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Protein

Histamine N-methyltransferase

Gene

HNMT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Inactivates histamine by N-methylation. Plays an important role in degrading histamine and in regulating the airway response to histamine.1 Publication

Catalytic activityi

S-adenosyl-L-methionine + histamine = S-adenosyl-L-homocysteine + N(tau)-methylhistamine.PROSITE-ProRule annotation1 Publication

Kineticsi

  1. KM=5.47 µM for histamine (at pH 8.0 and 25 degrees Celsius)1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei28Substrate1
    Binding sitei60S-adenosyl-L-methionine; via carbonyl oxygen1
    Binding sitei89S-adenosyl-L-methionine1
    Binding sitei94S-adenosyl-L-methionine1
    Binding sitei120S-adenosyl-L-methionine; via amide nitrogen1
    Binding sitei142S-adenosyl-L-methionine; via carbonyl oxygen1
    Binding sitei283Substrate1

    GO - Molecular functioni

    • histamine N-methyltransferase activity Source: UniProtKB

    GO - Biological processi

    • brain development Source: GO_Central
    • histamine catabolic process Source: UniProtKB
    • histidine catabolic process Source: Reactome
    • methylation Source: UniProtKB
    • respiratory gaseous exchange Source: ProtInc

    Keywordsi

    Molecular functionMethyltransferase, Transferase
    LigandS-adenosyl-L-methionine

    Enzyme and pathway databases

    BioCyciMetaCyc:HS07674-MONOMER
    BRENDAi2.1.1.8 2681
    ReactomeiR-HSA-2408508 Metabolism of ingested SeMet, Sec, MeSec into H2Se
    R-HSA-70921 Histidine catabolism
    SABIO-RKiP50135

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Histamine N-methyltransferase (EC:2.1.1.81 Publication)
    Short name:
    HMT
    Gene namesi
    Name:HNMT
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 2

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000150540.13
    HGNCiHGNC:5028 HNMT
    MIMi605238 gene
    neXtProtiNX_P50135

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Involvement in diseasei

    Mental retardation, autosomal recessive 51 (MRT51)1 Publication
    The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry.
    Disease descriptionA form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.
    See also OMIM:616739
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_07631260G → D in MRT51; no effect on protein abundance; no effect on protein localization to the cytoplasm; decreased thermal stability; decreased ligand affinity for S-adenosyl-L-methionine; loss of histamine N-methyltransferase activity. 1 PublicationCorresponds to variant dbSNP:rs758252808EnsemblClinVar.1
    Natural variantiVAR_076313208L → P in MRT51; loss of protein solubility; increased aggregation in the cytoplasm. 1 PublicationCorresponds to variant dbSNP:rs745756308EnsemblClinVar.1

    Keywords - Diseasei

    Disease mutation, Mental retardation

    Organism-specific databases

    DisGeNETi3176
    MalaCardsiHNMT
    MIMi616739 phenotype
    OpenTargetsiENSG00000150540
    Orphaneti88616 Autosomal recessive non-syndromic intellectual disability
    PharmGKBiPA190

    Chemistry databases

    ChEMBLiCHEMBL2190
    DrugBankiDB07106 4-(DIMETHYLAMINO)BUTYL IMIDOTHIOCARBAMATE
    DB00613 Amodiaquine
    DB00878 Chlorhexidine
    DB05381 Histamine
    DB01103 Quinacrine
    DB01752 S-Adenosyl-L-Homocysteine

    Polymorphism and mutation databases

    BioMutaiHNMT
    DMDMi1708272

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000840211 – 292Histamine N-methyltransferaseAdd BLAST292

    Proteomic databases

    EPDiP50135
    MaxQBiP50135
    PaxDbiP50135
    PeptideAtlasiP50135
    PRIDEiP50135
    ProteomicsDBi56195
    56196 [P50135-2]
    56197 [P50135-3]

    PTM databases

    iPTMnetiP50135
    PhosphoSitePlusiP50135

    Expressioni

    Gene expression databases

    BgeeiENSG00000150540 Expressed in 224 organ(s), highest expression level in adipose tissue
    CleanExiHS_HNMT
    GenevisibleiP50135 HS

    Organism-specific databases

    HPAiHPA035480
    HPA035481

    Interactioni

    Subunit structurei

    Monomer.1 Publication

    Protein-protein interaction databases

    BioGridi109418, 7 interactors
    IntActiP50135, 5 interactors
    STRINGi9606.ENSP00000280097

    Chemistry databases

    BindingDBiP50135

    Structurei

    Secondary structure

    1292
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliP50135
    SMRiP50135
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP50135

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the class I-like SAM-binding methyltransferase superfamily. HNMT family.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiENOG410IGS0 Eukaryota
    ENOG410ZU1D LUCA
    GeneTreeiENSGT00390000002862
    HOGENOMiHOG000231790
    HOVERGENiHBG051914
    InParanoidiP50135
    KOiK00546
    OMAiMDISDCF
    OrthoDBiEOG091G0DY6
    PhylomeDBiP50135
    TreeFamiTF331080

    Family and domain databases

    InterProiView protein in InterPro
    IPR016673 HHMT-like
    IPR029063 SAM-dependent_MTases
    PIRSFiPIRSF016616 HHMT, 1 hit
    SUPFAMiSSF53335 SSF53335, 1 hit
    PROSITEiView protein in PROSITE
    PS51597 SAM_HNMT, 1 hit

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket
    Isoform 1 (identifier: P50135-1) [UniParc]FASTAAdd to basket

    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.

    « Hide
            10         20         30         40         50
    MASSMRSLFS DHGKYVESFR RFLNHSTEHQ CMQEFMDKKL PGIIGRIGDT
    60 70 80 90 100
    KSEIKILSIG GGAGEIDLQI LSKVQAQYPG VCINNEVVEP SAEQIAKYKE
    110 120 130 140 150
    LVAKTSNLEN VKFAWHKETS SEYQSRMLEK KELQKWDFIH MIQMLYYVKD
    160 170 180 190 200
    IPATLKFFHS LLGTNAKMLI IVVSGSSGWD KLWKKYGSRF PQDDLCQYIT
    210 220 230 240 250
    SDDLTQMLDN LGLKYECYDL LSTMDISDCF IDGNENGDLL WDFLTETCNF
    260 270 280 290
    NATAPPDLRA ELGKDLQEPE FSAKKEGKVL FNNTLSFIVI EA
    Length:292
    Mass (Da):33,295
    Last modified:October 1, 1996 - v1
    Checksum:i9CCADD1EE0CCB653
    GO
    Isoform 2 (identifier: P50135-2) [UniParc]FASTAAdd to basket
    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.
    Show »
    Length:126
    Mass (Da):14,207
    Checksum:iD3215E15F10E7EB3
    GO
    Isoform 3 (identifier: P50135-3) [UniParc]FASTAAdd to basket

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

    Note: No experimental confirmation available.
    Show »
    Length:51
    Mass (Da):6,046
    Checksum:i722B5977BDD19382
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti199I → V in BAA03752 (PubMed:7943261).Curated1
    Sequence conflicti234N → D in AAH20677 (PubMed:15489334).Curated1

    Polymorphismi

    Variant Ile-105 has a reduced activity and seems to be linked with a predisposition to asthma.2 Publications

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_07631260G → D in MRT51; no effect on protein abundance; no effect on protein localization to the cytoplasm; decreased thermal stability; decreased ligand affinity for S-adenosyl-L-methionine; loss of histamine N-methyltransferase activity. 1 PublicationCorresponds to variant dbSNP:rs758252808EnsemblClinVar.1
    Natural variantiVAR_010252105T → I2 PublicationsCorresponds to variant dbSNP:rs11558538EnsemblClinVar.1
    Natural variantiVAR_076313208L → P in MRT51; loss of protein solubility; increased aggregation in the cytoplasm. 1 PublicationCorresponds to variant dbSNP:rs745756308EnsemblClinVar.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_04348247 – 51IGDTK → YQNCC in isoform 3. 1 Publication5
    Alternative sequenceiVSP_04348352 – 292Missing in isoform 3. 1 PublicationAdd BLAST241
    Alternative sequenceiVSP_04202764 – 292GEIDL…IVIEA → DCLIRGSSRVLKRNSCFILC STRQKDKPGMRIHDERSSEL PFGAARLESKSAFPSFLVSF ILF in isoform 2. 1 PublicationAdd BLAST229

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    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
    CCDSiCCDS2181.1 [P50135-1]
    CCDS33296.1 [P50135-2]
    CCDS33297.1 [P50135-3]
    PIRiG01409
    RefSeqiNP_001019245.1, NM_001024074.2 [P50135-3]
    NP_001019246.1, NM_001024075.1 [P50135-2]
    NP_008826.1, NM_006895.2 [P50135-1]
    UniGeneiHs.42151

