLLSTM.

Enzyme and pathway databases

BRENDA2.1.1.8. 247.

Gene expression databases

ArrayExpressP50135.
BgeeP50135.
CleanExHS_HNMT.
GermOnlineENSG00000150540. Homo sapiens.

Family and domain databases

InterProIPR016673. Histamine_N-methyltransferase.
[Graphical view]
PIRSFPIRSF016616. HHMT. 1 hit.
ProtoNetSearch...

Other Resources

DrugBankDB00613. Amodiaquine.
DB00667. Histamine Phosphate.
DB01103. Quinacrine.
NextBio12602.
SOURCESearch...

Entry information

Entry nameHNMT_HUMAN
AccessionPrimary (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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 2

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents