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Protein

Leucine carboxyl methyltransferase 1

Gene

LCMT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Methylates the carboxyl group of the C-terminal leucine residue of protein phosphatase 2A catalytic subunits to form alpha-leucine ester residues.1 Publication

Catalytic activityi

S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine = S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester.2 Publications

Kineticsi

  1. KM=0.1 µM for PP2AD1 Publication
  2. KM=1.3 µM for AdoMet1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei73S-adenosyl-L-methionine1 Publication1
    Binding sitei98S-adenosyl-L-methionine; via carbonyl oxygen1 Publication1
    Binding sitei122S-adenosyl-L-methionine1 Publication1
    Binding sitei198S-adenosyl-L-methionine; via carbonyl oxygen1 Publication1

    GO - Molecular functioni

    GO - Biological processi

    • cellular protein modification process Source: ProtInc
    • C-terminal protein methylation Source: MGI
    • negative regulation of protein complex assembly Source: MGI
    • protein methylation Source: MGI
    • regulation of apoptotic process Source: MGI
    • regulation of mitotic cell cycle spindle assembly checkpoint Source: MGI
    Complete GO annotation...

    Keywords - Molecular functioni

    Methyltransferase, Transferase

    Keywords - Ligandi

    S-adenosyl-L-methionine

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER-16510.
    ZFISH:MONOMER-16510.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Leucine carboxyl methyltransferase 1 (EC:2.1.1.233)
    Alternative name(s):
    Protein-leucine O-methyltransferase
    [Phosphatase 2A protein]-leucine-carboxy methyltransferase 1
    Gene namesi
    Name:LCMT1
    Synonyms:LCMT
    ORF Names:CGI-68
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 16

    Organism-specific databases

    HGNCiHGNC:17557. LCMT1.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi51451.
    OpenTargetsiENSG00000205629.
    PharmGKBiPA134928443.

    Chemistry databases

    DrugBankiDB00149. L-Leucine.

    Polymorphism and mutation databases

    BioMutaiLCMT1.
    DMDMi12643251.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002044221 – 334Leucine carboxyl methyltransferase 1Add BLAST334

    Proteomic databases

    EPDiQ9UIC8.
    PaxDbiQ9UIC8.
    PeptideAtlasiQ9UIC8.
    PRIDEiQ9UIC8.

    PTM databases

    iPTMnetiQ9UIC8.
    PhosphoSitePlusiQ9UIC8.

    Expressioni

    Gene expression databases

    BgeeiENSG00000205629.
    CleanExiHS_LCMT1.
    ExpressionAtlasiQ9UIC8. baseline and differential.
    GenevisibleiQ9UIC8. HS.

    Organism-specific databases

    HPAiHPA041559.
    HPA043530.

    Interactioni

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    FXR2P511162EBI-747632,EBI-740459

    Protein-protein interaction databases

    BioGridi119549. 10 interactors.
    IntActiQ9UIC8. 3 interactors.
    MINTiMINT-1448151.
    STRINGi9606.ENSP00000382021.

    Structurei

    Secondary structure

    1334
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi28 – 43Combined sources16
    Helixi51 – 53Combined sources3
    Helixi64 – 87Combined sources24
    Turni88 – 90Combined sources3
    Beta strandi92 – 97Combined sources6
    Helixi104 – 110Combined sources7
    Beta strandi116 – 122Combined sources7
    Helixi124 – 136Combined sources13
    Helixi138 – 147Combined sources10
    Beta strandi148 – 152Combined sources5
    Beta strandi159 – 161Combined sources3
    Beta strandi163 – 169Combined sources7
    Helixi175 – 184Combined sources10
    Beta strandi193 – 199Combined sources7
    Helixi201 – 203Combined sources3
    Helixi206 – 219Combined sources14
    Beta strandi221 – 230Combined sources10
    Helixi236 – 246Combined sources11
    Turni247 – 249Combined sources3
    Helixi255 – 259Combined sources5
    Helixi261 – 269Combined sources9
    Turni270 – 272Combined sources3
    Beta strandi274 – 280Combined sources7
    Helixi281 – 286Combined sources6
    Helixi290 – 299Combined sources10
    Helixi305 – 312Combined sources8
    Beta strandi315 – 323Combined sources9
    Turni325 – 328Combined sources4
    Helixi329 – 331Combined sources3

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3IEIX-ray1.90A/B/C/D/E/F/G/H1-334[»]
    3O7WX-ray2.00A23-232[»]
    A259-334[»]
    3P71X-ray2.70T1-334[»]
    ProteinModelPortaliQ9UIC8.
    SMRiQ9UIC8.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9UIC8.

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni171 – 172S-adenosyl-L-methionine binding2

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiKOG2918. Eukaryota.
    ENOG410YB9K. LUCA.
    GeneTreeiENSGT00530000063793.
    HOVERGENiHBG052313.
    InParanoidiQ9UIC8.
    KOiK18203.
    OMAiRATCDDA.
    OrthoDBiEOG091G0CW2.
    PhylomeDBiQ9UIC8.
    TreeFamiTF315087.

    Family and domain databases

    Gene3Di3.40.50.150. 1 hit.
    InterProiIPR016651. Leu_CO_MeTrfase_LCMT1.
    IPR007213. Ppm1/Ppm2/Tcmp.
    IPR029063. SAM-dependent_MTases.
    [Graphical view]
    PANTHERiPTHR13600. PTHR13600. 1 hit.
    PfamiPF04072. LCM. 1 hit.
    [Graphical view]
    PIRSFiPIRSF016305. LCM_mtfrase. 1 hit.
    SUPFAMiSSF53335. SSF53335. 1 hit.

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q9UIC8-1) [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
    MATRQRESSI TSCCSTSSCD ADDEGVRGTC EDASLCKRFA VSIGYWHDPY
    60 70 80 90 100
    IQHFVRLSKE RKAPEINRGY FARVHGVSQL IKAFLRKTEC HCQIVNLGAG
    110 120 130 140 150
    MDTTFWRLKD EDLLPSKYFE VDFPMIVTRK LHSIKCKPPL SSPILELHSE
    160 170 180 190 200
    DTLQMDGHIL DSKRYAVIGA DLRDLSELEE KLKKCNMNTQ LPTLLIAECV
    210 220 230 240 250
    LVYMTPEQSA NLLKWAANSF ERAMFINYEQ VNMGDRFGQI MIENLRRRQC
    260 270 280 290 300
    DLAGVETCKS LESQKERLLS NGWETASAVD MMELYNRLPR AEVSRIESLE
    310 320 330
    FLDEMELLEQ LMRHYCLCWA TKGGNELGLK EITY
    Length:334
    Mass (Da):38,379
    Last modified:December 1, 2000 - v2
    Checksum:iC8D200118E6F353D
    GO
    Isoform 2 (identifier: Q9UIC8-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-37: MATRQRESSI...GTCEDASLCK → MLPCARELPS...CSHLGLRSGR

    Show »
    Length:357
    Mass (Da):41,106
    Checksum:iFBC25BB4C0B61057
    GO
    Isoform 3 (identifier: Q9UIC8-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         136-190: Missing.

    Show »
    Length:279
    Mass (Da):32,172
    Checksum:i6573F21B2405F64B
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti49P → S in BAD97084 (Ref. 4) Curated1
    Sequence conflicti114L → P in BAB15270 (PubMed:14702039).Curated1
    Sequence conflicti248 – 249RQ → PS in AAD34063 (PubMed:10810093).Curated2
    Sequence conflicti251D → E in AAF18267 (PubMed:10600115).Curated1
    Sequence conflicti301F → L in BAB15270 (PubMed:14702039).Curated1
    Sequence conflicti306 – 307EL → DV in AAF18267 (PubMed:10600115).Curated2
    Sequence conflicti312 – 313MR → NA in AAF18267 (PubMed:10600115).Curated2

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0174281 – 37MATRQ…ASLCK → MLPCARELPSAAPDSTLLLT AQHWVANLFILATLIGWTVR SFFLGRMETCCSHLGLRSGR in isoform 2. 3 PublicationsAdd BLAST37
    Alternative sequenceiVSP_041416136 – 190Missing in isoform 3. CuratedAdd BLAST55

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF037601 mRNA. Translation: AAF18267.1.
    AF151826 mRNA. Translation: AAD34063.1.
    AK025884 mRNA. Translation: BAB15270.1.
    AK223364 mRNA. Translation: BAD97084.1.
    AK291885 mRNA. Translation: BAF84574.1.
    AK314409 mRNA. Translation: BAG37031.1.
    AC008741 Genomic DNA. No translation available.
    AC133552 Genomic DNA. No translation available.
    BC001214 mRNA. Translation: AAH01214.1.
    BC014217 mRNA. Translation: AAH14217.1.
    AL137283 mRNA. Translation: CAB70677.1.
    CCDSiCCDS45445.1. [Q9UIC8-1]
    CCDS45446.1. [Q9UIC8-3]
    PIRiT46352.
    RefSeqiNP_001027563.1. NM_001032391.1. [Q9UIC8-3]
    NP_057393.2. NM_016309.2. [Q9UIC8-1]
    XP_011544166.1. XM_011545864.1. [Q9UIC8-2]
    UniGeneiHs.337730.

    Genome annotation databases

    EnsembliENST00000380966; ENSP00000370353; ENSG00000205629. [Q9UIC8-3]
    ENST00000399069; ENSP00000382021; ENSG00000205629. [Q9UIC8-1]
    GeneIDi51451.
    KEGGihsa:51451.
    UCSCiuc002dnx.2. human. [Q9UIC8-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF037601 mRNA. Translation: AAF18267.1.
    AF151826 mRNA. Translation: AAD34063.1.
    AK025884 mRNA. Translation: BAB15270.1.
    AK223364 mRNA. Translation: BAD97084.1.
    AK291885 mRNA. Translation: BAF84574.1.
    AK314409 mRNA. Translation: BAG37031.1.
    AC008741 Genomic DNA. No translation available.
    AC133552 Genomic DNA. No translation available.
    BC001214 mRNA. Translation: AAH01214.1.
    BC014217 mRNA. Translation: AAH14217.1.
    AL137283 mRNA. Translation: CAB70677.1.
    CCDSiCCDS45445.1. [Q9UIC8-1]
    CCDS45446.1. [Q9UIC8-3]
    PIRiT46352.
    RefSeqiNP_001027563.1. NM_001032391.1. [Q9UIC8-3]
    NP_057393.2. NM_016309.2. [Q9UIC8-1]
    XP_011544166.1. XM_011545864.1. [Q9UIC8-2]
    UniGeneiHs.337730.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3IEIX-ray1.90A/B/C/D/E/F/G/H1-334[»]
    3O7WX-ray2.00A23-232[»]
    A259-334[»]
    3P71X-ray2.70T1-334[»]
    ProteinModelPortaliQ9UIC8.
    SMRiQ9UIC8.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi119549. 10 interactors.
    IntActiQ9UIC8. 3 interactors.
    MINTiMINT-1448151.
    STRINGi9606.ENSP00000382021.

    Chemistry databases

    DrugBankiDB00149. L-Leucine.

    PTM databases

    iPTMnetiQ9UIC8.
    PhosphoSitePlusiQ9UIC8.

    Polymorphism and mutation databases

    BioMutaiLCMT1.
    DMDMi12643251.

    Proteomic databases

    EPDiQ9UIC8.
    PaxDbiQ9UIC8.
    PeptideAtlasiQ9UIC8.
    PRIDEiQ9UIC8.

    Protocols and materials databases

    DNASUi51451.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000380966; ENSP00000370353; ENSG00000205629. [Q9UIC8-3]
    ENST00000399069; ENSP00000382021; ENSG00000205629. [Q9UIC8-1]
    GeneIDi51451.
    KEGGihsa:51451.
    UCSCiuc002dnx.2. human. [Q9UIC8-1]

    Organism-specific databases

    CTDi51451.
    DisGeNETi51451.
    GeneCardsiLCMT1.
    H-InvDBHIX0017913.
    HIX0022158.
    HGNCiHGNC:17557. LCMT1.
    HPAiHPA041559.
    HPA043530.
    MIMi610286. gene.
    neXtProtiNX_Q9UIC8.
    OpenTargetsiENSG00000205629.
    PharmGKBiPA134928443.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG2918. Eukaryota.
    ENOG410YB9K. LUCA.
    GeneTreeiENSGT00530000063793.
    HOVERGENiHBG052313.
    InParanoidiQ9UIC8.
    KOiK18203.
    OMAiRATCDDA.
    OrthoDBiEOG091G0CW2.
    PhylomeDBiQ9UIC8.
    TreeFamiTF315087.

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER-16510.
    ZFISH:MONOMER-16510.

    Miscellaneous databases

    EvolutionaryTraceiQ9UIC8.
    GeneWikiiLeucine_carboxyl_methyltransferase_1.
    GenomeRNAii51451.
    PROiQ9UIC8.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000205629.
    CleanExiHS_LCMT1.
    ExpressionAtlasiQ9UIC8. baseline and differential.
    GenevisibleiQ9UIC8. HS.

    Family and domain databases

    Gene3Di3.40.50.150. 1 hit.
    InterProiIPR016651. Leu_CO_MeTrfase_LCMT1.
    IPR007213. Ppm1/Ppm2/Tcmp.
    IPR029063. SAM-dependent_MTases.
    [Graphical view]
    PANTHERiPTHR13600. PTHR13600. 1 hit.
    PfamiPF04072. LCM. 1 hit.
    [Graphical view]
    PIRSFiPIRSF016305. LCM_mtfrase. 1 hit.
    SUPFAMiSSF53335. SSF53335. 1 hit.
    ProtoNetiSearch...

    Entry informationi

    Entry nameiLCMT1_HUMAN
    AccessioniPrimary (citable) accession number: Q9UIC8
    Secondary accession number(s): A6NL89
    , A8K770, Q53FC5, Q96CI5, Q9H6I9, Q9NTG4, Q9Y378
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: December 1, 2000
    Last modified: November 30, 2016
    This is version 142 of the entry and version 2 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 16
      Human chromosome 16: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. 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.