    Genome annotation databases

    EnsembliENST00000280096; ENSP00000280096; ENSG00000150540 [P50135-3]
    ENST00000280097; ENSP00000280097; ENSG00000150540 [P50135-1]
    ENST00000329366; ENSP00000333259; ENSG00000150540 [P50135-2]
    ENST00000410115; ENSP00000386940; ENSG00000150540 [P50135-1]
    ENST00000475675; ENSP00000419415; ENSG00000150540 [P50135-3]
    GeneIDi3176
    KEGGihsa:3176
    UCSCiuc002tvd.4 human [P50135-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    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
    CCDSiCCDS2181.1 [P50135-1]
    CCDS33296.1 [P50135-2]
    CCDS33297.1 [P50135-3]
    PIRiG01409
    RefSeqiNP_001019245.1, NM_001024074.2 [P50135-3]
    NP_001019246.1, NM_001024075.1 [P50135-2]
    NP_008826.1, NM_006895.2 [P50135-1]
    UniGeneiHs.42151

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB 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[»]
    ProteinModelPortaliP50135
    SMRiP50135
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi109418, 7 interactors
    IntActiP50135, 5 interactors
    STRINGi9606.ENSP00000280097

    Chemistry databases

    BindingDBiP50135
    ChEMBLiCHEMBL2190
    DrugBankiDB07106 4-(DIMETHYLAMINO)BUTYL IMIDOTHIOCARBAMATE
    DB00613 Amodiaquine
    DB00878 Chlorhexidine
    DB05381 Histamine
    DB01103 Quinacrine
    DB01752 S-Adenosyl-L-Homocysteine

    PTM databases

    iPTMnetiP50135
    PhosphoSitePlusiP50135

    Polymorphism and mutation databases

    BioMutaiHNMT
    DMDMi1708272

    Proteomic databases

    EPDiP50135
    MaxQBiP50135
    PaxDbiP50135
    PeptideAtlasiP50135
    PRIDEiP50135
    ProteomicsDBi56195
    56196 [P50135-2]
    56197 [P50135-3]

    Protocols and materials databases

    DNASUi3176
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000280096; ENSP00000280096; ENSG00000150540 [P50135-3]
    ENST00000280097; ENSP00000280097; ENSG00000150540 [P50135-1]
    ENST00000329366; ENSP00000333259; ENSG00000150540 [P50135-2]
    ENST00000410115; ENSP00000386940; ENSG00000150540 [P50135-1]
    ENST00000475675; ENSP00000419415; ENSG00000150540 [P50135-3]
    GeneIDi3176
    KEGGihsa:3176
    UCSCiuc002tvd.4 human [P50135-1]

    Organism-specific databases

    CTDi3176
    DisGeNETi3176
    EuPathDBiHostDB:ENSG00000150540.13
    GeneCardsiHNMT
    HGNCiHGNC:5028 HNMT
    HPAiHPA035480
    HPA035481
    MalaCardsiHNMT
    MIMi605238 gene
    616739 phenotype
    neXtProtiNX_P50135
    OpenTargetsiENSG00000150540
    Orphaneti88616 Autosomal recessive non-syndromic intellectual disability
    PharmGKBiPA190
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiENOG410IGS0 Eukaryota
    ENOG410ZU1D LUCA
    GeneTreeiENSGT00390000002862
    HOGENOMiHOG000231790
    HOVERGENiHBG051914
    InParanoidiP50135
    KOiK00546
    OMAiMDISDCF
    OrthoDBiEOG091G0DY6
    PhylomeDBiP50135
    TreeFamiTF331080

    Enzyme and pathway databases

    BioCyciMetaCyc:HS07674-MONOMER
    BRENDAi2.1.1.8 2681
    ReactomeiR-HSA-2408508 Metabolism of ingested SeMet, Sec, MeSec into H2Se
    R-HSA-70921 Histidine catabolism
    SABIO-RKiP50135

    Miscellaneous databases

    EvolutionaryTraceiP50135
    GenomeRNAii3176
    PROiPR:P50135
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000150540 Expressed in 224 organ(s), highest expression level in adipose tissue
    CleanExiHS_HNMT
    GenevisibleiP50135 HS

    Family and domain databases

    InterProiView protein in InterPro
    IPR016673 HHMT-like
    IPR029063 SAM-dependent_MTases
    PIRSFiPIRSF016616 HHMT, 1 hit
    SUPFAMiSSF53335 SSF53335, 1 hit
    PROSITEiView protein in PROSITE
    PS51597 SAM_HNMT, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiHNMT_HUMAN
    AccessioniPrimary (citable) accession number: P50135
    Secondary accession number(s): B2R9J3
    , Q546Z6, Q7Z7I2, Q8IU56, Q8WW98, Q9BRW6
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: October 1, 1996
    Last modified: November 7, 2018
    This is version 168 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    2. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health

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