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O60725

- ICMT_HUMAN

UniProt

O60725 - ICMT_HUMAN

Protein

Protein-S-isoprenylcysteine O-methyltransferase

Gene

ICMT

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 118 (01 Oct 2014)
      Sequence version 1 (01 Aug 1998)
      Previous versions | rss
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    Functioni

    Catalyzes the post-translational methylation of isoprenylated C-terminal cysteine residues.

    Catalytic activityi

    S-adenosyl-L-methionine + protein C-terminal S-farnesyl-L-cysteine = S-adenosyl-L-homocysteine + protein C-terminal S-farnesyl-L-cysteine methyl ester.PROSITE-ProRule annotation

    Cofactori

    Divalent cations. Probably zinc By similarity.By similarity

    GO - Molecular functioni

    1. cAMP response element binding protein binding Source: Ensembl
    2. protein C-terminal carboxyl O-methyltransferase activity Source: ProtInc
    3. protein C-terminal S-isoprenylcysteine carboxyl O-methyltransferase activity Source: UniProtKB-EC

    GO - Biological processi

    1. cellular protein modification process Source: ProtInc
    2. C-terminal protein methylation Source: ProtInc
    3. in utero embryonic development Source: Ensembl
    4. liver development Source: Ensembl
    5. multicellular organism growth Source: Ensembl
    6. positive regulation of cell proliferation Source: Ensembl
    7. protein targeting to membrane Source: ProtInc
    8. regulation of Ras protein signal transduction Source: Ensembl

    Keywords - Molecular functioni

    Methyltransferase, Transferase

    Keywords - Ligandi

    S-adenosyl-L-methionine

    Enzyme and pathway databases

    SABIO-RKO60725.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Protein-S-isoprenylcysteine O-methyltransferase (EC:2.1.1.100)
    Alternative name(s):
    Isoprenylcysteine carboxylmethyltransferase
    Prenylated protein carboxyl methyltransferase
    Short name:
    PPMT
    Prenylcysteine carboxyl methyltransferase
    Short name:
    pcCMT
    Gene namesi
    Name:ICMT
    Synonyms:PCCMT
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:5350. ICMT.

    Subcellular locationi

    Endoplasmic reticulum membrane 1 Publication; Multi-pass membrane protein 1 Publication

    GO - Cellular componenti

    1. endoplasmic reticulum Source: MGI
    2. endoplasmic reticulum membrane Source: UniProtKB-SubCell
    3. integral component of membrane Source: UniProtKB-KW
    4. membrane Source: ProtInc

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA29598.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 284284Protein-S-isoprenylcysteine O-methyltransferasePRO_0000209894Add
    BLAST

    Proteomic databases

    MaxQBiO60725.
    PaxDbiO60725.
    PRIDEiO60725.

    PTM databases

    PhosphoSiteiO60725.

    Expressioni

    Tissue specificityi

    Ubiquitously expressed. Expressed at higher levels in the cerebellum and putamen than in other brain regions. Abundant expression seen in the Purkinje cells and pontine neurons.1 Publication

    Gene expression databases

    ArrayExpressiO60725.
    BgeeiO60725.
    CleanExiHS_ICMT.
    GenevestigatoriO60725.

    Organism-specific databases

    HPAiHPA032025.

    Interactioni

    Protein-protein interaction databases

    BioGridi117026. 5 interactions.
    STRINGi9606.ENSP00000343552.

    Structurei

    3D structure databases

    ProteinModelPortaliO60725.
    SMRiO60725. Positions 153-275.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 1616CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini34 – 418LumenalSequence Analysis
    Topological domaini60 – 6910CytoplasmicSequence Analysis
    Topological domaini88 – 925LumenalSequence Analysis
    Topological domaini113 – 13119CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini150 – 1545LumenalSequence Analysis
    Topological domaini175 – 21238CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini229 – 2291LumenalSequence Analysis
    Topological domaini245 – 28440CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei17 – 3317HelicalSequence AnalysisAdd
    BLAST
    Transmembranei42 – 5918HelicalSequence AnalysisAdd
    BLAST
    Transmembranei70 – 8718HelicalSequence AnalysisAdd
    BLAST
    Transmembranei93 – 11220HelicalSequence AnalysisAdd
    BLAST
    Transmembranei132 – 14918HelicalSequence AnalysisAdd
    BLAST
    Transmembranei155 – 17420HelicalSequence AnalysisAdd
    BLAST
    Transmembranei213 – 22816HelicalSequence AnalysisAdd
    BLAST
    Transmembranei230 – 24415HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the class VI-like SAM-binding methyltransferase superfamily. Isoprenylcysteine carboxyl methyltransferase family.PROSITE-ProRule annotation

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG2020.
    HOGENOMiHOG000213961.
    HOVERGENiHBG019034.
    InParanoidiO60725.
    KOiK00587.
    OMAiTTWTHFG.
    OrthoDBiEOG7WHHC4.
    PhylomeDBiO60725.
    TreeFamiTF313769.

