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O60725 (ICMT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:ICMT
Synonyms:PCCMT
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length284 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Catalytic activity

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

Cofactor

Divalent cations. Probably zinc By similarity.

Subcellular location

Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.7.

Tissue specificity

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. Ref.6

Sequence similarities

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

Ontologies

Keywords
   Cellular componentEndoplasmic reticulum
Membrane
   DomainTransmembrane
Transmembrane helix
   LigandS-adenosyl-L-methionine
   Molecular functionMethyltransferase
Transferase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processC-terminal protein methylation

Traceable author statement PubMed 10441503. Source: ProtInc

cellular protein modification process

Traceable author statement Ref.1. Source: ProtInc

in utero embryonic development

Inferred from electronic annotation. Source: Ensembl

liver development

Inferred from electronic annotation. Source: Ensembl

multicellular organism growth

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

protein targeting to membrane

Traceable author statement Ref.1. Source: ProtInc

regulation of Ras protein signal transduction

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentendoplasmic reticulum

Inferred from direct assay Ref.1. Source: MGI

endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Traceable author statement PubMed 10441503. Source: ProtInc

   Molecular_functioncAMP response element binding protein binding

Inferred from electronic annotation. Source: Ensembl

protein C-terminal S-isoprenylcysteine carboxyl O-methyltransferase activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein C-terminal carboxyl O-methyltransferase activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 284284Protein-S-isoprenylcysteine O-methyltransferase
PRO_0000209894

Regions

Topological domain1 – 1616Cytoplasmic Potential
Transmembrane17 – 3317Helical; Potential
Topological domain34 – 418Lumenal Potential
Transmembrane42 – 5918Helical; Potential
Topological domain60 – 6910Cytoplasmic Potential
Transmembrane70 – 8718Helical; Potential
Topological domain88 – 925Lumenal Potential
Transmembrane93 – 11220Helical; Potential
Topological domain113 – 13119Cytoplasmic Potential
Transmembrane132 – 14918Helical; Potential
Topological domain150 – 1545Lumenal Potential
Transmembrane155 – 17420Helical; Potential
Topological domain175 – 21238Cytoplasmic Potential
Transmembrane213 – 22816Helical; Potential
Topological domain2291Lumenal Potential
Transmembrane230 – 24415Helical; Potential
Topological domain245 – 28440Cytoplasmic Potential

Sequences

Sequence LengthMass (Da)Tools
O60725 [UniParc].

Last modified August 1, 1998. Version 1.
Checksum: C86741B13ACA611C

FASTA28431,938
        10         20         30         40         50         60 
MAGCAARAPP GSEARLSLAT FLLGASVLAL PLLTRAGLQG RTGLALYVAG LNALLLLLYR 

        70         80         90        100        110        120 
PPRYQIAIRA CFLGFVFGCG TLLSFSQSSW SHFGWYMCSL SLFHYSEYLV TAVNNPKSLS 

       130        140        150        160        170        180 
LDSFLLNHSL EYTVAALSSW LEFTLENIFW PELKQITWLS VTGLLMVVFG ECLRKAAMFT 

       190        200        210        220        230        240 
AGSNFNHVVQ NEKSDTHTLV TSGVYAWFRH PSYVGWFYWS IGTQVMLCNP ICGVSYALTV 

       250        260        270        280 
WRFFRDRTEE EEISLIHFFG EEYLEYKKRV PTGLPFIKGV KVDL 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS61.1.
RefSeqNP_036537.1. NM_012405.3.
XP_005263494.1. XM_005263437.1.
UniGeneHs.515688.

3D structure databases

ProteinModelPortalO60725.
SMRO60725. Positions 153-275.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117026. 5 interactions.
STRING9606.ENSP00000343552.

Chemistry

BindingDBO60725.
ChEMBLCHEMBL4699.

PTM databases

PhosphoSiteO60725.

Proteomic databases

MaxQBO60725.
PaxDbO60725.
PRIDEO60725.

Protocols and materials databases

DNASU23463.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000343813; ENSP00000343552; ENSG00000116237.
GeneID23463.
KEGGhsa:23463.
UCSCuc001amk.3. human.

Organism-specific databases

CTD23463.
GeneCardsGC01M006282.
HGNCHGNC:5350. ICMT.
HPAHPA032025.
MIM605851. gene.
neXtProtNX_O60725.
PharmGKBPA29598.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2020.
HOGENOMHOG000213961.
HOVERGENHBG019034.
InParanoidO60725.
KOK00587.
OMATTWTHFG.
OrthoDBEOG7WHHC4.
PhylomeDBO60725.
TreeFamTF313769.

Enzyme and pathway databases

SABIO-RKO60725.

Gene expression databases

ArrayExpressO60725.
BgeeO60725.
CleanExHS_ICMT.
GenevestigatorO60725.

Family and domain databases

InterProIPR007269. ICMT_MeTrfase.
IPR025770. PPMT_MeTrfase.
[Graphical view]
PfamPF04140. ICMT. 1 hit.
[Graphical view]
PROSITEPS51564. SAM_ICMT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiICMT.
GenomeRNAi23463.
NextBio45777.
PROO60725.
SOURCESearch...

Entry information

Entry nameICMT_HUMAN
AccessionPrimary (citable) accession number: O60725
Secondary accession number(s): Q6FHT0
Entry history
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: August 1, 1998
Last modified: July 9, 2014
This is version 117 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM