O60725 (ICMT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	ICMT
Synonyms:	PCCMT

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	284 AA.
Sequence status	Complete.
Protein existence	Evidence 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 isoprenylcysteine O-methyltransferase family.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane
Domain	Transmembrane Transmembrane helix
Ligand	S-adenosyl-L-methionine
Molecular function	Methyltransferase Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	protein targeting to membrane Traceable author statement. Source: ProtInc
Cellular component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW membrane fraction Traceable author statement. Source: ProtInc
Molecular function	protein C-terminal S-isoprenylcysteine carboxyl O-methyltransferase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 284	284	Protein-S-isoprenylcysteine O-methyltransferase		PRO_0000209894
Regions
	Topological domain	1 – 16	16	Cytoplasmic Potential
	Transmembrane	17 – 33	17	Helical; Potential
	Topological domain	34 – 41	8	Lumenal Potential
	Transmembrane	42 – 59	18	Helical; Potential
	Topological domain	60 – 69	10	Cytoplasmic Potential
	Transmembrane	70 – 87	18	Helical; Potential
	Topological domain	88 – 92	5	Lumenal Potential
	Transmembrane	93 – 112	20	Helical; Potential
	Topological domain	113 – 131	19	Cytoplasmic Potential
	Transmembrane	132 – 149	18	Helical; Potential
	Topological domain	150 – 154	5	Lumenal Potential
	Transmembrane	155 – 174	20	Helical; Potential
	Topological domain	175 – 212	38	Cytoplasmic Potential
	Transmembrane	213 – 228	16	Helical; Potential
	Topological domain	229	1	Lumenal Potential
	Transmembrane	230 – 244	15	Helical; Potential
	Topological domain	245 – 284	40	Cytoplasmic Potential

Sequences

	Sequence		Length	Mass (Da)
	O60725 [UniParc]. Last modified August 1, 1998. Version 1. Checksum: C86741B13ACA611C	FASTA	284	31,938
	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

References

	« Hide 'large scale' referencesShow '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: 9614111] [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: 16710414] [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. , 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: 15489334] [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: 10649571] [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: 19158273] [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.
IPI	IPI00031458.
RefSeq	NP_036537.1. NM_012405.3.
UniGene	Hs.515688. Hs.716549.
3D structure databases
ProteinModelPortal	O60725.
ModBase	Search...
Protein-protein interaction databases
STRING	O60725.
PTM databases
PhosphoSite	O60725.
Proteomic databases
PRIDE	O60725.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000343813; ENSP00000343552; ENSG00000116237.
GeneID	23463.
KEGG	hsa:23463.
UCSC	uc001amk.1. human.
Organism-specific databases
CTD	23463.
GeneCards	GC01M006282.
H-InvDB	HIX0000076.
HGNC	HGNC:5350. ICMT.
HPA	HPA032025.
MIM	605851. gene.
neXtProt	NX_O60725.
PharmGKB	PA29598.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG19078.
HOGENOM	HBG737603.
HOVERGEN	HBG019034.
InParanoid	O60725.
OMA	ELKQITW.
OrthoDB	EOG4NZTTX.
PhylomeDB	O60725.
Gene expression databases
ArrayExpress	O60725.
Bgee	O60725.
CleanEx	HS_ICMT.
Genevestigator	O60725.
GermOnline	ENSG00000116237. Homo sapiens.
Family and domain databases
InterPro	IPR007269. ICMT_MeTrfase. [Graphical view]
KO	K00587.
Pfam	PF04140. ICMT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	45777.
SOURCE	Search...

Entry information

Entry name

ICMT_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 93 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.