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Protein

Histamine N-methyltransferase

Gene

HNMT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei28 – 281Substrate
    Binding sitei60 – 601S-adenosyl-L-methionine; via carbonyl oxygen
    Binding sitei89 – 891S-adenosyl-L-methionine
    Binding sitei94 – 941S-adenosyl-L-methionine
    Binding sitei120 – 1201S-adenosyl-L-methionine; via amide nitrogen
    Binding sitei142 – 1421S-adenosyl-L-methionine; via carbonyl oxygen
    Binding sitei283 – 2831Substrate

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Methyltransferase, Transferase

    Keywords - Ligandi

    S-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.

    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

    HGNCiHGNC:5028. HNMT.

    Subcellular locationi

    GO - Cellular componenti

    • cytoplasm Source: HPA
    • cytosol Source: Reactome
    • extracellular exosome Source: UniProtKB
    • neuron projection Source: GO_Central
    • nucleoplasm Source: HPA
    Complete GO annotation...

    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)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti60 – 601G → 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 Publication
    VAR_076312
    Natural varianti208 – 2081L → P in MRT51; loss of protein solubility; increased aggregation in the cytoplasm. 1 Publication
    VAR_076313

    Keywords - Diseasei

    Disease mutation, Mental retardation

    Organism-specific databases

    MalaCardsiHNMT.
    MIMi616739. phenotype.
    PharmGKBiPA190.

    Chemistry

    ChEMBLiCHEMBL2190.
    DrugBankiDB00613. Amodiaquine.
    DB00878. Chlorhexidine.
    DB00667. Histamine Phosphate.
    DB01103. Quinacrine.

    Polymorphism and mutation databases

    BioMutaiHNMT.
    DMDMi1708272.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 292292Histamine N-methyltransferasePRO_0000084021Add
    BLAST

    Proteomic databases

    EPDiP50135.
    MaxQBiP50135.
    PaxDbiP50135.
    PeptideAtlasiP50135.
    PRIDEiP50135.

    PTM databases

    iPTMnetiP50135.
    PhosphoSiteiP50135.

    Expressioni

    Gene expression databases

    BgeeiENSG00000150540.
    CleanExiHS_HNMT.
    GenevisibleiP50135. HS.

    Organism-specific databases

    HPAiHPA035480.
    HPA035481.

    Interactioni

    Subunit structurei

    Monomer.1 Publication

    Protein-protein interaction databases

    BioGridi109418. 7 interactions.
    IntActiP50135. 5 interactions.
    MINTiMINT-5001055.
    STRINGi9606.ENSP00000280097.

    Chemistry

    BindingDBiP50135.

    Structurei

    Secondary structure

    1
    292
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi8 – 103Combined sources
    Helixi12 – 2312Combined sources
    Helixi28 – 3811Combined sources
    Helixi40 – 434Combined sources
    Beta strandi44 – 463Combined sources
    Turni47 – 504Combined sources
    Beta strandi52 – 609Combined sources
    Helixi65 – 7713Combined sources
    Beta strandi82 – 887Combined sources
    Helixi92 – 10312Combined sources
    Beta strandi111 – 1166Combined sources
    Helixi120 – 1289Combined sources
    Turni129 – 1313Combined sources
    Beta strandi136 – 1438Combined sources
    Helixi145 – 1473Combined sources
    Helixi151 – 16010Combined sources
    Beta strandi162 – 17312Combined sources
    Beta strandi175 – 1773Combined sources
    Helixi178 – 1869Combined sources
    Helixi187 – 1893Combined sources
    Helixi201 – 21111Combined sources
    Beta strandi215 – 2206Combined sources
    Beta strandi223 – 2253Combined sources
    Helixi227 – 2304Combined sources
    Helixi235 – 24511Combined sources
    Beta strandi247 – 2493Combined sources
    Helixi250 – 2534Combined sources
    Helixi256 – 26510Combined sources
    Turni269 – 2713Combined sources
    Beta strandi272 – 2754Combined sources
    Beta strandi278 – 2825Combined sources
    Beta strandi285 – 2917Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    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. Positions 5-292.
    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

    Gene3Di3.40.50.150. 1 hit.
    InterProiIPR016673. HHMT-like.
    IPR029063. SAM-dependent_MTases.
    [Graphical view]
    PIRSFiPIRSF016616. HHMT. 1 hit.
    SUPFAMiSSF53335. SSF53335. 1 hit.
    PROSITEiPS51597. SAM_HNMT. 1 hit.
    [Graphical view]

    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)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti199 – 1991I → V in BAA03752 (PubMed:7943261).Curated
    Sequence conflicti234 – 2341N → D in AAH20677 (PubMed:15489334).Curated

    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)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti60 – 601G → 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 Publication
    VAR_076312
    Natural varianti105 – 1051T → I.2 Publications
    Corresponds to variant rs1801105 [ dbSNP | Ensembl ].
    VAR_010252
    Natural varianti208 – 2081L → P in MRT51; loss of protein solubility; increased aggregation in the cytoplasm. 1 Publication
    VAR_076313

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei47 – 515IGDTK → YQNCC in isoform 3. 1 PublicationVSP_043482
    Alternative sequencei52 – 292241Missing in isoform 3. 1 PublicationVSP_043483Add
    BLAST
    Alternative sequencei64 – 292229GEIDL…IVIEA → DCLIRGSSRVLKRNSCFILC STRQKDKPGMRIHDERSSEL PFGAARLESKSAFPSFLVSF ILF in isoform 2. 1 PublicationVSP_042027Add
    BLAST

    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

    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
    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. Positions 5-292.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi109418. 7 interactions.
    IntActiP50135. 5 interactions.
    MINTiMINT-5001055.
    STRINGi9606.ENSP00000280097.

    Chemistry

    BindingDBiP50135.
    ChEMBLiCHEMBL2190.
    DrugBankiDB00613. Amodiaquine.
    DB00878. Chlorhexidine.
    DB00667. Histamine Phosphate.
    DB01103. Quinacrine.

    PTM databases

    iPTMnetiP50135.
    PhosphoSiteiP50135.

    Polymorphism and mutation databases

    BioMutaiHNMT.
    DMDMi1708272.

    Proteomic databases

    EPDiP50135.
    MaxQBiP50135.
    PaxDbiP50135.
    PeptideAtlasiP50135.
    PRIDEiP50135.

    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.
    GeneCardsiHNMT.
    HGNCiHGNC:5028. HNMT.
    HPAiHPA035480.
    HPA035481.
    MalaCardsiHNMT.
    MIMi605238. gene.
    616739. phenotype.
    neXtProtiNX_P50135.
    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.

    Miscellaneous databases

    EvolutionaryTraceiP50135.
    GenomeRNAii3176.
    PROiP50135.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000150540.
    CleanExiHS_HNMT.
    GenevisibleiP50135. HS.

    Family and domain databases

    Gene3Di3.40.50.150. 1 hit.
    InterProiIPR016673. HHMT-like.
    IPR029063. SAM-dependent_MTases.
    [Graphical view]
    PIRSFiPIRSF016616. HHMT. 1 hit.
    SUPFAMiSSF53335. SSF53335. 1 hit.
    PROSITEiPS51597. SAM_HNMT. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiHNMT_HUMAN
    AccessioniPrimary (citable) accession number: P50135
    Secondary accession number(s): B2R9J3
    , Q546Z6, Q7Z7I2, Q8IU56, Q8WW98, Q9BRW6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: October 1, 1996
    Last modified: September 7, 2016
    This is version 153 of the entry and version 1 of the sequence. [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. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.