ICMT_HUMAN
ID ICMT_HUMAN Reviewed; 284 AA.
AC O60725; Q6FHT0;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Protein-S-isoprenylcysteine O-methyltransferase;
DE EC=2.1.1.100 {ECO:0000269|PubMed:9614111};
DE AltName: Full=Isoprenylcysteine carboxylmethyltransferase;
DE AltName: Full=Prenylated protein carboxyl methyltransferase;
DE Short=PPMT;
DE AltName: Full=Prenylcysteine carboxyl methyltransferase;
DE Short=pcCMT;
GN Name=ICMT; Synonyms=PCCMT;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, AND SUBCELLULAR LOCATION.
RC TISSUE=Myeloid;
RX PubMed=9614111; DOI=10.1074/jbc.273.24.15030;
RA Dai Q., Choy E., Chiu V., Romano J., Slivka S.R., Steitz S.A.,
RA Michaelis S., Philips M.R.;
RT "Mammalian prenylcysteine carboxyl methyltransferase is in the endoplasmic
RT reticulum.";
RL J. Biol. Chem. 273:15030-15034(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=10649571; DOI=10.1038/72101;
RA Lin X., Antalffy B., Kang D., Orr H.T., Zoghbi H.Y.;
RT "Polyglutamine expansion down-regulates specific neuronal genes before
RT pathologic changes in SCA1.";
RL Nat. Neurosci. 3:157-163(2000).
RN [7]
RP SUBCELLULAR LOCATION, AND MEMBRANE TOPOLOGY.
RX PubMed=19158273; DOI=10.1128/mcb.01719-08;
RA Wright L.P., Court H., Mor A., Ahearn I.M., Casey P.J., Philips M.R.;
RT "Topology of mammalian isoprenylcysteine carboxyl methyltransferase
RT determined in live cells with a fluorescent probe.";
RL Mol. Cell. Biol. 29:1826-1833(2009).
CC -!- FUNCTION: Catalyzes the post-translational methylation of isoprenylated
CC C-terminal cysteine residues. {ECO:0000269|PubMed:9614111}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[protein]-C-terminal S-[(2E,6E)-farnesyl]-L-cysteine + S-
CC adenosyl-L-methionine = [protein]-C-terminal S-[(2E,6E)-farnesyl]-L-
CC cysteine methyl ester + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:21672, Rhea:RHEA-COMP:12125, Rhea:RHEA-COMP:12126,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:90510,
CC ChEBI:CHEBI:90511; EC=2.1.1.100;
CC Evidence={ECO:0000269|PubMed:9614111};
CC -!- ACTIVITY REGULATION: Competitively inhibited by N-acetyl-S-trans,trans-
CC farnesyl-l-cysteine (AFC). {ECO:0000269|PubMed:9614111}.
CC -!- INTERACTION:
CC O60725; Q13520: AQP6; NbExp=3; IntAct=EBI-11721771, EBI-13059134;
CC O60725; Q3SXY8: ARL13B; NbExp=3; IntAct=EBI-11721771, EBI-11343438;
CC O60725; Q8N5M9: JAGN1; NbExp=3; IntAct=EBI-11721771, EBI-10266796;
CC O60725; P48051: KCNJ6; NbExp=3; IntAct=EBI-11721771, EBI-12017638;
CC O60725; P15941-11: MUC1; NbExp=3; IntAct=EBI-11721771, EBI-17263240;
CC O60725; Q13113: PDZK1IP1; NbExp=3; IntAct=EBI-11721771, EBI-716063;
CC O60725; Q6ZMZ0: RNF19B; NbExp=3; IntAct=EBI-11721771, EBI-2466594;
CC O60725; Q13049: TRIM32; NbExp=3; IntAct=EBI-11721771, EBI-742790;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:19158273, ECO:0000269|PubMed:9614111}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:19158273}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Expressed at higher levels
CC in the cerebellum and putamen than in other brain regions. Abundant
CC expression seen in the Purkinje cells and pontine neurons.
CC {ECO:0000269|PubMed:10649571}.
CC -!- SIMILARITY: Belongs to the class VI-like SAM-binding methyltransferase
CC superfamily. Isoprenylcysteine carboxyl methyltransferase family.
CC {ECO:0000255|PROSITE-ProRule:PRU00897}.
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DR EMBL; AF064084; AAC16554.1; -; mRNA.
DR EMBL; CR541671; CAG46472.1; -; mRNA.
DR EMBL; CR541711; CAG46512.1; -; mRNA.
DR EMBL; AL031847; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471130; EAW71522.1; -; Genomic_DNA.
DR EMBL; BC028168; AAH28168.1; -; mRNA.
DR CCDS; CCDS61.1; -.
DR RefSeq; NP_036537.1; NM_012405.3.
DR AlphaFoldDB; O60725; -.
DR SMR; O60725; -.
DR BioGRID; 117026; 128.
DR IntAct; O60725; 25.
DR MINT; O60725; -.
DR STRING; 9606.ENSP00000343552; -.
DR BindingDB; O60725; -.
DR ChEMBL; CHEMBL4699; -.