    Family and domain databases

    InterProiIPR007269. ICMT_MeTrfase.
    IPR025770. PPMT_MeTrfase.
    [Graphical view]
    PfamiPF04140. ICMT. 1 hit.
    [Graphical view]
    PROSITEiPS51564. SAM_ICMT. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O60725-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAGCAARAPP GSEARLSLAT FLLGASVLAL PLLTRAGLQG RTGLALYVAG    50
    LNALLLLLYR PPRYQIAIRA CFLGFVFGCG TLLSFSQSSW SHFGWYMCSL 100
    SLFHYSEYLV TAVNNPKSLS LDSFLLNHSL EYTVAALSSW LEFTLENIFW 150
    PELKQITWLS VTGLLMVVFG ECLRKAAMFT AGSNFNHVVQ NEKSDTHTLV 200
    TSGVYAWFRH PSYVGWFYWS IGTQVMLCNP ICGVSYALTV WRFFRDRTEE 250
    EEISLIHFFG EEYLEYKKRV PTGLPFIKGV KVDL 284
    Length:284
    Mass (Da):31,938
    Last modified:August 1, 1998 - v1
    Checksum:iC86741B13ACA611C
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF064084 mRNA. Translation: AAC16554.1.
    CR541671 mRNA. Translation: CAG46472.1.
    CR541711 mRNA. Translation: CAG46512.1.
    AL031847 Genomic DNA. Translation: CAI19441.1.
    CH471130 Genomic DNA. Translation: EAW71522.1.
    BC028168 mRNA. Translation: AAH28168.1.
    CCDSiCCDS61.1.
    RefSeqiNP_036537.1. NM_012405.3.
    XP_005263494.1. XM_005263437.1.
    UniGeneiHs.515688.

    Genome annotation databases

    EnsembliENST00000343813; ENSP00000343552; ENSG00000116237.
    GeneIDi23463.
    KEGGihsa:23463.
    UCSCiuc001amk.3. human.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF064084 mRNA. Translation: AAC16554.1 .
    CR541671 mRNA. Translation: CAG46472.1 .
    CR541711 mRNA. Translation: CAG46512.1 .
    AL031847 Genomic DNA. Translation: CAI19441.1 .
    CH471130 Genomic DNA. Translation: EAW71522.1 .
    BC028168 mRNA. Translation: AAH28168.1 .
    CCDSi CCDS61.1.
    RefSeqi NP_036537.1. NM_012405.3.
    XP_005263494.1. XM_005263437.1.
    UniGenei Hs.515688.

    3D structure databases

    ProteinModelPortali O60725.
    SMRi O60725. Positions 153-275.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 117026. 5 interactions.
    STRINGi 9606.ENSP00000343552.

    Chemistry

    BindingDBi O60725.
    ChEMBLi CHEMBL4699.

    PTM databases

    PhosphoSitei O60725.

    Proteomic databases

    MaxQBi O60725.
    PaxDbi O60725.
    PRIDEi O60725.

    Protocols and materials databases

    DNASUi 23463.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000343813 ; ENSP00000343552 ; ENSG00000116237 .
    GeneIDi 23463.
    KEGGi hsa:23463.
    UCSCi uc001amk.3. human.

    Organism-specific databases

    CTDi 23463.
    GeneCardsi GC01M006282.
    HGNCi HGNC:5350. ICMT.
    HPAi HPA032025.
    MIMi 605851. gene.
    neXtProti NX_O60725.
    PharmGKBi PA29598.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG2020.
    HOGENOMi HOG000213961.
    HOVERGENi HBG019034.
    InParanoidi O60725.
    KOi K00587.
    OMAi TTWTHFG.
    OrthoDBi EOG7WHHC4.
    PhylomeDBi O60725.
    TreeFami TF313769.

    Enzyme and pathway databases

    SABIO-RK O60725.

    Miscellaneous databases

    GeneWikii ICMT.
    GenomeRNAii 23463.
    NextBioi 45777.
    PROi O60725.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O60725.
    Bgeei O60725.
    CleanExi HS_ICMT.
    Genevestigatori O60725.

    Family and domain databases

    InterProi IPR007269. ICMT_MeTrfase.
    IPR025770. PPMT_MeTrfase.
    [Graphical view ]
    Pfami PF04140. ICMT. 1 hit.
    [Graphical view ]
    PROSITEi PS51564. SAM_ICMT. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Mammalian prenylcysteine carboxyl methyltransferase is in the endoplasmic reticulum."
      Dai Q., Choy E., Chiu V., Romano J., Slivka S.R., Steitz S.A., Michaelis S., Philips M.R.
      J. Biol. Chem. 273:15030-15034(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION.
      Tissue: Myeloid.
    2. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
      Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
      Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    3. "The DNA sequence and biological annotation of human chromosome 1."
      Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
      , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
      Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "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].
      Tissue: Brain.
    6. "Polyglutamine expansion down-regulates specific neuronal genes before pathologic changes in SCA1."
      Lin X., Antalffy B., Kang D., Orr H.T., Zoghbi H.Y.
      Nat. Neurosci. 3:157-163(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    7. "Topology of mammalian isoprenylcysteine carboxyl methyltransferase determined in live cells with a fluorescent probe."
      Wright L.P., Court H., Mor A., Ahearn I.M., Casey P.J., Philips M.R.
      Mol. Cell. Biol. 29:1826-1833(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, MEMBRANE TOPOLOGY.

    Entry informationi

    Entry nameiICMT_HUMAN
    AccessioniPrimary (citable) accession number: O60725
    Secondary accession number(s): Q6FHT0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 20, 2001
    Last sequence update: August 1, 1998
    Last modified: October 1, 2014
    This is version 118 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

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3