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Protein

Protein-S-isoprenylcysteine O-methyltransferase

Gene

ICMT

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

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

Zn2+By similarityNote: Divalent metal cations. Probably Zn2+.By similarity

GO - Molecular functioni

  1. protein C-terminal carboxyl O-methyltransferase activity Source: ProtInc
  2. 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
  9. regulation of RNA biosynthetic process Source: Ensembl
Complete GO annotation...

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 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:5350. ICMT.

Subcellular locationi

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1616CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei17 – 3317HelicalSequence AnalysisAdd
BLAST
Topological domaini34 – 418LumenalSequence Analysis
Transmembranei42 – 5918HelicalSequence AnalysisAdd
BLAST
Topological domaini60 – 6910CytoplasmicSequence Analysis
Transmembranei70 – 8718HelicalSequence AnalysisAdd
BLAST
Topological domaini88 – 925LumenalSequence Analysis
Transmembranei93 – 11220HelicalSequence AnalysisAdd
BLAST
Topological domaini113 – 13119CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei132 – 14918HelicalSequence AnalysisAdd
BLAST
Topological domaini150 – 1545LumenalSequence Analysis
Transmembranei155 – 17420HelicalSequence AnalysisAdd
BLAST
Topological domaini175 – 21238CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei213 – 22816HelicalSequence AnalysisAdd
BLAST
Topological domaini229 – 2291LumenalSequence Analysis
Transmembranei230 – 24415HelicalSequence AnalysisAdd
BLAST
Topological domaini245 – 28440CytoplasmicSequence AnalysisAdd
BLAST

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
Complete GO annotation...

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

BgeeiO60725.
CleanExiHS_ICMT.
ExpressionAtlasiO60725. baseline and differential.
GenevestigatoriO60725.

Organism-specific databases

HPAiHPA032024.
HPA032025.

Interactioni

Protein-protein interaction databases

BioGridi117026. 4 interactions.
STRINGi9606.ENSP00000343552.

Structurei

3D structure databases

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

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.
GeneTreeiENSGT00390000017394.
HOGENOMiHOG000213961.
HOVERGENiHBG019034.
InParanoidiO60725.
KOiK00587.
OMAiNEKAQSH.
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

        10         20         30         40         50
MAGCAARAPP GSEARLSLAT FLLGASVLAL PLLTRAGLQG RTGLALYVAG
60 70 80 90 100
LNALLLLLYR PPRYQIAIRA CFLGFVFGCG TLLSFSQSSW SHFGWYMCSL
110 120 130 140 150
SLFHYSEYLV TAVNNPKSLS LDSFLLNHSL EYTVAALSSW LEFTLENIFW
160 170 180 190 200
PELKQITWLS VTGLLMVVFG ECLRKAAMFT AGSNFNHVVQ NEKSDTHTLV
210 220 230 240 250
TSGVYAWFRH PSYVGWFYWS IGTQVMLCNP ICGVSYALTV WRFFRDRTEE
260 270 280
EEISLIHFFG EEYLEYKKRV PTGLPFIKGV KVDL
Length:284
Mass (Da):31,938
Last modified:July 31, 1998 - v1
Checksum:iC86741B13ACA611C
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

BioGridi117026. 4 interactions.
STRINGi9606.ENSP00000343552.

Chemistry

BindingDBiO60725.
ChEMBLiCHEMBL4699.

PTM databases

PhosphoSiteiO60725.

Proteomic databases

MaxQBiO60725.
PaxDbiO60725.
PRIDEiO60725.

Protocols and materials databases

DNASUi23463.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi23463.
GeneCardsiGC01M006282.
HGNCiHGNC:5350. ICMT.
HPAiHPA032024.
HPA032025.
MIMi605851. gene.
neXtProtiNX_O60725.
PharmGKBiPA29598.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG2020.
GeneTreeiENSGT00390000017394.
HOGENOMiHOG000213961.
HOVERGENiHBG019034.
InParanoidiO60725.
KOiK00587.
OMAiNEKAQSH.
OrthoDBiEOG7WHHC4.
PhylomeDBiO60725.
TreeFamiTF313769.

Enzyme and pathway databases

SABIO-RKO60725.

Miscellaneous databases

GeneWikiiICMT.
GenomeRNAii23463.
NextBioi45777.
PROiO60725.
SOURCEiSearch...

Gene expression databases

BgeeiO60725.
CleanExiHS_ICMT.
ExpressionAtlasiO60725. baseline and differential.
GenevestigatoriO60725.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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(1997) [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 (MAY-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(2005) [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(2003) [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(1999) [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(2008) [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 19, 2001
Last sequence update: July 31, 1998
Last modified: March 31, 2015
This is version 123 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

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 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.