DR iPTMnet; O60725; -.
DR PhosphoSitePlus; O60725; -.
DR BioMuta; ICMT; -.
DR EPD; O60725; -.
DR jPOST; O60725; -.
DR MassIVE; O60725; -.
DR PaxDb; O60725; -.
DR PeptideAtlas; O60725; -.
DR PRIDE; O60725; -.
DR ProteomicsDB; 49571; -.
DR Antibodypedia; 27272; 192 antibodies from 26 providers.
DR DNASU; 23463; -.
DR Ensembl; ENST00000343813.10; ENSP00000343552.5; ENSG00000116237.16.
DR GeneID; 23463; -.
DR KEGG; hsa:23463; -.
DR MANE-Select; ENST00000343813.10; ENSP00000343552.5; NM_012405.4; NP_036537.1.
DR UCSC; uc001amk.4; human.
DR CTD; 23463; -.
DR DisGeNET; 23463; -.
DR GeneCards; ICMT; -.
DR HGNC; HGNC:5350; ICMT.
DR HPA; ENSG00000116237; Low tissue specificity.
DR MIM; 605851; gene.
DR neXtProt; NX_O60725; -.
DR OpenTargets; ENSG00000116237; -.
DR PharmGKB; PA29598; -.
DR VEuPathDB; HostDB:ENSG00000116237; -.
DR eggNOG; KOG2628; Eukaryota.
DR GeneTree; ENSGT00390000017394; -.
DR HOGENOM; CLU_065200_0_1_1; -.
DR InParanoid; O60725; -.
DR OMA; GMVPQVW; -.
DR OrthoDB; 1479599at2759; -.
DR PhylomeDB; O60725; -.
DR TreeFam; TF313769; -.
DR BRENDA; 2.1.1.100; 2681.
DR PathwayCommons; O60725; -.
DR Reactome; R-HSA-163841; Gamma carboxylation, hypusine formation and arylsulfatase activation.
DR Reactome; R-HSA-9648002; RAS processing.
DR SABIO-RK; O60725; -.
DR SignaLink; O60725; -.
DR BioGRID-ORCS; 23463; 73 hits in 1088 CRISPR screens.
DR ChiTaRS; ICMT; human.
DR GeneWiki; ICMT; -.
DR GenomeRNAi; 23463; -.
DR Pharos; O60725; Tchem.
DR PRO; PR:O60725; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O60725; protein.
DR Bgee; ENSG00000116237; Expressed in diaphragm and 211 other tissues.
DR ExpressionAtlas; O60725; baseline and differential.
DR Genevisible; O60725; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0003880; F:protein C-terminal carboxyl O-methyltransferase activity; TAS:ProtInc.
DR GO; GO:0004671; F:protein C-terminal S-isoprenylcysteine carboxyl O-methyltransferase activity; IBA:GO_Central.
DR GO; GO:0006481; P:C-terminal protein methylation; IBA:GO_Central.
DR GO; GO:0036211; P:protein modification process; TAS:ProtInc.
DR GO; GO:0006612; P:protein targeting to membrane; TAS:ProtInc.
DR GO; GO:0046498; P:S-adenosylhomocysteine metabolic process; IEA:Ensembl.
DR GO; GO:0046499; P:S-adenosylmethioninamine metabolic process; IEA:Ensembl.
DR InterPro; IPR007269; ICMT_MeTrfase.
DR InterPro; IPR025770; PPMT_MeTrfase.
DR Pfam; PF04140; ICMT; 1.
DR PROSITE; PS51564; SAM_ICMT; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Membrane; Methyltransferase; Reference proteome;
KW S-adenosyl-L-methionine; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..284
FT /note="Protein-S-isoprenylcysteine O-methyltransferase"
FT /id="PRO_0000209894"
FT TOPO_DOM 1..16
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 17..33
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 34..41
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 42..59
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 60..69
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 70..87
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 88..92
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 93..112
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 113..131
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 132..149
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 150..154
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 155..174
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 175..212
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 213..228
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 229
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 230..244
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 245..284
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT BINDING 190
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:D6WJ77"
FT BINDING 197..200
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:D6WJ77"
FT BINDING 205
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:D6WJ77"
FT BINDING 210..213
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:D6WJ77"
FT BINDING 247
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:D6WJ77"
FT BINDING 251
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:D6WJ77"
SQ SEQUENCE 284 AA; 31938 MW; C86741B13ACA611C CRC64;
MAGCAARAPP GSEARLSLAT FLLGASVLAL PLLTRAGLQG RTGLALYVAG LNALLLLLYR
PPRYQIAIRA CFLGFVFGCG TLLSFSQSSW SHFGWYMCSL SLFHYSEYLV TAVNNPKSLS
LDSFLLNHSL EYTVAALSSW LEFTLENIFW PELKQITWLS VTGLLMVVFG ECLRKAAMFT
AGSNFNHVVQ NEKSDTHTLV TSGVYAWFRH PSYVGWFYWS IGTQVMLCNP ICGVSYALTV
WRFFRDRTEE EEISLIHFFG EEYLEYKKRV PTGLPFIKGV KVDL
