ID   ICMT_RAT                Reviewed;         284 AA.
AC   Q9WVM4; G3V7G5;
DT   20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT   07-OCT-2020, sequence version 2.
DT   27-MAR-2024, entry version 121.
DE   RecName: Full=Protein-S-isoprenylcysteine O-methyltransferase;
DE            EC=2.1.1.100 {ECO:0000250|UniProtKB:O60725};
DE   AltName: Full=Farnesyl cysteine carboxyl methyltransferase;
DE            Short=FCMT;
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 {ECO:0000312|RGD:621618};
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1] {ECO:0000312|Proteomes:UP000002494}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway {ECO:0000312|Proteomes:UP000002494};
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
RN   [2] {ECO:0000312|Proteomes:UP000002494}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway {ECO:0000312|EMBL:EDL81231.1};
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3] {ECO:0000312|EMBL:AAD42926.1}
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 53-284.
RC   STRAIN=Sprague-Dawley; TISSUE=Olfactory bulb;
RA   Otaki J.M., Firestein S.;
RT   "Molecular cloning of farnesyl cysteine carboxyl methyltransferase gene
RT   from rat olfactory bulb.";
RL   Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Catalyzes the post-translational methylation of isoprenylated
CC       C-terminal cysteine residues. {ECO:0000250|UniProtKB:O60725}.
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:0000250|UniProtKB:O60725};
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:O60725}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:O60725}.
CC   -!- SIMILARITY: Belongs to the class VI-like SAM-binding methyltransferase
CC       superfamily. Isoprenylcysteine carboxyl methyltransferase family.
CC       {ECO:0000305}.
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DR   EMBL; AC135674; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH473968; EDL81231.1; -; Genomic_DNA.
DR   EMBL; AF075595; AAD42926.1; -; mRNA.
DR   RefSeq; NP_579844.2; NM_133310.2.
DR   AlphaFoldDB; Q9WVM4; -.
DR   SMR; Q9WVM4; -.
DR   STRING; 10116.ENSRNOP00000014625; -.
DR   BindingDB; Q9WVM4; -.
DR   ChEMBL; CHEMBL2298; -.
DR   PhosphoSitePlus; Q9WVM4; -.
DR   PaxDb; 10116-ENSRNOP00000014625; -.
DR   Ensembl; ENSRNOT00000014625.6; ENSRNOP00000014625.3; ENSRNOG00000010953.7.
DR   Ensembl; ENSRNOT00055027142; ENSRNOP00055021880; ENSRNOG00055015966.
DR   Ensembl; ENSRNOT00060005985; ENSRNOP00060004406; ENSRNOG00060003637.
DR   Ensembl; ENSRNOT00065015996; ENSRNOP00065012095; ENSRNOG00065009955.
DR   GeneID; 170818; -.
DR   KEGG; rno:170818; -.
DR   UCSC; RGD:621618; rat.
DR   AGR; RGD:621618; -.
DR   CTD; 23463; -.
DR   RGD; 621618; Icmt.
DR   eggNOG; KOG2628; Eukaryota.
DR   GeneTree; ENSGT00390000017394; -.
DR   HOGENOM; CLU_065200_0_1_1; -.
DR   InParanoid; Q9WVM4; -.
DR   OMA; YFGWFWR; -.
DR   OrthoDB; 5473160at2759; -.
DR   PhylomeDB; Q9WVM4; -.
DR   TreeFam; TF313769; -.
DR   Reactome; R-RNO-163841; Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation.
DR   Reactome; R-RNO-9648002; RAS processing.
DR   SABIO-RK; Q9WVM4; -.
DR   PRO; PR:Q9WVM4; -.
DR   Proteomes; UP000002494; Chromosome 5.
DR   Proteomes; UP000234681; Chromosome 5.
DR   Bgee; ENSRNOG00000010953; Expressed in testis and 18 other cell types or tissues.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0008140; F:cAMP response element binding protein binding; ISO:RGD.
DR   GO; GO:0004671; F:protein C-terminal S-isoprenylcysteine carboxyl O-methyltransferase activity; IMP:RGD.
DR   GO; GO:0030282; P:bone mineralization; ISO:RGD.
DR   GO; GO:0008340; P:determination of adult lifespan; ISO:RGD.
DR   GO; GO:0048144; P:fibroblast proliferation; ISO:RGD.
DR   GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR   GO; GO:0001889; P:liver development; ISO:RGD.
DR   GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR   GO; GO:0035264; P:multicellular organism growth; ISO:RGD.
DR   GO; GO:0050905; P:neuromuscular process; ISO:RGD.
DR   GO; GO:0048146; P:positive regulation of fibroblast proliferation; ISO:RGD.
DR   GO; GO:0008104; P:protein localization; ISO:RGD.
DR   GO; GO:2000772; P:regulation of cellular senescence; ISO:RGD.
DR   GO; GO:0032880; P:regulation of protein localization; ISO:RGD.
DR   GO; GO:0046578; P:regulation of Ras protein signal transduction; ISO:RGD.
DR   GO; GO:0046498; P:S-adenosylhomocysteine metabolic process; IMP:RGD.
DR   GO; GO:0046499; P:S-adenosylmethioninamine metabolic process; IMP:RGD.
DR   GO; GO:0031929; P:TOR signaling; ISO:RGD.
DR   Gene3D; 1.20.120.1630; -; 1.
DR   InterPro; IPR007269; ICMT_MeTrfase.
DR   InterPro; IPR025770; PPMT_MeTrfase.
DR   PANTHER; PTHR12714; PROTEIN-S ISOPRENYLCYSTEINE O-METHYLTRANSFERASE; 1.
DR   PANTHER; PTHR12714:SF9; PROTEIN-S-ISOPRENYLCYSTEINE O-METHYLTRANSFERASE; 1.
DR   Pfam; PF04140; ICMT; 1.
DR   PROSITE; PS51564; SAM_ICMT; 1.
PE   2: Evidence at transcript 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_0000209896"
FT   TOPO_DOM        1..16
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        17..33
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        34..41
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        42..59
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        60..69
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        70..87
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        88..92
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        93..112
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        113..131
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        132..149
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        150..154
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        155..174
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        175..212
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        213..228
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        229
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        230..244
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        245..284
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
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;  31812 MW;  DCAB6EA1D6EE0827 CRC64;
     MAGCAARVPP GSEARLSLAT FLLGASVLAL PLLTRAGLQG RTGLALYVAG LNALLLLLYR
     PPRYQIAIRA CFLGFVFGCG VLLSFSQSSW NHFGWYVCSL SLFHYSEYLV TAVNNPKSLS
     LDSFLLNHSL EYTVAALSSW IEFTLENIFW PELKQITWLS AAGLLMVIFG ECLRKVAMFT
     AGSNFNHVVQ SEKSDTHTLV TSGVYAWCRH PSYVGWFYWS IGTQVMLCNP ICGVVYALTV
     WRFFRDRTEE EEISLIHFFG EEYLDYKKRV PTGLPFIKGV KVGL
//